Selecthealth Medical Policies Cardiovascular Policies

SelectHealth Medical Policies Cardiovascular Policies

Table of Contents

Policy Last Policy Title Number Revised Autologous Stem Cell Infusion For Myocardial Infarction 394 02/18/10 Carotid Artery Stenting (CAS) 461 09/28/10 Coronary Artery Disease Calcium Scoring (Cardiac CT Scan) To Assess 262 01/17/12 Cardiovascular Risk Heart Transplant: Adult 125 10/08/18 Heart Transplant: Children (Under Age 18) 126 02/26/20 Heart-Lung Transplant 127 09/15/06 Implantable Loop Recorder (ILR) 131 07/15/03 Intima-Media Thickness (IMT) Testing For The Assessment of Heart Disease 238 09/14/04 Risk (Heart Scan) Inttravascular Imaging (i.e. Intravascular Ultrasound [IVUS] and Optical 447 05/14/19 Coherence Tomography [OCT]) Intravascular Lithotripsy (IVL) 647 04/23/21 LDL Apheresis (Liposorber Device, Help System) 207 05/09/19 Left Atrial Appendage Closure (LAAC) Devices (e.g., Watchman®) 430 08/06/15 Magnetic Resonance Imaging (MRI) for Cardiovascular Indications 154 08/01/19 Noninvasive Fractional Flow Reserve Using CT Angiography 617 08/01/17 Nuclear Magnetic Resonance (NMR) of LDL Particle Numbers to Assess 498 03/07/12 Cardiovascular Risk Pectus Excavatum Surgery 160 01/12/10 Percutaneous Mitral Valve Repair (MITRACLIP®) 464 01/23/14 Percutaneous Transcatheter Closure For The Treatment of Atrial Septal 174 08/14/18 Defects (ASD) and Patent Foramen Ovale (PFO) Percutaneous Transluminal Angioplasty Stenting (PTAS) [ Intracranial Stenting] 495 12/05/11 Subcutaneous Implantable Defibrillator 535 08/24/21 Total Artificial Heart 436 10/19/15 Transcatheter Aortic Valve Implant (TAVI) Transcatheter Aortic Valve 444 08/23/19 Replacement (TAVR) Transcatheter Pulmonary Valve Replacement 483 06/17/21

CONTINUED...

By accessing and/or downloading SelectHealth policies, you automatically agree to the Medical and Coding/ Reimbursement Policy Manual Terms and Conditions. Cardiovascular Policies, Continued

Policy Last Policy Title Number Revised Transthoracic Electrical Biompedance (TEB) Testing 335 01/17/14 Ventricular Assist Devices 187 10/23/08 Vertical Autoprofiling (VAP ™) Cholesterol Test 298 02/15/06 Wearable Cardioverter Defibrillator 406 02/15/18 Wireless Cardiac Monitoring (e.g., Cardiomems) 642 09/28/20

By accessing and/or downloading SelectHealth policies, you automatically agree to the Medical and Coding/ Reimbursement Policy Manual Terms and Conditions. Cardiovascular Policies, Continued

MEDICAL POLICY

AUTOLOGOUS STEM CELL INFUSION FOR MYOCARDIAL INFARCTION

Policy # 394 Implementation Date: 3/5/08 Review Dates: 2/19/09, 2/17/11, 2/16/12, 4/25/13, 2/20/14, 3/19/15, 2/11/16, 2/16/17, 2/15/18, 2/5/19, 2/11/20 Revision Dates: 2/18/10

Disclaimer: 1. Policies are subject to change without notice. 2. Policies outline coverage determinations for SelectHealth Commercial, SelectHealth Advantage (Medicare/CMS), and SelectHealth Community Care (Medicaid/CHIP) plans. Refer to the “Policy” section for more information.

Description Acute myocardial infarction (AMI) is the death of heart muscle secondary to prolonged lack of oxygen due to blockage of the artery supplying the muscle. Approximately 1.5 million cases of AMI occur each year in the United States and cardiovascular disease is the leading cause of death in the U.S; approximately 500,000−700,000 deaths related to coronary artery disease (CAD) occur each year. Dead heart muscle reduces the heart’s ability to function properly which can result in result in congestive heart failure or other complications which impair an individual’s ability to function and may ultimately lead to an early death. Various therapies have been attempted to improve heart function in cases of ischemic heart disease. These include medical therapy, surgical excision of dead heart muscle, placement of left ventricular devices (LVD), and even heart transplantation or placement of a temporary artificial heart. Recently, stem cell transplantation has been tried to replace damaged heart cells with healthy viable cells. A relatively new concept of adult stem cell therapy predicts that stem cells can differentiate into cell types outside of their original lineage. Results from studies have suggested that blood line stem cells can change into heart muscle cells and vascular cells after transplantation into damaged heart tissue. Many studies have been done investigating stem cell infusions for the replacement of damaged heart cells. Various methods of administrating this therapy have been used with cells being implanted directly into heart muscle externally through the chest wall, through the veins leading to the heart and via heart catheterization into the coronary. Additionally, various cell lines have been used for this treatment including bone marrow cells, undifferentiated muscle cells, and peripheral blood cells, further clouding the question of efficacy. The exact mechanism in which stem cell transfer can improve perfusion and contractile performance of the injured heart remains unknown, and the controversies surrounding the ability of these cells to undergo this change continues to exist. However, irrespective of the mechanism, there appears to be a general agreement that stem cell transplantation has some impact on heart function post-MI. Questions remain, though, as to whether there is a significant clinical impact on patients.

Commercial Plan Policy

SelectHealth does NOT cover autologous stem cell infusion for myocardial infarction due to the lack of evidence proving clinical efficacy and many unanswered questions related to the optimal progenitor cells and methods to deliver stem cells. This meets the plan’s definition of investigational/experimental.

Cardiovascular Policies, Continued

Autologous Stem Cell Infusion for Mycardial Infarction, continued

SelectHealth Advantage (Medicare/CMS) (Preauthorization Required)

Coverage is determined by the Centers for Medicare and Medicaid Services (CMS); if a coverage determination has not been adopted by CMS, and InterQual criteria are not available, the SelectHealth Commercial policy applies. For the most up-to-date Medicare policies and coverage, please visit their search website http://www.cms.gov/medicare- coverage-database/overview-and-quick-search.aspx?from2=search1.asp& or the manual website

SelectHealth Community Care (Medicaid/CHIP) (Preauthorization Required)

Coverage is determined by the State of Utah Medicaid program; if Utah State Medicaid has no published coverage position and InterQual criteria are not available, the SelectHealth Commercial criteria will apply. For the most up-to-date Medicaid policies and coverage, please visit their website http://health.utah.gov/medicaid/manuals/directory.php or the Utah Medicaid code Look-Up tool

Summary of Medical Information A Medical Technology Assessment performed in March 2008 identified 37 articles, including a large number of randomized controlled trials, with most controls receiving normal saline injections or standard therapy. Most of these were small sample studies reporting outcomes over 3−6 months, and there was substantial heterogeneity in criteria for sample selection and infusion method. Of these studies, 28 studies focused on stem cells derived from bone marrow, 7 utilized circulating progenitor cells, and 2 used cells from skeletal myoblasts. A variety of cardiac outcomes were measured including change in left ventricular ejection fraction, global ejection fraction, various blood volume measures contractility, infarct size, and oxygen intake. Many of these studies suggest potential for stem-cell infusion to improve cardiac function. For example, the largest study to date, REPAIR-AMI, is a multi-site randomized controlled trial of 204 patients with acute myocardial infarction successfully re-perfused with stent implantation. Patients were infused with either bone-marrow-derived progenitor cells or placebo. At 4 months, global LVEF was significantly higher in the treatment group, having increased from a mean of 48.3 ± 9.2% to 53.8 ± 10.2%, compared with a change from 46.9 ± 10.4% to 49.9 ± 13.0%, in the placebo group. The treatment group also experienced greater improvement in regional contractility. In contrast, the ASTAMI randomized controlled trial of 100 patients found no difference between the bone marrow and placebo groups at 6 months in LVEF, end-diastolic volume, or infarct size. Similarly, LVEF was no different between treated and placebo patients at 18 months in the BOOST study of 60 patients. Far fewer studies measured important clinical outcomes such as mortality, additional cardiac events, and quality of life post-infusion. The REPAIR-AMI study reported fewer deaths, repeat myocardial infarctions, or revascularization procedures, in the treatment group compared with placebo at the one-year follow-up. Stem cell infusion resulted in improved exercise capacity at 6 months in the ASTAMI trial and at 12 months in a nonrandomized cohort of 20 patients. Treatment with stem-cells conferred no improvement in quality of life at 6 months in the ASTAMI trial. The TOPCARE-AMI study of 59 patients reported no additional cardiac events at 12 months in patients treated with circulating progenitor cells. Overall, while these studies suggest that stem cell infusion confers statistical improvement in cardiac functioning in the short-term, additional longitudinal studies are needed to evaluate whether the treatment reliably improves quality of life and reduces mortality from future cardiac events. Moreover, standardized procedures are needed for extraction and infusion in addition to better data on the appropriate patient population for this procedure. Several clinical trials are ongoing, which should contribute important data towards addressing these issues. A literature review in February 2010 identified a BCBS TEC Summary, concluding there was insufficient evidence to allow a conclusion on the benefits of progenitor cell therapy.

Cardiovascular Policies, Continued

Autologous Stem Cell Infusion for Mycardial Infarction, continued

Billing/Coding Information CPT CODES Not Covered: Investigational/Experimental/Unproven for This Indication 33999 Unlisted procedure, cardiac surgery

HCPCS CODES No specific codes identified

Key References 1. Summaries for patients. Can stem cells restore cardiac tissue after a heart attack? Ann Intern Med 140.9 (2004): I82. 2. Adelaide Health Technology Assessment (AHTA) on behalf of National Horizon Scanning Unit (HealthPACT and MSAC). Autologous bone marrow cell transplantation for myocardial infarction. 2007. Available: http://www.horizonscanning.gov.au/internet/horizon/publishing.nsf/Content/19C3AB9EE16F6D96CA25715C00039A50/$File/H ORIZON%20SCANNING%20REPORT-%20Autologous%20BMC%20for%20MI%20HF.pdf. Date Accessed: December 17, 2007. 3. Assmus B, Honold J, Schachinger V, et al. "Transcoronary transplantation of progenitor cells after myocardial infarction." N Engl J Med 355.12 (2006): 1222-32. 4. Assmus B, Schachinger V, Teupe C, et al. "Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI)." Circulation 106.24 (2002): 3009-17. 5. Assmus B, Walter DH, Lehmann R, et al. "Intracoronary infusion of progenitor cells is not associated with aggravated restenosis development or atherosclerotic disease progression in patients with acute myocardial infarction." Eur Heart J 27.24 (2006): 2989-95. 6. Bearzi C, Rota M, Hosoda T, et al. "Human cardiac stem cells." Proc Natl Acad Sci USA 104.35 (2007): 14068-73. 7. BCBS TEC Assessment. (2008). Autologous Progenitor Cell Therapy for the Treatment of Ischemic Heart Disease. BlueCross BlueShield Association. September. Available: http://www.bcbs.com/blueresources/tec/vols/23/23_04.pdf. Date Accessed: February 12, 2010. 8. Brehm M, Strauer BE. "Stem cell therapy in postinfarction chronic coronary heart disease." Nat Clin Pract Cardiovasc Med 3 Suppl 1 (2006): S101-4. 9. Britten MB, Abolmaali ND, Assmus B, et al. "Infarct remodeling after intracoronary progenitor cell treatment in patients with acute myocardial infarction (TOPCARE-AMI): mechanistic insights from serial contrast-enhanced magnetic resonance imaging." Circulation 108.18 (2003): 2212-8. 10. Chen S, Liu Z, Tian N, et al. "Intracoronary transplantation of autologous bone marrow mesenchymal stem cells for ischemic cardiomyopathy due to isolated chronic occluded left anterior descending artery." J Invasive Cardiol 18.11 (2006): 552-6. 11. Chen SL, Fang WW, Qian J, et al. "Improvement of cardiac function after transplantation of autologous bone marrow mesenchymal stem cells in patients with acute myocardial infarction." Chin Med J (Engl) 117.10 (2004): 1443-8. 12. Chen SL, Fang WW, Ye F, et al. "Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction." Am J Cardiol 94.1 (2004): 92-5. 13. Dimmeler S, Zeiher AM, Schneider MD. "Unchain my heart: the scientific foundations of cardiac repair." J Clin Invest 115.3 (2005): 572-83. 14. Erbs S, Linke A, Adams V, et al. "Transplantation of blood-derived progenitor cells after recanalization of chronic coronary artery occlusion: first randomized and placebo-controlled study." Circ Res 97.8 (2005): 756-62. 15. Garas S, Zafari AM. Myocardial Infarction. 2006. EMedicine. Available: http://www.emedicine.com/med/TOPIC1567.HTM. Date Accessed: December 17, 2007. 16. Ge J, Li Y, Qian J, et al. "Efficacy of emergent transcatheter transplantation of stem cells for treatment of acute myocardial infarction (TCT-STAMI)." Heart 92.12 (2006): 1764-7. 17. Herreros J, Prosper F, Perez A, et al. "Autologous intramyocardial injection of cultured skeletal muscle-derived stem cells in patients with non-acute myocardial infarction." Eur Heart J 24.22 (2003): 2012-20. 18. Janssens S, Dubois C, Bogaert J, et al. "Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial." Lancet 367.9505 (2006): 113-21. 19. Jyotsna M, Vemuganti GK, Reddy P, Chandra KS. "Autologous bone marrow-derived progenitor cell myocardial delivery for recent myocardial infarction patients following early angioplasty: results from a pilot study." Cardiovasc Revasc Med 7.4 (2006): 217-21. 20. Katritsis DG, Sotiropoulou P, Giazitzoglou E, Karvouni E, Papamichail M. "Electrophysiological effects of intracoronary transplantation of autologous mesenchymal and endothelial progenitor cells." Europace 9.3 (2007): 167-71. 21. Li ZQ, Zhang M, Jing YZ, et al. "The clinical study of autologous peripheral blood stem cell transplantation by intracoronary infusion in patients with acute myocardial infarction (AMI)." Int J Cardiol 115.1 (2007): 52-6. 22. Lunde K, Solheim S, Aakhus S, Arnesen H, Abdelnoor M, Forfang K. "Autologous stem cell transplantation in acute myocardial infarction: The ASTAMI randomized controlled trial. Intracoronary transplantation of autologous mononuclear bone marrow cells, study design and safety aspects." Scand Cardiovasc J 39.3 (2005): 150-8. 23. Lunde K, Solheim S, Aakhus S, et al. "Exercise capacity and quality of life after intracoronary injection of autologous mononuclear bone marrow cells in acute myocardial infarction: results from the Autologous Stem cell Transplantation in Acute Myocardial Infarction (ASTAMI) randomized controlled trial." Am Heart J 154.4 (2007): 710 e1-8. 24. Lunde K, Solheim S, Aakhus S, et al. "Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction." N Engl J Med 355.12 (2006): 1199-209. 25. Meluzin J, Janousek S, Mayer J, et al. "Three-, 6-, and 12-month results of autologous transplantation of mononuclear bone marrow cells in patients with acute myocardial infarction." Int J Cardiol (2007). 26. Meluzin J, Mayer J, Groch L, et al. "Autologous transplantation of mononuclear bone marrow cells in patients with acute myocardial infarction: the effect of the dose of transplanted cells on myocardial function." Am Heart J 152.5 (2006): 975 e9-15. 3

Cardiovascular Policies, Continued

Autologous Stem Cell Infusion for Mycardial Infarction, continued

27. Meyer GP, Wollert KC, Lotz J, et al. "Intracoronary bone marrow cell transfer after myocardial infarction: eighteen months' follow-up data from the randomized, controlled BOOST (BOne marrOw transfer to enhance ST-elevation infarct regeneration) trial." Circulation 113.10 (2006): 1287-94. 28. Mocini D, Staibano M, Mele L, et al. "Autologous bone marrow mononuclear cell transplantation in patients undergoing coronary artery bypass grafting." Am Heart J 151.1 (2006): 192-7. 29. Numaguchi Y, Sone T, Okumura K, et al. "The impact of the capability of circulating progenitor cell to differentiate on myocardial salvage in patients with primary acute myocardial infarction." Circulation 114.1 Suppl (2006): I114-9. 30. Obradovic S, Rusovic S, Balint B, et al. "Autologous bone marrow-derived progenitor cell transplantation for myocardial regeneration after acute infarction." Vojnosanit Pregl 61.5 (2004): 519-29. 31. Patel AN, Geffner L, Vina RF, et al. "Surgical treatment for congestive heart failure with autologous adult stem cell transplantation: a prospective randomized study." J Thorac Cardiovasc Surg 130.6 (2005): 1631-8. 32. Penicka M, Lang O, Widimsky P, et al. "One-day kinetics of myocardial engraftment after intracoronary injection of bone marrow mononuclear cells in patients with acute and chronic myocardial infarction." Heart 93.7 (2007): 837-41. 33. Perin EC, Dohmann HF, Borojevic R, et al. "Improved exercise capacity and ischemia 6 and 12 months after transendocardial injection of autologous bone marrow mononuclear cells for ischemic cardiomyopathy." Circulation 110.11 Suppl 1 (2004): II213-8. 34. Perin EC, Dohmann HF, Borojevic R, et al. "Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure." Circulation 107.18 (2003): 2294-302. 35. Ruan W, Pan CZ, Huang GQ, Li YL, Ge JB, Shu XH. "Assessment of left ventricular segmental function after autologous bone marrow stem cells transplantation in patients with acute myocardial infarction by tissue tracking and strain imaging." Chin Med J (Engl) 118.14 (2005): 1175-81. 36. Schachinger V, Assmus B, Britten MB, et al. "Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCARE-AMI Trial." J Am Coll Cardiol 44.8 (2004): 1690-9. 37. Schachinger V, Erbs S, Elsasser A, et al. "Improved clinical outcome after intracoronary administration of bone-marrow-derived progenitor cells in acute myocardial infarction: final 1-year results of the REPAIR-AMI trial." Eur Heart J 27.23 (2006): 2775-83. 38. Schachinger V, Erbs S, Elsasser A, et al. "Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction." N Engl J Med 355.12 (2006): 1210-21. 39. Smits PC, van Geuns RJ, Poldermans D, et al. "Catheter-based intramyocardial injection of autologous skeletal myoblasts as a primary treatment of ischemic heart failure: clinical experience with six-month follow-up." J Am Coll Cardiol 42.12 (2003): 2063- 9. 40. Strauer BE, Brehm M, Zeus T, et al. "Regeneration of human infarcted heart muscle by intracoronary autologous bone marrow cell transplantation in chronic coronary artery disease: the IACT Study." J Am Coll Cardiol 46.9 (2005): 1651-8. 41. Strauer BE, Brehm M, Zeus T, et al. "Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans." Circulation 106.15 (2002): 1913-8. 42. Wollert KC, Meyer GP, Lotz J, et al. "Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial." Lancet 364.9429 (2004): 141-8.

Disclaimer This document is for informational purposes only and should not be relied on in the diagnosis and care of individual patients. Medical and Coding/Reimbursement policies do not constitute medical advice, plan preauthorization, certification, an explanation of benefits, or a contract. Members should consult with appropriate healthcare providers to obtain needed medical advice, care, and treatment. Benefits and eligibility are determined before medical guidelines and payment guidelines are applied. Benefits are determined by the member’s individual benefit plan that is in effect at the time services are rendered. The codes for treatments and procedures applicable to this policy are included for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member. SelectHealth® makes no representations and accepts no liability with respect to the content of any external information cited or relied upon in this policy. SelectHealth updates its Coverage Policies regularly, and reserves the right to amend these policies without notice to healthcare providers or SelectHealth members. Members may contact Customer Service at the phone number listed on their member identification card to discuss their benefits more specifically. Providers with questions about this Coverage Policy may call SelectHealth Provider Relations at (801) 442-3692. No part of this publication may be reproduced, stored in a retrieval system or transmitted, in any form or by any means, electronic, mechanical, photocopying, or otherwise, without permission from SelectHealth. ”Intermountain Healthcare” and its accompanying logo, the marks of “SelectHealth” and its accompanying marks are protected and registered trademarks of the provider of this Service and or Intermountain Health Care, Inc., IHC Health Services, Inc., and SelectHealth, Inc. Also, the content of this Service is proprietary and is protected by copyright. You may access the copyrighted content of this Service only for purposes set forth in these Conditions of Use. © CPT Only – American Medical Association

Cardiovascular Policies, Continued

MEDICAL POLICY

CAROTID ARTERY STENTING (CAS)

Policy # 461 Implementation Date: 9/28/10 Review Dates: 9/15/11, 11/29/12, 12/19/13, 12/18/14, 12/10/15, 12/15/16, 12/21/17, 12/11/18, 12/15/19 Revision Dates:

Description Carotid artery disease (CAD) develops due to atherosclerosis or fibromuscular dysplasia. Symptoms from carotid stenosis are due to a reduction in blood flow. Either a cerebrovascular event (CVA) or transient ischemic event (TIA) will create neurological symptoms attributable to the limited blood flow or carotid stenosis. Typically, when the narrowing exceeds 50%, symptoms may develop. Standard recommendations are to treat symptomatic disease if the stenosis is > 50% or asymptomatic disease when identified, if the stenosis is > 70%. The standard method of correcting carotid artery stenosis is a carotid endarterectomy. Carotid artery stenting has been developed as a less invasive procedure for removing the stenosis. Carotid artery stenting (CAS) begins with carotid angioplasty, a non-surgical procedure performed after diagnostic testing. During angioplasty, a balloon catheter is guided to the area of the blockage or narrowing. When the balloon is inflated, a specially designed guide wire with a filter (embolic protection) is placed beyond the site of stenosis in the carotid artery. Once the filter is in place, a small balloon catheter is guided to the area of the blockage. When the balloon is inflated, the atherosclerotic plaque is compressed against the arterial walls and the diameter of the blood vessel is dilated to increase blood flow. The balloon is removed, and the stent then placed to maintain patency of the carotid artery. Eliminating the obstruction or enhancing the blood flow reduces the risk for TIA or strokes. Because carotid stenting is performed percutaneously, it offers a less invasive approach than carotid endarterectomy and may reduce perioperative complications in high-risk patients who have co-morbid conditions.

Commercial Plan Policy (No Preauthorization Required but criteria must be met)

SelectHealth covers carotid artery stenting (CAS) in limited circumstances as the current literature demonstrates improved outcomes in selected populations.

Criteria for coverage: 1. Extracranial carotid artery angioplasty performed with an FDA approved stent system AND distal embolic protection. AND 2. The patient is considered to be at high risk for open carotid endarterectomy. A member may be considered at high risk for open endarterectomy if they meet 1 or more of the following criteria: • New York Heart Association class III or IV congestive heart failure • Left ejection fraction of less than 30%

Cardiovascular Policies, Continued

Carotid Artery Stenting (CAS), continued

• Myocardial infarction within past 30 days, unstable angina, known severe coronary artery disease (left main coronary artery or 2 or more major arteries with stenosis ≥ 70%), or concurrent requirement for open heart surgery within 30 days • Severe chronic obstructive pulmonary disease • Contralateral carotid artery occlusion • Contralateral laryngeal nerve palsy • Previous radiation therapy to the neck or radical neck dissection • Previous ipsilateral endarterectomy with restenosis • Surgically inaccessible lesion • Inability to move the neck to a suitable position for surgery • Tracheostomy • Coagulopathy or other coagulation issues leading to contraindications for endarterectomy • Previous contralateral nerve palsy AND 3. Clinically must have: • Symptomatic stenosis equal to or greater than 50% or asymptomatic stenosis equal to or greater than 70% using carotid ultrasound or CT angiography OR • Fibromuscular dysplasia with similar clinical and radiographic findings in carotid atherosclerosis

SelectHealth Advantage (Medicare/CMS) (Preauthorization Required)

SelectHealth Community Care (Medicaid/CHIP) (Preauthorization Required)

Summary of Medical Information Several systematic reviews are available, and all describe the international studies comparing carotid artery stenting (CAS) and coronary artery endarterectomy (CEA). Most have concluded that CEA is the preferred method for symptomatic plaques over 50% and for asymptomatic patients with greater than 70% narrowing. The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) trial appears to have demonstrated a non-inferiority status for CAS compared with CEA. Previously, the international randomized studies have shown increased rates of intraoperative CVA during CAS limiting the role of CAS in CVD. CAS would be used only when there were strict contraindications for surgery.

Cardiovascular Policies, Continued

Carotid Artery Stenting (CAS), continued

CREST demonstrated low rates of periprocedural stroke and death in both treatment groups as compared with the other trials. For example, the rate of periprocedural stroke among symptomatic patients treated by carotid artery stenting was 6% in CREST but 9.6% in the EVA-3S. Compared with previous studies, CREST was the only trial which used MI (myocardial infarction) as an endpoint. CAS resulted in 1.1% risk of MI compared with CEA at 2.3%. Because MI was included as an endpoint along with CVA and death, the CREST trial results demonstrated that CAS showed comparative clinical outcomes compared with CEA. Critics have suggested that the increased rate of MI cannot be considered equivalent to CVA. They illustrate that both the increased economic and health status of the patient is much worse with a CVA. Thus, CEA should still be considered the standard of care for carotid revascularization. Many factors are important to emphasize with CREST and previous studies. Besides the influence of choosing endpoints as discussed above, the following issues are significant in determining the clinical outcomes of the studies. These include: • Technical proficiency of the proceduralist - Enhanced training improved results in CREST compared with previous studies where training for CAS was limited • The age of the patient - Younger patients favored CAS • Recent symptoms of either a TIA or CVA and the need for intervention favors CEA • Associated co–morbid condition which could increase perioperative mortality favoring CAS. Besides these factors, critics also illustrate there were different criteria to be included in the studies. For example, carotid ultrasound (US), magnetic resonance angiogram (MRA), and computed tomography (CT) carotid angiogram were the imaging techniques used for the diagnosis of carotid stenosis. International studies compared with CREST did not use the same thresholds, thus, direct comparisons of the studies, including their overall outcomes, are difficult to perform. Newer methods to avoid perioperative emboli have decreased the rate of stroke in CREST compared with previous studies. It is anticipated that future refinement will limit the events in the future. Unfortunately, all randomized studies have excluded a medical arm. This omission, especially with enhanced hypertension and cholesterol control, could significantly influence the outcomes of invasive trial. Overall, CREST challenges the prior international studies and suggests that in certain patient subgroups, equal or improved health outcomes may be achieved with CAS compared with CEA.

Billing/Coding Information Covered: For the conditions outline above CPT CODES 37215 Transcatheter placement of intravascular stent(s), cervical carotid artery, percutaneous: with distal embolic protection

HCPCS CODES No specific codes identified

Key References 1. Bates, ER, Babb, JD, Casey, DE, Jr., et al. (2007). ACCF/SCAI/SVMB/SIR/ASITN 2007 Clinical Expert Consensus Document on carotid stenting. Vasc Med 12.1: 35-83. 2. Baylor College of Medicine. (2010) Carotid Artery Stenting. Baylor College of Medicine. Available: http://www.debakeydepartmentofsurgery.org/home/content.cfm?proc_name=Carotid+Stenting&content_id=272. Date Accessed: August 14, 2010. 3. Brott, TG, Hobson, RW, 2nd, Howard, G, et al. (2010). Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med 363.1: 11-23. 4. Cleveland Clinic. (2010) What happens during the carotid angioplasty and stenting procedure? Cleveland Clinic. Available: http://my.clevelandclinic.org/heart/services/tests/procedures/carotidstent.aspx#3. Date Accessed: August 4, 2010. 5. Ederle, J, Dobson, J, Featherstone, RL, et al. (2010). Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial. Lancet 375.9719: 985-97. 6. Hollander, M, Bots, ML, Del Sol, AI, et al. (2002). Carotid plaques increase the risk of stroke and subtypes of cerebral infarction in asymptomatic elderly: the Rotterdam study. Circulation 105.24: 2872-7. 7. Hopkins, LN, Roubin, GS, Chakhtoura, EY, et al. (2010). The Carotid Revascularization Endarterectomy versus Stenting Trial: credentialing of interventionalists and final results of lead-in phase. J Stroke Cerebrovasc Dis 19.2: 153-62. 8. Mas, JL, Chatellier, G, Beyssen, B, et al. (2006). Endarterectomy versus stenting in patients with symptomatic severe carotid stenosis. N Engl J Med 355.16: 1660-71.

Cardiovascular Policies, Continued

Carotid Artery Stenting (CAS), continued

9. Mayo Clinic. (2010) Carotid Artery Disease. Mayo Clinic. Available: http://www.mayoclinic.com/health/carotid-artery- disease/DS01030. Date Accessed: August 3, 2010. 10. Medical Technology Directory. (2009) Carotid Angioplasty and Stenting for Carotid Artery Stenosis. September 29. Winifred S. Hayes I. 11. Nadalo, LAW, M.C. (2009) Carotid Artery, Stenosis. emedicine. Available: http://emedicine.medscape.com/article/417524- overview. Date Accessed: August 3, 2010, 12. Polisena, J, Banks, R. (2009) Carotid Artery Stenting vs. Carotid Endarterectomy: A Review of the Clinical and Cost- Effectiveness. September 22. Canadian Agency for Drugs and Technologies in Health (CADTH). 13. Radiology Associates of Northern Kentucky. (2010) Carotid Artery Stenting. Radiology Associates of Northern Kentucky. Available: http://www.radassociatesnky.com/int_CarotidArteryStenting.html. Date Accessed: August 4, 2010. 14. Safian, RD, Jaff, MR, Bresnahan, JF, et al. (2010). Protected Carotid Stenting in High-Risk Patients: Results of the SpideRX Arm of the Carotid Revascularization with ev3 Arterial Technology Evolution Trial. J Interv Cardiol. 15. Stork, S, van den Beld, AW, von Schacky, C, et al. (2004). Carotid artery plaque burden, stiffness, and mortality risk in elderly men: a prospective, population-based cohort study. Circulation 110.3: 344-8. 16. Technology Evaluation Center. (2007) Angioplasty and Stenting of the Cervical Carotid Artery with Embolic Protections of the Cerebral Circulation. June. BCBS TEC Assessment Program. 17. Tice, JA. (2009) Carotid Artery Stenting. June 17. California Technology Assessment Forum (CTAF). 18. Wilterdink, JLF, K.L.; Kistler, J.P. (2010) Pathophysiology of symptoms from carotid atherosclerosis. April 12, 2010. Up to Date. Available: http://www.uptodate.com/online/content/topic.do?topicKey=cva_dise/5449&selectedTitle=4%7E150&source=search_result. Date Accessed: August 20, 2010. 19. Kernan, W.N., Ovbiagele, B., Black. H. R., et al. (2014). Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack. AHA/ASA Guideline. Retrieved from: http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STR.0000000000000024/-/DC1.

Cardiovascular Policies, Continued

MEDICAL POLICY

CORONARY ARTERY DISEASE CALCIUM SCORING (CARDIAC CT SCAN) TO ASSESS CARDIOVASCULAR RISK

Policy # 262 Implementation Date: 2/17/05 Review Dates: 6/22/06, 7/12/07, 8/23/07, 8/21/08, 8/13/09, 5/19/11, 4/25/13, 2/20/14, 3/19/15, 2/11/16, 2/16/17, 2/15/18, 2/5/19, 4/15/20 Revision Dates: 3/22/10, 1/17/12

Description Coronary heart disease (CHD) refers to any disease that affects the coronary arteries (coronary artery disease) or cardiac muscle. Atherosclerosis is an important risk factor in the development of CHD. Multiple factors contribute to the pathogenesis of atherosclerosis including endothelial dysfunction, dyslipidemia, inflammatory and immunologic factors, plaque rupture, and smoking. Assessing risk for developing early CAD can be done using variously using multiple methods. First and foremost, a complete assessment of risk factors using a history and physical examination along with calculation of the Framingham risk score which is a validated risk assessment tool. One method being promoted as a screen for early CAD in patients of low or intermediate cardiac risk is CT calcium scoring. This non-invasive imaging study assesses for the presence, location and extent of calcified plaque in the coronary arteries. Because calcium may be a marker of CAD, the amount of calcium detected on a cardiac CT scan has been proposed as a helpful prognostic tool in determining if further testing may be warranted. The findings on cardiac CT are expressed as a calcium score. A negative cardiac CT scan shows no calcification within the coronary arteries. A positive test suggests CAD to be present. Some studies have indicated the greater the calcium load, the more likely the presence of CAD. Recent studies have suggested a calcium score > 400 may be a cut-off level that correlates with a high probability of CAD being present and further testing being warranted especially in patients with no symptoms or at low or intermediate risk for developing CAD. CT calcium scoring can be performed using a variety of computerized tomography (CT) technologies. These include, electron beam (ultrafast) CT (EBCT), spiral (helical) CT, and multi-slice or multi-detector CT (MSCT or MDCT).

Commercial Plan Policy

SelectHealth does NOT cover cardiac CT calcium scoring for the assessment of cardiovascular risk using ANY technique. The literature showing clinical validity fails to clearly demonstrate a role for cardiac CT calcium scoring. This meets the plan’s definition of investigational/experimental.

SelectHealth Advantage (Medicare/CMS) (No Preauthorization Required but criteria may apply if appropriate)

Coverage is determined by the Centers for Medicare and Medicaid Services (CMS); if a coverage determination has not been adopted by CMS, and InterQual criteria

Cardiovascular Policies, Continued

Coronary Artery Disease Calcium Scoring (Cardiac CT Scan) to Assess Cardiovascular Risk, continued

are not available, the SelectHealth Commercial policy applies. For the most up-to-date Medicare policies and coverage, please visit their search website http://www.cms.gov/medicare- coverage-database/overview-and-quick-search.aspx?from2=search1.asp& or the manual website

SelectHealth Community Care (Medicaid/CHIP) (No Preauthorization Required but criteria may apply if appropriate)

Summary of Medical Information It is clear that calcium scoring by all of these methods is highly sensitive in detecting coronary artery calcification, with most of the evidence coming from studies performed with EBCT; evidence from multislice CT is clearly only emerging. There may be meaningful differences in the different CT technologies, including the CT protocols, calcium-scoring algorithms, and radiation exposure; but this is not yet well delineated. Additionally, there are many indications for which calcium scoring is being studied, and an extensive literature base. Multiple studies using EBCT have shown a strong correlation between calcium scores and quantities of atherosclerotic plaque; however, no study has yet reported the use of coronary calcium scores to improve the direct health outcomes of myocardial infarction or coronary death, much less the gold standard of all- cause mortality. This gap in evidence between the value of calcium scoring in predicting coronary risk and the improvement in direct health outcomes is brought into further question by two studies by O’Malley et al. that demonstrate that risk information obtained from calcium scoring may have no impact on CAD- related risk factors. If fact, case management may be more effective in changing risk factors and thus health outcomes. There is a distinct lack of consensus in the literature about the value and role of CT-based calcium scoring, and perhaps fluoroscopy-based calcium scoring; with multiple clinical trials examining the use of such scoring in many different settings, followed by multiple editorial comments discussing the pros and cons of the studies and use of calcium scoring. Additionally, O’Malley et al.’s recent economic study suggests that calcium scoring by EBCT is very expensive given its expected benefits (i.e., > $50,000 /QALY). In this study, the projected marginal cost per QALY is sensitive to many variables, but most sensitive to the marginal cost of identifying additional patients for whom it is appropriate to treat, the efficacy of primary prevention, and the utility of life with a diagnosis of being “at risk” for CVD and taking lifelong medications. These figures were based on data from published trials and, where data was absent, expert opinion. In any case, this cost estimate likely represents the best-case scenario; i.e., what would be expected in controlled settings and not the real world of unfettered medical practice. ICSI, in its 2004 technology assessment, arrived at the following conclusions: • No study has yet reported the use of coronary calcium scores to improve the direct health outcomes of myocardial infarction or coronary death • In asymptomatic persons EBCT tests for CAC: • Are not recommended as a screening test in the absence of risk factors. • May be useful as a screening test if one or a few risk factors are present (intermediate risk patients) and the test could be helpful in determining the need to begin a primary prevention regimen. • Have been found to be better than conventional risk factors alone in predicting future coronary artery events in high risk patients (Conclusion Grade I based on Class B evidence). However, risk factor assessment and other non-invasive tests are more widely available. EBCT is not usually necessary to start primary prevention treatment when diabetes or multiple risk factors are present.

Cardiovascular Policies, Continued

Coronary Artery Disease Calcium Scoring (Cardiac CT Scan) to Assess Cardiovascular Risk, continued

• Are highly sensitive but not specific enough in the individual patient to use for diagnosis or exclusion of coronary obstruction or stenosis (Conclusion Grade II based on Class C and D evidence). • In patients with symptoms of coronary artery disease the issue is not primary prevention but diagnosis and management. For diagnosis of obstructive coronary artery disease, coronary artery calcification is a stronger independent predictor than risk factors. Direct comparisons of EBCT with other non-invasive tests for diagnosis are lacking. • Serial EBCT calcium scores indicate that the development of coronary artery calcification is slowed during lipid-lowering therapy. The clinical significance of this is unknown. • EBCT and helical CT are safe procedures; there is no direct harm to the patient. The potential for inappropriate and invasive follow-up must be considered. • Practitioners should use caution when comparing calcium scoring from different types of scanners (helical CT and EBCT). The use of helical CT to assess coronary artery calcification is not as well documented as is EBCT. There is insufficient data on the predictive value of a calcium score calculated from a helical CT scan (Conclusion Grade III based on Class C and D evidence). Although there are no prognostic data comparing the results of helical CT or EBCT studies, there are differences between the procedures that would suggest that findings from EBCT studies cannot be applied to helical CT studies. • Additional questions remain about the relationship between calcium scoring and the likelihood of coronary events because of the following factors: • Calcium does not collect exclusively at sites with severe stenosis • EBCT calcium scores do not identify the location of specific vulnerable lesions • Substantial non-calcified plaque is frequently present in the absence of coronary artery calcification • There are no proven relationships between coronary artery calcification and the probability of plaque rupture In the July 2004 Hayes report on multislice CT, this CT method is given ‘D’ ratings “across the board” based, apparently, on Hayes view that while “the technology is safe and feasible in selected patients, there is no evidence of improved diagnosis or health outcomes as a result of its use”. Yet, in a separate Hayes report on EBCT, 2 indications are given ‘B’ ratings in spite of making the very same statements about lack of direct evidence of benefit. This apparent incongruence would suggest that it may be appropriate to question the Hayes’ ratings for these technologies (including helical CT). At best, the ‘B’ ratings can be assumed to be limited to evidence of indirect benefit rather than direct benefit to patient outcomes. A 2004 study from the Mayo Clinic by Meissner et al. has suggested that the use of calcium scoring of coronary arteries may require rethinking. ‘There is some data to suggest that “aortic” atherosclerosis may not be an independent risk factor for vascular events in the general population.” An updated literature review completed in February 2010 continued to identify shortfalls in the current literature. Though the ACCF/AHA published a consensus document in 2007 on role of CT calcium scoring is cardiovascular risk assessment, it only reviewed literature from 1998 to 2005 and acknowledged limitations to the published literature making evidence-based conclusions difficult to draw. Further, this document noted the lack of unanimity to the conclusions and that current literature lacked “the scientific rigor to be evaluated by the formal American College of Cardiology/American Heart Association (ACC/AHA) Practice Guidelines process.” This document essentially represents level III evidence. Subsequent to the ACC/AHHA consensus document the additional published literature also fails to conclusively demonstrate the role of CT calcium scoring due to questions as to the sensitivity and specificity in assessing the presence of coronary artery disease in asymptomatic patients. This was demonstrated by Cheng et al. in their study evaluating low to intermediate risk asymptomatic patients. In this study nearly 10% of patients had significant CAD despite low calcium scoring. This finding was similarly demonstrated By Henneman et al. in 2008. In this study, though assessing symptomatic patients, 39% of patients demonstrated non-calcified plaques and only 14% had calcified plaques with 13% demonstrating no coronary calcium. 3

Cardiovascular Policies, Continued

Coronary Artery Disease Calcium Scoring (Cardiac CT Scan) to Assess Cardiovascular Risk, continued

Ho et al., however, reached opposite conclusions, identifying a high level of correlation between coronary calcium burden and coronary stenoses. They found no significant coronary disease in patients without coronary calcium and concluded a CAC score > 400 was significantly associated with multidetector CT angiographic stenoses independently of traditional risk factors. Though not completely refuting this perspective, Nucifora et al. showed a strong positive relationship between Framingham Risk Scores and the extent of athersoclerosis and yet only identified obstructive CAD in 155 of low risk patients and 43% of intermediate risk patients for patients with a CACS > 400. Other studies assessing comparing CACS with physiologic testing for CAD also demonstrated similar sensitivity and specificity issues. For instance, Ramakrishna et al. found only a limited correlation between CACS and exercise echocardiography, noting even in patients with a CACS > 400 66% had normal stress eco studies. Inversely, Schenker et al. in their study of 95 intermediate risk patients demonstrated a low calcium score < 400 holds 21.7% chance of having an abnormal PET myocardial perfusion study. Sung et al. also showed this lack of correlation between CACS in 9% and introduced the concept that other variables such as age impact the findings of CT calcium studies. Sosnowski et al. suggest gender may also bias the findings. A Medical Technology Assessment performed in December 2011 did not identify any new systematic reviews, but did identify 12 primary studies related to CT calcium scoring. These studies failed to conclusively demonstrate the role of CT calcium scoring due to questions as to the sensitivity and specificity in assessing the presence of coronary artery disease in asymptomatic patients. For all the methodological strengths of the studies, there is still considerable question as to who should have CT calcium scoring. It has yet to be proven definitively that a relationship between calcium scoring and future heart events exists because of the following factors: • Calcium does not present necessarily in the same places as severe stenosis • Calcium scores do not ascertain the exact locations of calcified plaques • Non-calcified plaque is often present in the absence of coronary artery calcification • There is no proven relationship between calcification and the prospect of plaque rupture The evidence for the role of CT calcium scoring in risk assessment remains undefined. Though some studies demonstrate favorable correlation others show lower specificity for significant coronary artery disease and raise continued questions as to the value of this test in ruling out CAD in asymptomatic patients. In a recent Hayes report (2017), evidence meeting inclusion criteria for effectiveness outcomes are composed of prospective cohort studies and randomized control trials (RTCs) enrolling 450 to 9715 asymptomatic adults each. Four of the cohort studies evaluated the incremental predictive value of CAC when added to global risk assessment instruments (primarily FRS) with respect to clinical outcomes at 5 to 15 years follow-up; 1 assessed its use instead of FRS at a median of 8.1 years follow-up. The RCTs evaluated whether using CAC and informing patients of the results led to improved clinical outcomes. These studies were not designed to address safety issues. In conclusion, moderate-quality evidence strongly suggests that CAC improves predictive value and risk level classification compared with office-based risk assessment in asymptomatic adults. This benefit is particularly marked in asymptomatic adults initially classified as at intermediate risk of a CAD event. Among 3 studies, 44% to 66% of those initially classified were reclassified once CAC scores were considered. However, current evidence is insufficient and does not yet demonstrate that use of CAC scoring translates into improved clinical outcomes (i.e., reduced cardiac events).

Billing/Coding Information Not covered: Investigational/Experimental/Unproven for this indication CPT CODES 75571 Computed tomography, heart, without contrast material, with quantitative evaluation of coronary calcium

HCPCS CODES S8092 Electron beam computed tomography (Ultrafast CT, cine CT) 4

Cardiovascular Policies, Continued

Coronary Artery Disease Calcium Scoring (Cardiac CT Scan) to Assess Cardiovascular Risk, continued

Key References 1. Alqarqaz, M, Zaidan, M, Al-Mallah, MH. (2011). Prevalence and predictors of atherosclerosis in symptomatic patients with zero calcium score. Acad Radiol. 18. 11:1437-41. 2. Bonow. R.O. (2011) Braunwald's Heart Disease. Saunders Elseiver. Last Update: Available: http://www.mdconsult.com/books/page.do? eid=4-u1.0-B978-1-4377-0398-6.00122-0&isbn=978-1-4377-0398- 6&uniqId=304747635-3#4-u1.0-B978-1-4377-0398-6.00122-0. Date Accessed: November 29, 2011, 2011. 3. Canadian Coordinating Office for Health Technology Assessment (CCOHTA): Multislice/spiral computed tomography for screening for coronary artery disease. Pwee K H. 2003 (Issues in Emerging Health Technologies Issue 43): 4 4. Catalan, P, Leta, R, Hidalgo, A, et al. (2011). Ruling out coronary artery disease with noninvasive coronary multidetector CT angiography before noncoronary cardiovascular surgery. Radiology. 258. 2:426-34. 5. Chang, AM, Le, J, Matsuura, AC, et al. (2011). Does Coronary Artery Calcium Scoring Add to the Predictive Value of Coronary Computed Tomography Angiography for Adverse Cardiovascular Events in Low-risk Chest Pain Patients? Acad Emerg Med. 18. 10:1065-71. 6. Cheng VY, Lepor NE, Madyoon H, et al. Presence and severity of noncalcified coronary plaque on 64-slice computed tomographic coronary angiography in patients with zero and low coronary artery calcium. Am J Cardiol 99.9 (2007): 1183-6. 7. Craig, SR, Amin, RV, Russell, DW, et al. (2000). Blood cholesterol screening influence of fasting state on cholesterol results and management decisions. J Gen Intern Med. 15. 6:395-9. 8. Dewey M, Hamm B. Cost effectiveness of coronary angiography and calcium scoring using CT and stress MRI for diagnosis of coronary artery disease. Eur Radiol 17.5 (2007): 1301-9. 9. Diederichsen, AC, Sand, NP, Norgaard, B, et al. (2011). Discrepancy between coronary artery calcium score and HeartScore in middle-aged Danes: the DanRisk study. Eur J Cardiovasc Prev Rehabil. 10. Ellis, CJ, Legget, ME, Edwards, C, et al. (2011). High calcium scores in patients with a low Framingham risk of cardiovascular (CVS) disease: implications for more accurate CVS risk assessment in New Zealand. N Z Med J. 124. 1335:13-26. 11. Ford, ES, Giles, WH, Mokdad, AH. (2004). The distribution of 10-Year risk for coronary heart disease among US adults: findings from the National Health and Nutrition Examination Survey III. J Am Coll Cardiol. 43. 10:1791-6. 12. Garvey CJ, Hanlon R. Computed tomography in clinical practice. BMJ 324.7345 (2002): 1077-80. 13. Gerber TC, Manning WJ. Noninvasive coronary angiography with cardiac computed tomography and cardiovascular magnetic resonance. 17.3. June 11, 2009. UpToDate. Available: http://www.utdol.com/online/content/topic.do?topicKey=noninvas/16702&selectedTitle=11%7E150&source=search_result#H5. Date Accessed: February 9, 2010. 14. Gerber, TC. (2011) Radiation dose and risk of malignancy from cardiovascular imaging. Up to Date. Last Update: November 17, 2010. Available: http://www.uptodate.com/contents/radiation-dose-and-risk-of-malignancy-from-cardiovascular- imaging?source=preview&anchor=H8&selectedTitle=1~150#H8. Date Accessed: December 13, 2011. 15. Greenland P, Bonow RO, Brundage BH, et al. ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain: a report of the American College of Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/AHA Writing Committee to Update the 2000 Expert Consensus Document on Electron Beam Computed Tomography) developed in collaboration with the Society of Atherosclerosis Imaging and Prevention and the Society of Cardiovascular Computed Tomography. J Am Coll Cardiol 49.3 (2007): 378-402. 16. Greenland P, LaBree L, Azen SP, et al. Coronary artery calcium score combined with Framingham score for risk prediction in asymptomatic individuals. JAMA. 2004 Jan 14;291(2):210-5. 17. Greuter MJ, Dijkstra H, Groen JM, et al. 64 slice MDCT generally underestimates coronary calcium scores as compared to EBT: a phantom study. Med Phys 34.9 (2007): 3510-9. 18. Groen JM, Greuter MJ, Vliegenthart R, et al. Calcium scoring using 64-slice MDCT, dual source CT and EBT: a comparative phantom study. Int J Cardiovasc Imaging 24.5 (2008): 547-56. 19. Hayes Directory. (2007) Multislice Computed Tomography for Detection of Coronary Artery Disease. Winifred S. Hayes I. Updated: July 15, 2011. 20. Hayes report: Coronary Artery Calcium Scoring for Risk Assessment and Stratification of Coronary Artery Disease in Asymptomatic, February 2017. 21. Hayes report: EBCT for Coronary Artery Disease, June 2003. 22. Hayes report: Helical Computed Tomography For Coronary Artery Disease, February 2000. 23. Hayes report: Multislice Spiral CT for Detection and Evaluation of CAD, July 2004. 24. Henneman MM, Schuijf JD, Pundziute G, et al. Noninvasive evaluation with multislice computed tomography in suspected acute coronary syndrome: plaque morphology on multislice computed tomography versus coronary calcium score. J Am Coll Cardiol 52.3 (2008): 216-22. 25. Ho JS, Fitzgerald SJ, Stolfus LL, et al. Relation of a coronary artery calcium score higher than 400 to coronary stenoses detected using multidetector computed tomography and to traditional cardiovascular risk factors. Am J Cardiol 101.10 (2008): 1444-7. 26. Horiguchi J, Yamamoto H, Hirai N, et al. Variability of repeated coronary artery calcium measurements on low-dose ECG-gated 16-MDCT. AJR Am J Roentgenol 187.1 (2006): W1-6. 27. Hunold, P, Vogt, FM, Schmermund, A, et al. (2003). Radiation exposure during cardiac CT: effective doses at multi-detector row CT and electron-beam CT. Radiology. 226. 1:145-52. 28. Institute for Clinical Systems Improvement. Electron-Beam and Helical Computed Tomography for Coronary Artery Disease. Approved May 2004. 29. Intermountain Healthcare. (2010) New Risk Score Tool Developed in Utah Improves Ability to Predict Patients At Risk for Cardiac Disease and Death. Intermountain Healthcare. Last Update: March 17, 2010. Available: http://intermountainhealthcare.org/About/News/Pages/home.aspx?NewsID=341. Date Accessed: November 29, 2011, 2011. 30. Karp I, Abrahamowicz M, Bartlett G, Pilote L. Updated risk factor values and the ability of the multivariable risk score to predict coronary heart disease. Am J Epidemiol. 2004 Oct 1;160(7):707-16. 31. Kirsch, J, Buitrago, I, Mohammed, TL, et al. (2011). Detection of coronary calcium during standard chest computed tomography correlates with multi-detector computed tomography coronary artery calcium score. Int J Cardiovasc Imaging. 32. Kulkarni, KR. (2006). Cholesterol profile measurement by vertical auto profile method. Clin Lab Med. 26. 4:787-802. 33. Kwon, SW, Kim, YJ, Shim, J, et al. (2011). Coronary artery calcium scoring does not add prognostic value to standard 64- section CT angiography protocol in low-risk patients suspected of having coronary artery disease. Radiology. 259. 1:92-9. 5

Cardiovascular Policies, Continued

Coronary Artery Disease Calcium Scoring (Cardiac CT Scan) to Assess Cardiovascular Risk, continued

34. Laudon, DA, Behrenbeck, TR, Wood, CM, et al. (2010). Computed tomographic coronary artery calcium assessment for evaluating chest pain in the emergency department: long-term outcome of a prospective blind study. Mayo Clin Proc. 85. 4:314-22. 35. Leber, AW, Knez, A, von Ziegler, F, et al. (2005). Quantification of obstructive and nonobstructive coronary lesions by 64-slice computed tomography: a comparative study with quantitative coronary angiography and intravascular ultrasound. J Am Coll Cardiol. 46. 1:147-54. 36. Leschka S, Scheffel H, Desbiolles L, et al. Combining dual-source computed tomography coronary angiography and calcium scoring: added value for the assessment of coronary artery disease. Heart 94.9 (2008): 1154-61. 37. Ma ES, Yang ZG, Li Y, Dong ZH, et al. Correlation of calcium measurement with low dose 64-slice CT and angiographic stenosis in patients with suspected coronary artery disease. Int J Cardiol. (2008). 38. Manning, WJ. (2011) Echocardiography essentials: Physics and instrumentation. Up to Date. Last Update: August 22, 2011. Available: http://www.uptodate.com/contents/echocardiography-essentials-physics-and- instrumentation?source=search_result&search=echocardiography&selectedTitle=2~150. Date Accessed: November 29, 2011. 39. Meissner I, Khandheria BK, Sheps SG, et al. Atherosclerosis of the aorta: risk factor, risk marker, or innocent bystander? A prospective population-based transesophageal echocardiography study. J Am Coll Cardiol. 2004 Sep 1;44(5):1018-24. 40. Min JK, Shaw LJ, Berman DS. Cost-effective applications of cardiac computed tomography in coronary artery disease." Expert Rev Cardiovasc Ther 6.1 (2008): 43-55. 41. Naghavi M, Falk E, Hecht HS, Shah PK. "The first SHAPE (Screening for Heart Attack Prevention and Education) guideline." Crit Pathw Cardiol 5.4 (2006): 187-90. 42. Nucifora G, Schuijf JD, van Werkhoven JM, et al. "Prevalence of coronary artery disease across the Framingham risk categories: coronary artery calcium scoring and MSCT coronary angiography. J Nucl Cardiol 16.3 (2009): 368-75. 43. Okabe T, Mintz GS, Weigold WG, et al. The predictive value of computed tomography calcium scores: a comparison with quantitative volumetric intravascular ultrasound. Cardiovasc Revasc Med 10.1 (2009): 30-5. 44. O'Malley PG, Feuerstein IM, Taylor AJ. Impact of electron beam tomography, with or without case management, on motivation, behavioral change, and cardiovascular risk profile: a randomized controlled trial. JAMA. 2003 May 7;289(17):2215-23. Ewy GA. The search for the "holy grail" of clinically significant coronary atherosclerosis. Arch Intern Med. 2004 Jun 28;164(12):1266-8. Editorial. 45. O'Malley PG, Greenberg BA, Taylor AJ. Cost-effectiveness of using electron beam computed tomography to identify patients at risk for clinical coronary artery disease. Am Heart J. 2004 Jul;148(1):106-13. 46. O'Malley PG, Rupard EJ, Jones DL, et al. Does the diagnosis of coronary calcification with electron beam computed tomography motivate behavioral change in smokers? Mil Med. 2002 Mar;167(3):211-4. PMID: 11901568 47. Petretta, M, Daniele, S, Acampa, W, et al. (2011). Prognostic value of coronary artery calcium score and coronary CT angiography in patients with intermediate risk of coronary artery disease. Int J Cardiovasc Imaging. 48. Pham PH, Rao DS, Vasunilashorn F, et al. Computed tomography calcium quantification as a measure of atherosclerotic plaque morphology and stability. Invest Radiol 41.9 (2006): 674-80. 49. Pletcher MJ, Tice JA, Pignone M, Browner WS. Using the coronary artery calcium score to predict coronary heart disease events: a systematic review and meta-analysis. Arch Intern Med. 2004 Jun 28;164(12):1285-92.: 50. Podrid, PJ. (2011) ECG tutorial: Basic principles of ECG analysis. Up to Date. Last Update: April 17, 2011. Available: http://www.uptodate.com/contents/ecg-tutorial-basic-principles-of-ecg- analysis?source=search_result&search=electrocardiography&selectedTitle=1~150. Date Accessed: November 29, 2011. 51. Polonsky, TS, McClelland, RL, Jorgensen, NW, et al. (2010). Coronary artery calcium score and risk classification for coronary heart disease prediction. JAMA. 303. 16:1610-6. 52. Rackley CE. Pathogenesis of atherosclerosis. 173. May 12, 2009. UpToDate. Available: http://www.utdol.com/online/content/topic.do?topicKey=chd/21090&source=see_link. Date Accessed: February 9, 2010. 53. Rackley, CE. (2009) Pathogenesis of atherosclerosis. UpToDate. Last Update: May 12, 2009. Available: http://www.utdol.com/online/content/topic.do?topicKey=chd/21090&source=see_link. Date Accessed: February 9, 2010. 54. Radiological Society of North America. (2009) Cardiac CT for Calcium Scoring. Radiological Society of North America (RSNA). Last Update: June 26, 2009. Available: http://www.radiologyinfo.org/en/info.cfm?pg=ct_calscoring. Date Accessed: February 9, 2010. 55. Radiological Society of North America. Cardiac CT for Calcium Scoring. June 26, 2009. Radiological Society of North America (RSNA). Available: http://www.radiologyinfo.org/en/info.cfm?pg=ct_calscoring. Date Accessed: February 9, 2010. 56. Radiologyinfo.org. (2011) Cardiac MRI. Radiologyinfo.org. Last Update: Available: http://www.radiologyinfo.org/en/info.cfm?pg=ct_calscoring. Date Accessed: November 29, 2011. 57. Raggi P, Khan A, Arepali C, Stillman AE. Coronary artery calcium scoring in the age of CT angiography: what is its role? Curr Atheroscler Rep 10.5 (2008): 438-43. 58. Ramakrishna G, Breen JF, Mulvagh SL, et al. Relationship between coronary artery calcification detected by electron-beam computed tomography and abnormal stress echocardiography: association and prognostic implications. J Am Coll Cardiol 48.10 (2006): 2125-31. 59. Rosman J, Shapiro M, Pandey A, et al. Lack of correlation between coronary artery calcium and myocardial perfusion imaging. J Nucl Cardiol 13.3 (2006): 333-7. 60. Rugulies R. Depression as a predictor for coronary heart disease. a review and meta-analysis. Am J Prev Med. 2002 Jul;23(1):51-61. Review. 61. Russo, V, Zavalloni, A, Bacchi Reggiani, ML, et al. (2010). Incremental prognostic value of coronary CT angiography in patients with suspected coronary artery disease. Circ Cardiovasc Imaging. 3. 4:351-9. 62. Schenker MP, Dorbala S, Hong EC, et al. Interrelation of coronary calcification, myocardial ischemia, and outcomes in patients with intermediate likelihood of coronary artery disease: a combined positron emission tomography/computed tomography study. Circulation 117.13 (2008): 1693-700. 63. Schepis T, Gaemperli O, Koepfli P, et al. Added value of coronary artery calcium score as an adjunct to gated SPECT for the evaluation of coronary artery disease in an intermediate-risk population. J Nucl Med 48.9 (2007): 1424-30. 64. Scholte AJ, Schuijf JD, Kharagjitsingh AV, et al. Different manifestations of coronary artery disease by stress SPECT myocardial perfusion imaging, coronary calcium scoring, and multislice CT coronary angiography in asymptomatic patients with type 2 diabetes mellitus. J Nucl Cardiol 15.4 (2008): 503-9. 65. Schuijf JD, Wijns W, Jukema JW, et al. A comparative regional analysis of coronary atherosclerosis and calcium score on multislice CT versus myocardial perfusion on SPECT. J Nucl Med 47.11 (2006): 1749-55. 6

Cardiovascular Policies, Continued

Coronary Artery Disease Calcium Scoring (Cardiac CT Scan) to Assess Cardiovascular Risk, continued

66. Sosnowski M, Pysz P, Szymanski L, et al. Negative calcium score and the presence of obstructive coronary lesions in patients with intermediate CAD probability. Int J Cardiol (2009). 67. Sung J, Lim SJ, Choe Y, et al. Comparison of the coronary calcium score with the estimated coronary risk. Coron Artery Dis 19.7 (2008): 475-9. 68. Takalkar, A. (2011) Cardiac Assessment with PET. Saunders Elseiver. Last Update: Available: http://www.mdconsult.com/das/article/body/304695745- 12/jorg=clinics&source=&sp=24390745&sid=0/N/866749/1.html?issn=#S1556859811000757. Date Accessed: November 29, 2011. 69. Townsend, CM. (2008) SABISTON TEXTBOOK of SURGERY: The Biological Basis of Modern Surgical Practice. Sunders Elseiver. Last Update: Available: http://www.mdconsult.com/books/page.do?eid=4-u1.0-B978-1-4160-3675-3.50065-4-- cesec26&isbn=978-1-4160-3675-3&uniqId=304695745-12#4-u1.0-B978-1-4160-3675-3.50065-4--cesec29. Date Accessed: November 29, 2011. 70. University of Washington. (2011) Diagnosis of Coronary Artery Disease. University of Washington. Last Update: Available: http://faculty.washington.edu/momus/PB/diagnosi.htm. Date Accessed: November 29, 2011. 71. University of Wisconsin-Madison. (2011) Heart, Vascular and Thoracic Care. University of Wisconsin-Madison. Last Update: Available: http://www.uwhealth.org/heart-cardiovascular/cardiac-computed-tomography-angiography-ccta/11773. Date Accessed: November 29, 2011. 72. Up to Date. (2011) LAR of all cancer from 64-slice CCTA. Up to Date. Last Update: Available: http://www.uptodate.com/contents/image?imageKey=CARD/28290. Date Accessed: December 13, 2011. 73. van Kempen, BJ, Spronk, S, Koller, MT, et al. (2011). Comparative effectiveness and cost-effectiveness of computed tomography screening for coronary artery calcium in asymptomatic individuals. J Am Coll Cardiol. 58. 16:1690-701. 74. Wessel TR, Arant CB, Olson MB, et al. Relationship of physical fitness vs body mass index with coronary artery disease and cardiovascular events in women. JAMA. 2004 Sep 8;292(10):1179-87. 75. Wilson PW. Epidemiology and prognosis of coronary heart disease. 17.3. July 15, 2009. UpToDate. Available: http://www.utdol.com/online/content/topic.do?topicKey=chd/64193&selectedTitle=2%7E150&source=search_result. Date Accessed: February 9, 2010. 76. Wilson, P. (2011) Estimation of cardiovascular risk in an individual patient without known cardiovascular disease. Up to Date. Last Update: June 16, 2011. Available: http://www.uptodate.com/contents/estimation-of-cardiovascular-risk-in-an-individual- patient-without-known-cardiovasculardisease?source=search_result&search=framingham+risk+score&selectedTitle=1~40#H9. Date Accessed: November 29, 2011. 77. Wilson, PW. (2009) Epidemiology and prognosis of coronary heart disease. UpToDate. Last Update: July 15, 2009. Available: http://www.utdol.com/online/content/topic.do?topicKey=chd/64193&selectedTitle=2%7E150&source=search_result. Date Accessed: February 9, 2010. 78. Yanowitz FG. Screening for coronary heart disease. 17.3. September 1, 2009. UpToDate. Available: http://www.utdol.com/online/content/topic.do?topicKey=chd/49062&selectedTitle=5%7E150&source=search_result. Date Accessed: February 9, 2010. 79. Yanowitz, FG. (2009) Screening for coronary heart disease. UpToDate. Last Update: September 1, 2009. Available: http://www.utdol.com/online/content/topic.do?topicKey=chd/49062&selectedTitle=5%7E150&source=search_result. Date Accessed: February 9, 2010.

Cardiovascular Policies, Continued

MEDICAL POLICY

HEART TRANSPLANT: ADULT

Policy # 125 Implementation Date: 2/10/99 Review Dates: 1/4/00, 2/27/01, 5/21/01, 5/13/02, 5/25/03, 4/22/04, 4/17/06, 5/17/07, 4/24/08 4/23/09, 8/19/10, 9/15/11, 4/25/13, 2/20/14, 3/19/15, 2/16/17, 10/4/18, 10/15/19 Revision Dates: 5/30/04, 1/28/10, 2/14/12, 2/16/16, 10/12/17, 10/8/18

Description Cardiac transplantation remains the treatment of choice for many patients with end-stage heart failure (HF) with severely impaired functional capacity, despite optimal medical therapy. Although barriers to long-term survival remain, the outcome among transplant recipients has improved over several decades as a result of careful recipient and donor selection, advances in immunosuppression, and the prevention and treatment of opportunistic infections.

In the most recent registry report, the median survival for heart transplants performed between 1982 and June 2015 was 11 years for adult recipients and 16 years for pediatric recipients. Patient survival has steadily improved since the 1980s, with one-year survival rates now exceeding 85 percent for adult patients and 90 percent for pediatric patients transplanted in the most current era (2009 through June 2015). The major survival gains are limited to the first 6 to 12 months, with a long-term attrition rate of 3.4 percent per year thereafter, remaining largely unchanged. The improvement is probably larger than it appears since the risk profile of recipients and the age of donors continue to increase.

Commercial Plan Policy

SelectHealth covers adult heart transplants for patients meeting the plan criteria for coverage as outlined below. Transplantation benefits and coverage will be determined only after the review of the work-up from the requesting transplant team has been completed. The work- up will be covered only for approved organ transplants.

To qualify for coverage, adult candidates for transplant must meet the following criteria (except for special cardiac conditions*): 1. The patient has end-stage cardiac disease that is irreversible and progressive, with limited life expectancy, and with no available reasonable alternative medical or surgical therapy

2. NYHA Class III or Class IV cardiac dysfunction (see below for definition of NYHA functional classifications)

3. Must have at least one of the following diagnoses:

4. Coronary artery disease/ischemic cardiomyopathy

5. Idiopathic dilated cardiomyopathy

Cardiovascular Policies, Continued

Heart Transplant: Adult, continued

6. Valvular heart disease

7. Myocarditis

8. Restrictive cardiomyopathy

9. Congenital heart disease

10. Adriamycin cardiomyopathy

11. Peripartum cardiomyopathy

12. Hypertrophic cardiomyopathy

13. Infiltrative cardiomyopathy—only if confined to heart (if not, it is an absolute contraindication)

14. Chagas Disease

15. *Unresectable Primary Cardiac Tumor

16. *Intractable life-threatening arrhythmias

17. *Severe cardiac allograft vasculopathy

18. When pulmonary hypertension exists, pulmonary vascular resistance less than or equal to 5 wood units with or without afterload reduction (e.g., Nitroprusside, etc.)

19. A reasonable expectation that the patient's quality of life, i.e., physical and social function suited to activities of daily living, will be improved

20. Strong motivation by the patient to undergo the procedure and a thorough understanding by the patient and family of the magnitude of the operation, its risks, and sequelae, including lifetime follow-up

21. Medical assessment that the patient will have a tolerance for immunosuppressive therapy and that no other major system disease or anomaly is present which would preclude surgery or a reasonable chance of survival

22. A psychosocial evaluation has been performed by a psychologist/psychiatrist independent of the transplant program who has specifically evaluated the patient to determine their appropriate candidacy for the procedure, have a clear understanding of the procedure and its impact, have no active psychological /psychiatric conditions which may interfere with the patient’s ability to follow through with necessary pre- and post- transplant treatment protocols, and has demonstrated compliance with therapy in the past

23. Medical and social assessment that the patient has sufficient social stability to provide assurance that he/she will cooperate with the long-term follow-up and the immunosuppressive program, which is required

24. Age at time of transplant listing: > 18 and ≤ 70 years

25. Peripheral vascular disease is a relative contraindication for transplantation when its presence limits rehabilitation and revascularization is not a viable option 2

Cardiovascular Policies, Continued

Heart Transplant: Adult, continued

Absolute Contraindications: 1. Severe, irreversible pulmonary hypertension

2. Pulmonary disease as listed below:

a. Cystic fibrosis

b. Obstructive pulmonary disease (FEV < 65% of predicted)

c. Restrictive pulmonary disease (FVC < 50% of predicted)

d. Unresolved pulmonary roentgenographic abnormalities of unclear etiology

e. Unresolved pulmonary infarction

3. Vascular disease

4. Unresolved GI bleeding

5. Unresolved diverticulitis

6. Irreversible liver disease

7. Hepatitis B antigen positivity

8. Untreated positive Hepatitis C serology with severe pathology on liver biopsy and/or elevated transaminases

9. Active malignant disease

10. Active infection

11. Neuromuscular disorders with physical limitations impacting survival/QOL post- transplant

12. Acute psychiatric illness

13. Past alcohol or substance abuse unless successful counseling and follow-up documented along with documented abstinence (usually greater than 3 months)

14. History of medical non-compliance

Relative Contraindications: 1. History of psychiatric illness

2. Morbid obesity (Body Mass Index > 35 kg/m²)

3. Renal insufficiency as manifested a creatinine clearance below 30 mL/min. The concern in this setting is the superimposed nephrotoxicity of long-term cyclosporine therapy.

4. HIV positivity (can be considered if ALL the following):

a. No active or prior opportunistic infections or CNS lymphoma, or visceral Kaposi sarcoma, 3

Cardiovascular Policies, Continued

Heart Transplant: Adult, continued

b. Clinically stable and compliant on combination antiretroviral therapy (cART) for 3 months,

c. Have undetectable HIV RNA and have CD4 counts > 200 cells/μl for > 3 months).

5. Advanced hepatic disease. Cirrhosis, for example, can limit survival and increase perioperative morbidity, particularly if a coagulopathy is present.

6. Diabetes mellitus with end-organ dysfunction (other than non-proliferative retinopathy), chronic infections, leg ulcers, or persistent poor glycemic control (HbA1C > 7.5% despite optimal effort

Several other conditions increase the rate of perioperative complications or interact poorly with immunosuppressive agents. Included in this group are advanced peripheral vascular disease, morbid obesity, active peptic ulcer disease, cholelithiasis, and diverticulosis. All cardiac transplantation candidates should undergo a complete psychosocial evaluation during the initial screening process. This may identify social and behavioral factors that cause difficulty during the waiting period, convalescence, and long-term post-operative management. The patient must understand that full cooperation and compliance are critical to the safe and effective use of immunosuppressive agents. Finally, patients must be screened for the use and abuse of alcohol and other recreational drugs. Active drug or alcohol abuse should be considered an absolute contraindication for transplantation. Although post-transplant recidivism is a frequent occurrence in patients in "recovery," survival may not be reduced. New York Heart Association (NYHA) Functional Cardiac Classifications: 1. Patients with cardiac disease but without resulting limitations of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea or anginal pain.

2. Patients with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain.

3. Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary physical activity causes fatigue, palpitation, dyspnea, or anginal pain.

4. Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.

SelectHealth Advantage (Medicare/CMS)

Cardiovascular Policies, Continued

Heart Transplant: Adult, continued

SelectHealth Community Care (Medicaid/CHIP)

Summary of Medical Information In 2001, the Clinical Practice Committee of the American Society of Transplantation published recommendations for considering transplantation in patients with cardiac conditions that have not responded to maximal medical management. Improved survival should be the primary indication for cardiac transplantation and the primary selection task is to predict the prognosis in severe heart failure. Many predictors of poor prognosis have been identified, including NYHA functional class III or IV, reduced left ventricular ejection fraction (LVEF), and hyponatremia. However, there is sufficient overlap that these factors are of limited use in a particular individual. This is not surprising in view of the complexity of HF and the multiple neurohumoral, hemodynamic, and electrophysiological factors that may contribute to morbidity and mortality. In general, the peak VO2 appears to provide the most objective assessment of functional capacity in patients with HF, and may be the best predictor of when to list an individual patient for cardiac transplantation. The 2002 task force of the ACC/AHA has given a class I recommendation to the use of exercise testing with ventilator gas analysis for this purpose. The value of using the peak VO2 for this purpose is illustrated by a study of 114 consecutive ambulatory patients with advanced disease referred for possible cardiac transplantation. Three groups of patients were prospectively divided and had their outcomes compared based on their VO2 outcomes. They were comparable with regards to other clinical parameters of disease severity, including NYHA functional class, LVEF, and cardiac index. The 1-year survival of the healthier patients in group 2 was 94%, an outcome that was similar to that in transplanted patients in group 1. The prognosis was poorest in group 3, although survival varied with the peak VO2 in this group. Patients with a value less than or equal to 10 mL/kg per min had the lowest survival, while those between 10−14 mL/kg per min had an outcome that was only slightly worse than patients in group 1. Thus, patients with a profoundly reduced exercise capacity of 10 mL/kg per min are likely to experience the most pronounced improvement in survival with transplantation. The small survival benefit seen for group 3 patients with a peak VO2 of 10−14 mL/kg per min illustrates the difficulty in selection of patients for transplantation. Many of these patients will benefit from transplantation, particularly those with a peak VO2 of 12 mL/kg per min. Patients in this intermediate range of peak VO2 who are initially considered too well for transplantation should have several measurements of exercise capacity over a period of time. Some will improve on repeated testing, but those with persistent values of 10−12 mL/kg per min and poor exercise tolerance should generally be considered for transplantation. Repeated hospitalization and/or the requirement for increasing medical therapy are additional indicators of likely benefit from transplantation. It must be emphasized that these observations and recommendations for transplantation are applicable only if a severely reduced peak VO2 is caused by HF. Proper interpretation of the test requires that the patient achieve the anaerobic threshold, indicating that the level of exercise performed exceeded that which can be supported by the cardiovascular system on an aerobic basis. Factors that can prematurely terminate the test must be excluded, including significant peripheral vascular disease, arthritis, or angina pectoris. The peak VO2 should also be interpreted in light of the patient's age, lifestyle, and expectations. A peak VO2 of 14 mL/kg per min may represent mild impairment to a 60-year-old patient, but marked impairment to a 20-year-old patient. Although peak VO2 is generally used to guide the selection of heart transplant candidates, a single variable cannot provide an optimal risk profile. As a result, several risk models have been developed that use factors identified in multivariable survival analysis to establish a risk score for prognosis in these patients. 5

Cardiovascular Policies, Continued

Heart Transplant: Adult, continued

One model that has been validated prospectively is the Heart Failure Survival Score (HFSS). This score was derived from a multivariable analysis of 268 ambulatory patients referred for consideration of cardiac transplantation and validated in 199 similar patients. Seven variables were used as predictors of survival in the HFSS. These include the presence or absence of: coronary artery disease, resting heart rate, left ventricular ejection fraction, mean arterial blood pressure, presence or absence of an interventricular conduction delay on ECG, serum sodium, and peak VO2. In an invasive version of the HFSS, pulmonary capillary wedge pressure is included as an eighth variable. The HFSS then stratifies patients into low-, medium-, and high-risk categories, based upon a sum of the variables above multiplied by defined coefficients. Among the patients in the validation sample, one-year survival rates without transplant for these three strata were 88%, 60%, and 35%, respectively. Other risk models exist and are used by various centers to assess patients’ candidacy for heart transplantation. Although the most common indication for heart transplantation is severe HF refractory to medical therapy, the operation may be recommended in other circumstances. These include severely limiting ischemia not amenable to interventional or surgical revascularization, recurrent symptomatic ventricular tachyarrhythmias refractory to medical therapy, an implantable cardioverter-defibrillator, surgery, and rarely, for the management of cardiac tumors. Even the patient who meets the above requirements must be excluded from transplantation when one or more absolute contraindications are demonstrated by standard evaluation procedures. In addition, relative contraindications must be taken into account in judging whether a patient is likely to benefit from heart transplantation. Absolute contraindications include pulmonary vascular resistance (PVR) greater than 4−6 Wood units (320−480 dynes-sec/cm5) (normal 1.5 Wood units [120 dynes-sec/cm5]) or a transpulmonary gradient (mean pulmonary artery pressure minus mean pulmonary capillary wedge pressure) above 15 mmHg have an increased risk of right ventricular failure in the immediate postoperative period. Patients whose PVR can be pharmacologically reduced to below 4 Wood units (320 dynes-sec/cm5) are usually considered acceptable for transplantation. In one report, for example, the 3-month mortality rate was higher in patients whose PVR was above 2.5 Wood units compared to those with lower values (17.9% versus 6.9%). However, the 3-month mortality was only 3.8% in those with initially high values that were reduced by nitroprusside,` compared to 41% and 28%, respectively, in those who were resistant to nitroprusside or who only responded at a dose that caused systemic hypotension. None of the patients with reversible pulmonary hypertension developed right ventricular failure after transplantation. Two other absolute contraindications to transplantation are active infection and malignancy of any kind, both of which can be worsened by the immunosuppressive therapy given to prevent transplant rejection. Heart transplantation in patients with clinically important chronic viral infection remains a subject of active debate. Individuals with chronic hepatitis B or hepatitis C infections who undergo heart transplantation have an increased frequency of liver disease. However, it has been difficult to show that survival after heart transplantation is poorer in the presence of positive hepatitis B or C serology. As a result, practices of individual centers differ. Since the frequency of progressive liver disease appears to be more common with hepatitis B than with hepatitis C, many transplant programs will accept candidates who are anti-HCV antibody positive, but not those who are HBsAg positive. HIV infection has been considered to be an absolute contraindication to heart transplantation, primarily because of concerns about the increased frequency of infectious and malignant complications and the previously poor survival of such patients. However, the advent of highly active antiretroviral therapy has changed the prognosis of HIV. As a result, the view has been expressed that HIV infection itself should not be sufficient reason to refuse transplantation. Among the relative contraindications to cardiac transplantation, age has historically been a major factor. Many programs have routinely excluded patients over the age of 60–65. However, carefully selected patients in this age group or older have a survival rate comparable to that in younger patients. One report compared 63 patients transplanted at 65 years of age or older (mean age 67) to 63 matched younger patients (mean age 48). Survival was comparable for both groups at 1, 3, 5, and 10 years; there was also no significant difference in the incidence of rejection or infection. As a result, most centers now focus on the patient's "physiologic" age, with emphasis on the functional integrity of major organ systems and the absence of exclusionary comorbid diseases. Diabetes mellitus, even without evidence of significant end-organ damage (neuropathy, retinopathy, or nephropathy), is a relative contraindication to heart transplantation. However, the outcome in properly 6

Cardiovascular Policies, Continued

Heart Transplant: Adult, continued

selected patients is comparable to that in nondiabetics. This was illustrated in an analysis of 345 consecutive heart transplant recipients, 101 with diabetes. Diabetics, compared to nondiabetics, had a non-significant trend toward decreased survival at one year (85% vs. 91%) but comparable survival at 5 years (82%). Rates of infection severe enough to require hospitalization were higher among diabetics at 90 days (14% vs. 3%) and 4 years (29% vs. 15%). There were no differences in the incidence of rejection, transplant coronary disease, or renal dysfunction. Advanced obstructive and/or restrictive lung disease is associated with a higher incidence of postoperative lung complications, including infection associated with immunosuppressive therapy. Objective exclusion criteria include a forced one-second expiratory volume of less than 1.0 liter; a forced vital capacity of less than 50% of predicted; or a forced expiratory volume-to-vital capacity ratio of less than 1.0. In addition, recent pulmonary embolism with or without infarction should delay transplantation, because secondary infection in the affected lobe may occur postoperatively. Before putting the patient on the transplant list, most centers treat this disorder with systemic anticoagulants for 6−8 weeks or until radiographic evidence of resolution is seen. A January 2012 Medical Technology Assessment focused on the maximum age at transplant. Nine primary literature articles and no systematic reviews were identified regarding heart transplantation as it relates to upper age limitations. A total of 16,892 patients reported in these studies underwent heart transplantation. Though the articles, in general, did well to report follow-up times and age ranges of participants, few appropriately matched patients for age, sex, weight, or presence of comorbidities such as diabetes mellitus. Only 2 of the 9 papers (Crespo-Leiro et al. and Morgan et al.) specifically addressed the safety and efficacy of heart transplantation in patients > 65 years of age and < 65 years of age. Both groups noted that among carefully selected patients aged more than 65 years, heart transplantation can be performed without incurring a greater risk of rejection or death than in patients aged less than 65 years. From the literature, it is notable that among the relative contraindications to cardiac transplantation, age has historically been a major factor. Many programs have routinely excluded patients over the age of 60−65 while advocating the view that physiologic age is more important than chronological age. Speaking to the issue of the outcomes related to transplanting a more mature population, a report based on United Network for Organ Sharing (UNOS) data for 14,401 first-time transplant recipients between 1999 and 2006 demonstrated that patients ≥ 60 years of age more frequently had comorbidities than younger patients and that their overall survival post-transplant was lower than in younger patients. However, cumulative five-year survival for patients ≥ 60 years of age was only slightly lower than that for younger patients (69% vs. 75%). There is no data to suggest that this disparity is a direct result of the heart transplantation itself. Multivariate analysis revealed recipient age ≥ 60 years, donor age, ischemic time, creatinine, hypertension, and diabetes to be independent predictors of mortality. One of the most significant studies demonstrating the lack of age as being a significant variable affecting outcome was the 2006 ISHLT update on the listing criteria and management of cardiac transplantation candidates. This study suggested that most patients 70 years of age or younger and carefully selected patients over age 70 can be considered for cardiac transplantation. This finding is supported by the majority of additional references cited in this report.

Billing/Coding Information CPT CODES 33940 Donor cardiectomy (including cold preservation) 33944 Backbench standard preparation of cadaver donor heart allograft prior to transplantation, including dissection of allograft from surrounding soft tissues to prepare aorta, superior vena cava, inferior vena cava, pulmonary artery, and left atrium for implantation 33945 Heart transplant, with or without recipient cardiectomy

HCPCS CODES Not covered: Investigational/Experimental/Unproven for this indication S2152 Solid organ(s), complete or segmental, single organ or combination of organs; deceased or living donor(s), procurement, transplantation, and related complications including: drugs; supplies; hospitalization with outpatient follow-up; medical/surgical, diagnostic, 7

Cardiovascular Policies, Continued

Heart Transplant: Adult, continued

emergency, and rehabilitative services; and the number of days of pre- and post- transplant care in the global definition S9975 Transplant related lodging, meals and transportation, per diem

Key References 1. Comparative analysis of outcome. J Thorac Cardiovasc Surg 121.3: 532-41. 2. Botta, DM. (2011) Heart Transplantation. October 26, 2011. Medscape. Available: http://emedicine.medscape.com/article/429816-overview#a0104. Date Accessed: December 30, 2011. 3. Carey, WD. (2010) Current Clinical Medicine. Saunders Elsevier. Available: http://www.mdconsult.com/books/page.do?eid=4- u1.0-B978-1-4160-6643-9.00236-8&isbn=978-1-4160-6643-9&uniqId=310518069-8#4-u1.0-B978-1-4160-6643-9.00236-8. Date Accessed: January 5, 2012. 4. Colucci, Wilson S. UpToDate, (2004). Chapter on Indications and Exclusions for Cardiac Transplantation. 5. Colucci, WS. (2011) Evaluation of the patient with suspected heart failure. March 8, 2010. Up to Date. Available: http://www.uptodate.com/contents/evaluation-of-the-patient-with-suspected-heartfailure?source=search_result&search=heart+failure&selectedTitle=2~150. Date Accessed: January 10, 2012. 6. Colucci, WS. (2011) Indications and contraindications for cardiac transplantation. February 18, 2011. Up to Date. Available: http://www.uptodate.com/contents/indications-and-contraindications-for-cardiac-transplantation. Date Accessed: January 6, 2012. 7. Crespo-Leiro, MG, Paniagua-Martin, MJ, Muniz, J, et al. (2005). Long-term results of heart transplant in recipients older and younger than 65 years: a comparative study of mortality, rejections, and neoplasia in a cohort of 445 patients. Transplant Proc 37.9: 4031-2. 8. Daneshvar, D, Czer, LS, Phan, A, et al. (2011). Heart transplantation in patients aged 70 years and older: a two-decade experience. Transplant Proc 43.10: Blanche, C, Blanche, DA, Kearney, B, et al. (2001). Heart transplantation in patients seventy years of age and older: A 3851-6. 9. Demers, P, Moffatt, S, Oyer, PE, et al. (2003). Long-term results of heart transplantation in patients older than 60 years. J Thorac Cardiovasc Surg 126.1: 224-31. 10. Eisen, HJ. (2011) Patient information: Heart transplantation. September 29. Up to Date. Available: http://www.uptodate.com/contents/patient-information-heart-transplantation. Date Accessed: January 6, 2012. 11. Forni, A, Faggian, G, Chiominto, B, et al. (2007). Heart transplantation in older candidates. Transplant Proc 39.6: 1963-6. 12. Gibbons, RJ, Balady, GJ, Bricker, JT, et al. (2002). ACC/AHA 2002 guideline update for exercise testing: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines). Circulation; 106:1883. 13. Goldman, L. (2011) Goldman's Cecil Medicine. Saunders Elsevier. Available: http://www.mdconsult.com/books/pagedo?eid=4- u1.0-B978-1-4377-1604-7.00082-8&isbn=978-1-4377-1604-7&uniqId=311439269-5#4-u1.0-B978-1-4377-1604-7.00082-8. Date Accessed: January 10, 2012. 14. Heartfailure.org. (2012) Heart Failure. Heartfailure.org. Available: http://www.heartfailure.org/eng_site/hf.asp. Date Accessed: January 10, 2012. 15. Hunt, SA, Abraham, WT, Chin, MH, et al. (2009). 2009 Focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation. J Am Coll Cardiol 53.15: e1-e90. 16. Marelli, D, Kobashigawa, J, Hamilton, MA, et al. (2008). Long-term outcomes of heart transplantation in older recipients. J Heart Lung Transplant 27.8: 830-4. 17. Mehra, MR, Kobashigawa, J, Starling, R, et al. (2006). Listing criteria for heart transplantation: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates--2006. J Heart Lung Transplant 25.9: 1024- 42. 18. Morgan, JA, John, R, Weinberg, AD, et al. (2003). Long-term results of cardiac transplantation in patients 65 years of age and older: a comparative analysis. Ann Thorac Surg 76.6: 1982-7. 19. Nagendran, J, Wildhirt, SM, Modry, D, et al. (2004). A comparative analysis of outcome after heart transplantation in patients aged 60 years and older: the University of Alberta experience. J Card Surg 19.6: 559-62. 20. Robbins, RC, Barlow, CW, Oyer, PE, et al. (1999). Thirty years of cardiac transplantation at Stanford University. J Thorac Cardiovasc Surg; 117:939. 21. Steinman, TI, Becker, BN, Frost, AE, et al. (2001). Guidelines for the referral and management of patients eligible for solid organ transplantation. Transplantation 71.9: 1189-204. 22. The Registry of the International Society for Heart and Lung Transplantation: (1992). Ninth official report. J Heart Lung Transplant; 11:599. 23. UCSF Medical Center. (2012). Heart Failure Treatment. January 9, 2012. UCSF Medical Center. Available: http://www.ucsfhealth.org/conditions/heart_failure/treatment.html. Date Accessed: January 10, 2012. 24. Weiss, ES, Nwakanma, LU, Patel, ND, et al. (2008). Outcomes in patients older than 60 years of age undergoing orthotopic heart transplantation: an analysis of the UNOS database. J Heart Lung Transplant 27.2: 184-91. 25. Wilbur, J. (2005) Diagnosis and Management of Heart Failure in the Outpatient Setting. Saunders. Available: http://www.mdconsult.com/das/article/body/311439269- 3/jorg=journal&source=&sp=15908512&sid=0/N/508069/1.html?issn=0095-4543#S0095454305000801. Date Accessed: January 10, 2012. 26. ISHLT GUIDELINE The 2016 International Society for Heart Lung, Transplantation listing criteria for heart transplantation: A 10-year update, Mandeep R. Mehra, MD (Chair)et al, The Journal of Heart and Lung Transplantation, Vol 35, No 1, January 2016. 27. Pham, Michael X. UpToDate, (2018). Prognosis after cardiac transplantation in adults.

Cardiovascular Policies, Continued

Heart Transplant: Adult, continued

Cardiovascular Policies, Continued

MEDICAL POLICY

HEART TRANSPLANT: CHILDREN (UNDER AGE 18)

Policy # 126 Implementation Date: 2/10/99 Review Dates: 1/4/00, 2/27/01, 5/21/01, 5/13/02, 6/25/03, 4/22/04, 4/19/05, 4/20/06, 8/23/07, 8/21/08, 8/13/09, 9/15/11, 11/29/12, 10/24/13, 10/23/14, 10/15/15, 2/16/17, 2/15/18, 2/5/19, 2/13/20 Revision Dates: 9/15/06, 8/19/10, 2/16/16, 2/26/20

Description Worldwide, > 700 pediatric heart transplantation procedures are performed each year, representing about 12% of the total number of heart transplants performed. Most pediatric heart transplantation programs now have 5-year survival rates in excess of 80%.

Commercial Plan Policy

SelectHealth covers heart transplant in children under age 18 with limitations as outlined below.

Guidelines for coverage include all the following: 1. The patient was evaluated and accepted for transplant by a paneled transplant team. 2. The patient has end-stage cardiac disease, which is irreversible and progressive, a limited life expectancy or documented progressive (but partially reversible) pulmonary hypertension, or both, and no available reasonable alternative medical or surgical therapy. 3. The patient suffers from New York Heart Association (NYHA) Class III or Class IV cardiac dysfunction - when criteria can be applied (see below for definition of NYHA Classes) despite maximal medical therapy. 4. One of the following diagnoses: a. Cardiomyopathy b. Inoperable congenital heart disease, for which there is no reasonable corrective operation c. Myocarditis d. Cardiac tumor 5. Pulmonary vascular resistance < 8 wood units with Nitroprusside or other vasodilators. (Does not apply to infancy). 6. A reasonable expectation that the patient's quality of life, i.e., physical and social function suited to activities of daily living, will be improved.

Cardiovascular Policies, Continued

Heart Transplant Children: Under Age 18, continued

7. Strong motivation and emotional stability of parent/guardian, a thorough understanding by the patient and family of the magnitude of the operation and its sequelae, including lifetime follow-up. 8. Medical assessment that the patient will have a tolerance for immunosuppressive therapy and that no other major system disease or anomaly is present which would preclude surgery or a reasonable survival. 9. Medical and social assessment that the parent/guardian and child have sufficient social stability to provide assurance that he/she will cooperate with the long-term follow-up and the immunosuppressive program which is required. 10. Child is > 36 weeks gestational age and weight > 2.2 kilograms.

Absolute Contraindications 1. Gestational age ≤ 36 weeks and/or weight less than 2.2 kilograms. 2. Active Systemic infection a. Viral (including symptomatic congenital viral infection, active HIV, HBV) b. Bacterial (including active TB) 3. Irreversible and severe renal, hepatic, CNS or pulmonary dysfunction. 4. Juvenile onset (insulin-dependent) diabetes mellitus with end-organ dysfunction (other than non-proliferative retinopathy) or chronic infections or persistent poor glycemic control (HbA1C > 7.5% despite optimal effort). 5. Active/unresolved alcohol or drug abuse. 6. Active malignancy or history of malignancy with high rate of recurrence 7. Severe dysmorphism, with limited life expectancy

Relative Contraindications 1. Psychosocial considerations as listed below: a. Strong history of parent/guardian alcohol and/or substance abuse. b. Documented parent/guardian child abuse or neglect. c. Family unable to support long-term medical needs of recipient. d. Parent/guardian with cognitive/psychiatric impairment severe enough to limit comprehension of medical regimen. e. Documented parent/guardian and/or patient noncompliance with previous medical care. 2. HIV positivity (transplant can be considered if ALL the following) a. No active or prior opportunistic infections or CNS lymphoma, or visceral Kaposi sarcoma, b. Clinically stable and compliant on combination antiretroviral therapy (cART) c. Have undetectable HIV RNA and have CD4 counts > 200 cells/μl for > 3 months.

New York Heart Association (NYHA) Functional Cardiac Classifications: NYHA I: Patients with cardiac disease but without resulting limitations of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea or anginal pain. NYHA II: Patients with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain. 2

Cardiovascular Policies, Continued

Heart Transplant Children: Under Age 18, continued

NYHA III: Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary physical activity causes fatigue, palpitation, dyspnea, or anginal pain. NYHA IV: Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.

SelectHealth Advantage (Medicare/CMS)

SelectHealth Community Care (Medicaid/CHIP)

Summary of Medical Information The 4 main etiologies leading to conditions that might require heart transplantation are errors in the formation of the heart, cardiac tumors, infections, and toxins (either endogenous or exogenous), leading to damage to the myocardium. Many of the congenital anomalies, including congenital cardiomyopathy, are now known to have specific chromosomal abnormalities associated with them. Conditions considered for pediatric heart transplantation include the following: • Cardiomyopathy (i.e., dilated, hypertrophic, restrictive) • Anatomically uncorrectable congenital heart disease (e.g., HLHS, pulmonary atresia with intact ventricular septum plus sinusoids, congenitally corrected transposition of the great arteries with single ventricle and heart block, severely unbalanced atrioventricular septal defects) • Congenital heart disease at high risk for repair (e.g., severe Shone complex, interrupted aortic arch and severe subaortic stenosis, critical aortic stenosis with severe endocardial fibroelastosis, Ebstein anomaly in a symptomatic newborn) • Refractory heart failure • Unresectable symptomatic cardiac neoplasms

Cardiovascular Policies, Continued

Heart Transplant Children: Under Age 18, continued

HCPCS CODES S2152 Solid organ(s), complete or segmental, single organ or combination of organs; deceased or living donor(s), procurement, transplantation, and related complications; including: drugs; supplies; hospitalization with outpatient follow-up; medical/surgical, diagnostic, emergency, and rehabilitative services; and the number of days of pre- and post-transplant care in the global definition

Key References

1. ISHLT GUIDELINE. The 2016 International Society for Heart Lung, Transplantation listing criteria for heart transplantation: A 10-year update, Mandeep R. Mehra, MD (Chair)et al, The Journal of Heart and Lung Transplantation, Vol 35, No 1, January 2016 2. ISHLT website. https://ishltregistries.org/registries/quarterlyDataReportResults.asp?organ=HR&rptType=all&continent=4. Accessed December 31, 2019. 3. Lee, TM, Hsu DT, Kantor P et al. (2017). Pediatric Cardiomyopathies. Circ Res. 121.7: 855-73. 4. Mehra MR, Canter CE, Hannan MM et al. (2016). The 2016 International Society for Heart Lung Transplantation listing criteria for heart transplantation: A 10-year update. J Heart Lung Transplant 35.1: 1-23. 5. Organ Procurement and Transplantation Network. National Data. Available at https://optn.transplant.hrsa.gov/data/view-data- reports/national-data/#. Accessed December 31, 2019. 6. Rossano JW, Singh TP, Cherikh WS et al (2019). The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Twenty-second pediatric heart transplantation report – 2019; Focus theme: Donor and recipient size match. J Heart Lung Transplant. 38.10: 1028-41. 7. Rossano JW, Shaddy RE. (2014). Heart Failure in Children: Etiology and Treatment. J Pedatr. 165.2: 228-33. 8. Rossano JW, Dipchand AI, Edwards LB, et al. The Registry of the International Society for Heart and Lung Transplantation: Nineteenth Pediatric Heart Transplantation Report-2016; Focus Theme: Primary Diagnostic Indications for Transplant. J Heart Lung Transplant. 2016 Oct. 35.10:1185-1195. 9. Thrush PT, Hoffman TM. (2014). Pediatric heart transplantation—indications and outcomes in the current era. J Thorac Dis. 6.8: 1080-1096.

Cardiovascular Policies, Continued

MEDICAL POLICY

HEART-LUNG TRANSPLANT

Policy # 127 Implementation Date: 2/10/99 Review Dates: 1/4/00, 2/27/01, 5/21/01, 5/13/02, 6/25/03, 4/22/04, 4/22/05, 8/23/07, 8/21/08, 8/13/09, 8/19/10, 9/15/11, 7/18/13, 6/11/15, 6/16/16, 6/15/17, 7/20/18, 6/13/19, 6/18/20 Revision Dates: 9/15/06

Description Cardiopulmonary transplantation (heart and lung transplantation) is the simultaneous surgical replacement of the heart and lungs in patients with end-stage cardiac and pulmonary disease. This procedure remains a viable therapeutic alternative for patients in specific disease states, although the frequency of application has substantially diminished in recent years.

Commercial Plan Policy

SelectHealth covers heart-lung transplantation with limitations as outlined below. Criteria for coverage must include all the following: 1. The patient has been evaluated and accepted as a candidate for transplant by a paneled transplant team. 2. Review of the transplant team demonstrates that patient has a significant and reasonable probability for improved health post-transplant. 3. Transplant is not being performed as part of an investigational trial.

SelectHealth Advantage (Medicare/CMS)

SelectHealth Community Care (Medicaid/CHIP)

Cardiovascular Policies, Continued

Heart-Lung Transplant, continued

Summary of Medical Information The International Society Heart and Lung Transplantation (ISHLT) summarized the distribution of diagnoses leading to heart-lung transplantation from 1982 to 2004. The 3 leading indications were: • Congenital heart disease with Eisenmenger syndrome: 32% • Idiopathic pulmonary arterial hypertension: 25% • Cystic fibrosis: 16% Heart-lung transplantation may also be required in patients with end-stage parenchymal lung disease who also have severely compromised left ventricular function (e.g., sarcoidosis). The joint guidelines from the American Thoracic Society/American Society for Transplant Physicians/European Respiratory Society and the ISHLT guidelines suggest an age limit for heart-lung transplantation of 55 years. Among patients with severe lung disease, referral for heart-lung transplantation should be made if the patient is a New York Heart Association (NYHA) class III or IV heart failure despite optimal surgical and medical treatment. Malignant ventricular arrhythmias not amenable to pharmacologic or electrophysiologic interventions (including an implantable cardioverter-defibrillator) in patients with end-stage lung disease are rare indications for the combined procedure. Patients with idiopathic pulmonary arterial hypertension with preserved left ventricular function are best treated with double-lung transplantation. Combined heart-lung transplantation is the preferred procedure for patients with complex congenital heart disease with Eisenmenger syndrome, including those with single ventricle anatomy, unsuccessfully repaired or uncorrectable lesions, and/or severely depressed left ventricular function. On the other hand, bilateral lung transplantation with repair of the congenital defect is the recommended procedure in patients with simple congenital heart disease. These lesions include: • Atrial or ventricular septal defect • Scimitar syndrome • Pulmonary venous stenosis • A functionally inadequate vascular bed as with multiple peripheral pulmonary arterial stenoses or pulmonary arteriovenous malformations. Orthotopic heart transplantation alone has been performed in patients with congenital heart disease and a physiologic single lung (e.g., unilateral pulmonary venous stenosis, or due to previous aortopulmonary shunt procedure). Heart-lung transplant recipients receive an "en bloc" harvested heart and lung allograft and can be listed under both the lung and heart allocation systems. The lung allocation system in the United States was changed by United Network for Organ Sharing (UNOS) in 2005 from a system that prioritized patients by the amount of time accumulated on the waiting list to a system that incorporates the severity of disease and the likelihood of survival following transplantation into a "lung allocation score." This score, which includes many variables, dictates a patient's priority for organ allocation; time on the waiting list is no longer the driving factor. The lung allocation scoring system has no equivalent to the status 1A listing by which cardiac recipients obtain the highest priority for allocation of donor hearts. It has been argued that the lung allocation scoring system does not adequately reflect the severity of disease in patients with pulmonary arterial hypertension who are better served by the cardiac listing criteria. Thus, patients listed for combined heart-lung transplantation may in some areas be listed as a status 1A heart and obtain a heart and lung bloc via this mechanism. However, the criteria for 1A heart listings are not always applicable to patients with pulmonary hypertension or complex cyanotic congenital heart disease; as a result, an application for 1A status with exemption may be necessary.

Billing/Coding Information CPT CODES 33930 Donor cardiectomy-pneumonectomy (including cold preservation) 33933 Backbench standard preparation of cadaver donor heart/lung allograft prior to transplantation, including dissection of allograft from surrounding soft tissues to prepare aorta, superior vena cava, inferior vena cava, and trachea for implantation 2

Cardiovascular Policies, Continued

Heart-Lung Transplant, continued

33935 Heart-lung transplant with recipient cardiectomy-pneumonectomy 33940 Donor cardiectomy (including cold preservation) 33944 Backbench standard preparation of cadaver donor heart allograft prior to transplantation, including dissection of allograft from surrounding soft tissues to prepare aorta, superior vena cava, inferior vena cava, pulmonary artery, and left atrium for implantation 33945 Heart transplant, with or without recipient cardiectomy

HCPCS CODES S2054 Transplantation of multivisceral organs S2055 Harvesting of donor multivisceral organs, with preparation and maintenance of allografts; from cadaver donor S2060 Lobar lung transplantation S2061 Donor lobectomy (lung) for transplantation, living donor S2152 Solid organ(s), complete or segmental, single organ or combination of organs; deceased or living donor(s) , procurement, transplantation, and related complications; including: drugs; supplies; hospitalization with outpatient follow-up; medical/surgical, diagnostic, emergency, and rehabilitative services; and the number of days of pre- and post-transplant care in the global definition

Key References 1. Doyle, RL & Nador, RG. Heart-lung transplantation. 2006. http://www.utdol.com/utd/content/topic.do?topicKey= hrt_tran/5634&type=A&selectedTitle=1~19. Date accessed: 9/15/06. 2. Mancini, MC. Heart-lung transplantation. 2006. http://www.emedicine.com/med/topic2603.htm. Date accessed: 9/15/06.

Cardiovascular Policies, Continued

MEDICAL POLICY

IMPLANTABLE LOOP RECORDERS (ILR)

Policy # 131 Implementation Date: 7/15/03 Review Dates: 2/26/04, 1/13/05, 1/3/06, 2/16/07, 2/21/08, 2/19/09, 2/18/10, 2/17/11, 2/16/12, 4/25/13, 2/20/14, 3/19/15, 2/11/16, 2/16/17, 2/15/18, 2/5/19, 2/11/20 Revision Dates:

Description The implantable loop recorder (ILR) is an implantable, self-sensing, and/or patient-activated monitoring system that records electrocardiography data. It is designed to diagnose a cardiac cause of syncope when the standard work-up, including non-invasive tests, is not diagnostic. Electrodes in the device sense the heart's activity through human tissue, so there is no need for any intravenous leads. When symptoms occur, the patient uses an external activator device to record electrocardiogram (ECG) data for analysis by a physician; the Reveal® Plus device has an autosensing feature that can be programmed to automatically begin recording when it senses an arrhythmia. The monitor can store up to 40 minutes of preceding signals after an episode of spontaneous syncope. The device is removed after the battery has failed (14–18 months) or earlier, if a definitive diagnosis has been established. The ILR is implanted subcutaneously under local anesthetic in a single incision procedure in a left pectoral or mammary location. The projected life of the battery is approximately 14 months. The manufacturer recommends that the device be explanted (removed) when it is no longer clinically necessary, or when the battery is depleted. The electrodes are self-contained within the recorder. The ILR system consists of the following elements: 1. A subcutaneously placed, programmable cardiac event recorder with looping memory. 2. A handheld telemetry unit; which is used by the patient to activate electrocardiographic storage. 3. A programmer; which is used to program the event recorder and retrieve, display, and print stored data.

Commercial Plan Policy

SelectHealth covers implantable loop recorders.

SelectHealth Advantage (Medicare/CMS)

Cardiovascular Policies, Continued

Implantable Loop Recorder (ILR), continued

SelectHealth Community Care (Medicaid/CHIP)

Summary of Medical Information Syncope is the abrupt and transient loss of consciousness associated with absence of postural tone, followed by a rapid and usually complete recovery. This symptom is alarming for the individual, witnesses, family, and physicians. Although syncope can be a harbinger of a multitude of disease processes and can mimic the appearance of a cardiac arrest, it is most often benign and self-limited. Nevertheless, injuries associated with syncopal attacks occur in 35% of patients, and recurrent episodes can be psychologically devastating. In addition, syncope can be a premonitory sign of sudden cardiac death, especially in patients with organic heart disease. The common pathway of all forms of syncope is a sudden decrease or brief cessation of cerebral blood flow. The causes can be classified into 7 main groups: unknown origin (estimated 34% of total), neurally- mediated (24%), cardiac (18%), neurological (10%), orthostatic hypotension (8%), medication-related (3%), and psychiatric disorders (2%). Since a syncopal episode can occur without warning, it sometimes causes injuries due to falls and other accidents. Syncope is common and accounts for around 6% of all hospital admissions and 3% of emergency room visits. Forty-three percent of patients experience recurrent syncope with an approximate 5% first year mortality in patients with unexplained syncope. Moreover, it does not always have a benign course, with mortality rates up to 33% at one year in patients with a structural cardiac disorder. In addition, costs for investigation for syncope ("diagnostic odysseys") are substantial, and about 25% of all patients remain undiagnosed. A major problem in the diagnosis of the underlying cause is that syncope is a transient symptom and not a disease. Typically, patients are asymptomatic at the time of assessment, and thus, the likelihood of capturing a spontaneous event during diagnostic testing is low. The cause of syncope is not determined after history, physical examination, or surface ECG, in 38−47%% of patients. Even after further referral for tilt-table and electrophysiological testing, 10%−26% of patients will remain undiagnosed. Other tests that can be employed include 24−48-hour halter or prolonged cardiac monitoring. Ambulatory event monitors (AEMs) were developed to provide longer periods of monitoring and may be useful when the initial evaluation is non-diagnostic or when symptoms are infrequent. Ambulatory event monitors (AEMs) are intermittent recorders that can be used for longer periods (weeks to months) of monitoring to provide briefer, intermittent recordings to investigate events that occur infrequently. Intermittent recorders can be worn continuously or be attached by the patient when symptoms occur. They are activated after the onset of symptoms. Some recorders are implanted under the skin for long- term recordings (Medtronic's Reveal implantable loop recorder). Ambulatory event monitors are useful if symptoms are quite brief, or if symptoms include only very brief or no patient incapacitations, so that the patient, or a companion, can activate the recorder. These devices are often capable of downloading data trans-telephonically. There are several types of AEMs available: 1. Noncontinuous devices with memory. These devices are carried by the patient and applied to the precordial area when symptoms occur (e.g., HeartCard Cardiac Event Recorder). The limitations are that an arrhythmia may be of short duration and not captured by the device or the patient may be incapacitated and unable to apply the device while symptomatic. 2. Continuous memory loop devices. These devices are worn continuously and can continuously store EKG data so that when symptoms occur, the patient activates the device, and the EKG is recorded from the memory loop for the preceding 30−90 seconds and approximately 1 minute after. 3. Implantable continuous memory loop devices. These devices are inserted under the skin in the chest area during an outpatient surgical procedure. When symptoms occur, the patient activates 2

Cardiovascular Policies, Continued

Implantable Loop Recorder (ILR), continued

the handheld activator over the recorder to activate the storage of cardiac rhythms; the newest generation of this device (Medtronic's Reveal Plus) also has an autosensing feature. The device may be used for more than 1 year's duration and has a projected battery life of 14 months, at which time the device must be surgically removed. Current published evidence consists of numerous case series and studies and several controlled trials; and at least 1 economic study. Additionally, there is an abstract of a relatively large (n = 201) randomized trial (EaSyAS) reported at the European Society of Cardiology annual meeting in 2002. With the exception of the EaSyAS trial, virtually all of the biggest available trials and several smaller series, including the economic trial, were sponsored by the manufacturer (Medtronic) and the authors are part of the (Medtronic) Reveal Investigators group. Additionally, these studies are not without flaws. That being said, both the RCTs and case studies consistently demonstrate substantial improvements in diagnostic yield (i.e., of recurrent, unexplained syncope), in an assortment of patient populations. However, both the Krahn randomized trial and the EaSyAS trial demonstrated no difference in patient outcomes and the EaSyAS trial also demonstrated increased treatment costs (without a significant difference in outcomes). Krahn et al. demonstrated dramatic improvements in costs per diagnosis; however, this trial must be interpreted with caution due to the authors' affiliations with Medtronic. The EaSyAS trial demonstrated increased costs for treatment in the ILR group vs. conventional work-up of a recurrent, unexplained syncope population. Thus, there are probable substantial improvements in diagnostic yield, possible reductions in diagnostic costs in, as yet, ill-defined patient populations; but little direct evidence of improved patient outcomes and some evidence of increased costs for treatment (without improvements in patient outcomes). Many questions remain, however, about just who these patients are and which of them would actually benefit from a diagnosis. As Noll stated in Internal Medicine News: "We have a diagnosis in these patients, but we are not able to treat them appropriately. This raises the question, then, of whether we really need to diagnose these patients if there are no good methods to influence outcome."

Billing/Coding Information CPT CODES 33282 Implantation of patient-activated cardiac event recorder 33284 Removal of an implantable, patient-activated cardiac event recorder 93285 Programming device evaluation (in person) with iterative adjustment of the implantable device to test the function of the device and select optimal permanent programmed values with physician analysis, review and report; implantable loop recorder system 93291 Interrogation device evaluation (in person) with physician analysis, review and report, includes connection, recording and disconnection per patient encounter; implantable loop recorder system, including heart rhythm derived data analysis 93298 Interrogation device evaluation(s), (remote) up to 30 days; implantable loop recorder system, including analysis of recorded heart rhythm data, physician analysis, review(s) and report(s) 93299 Interrogation device evaluation(s), (remote) up to 30 days; implantable cardiovascular monitor system or implantable loop recorder system, remote data acquisition(s), receipt of transmissions and technician review, technical support and distribution of results

HCPCS CODES C1764 Event recorder, cardiac (implantable) E0616 Implantable cardiac event recorder with memory, activator, and programmer

Key References 1. National Horizon Scanning Centre report, The University of Birmingham, UK. Insertable Loop Recorders for the Diagnosis of Syncope. 1/2002. 2. Krahn AD, Klein GJ, Fitzpatrick A, Seidl K, Zaidi A, Skanes A, Yee R. Predicting the outcome of patients with unexplained syncope undergoing prolonged monitoring. Pacing Clin Electrophysiol. 2002 Jan;25(1):37-41. PMID: 11877934 3. Seidl K, Rameken M, Breunung S, Senges J, Jung W, Andresen D, van Toor A, Krahn AD, Klein GJ; Reveal-Investigators. Diagnostic assessment of recurrent unexplained syncope with a new subcutaneously implantable loop recorder. Europace. 2000 Jul;2(3):256-62. PMID: 11227598 3

Cardiovascular Policies, Continued

Implantable Loop Recorder (ILR), continued

4. Krahn AD, Klein GJ, Yee R, Skanes AC; REVEAL Investigators. Predictive value of presyncope in patients monitored for assessment of syncope. Am Heart J. 2001 May;141(5):817-21. PMID: 11320372 5. Krahn AD, Klein GJ, Yee R, Takle-Newhouse T, Norris C. Use of an extended monitoring strategy in patients with problematic syncope. Reveal Investigators. Circulation. 1999 Jan 26;99(3):406-10. PMID: 9918528 6. Krahn AD, Klein GJ, Yee R, Skanes AC. Randomized assessment of syncope trial: conventional diagnostic testing versus a prolonged monitoring strategy. Circulation. 2001 Jul 3;104(1):46-51. PMID: 11435336 7. Sulke N. Eastbourne Syncope Assessment Study (EASYAS). European Society of Cardiology XXIV Annual Meeting. Berlin, 8/31 - 9/4/02 8. Krahn AD, Klein GJ, Yee R, Manda V. The high cost of syncope: cost implications of a new insertable loop recorder in the investigation of recurrent syncope. Am Heart J. 1999 May;137(5):870-7. PMID: 10220636 9. Ashby DT, Cehic DA, Disney PJ, Mahar LJ, Young GD. A retrospective case study to assess the value of the implantable loop recorder for the investigation of undiagnosed syncope. Pacing Clin Electrophysiol. 2002 Aug;25(8):1200-5. PMID: 12358170 10. Nierop PR, van Mechelen R, van Elsacker A, Luijten RH, Elhendy A. Heart rhythm during syncope and presyncope: results of implantable loop recorders. Pacing Clin Electrophysiol. 2000 Oct;23(10 Pt 1):1532-8. PMID: 11060875 11. Chrysostomakis SI, Klapsinos NC, Simantirakis EN, Marketou ME, Kambouraki DC, Vardas PE. Sensing issues related to the clinical use of implantable loop recorders. Europace. 2003 Apr;5(2):143-8.PMID: 12633638 12. Huikuri HV, Mahaux V, Bloch-Thomsen PE. Cardiac arrhythmias and risk stratification after myocardial infarction: results of the CARISMA pilot study. Pacing Clin Electrophysiol. 2003 Jan;26(1 Pt 2):416-9. PMID: 12687857 13. Krahn AD, Klein GJ, Yee R, Norris C. Final results from a pilot study with an implantable loop recorder to determine the etiology of syncope in patients with negative noninvasive and invasive testing. Am J Cardiol. 1998 Jul 1;82(1):117-9. PMID: 9671019 14. Paylos JM, Aguilar Torresa R. [Usefulness of the implantable subcutaneous recorder in the diagnosis of recurrent syncope of unknown etiology in patients without structural heart disease and negative tilt test and electrophysiological study] Rev Esp Cardiol. 2001 Apr;54(4):431-42. Spanish. Erratum in: Rev Esp Cardiol 2001 Jul;54(7):929. PMID: 11282048 15. Armstrong VL, Lawson J, Kamper AM, Newton J, Kenny RA. The use of an implantable loop recorder in the investigation of unexplained syncope in older people. Age Ageing. 2003 Mar;32(2):185-8. PMID: 12615562 16. Mieszczanska H, Ibrahim B, Cohen TJ. Initial clinical experience with implantable loop recorders. J Invasive Cardiol. 2001 Dec;13(12):802-4. PMID: 11731693 17. Connolly SJ, Sheldon R, Thorpe KE, Roberts RS, Ellenbogen KA, Wilkoff BL, Morillo C, Gent M; VPS II Investigators. Pacemaker therapy for prevention of syncope in patients with recurrent severe vasovagal syncope: Second Vasovagal Pacemaker Study (VPS II): a randomized trial. JAMA. 2003 5/7;289(17):2224-9. PMID: 12734133 18. Flevari P, Livanis EG, Theodorakis GN, Zarvalis E, Mesiskli T, Kremastinos DT. Vasovagal syncope: a prospective, randomized, crossover evaluation of the effect of propranolol, nadolol and placebo on syncope recurrence and patients' well- being. J Am Coll Cardiol. 2002 Aug 7;40(3):499-504. PMID: 12142117 19. Kenny RA. SAFE PACE 2: Syncope and Falls in the Elderly--Pacing and Carotid Sinus Evaluation: a randomized controlled trial of cardiac pacing in older patients with falls and carotid sinus hypersensitivity. Europace. 1999 Jan;1(1):69-72. PMID: 11220545 20. Roche F, Gaspoz JM, Pichot V, Costes F, Isaaz K, Ferron C, Roche C, Geyssant A, Lacour JR, Barthelemy JC. Accuracy of an automatic and patient-triggered long-term solid memory ambulatory cardiac event recorder. Am J Cardiol. 1997 Oct 15;80(8):1095-8. PMID: 9352989 21. Giancaterino, S., Florentino, L., Nishimura, M., & Hsu, J. (2018). Current and Future Use of Insertable Cardiac Monitors. J Am Coll Cardiol EP, 4:1383–1386. 22. Silva, J., Bromberg, B., Emge, F., Bowman, T., & VanHare, G. (2016). Implantable Loop Recorder Monitoring for Refining Management of Children With Inherited Arhythmia Syndromes. J Am Heart Assoc, 5:e003632. doi:10.1161/JAHA.116.003632

Cardiovascular Policies, Continued

MEDICAL POLICY

INTIMA-MEDIA THICKNESS (IMT) TESTING FOR THE ASSESSMENT OF HEART DISEASE RISK (HEART SCAN)

Policy # 238 Implementation Date: 9/14/04 Review Dates: 10/18/05, 10/19/06, 10/18/07, 12/18/08, 12/17/09, 12/16/10, 12/15/11, 7/18/13, 6/19/14, 6/11/15, 6/16/16, 6/15/17, 7/20/18, 6/13/19, 6/18/20 Revision Dates:

Description Intima-media testing involves the application of B-mode ultrasound to the carotid artery to determine quantitative arterial intima-media wall thickness (IMT) of the artery. This is used as a surrogate to estimate intima-media wall-thickening in the coronary arteries. A relationship between common carotid artery intima-media thickness and angiographic presence and extent of coronary artery disease has been reported in several studies. These studies suggest that patients at high risk for an adverse coronary event can be identified early, before the patient is symptomatic through use of these surrogate markers. Data from a National Heart Lung and Blood Institute study indicates that carotid arterial IMT incorporates additional, independent information on prediction of coronary events beyond angiographic measurements of lumen narrowing.

Commercial Plan Policy

SelectHealth does NOT cover intima-media thickness (IMT) testing to assess cardiovascular risk in any population. This meets the plan’s definition of experimental/investigational.

SelectHealth Advantage (Medicare/CMS)

SelectHealth Community Care (Medicaid/CHIP)

Cardiovascular Policies, Continued

Intima Media Thickness (IMT) Testing for the Assessment of Heart Disease Risk (Heart Scan), continued

Summary of Medical Information The current state of the literature has clearly established that carotid IMT, with its numerous methods and sub sites (e.g., common, internal, bifurcation, maximal, mean/average), is highly correlated with a variety of traditional risk factors for coronary artery disease (CAD) as well as for CAD-related events (i.e., MI, stroke). The evidence supporting the belief that carotid IMT provides additional predictive capability beyond traditional risk factors is mixed; however, the weight of the evidence seems to suggest that indeed carotid IMT does provide some additional predictive capability beyond traditional risk factor assessment. One report suggests that IMT is equal in weight/value to nine separate traditional risk factors. However, the predictive ability of carotid IMT seems to vary widely between subpopulations of people at elevated risk for CAD without a history of CAD-related events as a function of age, gender, and the presence and degree of other risk factors. Additionally, it is not clear whether the additional predictive capacity of carotid IMT would persist when adjusted for the entire risk factor profile now being proposed by Intermountain’s Cardiovascular Services group (which includes c-reactive protein and serum homocysteine in addition to the more traditional Framingham risk factors). To date, there have been no studies that have prospectively followed appropriate patient groups to determine whether the addition of carotid IMT to a standard and complete battery of risk factors (comparable to the profile now being advocated by Intermountain’s CV Services) changes treatment decisions and/or leads to meaningful improvements in patient outcomes. Current literature evaluates IMT as a risk factor. However, no studies are available to assess IMT and treatment outcomes to reduce coronary cerebrovascular events or death from atherosclerosis. Additional concerns/issues include: • IMT “… is complex and expensive …” (Nichols et al.,1999) • “The differences in carotid-artery intima-media thickness between patients at high risk and those at low risk are too small for common clinical use (Nichols et al., 1999).” • There seems to be consensus suggesting that carotid IMT is an early-to-intermediate or late- intermediate marker when atherosclerosis is still limited to the arterial wall, whereas coronary angiography measures atherosclerosis in its late stages. Traditional risk factors generally are measures (albeit indirect and sometimes weak) of the numerous factors at play throughout the process but their predictive capacity may diminish with age and advanced disease. Thus, the value of carotid IMT may be at its highest during the early-to-late “intermediate” period of atherosclerosis and less useful in the earliest and possibly latest stages of disease. • “The association between IMT and risk of MI did not show a clearly linear pattern (Bots et al., Circulation 1997).” Thus, use of a linear algorithm may not be valid for this indication. • IMT measurement protocols have yet to be standardized and concerns remain about quality control of IMT facilities outside of tightly-controlled clinical trials. • Atherosclerosis is a focal, patchy disease, thus, measures of carotid IMT may not reflect the process in other vessels. • “Whether increased common carotid intima-media thickness itself reflects local atherosclerosis is still a subject of debate. It may merely reflect an adaptive response of the vessel wall to changes in sheer stress, tensile stress, and blood flow and subsequent changes in lumen diameter (Bots et al., Circulation 1997).” • “We believe that the primary ill effect is not the increase in carotid-artery thickness in itself, but rather the increase in the stiffness of the vessel that results from increased wall thickness and content (Nichols et al., 1999).”

Billing/Coding Information Not covered: Investigational/Experimental/Unproven for this indication CPT CODES 0126T Common carotid intima-media thickness (IMT) study for evaluation of atherosclerotic burden or coronary heart disease risk factor assessment

Cardiovascular Policies, Continued

INtima Media Thickness (IMT) Testing for the Assessment of Heart Disease Risk (Heart Scan), continued

HCPCS CODES No specific codes identified

Key References 1. Disclaimer American Heart Association Conference Proceedings--Beyond Secondary Prevention: Identifying the High-Risk Patient for Primary Prevention, published in Circulation/00 2. Bots ML, Hoes AW, Koudstaal PJ, Hofman A, Grobbee DE. Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study. Circulation. 1997 Sep 2;96(5):1432-7. 3. Bots ML, Hofman A, Grobbee DE. Increased common carotid intima-media thickness. Adaptive response or a reflection of atherosclerosis? Findings from the Rotterdam Study. Stroke. 1997 Dec;28(12):2442-7. 4. Chambless L, Heiss G, Folsom A, Rosamond W, Szklo M, et al. Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: The Atherosclerosis Risk in Communities (ARIC) Study/87 - 1993. Amer J Epidemiol 1997; 146:483-94. 5. Comment to O’Leary article, above. Nichols WW. Pepine CJ. O'Rourke MF. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke. N Engl Med 340(22):1762-3/99 Jun 3. 6. del Sol AI, Moons KG, Hollander M, Hofman A, Koudstaal PJ, Grobbee DE, Breteler MM, Witteman JC, Bots ML. Is carotid intima-media thickness useful in cardiovascular disease risk assessment? The Rotterdam Study. Stroke. 2001 Jul;32(7):1532- 8. Chambless LE, Folsom AR, Davis V, Sharrett R, Heiss G, Sorlie P, Szklo M, Howard G, Evans GW. Risk factors for progression of common carotid atherosclerosis: the Atherosclerosis Risk in Communities Study/87-1998. Am J Epidemiol. 2002 Jan 1;155(1):38-47. 7. Hodis H, Mack W, et al. The role of carotid-arterial intima-media thickness in predicting clinical coronary events. Annals of Internal Medicine 1998; 128: 262-269. 8. Iglesias del Sol A, Bots ML, Grobbee DE, Hofman A, Witteman JC. Carotid intima-media thickness at different sites: relation to incident myocardial infarction. The Rotterdam Study. Eur Heart J. 2002 Jun;23(12):934-40. 9. Kastelein JJ, Bots, MLD et al. Statin therapy with ezetimibe or niacin in high-risk patients. N Engl Med. 2009 Nov 26;361(22)2180-3 10. Nichols WW, Pepine CJ, O'Rourke MF. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke. N Engl J Med. 1999 Jun 3;340(22):1762-3. 11. O'Leary D, Polack J, Kronmal R, Manolio T, Burke G, et al. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. N Engl Med Jan 1999;340: 14-22.

Cardiovascular Policies, Continued

MEDICAL POLICY

INTRAVASCULAR IMAGING (I.E., INTRAVASCULAR ULTRASOUND (IVUS) AND OPTICAL COHERENCE TOMOGRAPHY (OCT))

Policy # 447 Implementation Date: 6/8/10 Review Dates: 9/15/11, 6/20/13, 4/17/14, 5/7/15, 4/14/16, 4/27/17, 6/21/18, 4/27/19, 4/15/20 Revision Dates: 5/1/12, 11/28/17, 5/14/19

Description There are many types of vascular diseases, and about 79 million Americans have one or more of them. One form of vascular disease is coronary artery disease (CAD) which affects about 14 million men and women in the United States. Peripheral vascular disease (PVD) refers to diseases of blood vessels outside the heart and brain. It’s often a narrowing of vessels that carry blood to the legs, arms, stomach, or kidneys. PVD can arise from a variety of problems such as chronic venous insufficiency or atherosclerosis. Peripheral artery disease (PAD) is a subset of organic PVD and the terms are sometimes used interchangeably. Estimates indicate that 8−10 million Americans (2.6%−3.2%) are affected by PAD. A variety of invasive and noninvasive techniques may be used in determining the severity of CAD and PVD. Cardiac angiography (ICA), also known as cardiac catheterization is an invasive procedure, and is the gold standard for diagnosing CAD and is the primary method used to help delineate coronary anatomy. Other invasive tests include computed tomography (CT) angiography, cardiac MRI, angiography, and venography. Less invasive tests include cardiac MRI and nuclear imaging studies such as SPECT or PET. The clinical evaluation for PAD is noninvasive and can be done in the office setting using the ankle- brachial index (ABI), a comparison of the systolic blood pressure (SBP) in the dorsalis pedis and posterior tibial arteries in the leg with the brachial artery of the arm. Other noninvasive tests include Doppler ultrasound, CT, and MRI. More invasive tests comprise of CT angiography (CTA) and MR angiography (MRA). Intravascular ultrasonography (IVUS) is an invasive, catheter-based imaging procedure that uses sound waves to see inside the vessels within the body. IVUS provides a standard sonographic image to assess the lumen, the vessel wall, and the atherosclerotic process within the wall simultaneously. Ultrasound transmitted from the transducer will "bounce" back whenever it encounters an interface of different acoustic impedance. Acoustic impedance is primarily dependent upon the density of the tissue. Therefore, ultrasound emitted from the transducer will traverse the blood with minimal reflection but will be highly reflected when it meets the intima of the blood vessel. IVUS is useful in the catheterization laboratory when angiography alone cannot clarify the anatomy or the status after percutaneous vascular intervention adequately. It can also be used in the baseline assessment of a target lesion before a percutaneous vascular intervention. The most common way IVUS is used is to assess the adequacy of deployment of coronary stents, including the extent of the stent apposition and determination of the minimum luminal diameter within the stent. Optical coherence tomography (OCT) is an imaging technique that uses near-infrared light to image the coronary arteries. Potential applications in cardiology include evaluating the characteristics of coronary artery plaques for the purpose of risk stratification and following coronary stenting to determine the success of the procedure.

Cardiovascular Policies, Continued

Intravascular Imaging (i.e., Intravascular Ultrasound [IVUS] and Optical Coherence Tomography [OCT]), continued

Optical coherence tomography (OCT) has important similarities to intravascular ultrasound (IVUS), and also important differences. Ultrasound (US) uses acoustic waves for imaging, while OCT uses near- infrared electromagnetic light waves. OCT generates cross-sectional images by using the time delay and intensity of light reflected from internal tissue structures. The main obstacle to OCT is the difficulty of imaging through blood, necessitating saline flushes or occlusion techniques to obtain images. Frequency- domain OCT (FD-OCT) is a newer generation device that partially alleviates this problem by allowing faster scanning and less need for blood clearing.

Optical coherence tomography (OCT) is intended as an alternative to intravascular ultrasound (IVUS) for imaging the coronary arteries. Therefore, the most relevant type of studies in evaluating the utility of OCT includes a head-to-head comparison between OCT and IVUS. These studies are limited by the lack of a true gold standard for intravascular imaging but nevertheless can compare the frequency and type of findings between the two types of imaging. Single-arm case series of OCT provide less useful information. Results from case series can characterize the findings that are obtained from OCT, use these findings to predict future events, and then provide important information on adverse events. However, case series provide limited data on the comparative efficacy of OCT and IVUS.

Commercial Plan Policy (No Preauthorization Required but criteria must be met)

SelectHealth covers intravascular imaging, such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT) in coronary arteries as an adjunct to coronary angiography in limited circumstances. Clinical circumstances in which IVUS and OCT is covered: • As a method for both guidance of placement of endoluminal devices and immediate assessment of the results of intracoronary interventional procedures (e.g., angioplasty, atherectomy, stenting); including those performed on coronary grafts • Assess anomalous coronary anatomy; • As a conclusive study to assess suspected left main stem coronary artery disease not revealed by coronary angiogram

SelectHealth covers intravascular imaging for peripheral arterial and venous disease (non-coronary) as an adjunct to peripheral angiography, angioplasty with and without stent placement, and to guide the placement of intravascular vena cava filters.

SelectHealth does NOT cover intravascular imaging for screening of coronary artery disease, diagnosing coronary vulnerable plaques, and its use in other coronary procedures. This meets the plan’s definition of investigational/experimental.

SelectHealth Advantage (Medicare/CMS) (No Preauthorization Required but criteria may apply if appropriate)

Cardiovascular Policies, Continued

Intravascular Imaging (i.e., Intravascular Ultrasound [IVUS] and Optical Coherence Tomography [OCT]), continued

SelectHealth Community Care (Medicaid/CHIP) (No Preauthorization Required but criteria may apply if appropriate)

Summary of Medical Information Although intravascular ultrasound devices have only been available for a relatively short time, an array of studies demonstrating numerous diagnostic and therapeutic applications in interventional cardiology has been reported. Numerous studies support IVUS as a safe, accurate, and reproducible method of detecting coronary vessel wall structure and disease and visualizing the dynamic changes before, during and after PCI. IVUS can differentiate coronary vessel wall components and types of atherosclerotic plaque which aids in determining what if any treatment is indicated. This is especially helpful when angiography results are ambiguous. The maturity of the technology is such that IVUS currently has a place as a clinical decision-making tool in patients with symptoms and intermediate lesions, as a provisional study to assess left main stem disease suspected but not disclosed by coronary angiography, and as a method for both guidance of endoluminal devices and immediate assessment of the results of therapeutic techniques, including balloon angioplasty, atherectomy, and intravascular stent deployment. Wellons et al. stated that reports have demonstrated the benefit of prophylactic inferior vena cava filter (IVCF) placement to prevent pulmonary embolism. This study evaluated the potential for the bedside placement of a removable IVCF under "real-time" IVUS guidance. A total of 20 trauma patients underwent intensive care unit placement of a removable IVCF with IVUS guidance. All patients had ultrasonography of the femoral veins after placement to rule out post-procedure femoral vein thrombosis and radiographs to identify filter location. Nineteen of 20 IVCFs were placed at approximately the L2 level as verified by radiography. One patient had a large IVC (34 mm) and underwent bilateral common iliac IVCF placement under IVUS. Within 3 weeks of placement, 12 IVCFs were retrieved. Of the remaining 8 patients, 6 had indications for permanent implantation, 2 had contralateral deep venous thrombosis, and 1 had ipsilateral deep venous thrombosis. The authors concluded that bedside insertion of a removable IVCF with IVUS guidance and its removal are simple, safe, and accurate. Passman et al. stated that bedside placement of ICVF by using either trans-abdominal duplex ultrasonography or IVUS has been shown to be safe and effective. The authors reviewed techniques for bedside filter placement with trans- abdominal duplex ultrasonography, IVUS with dual venous access, and IVUS with single venous access. They noted that trans-abdominal duplex ultrasonography and IVUS remain their preferred techniques for filter placement when feasible, especially in critically ill and immobilized patients. de Ribamar Costa et al. found the drug-eluting stent (DES) era, stent expansion remains an important predictor of re-stenosis and sub-acute thrombosis. Compliance charts are developed to predict final minimum stent diameter (MSD) and area (MSA). The objectives of the study were 2-fold: (i) to evaluate DES expansion by comparing IVUS-measured MSD and MSA against the values predicted by compliance charts and (ii) to compare each DES against its bare-metal stent (BMS) equivalent. These researchers enrolled 200 patients with de novo coronary lesions treated with single, greater than 2.5-mm Cypher (Cordis, Johnson & Johnson, Miami Lakes, FL) (sirolimus-eluting stent [SES], n = 133) or Taxus (Boston Scientific, Natick, MA) (paclitaxel-eluting stent [PES], n = 67) stent under IVUS guidance without another post-dilation balloon. They used a comparison cohort of 65 equivalent BMS (Express 2 [Boston Scientific], n = 37; Bx Velocity [Cordis, Johnson & Johnson], n = 28) deployed under similar conditions. The DES achieved only 7 % +/- 10% of predicted MSD and 66% +/- 17% of predicted MSA; this was similar for SES and PES. Furthermore, 24% of SES and 28% of PES did not achieve a final MSA of 5 mm2 a consistent predictor of DES failure. The SES achieved 75% +/- 10% of predicted MSA vs. 75% +/- 9% for Bx Velocity (p = 0.9). The PES achieved 79.9% +/- 14% of predicted MSA vs. 79% +/- 10% for Express 2 (p = 0.8). Lesion morphology, arc and length of calcium, stent diameter and length, and implantation pressures did not affect expansion. The authors concluded that compliance charts fail to predict final MSD and MSA. A considerable percentage of DES does not achieve minimum standards of stent expansion. The SES and PES achieve similar expansion to their BMS platform, indicating that the polymer coating does not affect DES expansion in vivo. However, stent expansion cannot be predicted from pre-intervention IVUS lesion assessment. 3

Cardiovascular Policies, Continued

Intravascular Imaging (i.e., Intravascular Ultrasound [IVUS] and Optical Coherence Tomography [OCT]), continued

The randomized TAXUS II trial evaluates the polymer-based paclitaxel-eluting Taxus stent in slow- and moderate-release formulations. Tsuchida et al. examined the consistency between angiographic and IVUS outcomes of late lumen loss (late loss) and neointimal growth to measure restenotic plaque load in Taxus and BMS. Serial angiographic and IVUS analyses were available in 155 event-free patients (BMS, n = 74; Taxus stent, n = 81) after the procedure, at 6 months, and at 2 years. For this sub-analysis, quantitative coronary angiographic (QCA) and IVUS measurements were used to derive late loss and neointimal volume. From after the procedure to 6 months, QCA and IVUS showed matching results for the 2 groups with significant decreases in late loss and neointimal volume in the Taxus versus the control group. From 6 months to 2 years, QCA and IVUS measurements also showed results similar to those in the control group, demonstrating neointimal compaction over time. However, in the Taxus group, QCA late loss showed a non-significant decrease from 6 months to 2 years, whereas IVUS neointimal volume increased. The authors concluded that although QCA and IVUS results were similar over the first 6 months, long-term assessment of changes in re-stenotic plaque load showed discrepant findings for the Taxus stent. These findings suggest the need for critical re-evaluation of current end points and the use of more precise techniques to detect lumen and stent boundaries. Hoffmann and colleagues identified the impact of incomplete stent apposition (ISA) after drug-eluting stent implantation determined by IVUS on late clinical events is not well-defined. These researchers assessed the clinical impact of ISA after sirolimus-eluting stent (SES) placement during a follow-up period of 4 years. Intravascular ultrasound at angiographic follow-up was available in 325 patients (SES, n = 180; BMS, n = 145); IVUS images were reviewed for the presence of ISA defined as one or more unopposed stent struts. Frequency, predictors and clinical sequel of ISA at follow-up after SES and BMS implantation were determined. Incomplete stent apposition at follow-up was more common after SES (n = 45 [25%]) than after BMS (n = 12 (8.3%), p < 0.001). Canadian Cardiology Society class III or IV angina at stent implantation (odds ratio (OR) = 4.69, 95% CI 2.15 to 10.23, p < 0.001) and absence of diabetes (OR = 3.42, 95% CI 1.05 to 11.1, p = 0.041) were predictors of ISA at follow-up after SES placement. Rate of myocardial infarction tended to be slightly higher for ISA than for non-ISA patients. When only SES patients were considered, major adverse cardiac event free survival at 4 years was identical for those with and without ISA at follow-up (11.1% vs. 16.3%, p = 0.48). The authors concluded that ISA at follow-up is more common after SES implantation than after BMS implantation. Considering the current very sensitive IVUS definition, ISA appears to be an IVUS finding without significant impact on the incidence of major adverse cardiac events even during long-term follow-up. García-García et al. stated that detection of coronary vulnerable plaques in vivo is essential for studying their natural history and assessing potential treatment modalities and, therefore, may have an important impact on the prevention of acute myocardial infarction and death. Currently, conventional grayscale IVUS, IVUS-virtual histology (IVUS-VH) and paleography data are being collected with the same catheter during the same pullback. A combination of this catheter with either thermography capability or additional imaging, such as optical coherence tomography or spectroscopy, would be an exciting development. Intravascular magnetic resonance imaging also holds much promise. To date, none of the techniques described above has been sufficiently validated and, most importantly, their predictive value for adverse cardiac events remains elusive. The authors noted that very rigorous and well-designed studies are needed for defining the role of each diagnostic modality. In this regard, Ibañez and colleagues consider IVUS as an investigational technique for the visualization as well as the compositional characterization of atheromatous plaques. Clementi et al. noted that plaque reduction with the use of pioglitazone and statin combination therapy has been observed in carotid plaque. These researchers examined the effect of combination therapy with statins and pioglitazone on coronary plaque regression and composition with the use of IVUS and IVUS- VH. These investigators analyzed 29 plaques in 25 diabetic patients with angiographic evidence of non- significant coronary lesions with IVUS-VH. Patients were treated with 80 mg of atorvastatin and 30 mg of pioglitazone daily for 6 months. After 6 months of therapy, IVUS-VH of each lesion was re-acquired. Mean elastic external membrane volume was significantly reduced between baseline and follow-up (343.0 mm vs. 320.5 mm; p < 0.05) as was mean total atheroma volume (179.3 mm vs. 166.6 mm; p < 0.05). Change in total atheroma volume showed a 6.3% mean reduction. Areas of fibrous tissue, fibro- lipidic tissue and calcium decreased over the 6 months of follow-up, although not significantly. On the other hand, the necrotic core increased from 9% to 14% (p < 0.05). The authors concluded that these findings demonstrated that atorvastatin/pioglitazone association is able to induce significant regression of coronary atherosclerosis, acting on plaque composition. Moreover, they noted that their findings are preliminary results and will be confirmed in an ongoing randomized placebo-controlled multi-center trial.

Cardiovascular Policies, Continued

Intravascular Imaging (i.e., Intravascular Ultrasound [IVUS] and Optical Coherence Tomography [OCT]), continued

An assessment prepared for the Agency for Healthcare Research and Quality concluded that currently, neither IVUS nor other imaging technologies can reliably identify vulnerable plaque prospectively, i.e., before rupture. A Medical Technology Assessment performed in April 2012 focused on IVUS for peripheral vascular disease. The quantity and quality of literature detailing IVUS in peripheral vascular disease is limited compared with the use of IVUS in coronary artery disease. Only 1 systematic review on IVUS in PVD was identified. This review from Australian Medical Services Advisory Committee published in 2002 combined data from coronary and peripheral IVUS. They concluded that despite being safe the cost effectiveness for IVUS had not been established. Assessment of the literature found that IVUS in non-coronary PVD can be utilized in venous occlusion, placement of IVC filter, aortic dissection, aortic aneurysms, medium and small PVD and in totally occluded arterial vessels. The most robust literature supporting IVUS has been published by Buckley et al. Between 1992-1995 52 patients with 71 limb procedures involving the ileac artery participated in a non-randomized study and followed prospectively. The mean time of follow up was 62 months for IVUS patients and 58 months for patients treated without IVUS. Patency rates were 100% at 3 and 6 years in the IVUS group and 82% and 69% respectively in the non-IVUS group. Also 23% of patients in the non-IVUS group required another procedure due to re-stenosis. Other articles have shown a 1−4 mm underestimation by angiography compared with IVUS representing 62% of the patients studied. Forty percent of the stents used would have been under deployed if angiography were used alone. Many believe this scenario leads to failure of the endovascular intervention and re-stenosis within the follow-up period. Additional benefits for IVUS may: 1) Limit radiation exposure; 2) Reduce the risk of acute renal failure in predisposed patients with CKD 2-4; 3) Avoid contrast in contrast-allergic patients; 4) Define vessel anatomy and pathology compared with angiography to enhance more accurate stent placement thus decreasing stent re-stenosis rates; 5) Assist the identification of the true lumen in aortic dissection. Many of these claims have not been documented in randomized controlled studies. Countering the benefits of IVUS expressed by Kawasaki et al., and Dangas et al. other experts express caution with IVUS. Their concerns are the limited data supporting improved outcomes and the additional expense and time during the procedure when IVUS is utilized. The literature demonstrates stent placement using IVUS guidance results in a statistically significant reduction in the number of patients that will require revision surgeries for ill-fitting or misplaced stents in the peripheral vascular system in comparison to patients in whom stents were placed using CTA. IVUS is able to more accurately demonstrate the extent of lesions in peripheral vessels than CTA and it appears to have good sensitivity and specificity for detection of plaque dissections and media rupture but lower sensitivity for the detection of plaque rupture or thrombus formation. A smaller number of studies evaluate the clinical utility of OCT for follow-up evaluation post-stenting. Capodanno et al. (2009) compared OCT with IVUS for stent evaluation in 20 patients who had stent implantation 6 months prior. The parameters that were compared included stent length, vessel luminal area, stent area, and the percent of stent coverage with neoendothelial cells. The measurement of stent length was similar between IVUS and OCT (16.3 + 3.0 mm vs. 16.2 + 3.8 mm, p=0.82). However, the other measured parameters differed between groups. Vessel luminal area was significantly lower by OCT compared to IVUS (3.83 + 1.60 mm2 vs. 4.05 + 1.44 mm2, p=0.82), while stent area was significantly higher with OCT (6.61 mm2+ 1.39 vs. 6.17 + 1.07 mm2, p<0.001). The percentage of tissue coverage was also higher with OCT (43.4 + 16.1% vs. 35.5 + 16.4%), suggesting that IVUS underestimates stent coverage compared with OCT. Inoue et al. (2011) used OCT to evaluate 25 patients who had previously undergone PCI with drug-eluting stents. OCT was performed at a mean of 236 + 39 days post-PCI. OCT identified neointimal coverage of the stent in 98.4% of cases. In 0.52%, there was evidence of stent malposition and a lack of neointimal coverage. Full neointimal coverage was evident in 37% of stents. In 7.2% of patients, there was evidence of a low-intensity area surrounding the struts, which is thought to be indicative of abnormal neointimal maturation. There were no intra-stent thrombi identified and no major complications of the procedure. The use of OCT as a follow-up to stenting can determine the extent of neoendothelial covering within the first year of stenting. This parameter is predictive of future stent-related events and has been used as an 5

Cardiovascular Policies, Continued

Intravascular Imaging (i.e., Intravascular Ultrasound [IVUS] and Optical Coherence Tomography [OCT]), continued

intermediate outcome in stenting trials. However, the clinical relevance of measuring stent neo- endothelialization has not been demonstrated. While this might provide prognostic information, it is not clear how management would be changed, or health outcomes improved. As an adjunct to PCI, OCT may improve upon the ability of IVUS to pick up clinically relevant abnormalities, and this may lead to changes in management. A single small RCT did not report any advantage of OCT over IVUS for achieving optimal stent placement. Overall, the current evidence is limited and includes relatively small numbers of patients who have been evaluated by OCT. As a result, it is not possible to determine the degree of improvement with OCT, or the clinical significance of this improvement. Therefore, the use of OCT as an adjunct to PCI is considered investigational. For the indications of risk stratification of coronary plaques and follow-up of stenting, OCT may also be more accurate than IVUS for imaging of superficial structures. However, the clinical utility of IVUS has not been demonstrated for these indications, since test results do not lead to changes in management that improve outcomes. Therefore, clinical utility has not been demonstrated for OCT for the same reasons. As a result, OCT is considered investigational for risk stratification of coronary plaques and for follow-up post-stent implantation. Blackham et al (2015) noted that OCT is a modern intra-vascular imaging modality that has the capability to provide detailed, in-vivo characterization of the arterial wall and atherosclerotic plaque. The current understanding of the appearance of atherosclerotic plaque via OCT is largely based on coronary arterial studies where OCT information has been employed to guide therapeutic management and permits the immediate evaluation of PCI. The clinical success of OCT in the coronary arteries has laid the foundation for investigation of the carotid artery and thus, stroke risk assessment. The authors reported the novel use of OCT for tissue characterization of severe stenosis subsequent to carotid artery stenting, both before and after treatment with cutting balloon angioplasty. An UpToDate review on “Evaluation of carotid artery stenosis” (Furie, 2015) does not mention optical coherence tomography as a diagnostic tool. Hoffmann et al (2016) stated that rupture risk assessment of an intracranial aneurysm (IA) is an important factor for indication of therapy. Until today, there is no suitable objective prediction method. Conventional imaging modalities cannot assess the IA's vessel wall. These researchers investigated the ability of intravascular OCT as a new tool for the characterization and evaluation of IAs. An experimental set-up for acquisition of geometrical aneurysm parameters was developed. Object of basic investigation was a silicone phantom with 6 IAs from patient data. For structural information, 3 circles of Willis were dissected and imaged post-mortem. All image data were post-processed by medical imaging software. Geometrical image data of a phantom with 6 different IAs were acquired. The geometrical image data showed a signal loss, e.g., in aneurysms with a high bottle-neck ratio. Imaging data of vessel specimens were evaluated with respect to structural information that is valuable for the characterization of IAs. Those included thin structures (intimal flaps), changes of the vessel wall morphology (intimal thickening, layers), adjacent vessels, small vessel outlets, arterial branches and histological information. The authors concluded that intra-vascular OCT provides new possibilities for diagnosis and rupture assessment of IAs. However, currently used imaging system parameters have to be adapted and new catheter techniques have to be developed for a complete assessment of the morphology of IAs. Kimura et al (2015) stated that periprocedural myocardial injury (PMI) is not an uncommon complication and is related to adverse cardiac events after PCI. These researchers investigated the predictors of PMI in patients with stable angina pectoris (SAP) on intra-vascular imaging. They enrolled 193 SAP patients who underwent pre-PCI IVUS and OCT. Clinical characteristics, lesion morphology, and long-term follow- up data were compared between patients with and without PMI, defined as post-PCI elevation of high- sensitivity cardiac troponin-T. Periprocedural myocardial injuries were observed in 79 patients (40.9%). Estimated glomerular filtration rate (OR, 0.973; 95% CI: 0.950 to 0.996; p = 0.020), greater than or equal to 2 stents (OR, 3.100; 95 % CI: 1.334 to 7.205; p = 0.009), final myocardial blush grade 0 to 2 (OR, 4.077; 95% CI: 1.295 to 12.839; p = 0.016), and IVUS-identified echo-attenuated plaque (EA; OR, 3.623; 95% CI: 1.700 to 7.721; p < 0.001) and OCT –TCFA(OR, 3.406; 95% CI: 1.307 to 8.872; p = 0.012) were independent predictors of PMI on multi-variate logistic regression analysis. A combination of EA and OCT-TCFA had an 82.4% positive predictive value (PPV) for PMI. On Cox proportional hazards analysis, PMI was an independent predictor of adverse cardiac events during 1-year follow-up (hazard ratio [HR], 2.984; 95% CI: 1.209 to 7.361; p = 0.018). The authors concluded that plaque morphology assessment using pre-PCI IVUS and OCT may be useful for predicting PMI in SAP patients.

Cardiovascular Policies, Continued

Intravascular Imaging (i.e., Intravascular Ultrasound [IVUS] and Optical Coherence Tomography [OCT]), continued

Losif and co-workers (2016) stated that due to its high spatial resolution, intravascular OCT has been used as a valid method for in-vivo evaluation of several types of coronary stents at straight lumen and bifurcation sites. These researchers evaluated its effectiveness for flow diverting stents deployed in arterial bifurcation sites involving jailing of a side branch. A total of 4 large white swine were stented with flow diverting stents covering the right common carotid artery-ascending pharyngeal artery bifurcation. After 12 weeks of follow-up the animals were evaluated by digital subtraction angiography and intravascular OCT and subsequently sacrificed. Neointimal thickness on the parent arteries and the free segments of the stent were measured. The stented arteries were harvested and underwent scanning electron microscopy (SEM) imaging. Ostia surface values were measured with OCT three-dimensional (3D) reconstructions and SEM images. All endovascular procedures and OCT pullback runs were feasible. Stent apposition was satisfactory on the immediate post-stent OCT reconstructions. At 12-week controls, all stents and jailed branches were patent. Mean neointimal thickness was 0.11 ± 0.04 mm on the free segments of the stent. The mean ostia surface at 12 weeks was 319,750 ± 345,533 μm2 with 3D-OCT reconstructions and 351,198 ± 396,355 μm2 with SEM image-derived calculations. Good correlation was found for ostia surface values between the 2 techniques; the values did not differ significantly in this preliminary study. The authors concluded that intravascular OCT appeared to be a promising technique for immediate and follow-up assessment of the orifice of arterial branches covered by flow diverting stents. In conclusion, Optical coherence tomography (OCT) is an imaging technique that has some advantages over intravascular ultrasound (IVUS) for imaging coronary arteries. It has a higher resolution and provides greater detail for accessible structures compared to IVUS. Case series have demonstrated that OCT can be performed with a high success rate and few complications. Head-to-head comparisons of OCT and IVUS report that OCT picks up additional abnormalities that are not detected by IVUS, implying that OCT is a more sensitive test compared to IVUS.

Billing/Coding Information Covered: For the conditions outlined above CPT CODES Noncoronary Vessels

37252 Intravascular ultrasound (noncoronary vessel) during diagnostic evaluation and/or therapeutic intervention, including radiological supervision and interpretation; initial noncoronary vessel (List separately in addition to code for primary procedure) 37253 ; each additional noncoronary vessel (List separately in addition to code for primary procedure

Coronary Vessels 92978 Endoluminal imaging of coronary vessel or graft using intravascular ultrasound (IVUS) or optical coherence tomography (OCT) during diagnostic evaluation and/or therapeutic intervention including imaging supervision, interpretation and report; initial vessel (List separately in addition to code for primary procedure) 92979 ; each additional vessel (List separately in addition to code for primary procedure)

HCPCS CODES C1753 Catheter, intravascular ultrasound

Key References 1. Abizaid AS, Mintz GS, Abizaid A, et al. (1999). One-year follow-up after intravascular ultrasound assessment of moderate left main coronary artery disease in patients with ambiguous angiograms. J Am Coll Cardiol.;34(3):707-715. 2. Abizaid AS, Mintz GS, Mehran R, et al. (1999). Long-term follow-up after percutaneous transluminal coronary angioplasty was not performed based on intravascular ultrasound findings: Importance of lumen dimensions. Circulation.;100(3):256-261. 3. Arko, F, Mettauer, M, McCollough, R, et al. (1998). Use of intravascular ultrasound improves long-term clinical outcome in the endovascular management of atherosclerotic aortoiliac occlusive disease. J Vasc Surg 27.4: 614-23. 4. Arthurs, ZM, Bishop, PD, Feiten, LE, et al. (2010). Evaluation of peripheral atherosclerosis: a comparative analysis of angiography and intravascular ultrasound imaging. J Vasc Surg 51.4: 933-8; discussion 939.

Cardiovascular Policies, Continued

Intravascular Imaging (i.e., Intravascular Ultrasound [IVUS] and Optical Coherence Tomography [OCT]), continued

5. Ashley, DW, Gamblin, TC, Burch, ST, et al. (2001). Accurate deployment of vena cava filters: comparison of intravascular ultrasound and contrast venography. J Trauma 50.6: 975-81. 6. Azizzadeh, A, Valdes, J, Miller, CC, 3rd, et al. (2011). The utility of intravascular ultrasound compared to angiography in the diagnosis of blunt traumatic aortic injury. J Vasc Surg 53.3: 608-14. 7. Bakal, CW. (2003). Advances in imaging technology and the growth of vascular and interventional radiology: a brief history. J Vasc Interv Radiol 14.7: 855-60. 8. Bandyk, DF, Armstrong, PA. (2009). Use of intravascular ultrasound as a "Quality Control" technique during carotid stent- angioplasty: are there risks to its use? J Cardiovasc Surg (Torino) 50.6: 727-33. 9. Banerjee, AK, Pearson, J, Gilliland, EL, et al. (1992). A six year prospective study of fibrinogen and other risk factors associated with mortality in stable claudicants. Thromb Haemost 68.3: 261-3. 10. Berry E, Kelly S, Hutton J, et al. (2000). Intravascular ultrasound-guided interventions in coronary artery disease: A systematic literature review, with decision-analytic modelling, of outcomes and cost-effectiveness. Health Technol Assess.;4(35): 1-117. 11. Blackham KA, Kim BS, Jung RS, et al. In vivo characterization of carotid neointimal hyperplasia by use of optical coherence tomography: Before and after cutting balloon angioplasty. J Neuroimaging. 2015;25(6):1044-1046. 12. Boston Scientific. (2012) Coronary Intravascular Ultrasound (IVUS). Boston Scientific. Available: http://www.bostonscientific.com/procedure/ProcedureLanding.bsci/,,/navRelId/1000.1002/method/Procedure/id/10000811/seo. serve. Date Accessed: April 2, 2012. 13. Bourassa MG, Butnaru A, Lesperance J, Tardif JC. (2003). Symptomatic myocardial bridges: Overview of ischemic mechanisms and current diagnostic and treatment strategies. J Am Coll Cardiol.;41(3):351-359. 14. Bradby, GV, Valente, AJ, Walton, KW. (1978). Serum high-density lipoproteins in peripheral vascular disease. Lancet 2.8103: 1271-4. 15. Buckley, CJ, Arko, FR, Lee, S, et al. (2002). Intravascular ultrasound scanning improves long-term patency of iliac lesions treated with balloon angioplasty and primary stenting. J Vasc Surg 35.2: 316-23. 16. Canadian Coordinating Office for Health Technology Assessment (CCOHTA). (2003). Intravascular coronary ultrasound (IVUS). Pre-Assessment No. 23. Ottawa, ON: CCOHTA; October. 17. Cansella G, Klauss V, Otttani F, et al. (2003). Impact of intravascular ultrasound-guided stenting on long-term clinical outcome: A meta-analysis of available studies comparing intravascular ultrasound-guided and angiographyically guided stenting. Catheter Cardiovasc Interv;59(3):314-321. 18. Cantin, B, Moorjani, S, Dagenais, GR, et al. (1995). Lipoprotein(a) distribution in a French Canadian population and its relation to intermittent claudication (the Quebec Cardiovascular Study). Am J Cardiol 75.17: 1224-8. 19. Capodanno D, Prati F, Pawlowsky T et al. Comparison of optical coherence tomography and intravascular ultrasound for the assessment of in-stent tissue coverage after stent implantation. EuroIntervention 2009; 5(5):538-43. 20. Cavaye DM, White RA, Kopchok GE, et al. (1992). Intravascular ultrasound imaging: The new standard for guidance and assessment of endovascular interventions? J Clin Laser Med Surg.;10(5):349-353. 21. Cavaye DM, White RA, Kopchok GE. (1993). Intravascular ultrasound imaging. Am J Card Imaging.;7(2):109-119. 22. Clementi, F., M. Di Luozzo, R. Mango, G. Luciani, A. Trivisonno, F. Pizzuto, E. Martuscelli, J. L. Mehta and F. Romeo (2009). "Regression and shift in composition of coronary atherosclerotic plaques by pioglitazone: insight from an intravascular ultrasound analysis." J Cardiovasc Med (Hagerstown) 10(3): 231-237. 23. Conen, D, Rexrode, KM, Creager, MA, et al. (2009). Metabolic syndrome, inflammation, and risk of symptomatic peripheral artery disease in women: a prospective study. Circulation 120.12: 1041-7. 24. Cronenwett, JL. (2010) Rutherford's Vascular Surgery. 7. Elsevier. Available: http://www.mdconsult.com/books/page.do?eid=4-u1.0-B978-1-4160-5223-400014-7--s0085&isbn=978-1-4160-5223- 4&uniqId=327426791-3#4-u1.0-B978-1-4160-5223-4.00014-7--s0085. Date Accessed: April 2, 2012. 25. Dangas, G, Laird, JR, Jr., Mehran, R, et al. (2001). Intravascular ultrasound-guided renal artery stenting. J Endovasc Ther 8.3: 238-47. 26. de Ribamar Costa J Jr, Mintz GS, Carlier SG, et al. (2007). Intravascular ultrasound assessment of drug-eluting stent expansion. Am Heart J.;153(2):297-303. 27. Diethrich EB, Pauliina Margolis M, et al. (2007). Virtual histology intravascular ultrasound assessment of carotid artery disease: The Carotid Artery Plaque Virtual Histology Evaluation (CAPITAL) study. J Endovasc Ther;14(5):676-686. 28. Escolar E, Weigold G, Fuisz A, Weissman NJ. (2006). New imaging techniques for diagnosing coronary artery disease. CMAJ.;174(4):487-495. 29. Fassa AA, Wagatsuma K, Higano ST, et al. (2005). Intravascular ultrasound-guided treatment for angiographically indeterminate left main coronary artery disease: a long-term follow-up study. J Am Coll Cardiol. Jan 18;45(2):204-11. 30. Furie KL. Evaluation of carotid artery stenosis. UpToDate Inc., Waltham, MA. Last reviewed July 2015. 31. Fedele S, Biondi-Zoccai G, Kwiatkowski P et al. Reproducibility of coronary optical coherence tomography for lumen and length measurements in humans (The CLI-VAR [Centro per la Lotta contro l'Infarto-VARiability] study). Am J Cardiol 2012; 110(8):1106-12. 32. García-García HM, Gonzalo N, Granada JF, et al. (2008). Diagnosis and treatment of coronary vulnerable plaques. Expert Rev Cardiovasc Ther;6(2):209-222. 33. Garret, HE, Jr., Abdullah, AH, Hodgkiss, TD, et al. (2003). Intravascular ultrasound aids in the performance of endovascular repair of abdominal aortic aneurysm. J Vasc Surg 37.3: 615-8. 34. Gaster AL, SU, Larsen J, et al. (2003). Continued improvement of clinical outcome and cost effectiveness following intravascular ultrasound guided PCI: insights from a prospective, randomized study. Heart. Sep;89(9):1043-9. 35. German Agency for Health Technology Assessment at the German Institute for Medical Documentation and Information (DAHTA) (DIMDI).( 2003). The value of intravascular ultrasound (IVUS) for diagnostic and therapeutic coronary angiography. A medical health technology assessment. Summary. Cologne, Germany: German Agency for Health Technology Assessment at the German Institute for Medical Documentation and Information (DAHTA) (DIMDI). 36. Gil RJ, Pawłowski T, Dudek D, Horszczaruk G, Zmudka K, Investigators of Direct Stenting vs Optimal Angioplasty Trial (DIPOL), et al. (2007). Comparison of angiographically guided direct stenting technique with direct stenting and optimal balloon angioplasty guided with intravascular ultrasound. The multicenter, randomized trial results. Am Heart J. Oct;154(4):669-75. 37. Gonzalo N, Tearney GJ, Serruys PW et al. Second-generation optical coherence tomography in clinical practice. High-speed data acquisition is highly reproducible in patients undergoing percutaneous coronary intervention. Rev Esp Cardiol 2010; 63(8):893-903.

Cardiovascular Policies, Continued

Intravascular Imaging (i.e., Intravascular Ultrasound [IVUS] and Optical Coherence Tomography [OCT]), continued

38. Greenhalgh, RM, Rosengarten, DS, Mervart, I, et al. (1971). Serum lipids and lipoproteins in peripheral vascular disease. Lancet 2.7731: 947-50. 39. Gϋlel O, Sipahi Í, Tuzcu EM. (2007). Intravascular ultrasound: questions and answers. Anadolu Kardiyol Derg.7:169-78. 40. Hardt SE, Bekeredjian R, Brachmann J, et al. Intravascular ultrasound for evaluation of initial vessel patency and early outcome following directional coronary atherectomy. Catheter Cardiovasc Interv. 1999;47(1):14-22. 41. Hibberd MG, Vuille C, Weyman AE. (1992). Intravascular ultrasound: Basic principles and role in assessing arterial morphology and function. Am J Card Imaging.;6(4):308-324. 42. Hirsch, AT, Criqui, MH, Treat-Jacobson, D, et al. (2001). Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA 286.11: 1317-24. 43. Hoffmann R, Morice MC, Moses JW, et al. (2008). Impact of late incomplete stent apposition after sirolimus-eluting stent implantation on 4-year clinical events: Intravascular ultrasound analysis from the multicentre, randomised, RAVEL, E-SIRIUS and SIRIUS trials. Heart;94(3):322-328. 44. Ibañez B, Badimon JJ, Garcia MJ. (1999). Diagnosis of atherosclerosis by imaging. Am J Med. 2009;122(1 Suppl): S15-S25. 45. Inoue T, Shite J, Yoon J et al. Optical coherence evaluation of everolimus-eluting stents 8 months after implantation. Heart 2011; 97(17):1379-84. 46. Iosif C, Saleme S, Ponsonnard S, et al. Intravascular optical coherence tomography for the evaluation of arterial bifurcations covered by flow diverters. J Neurointerv Surg. 2016 Jan 27 [Epub ahead of print]. 47. Jang IK, Bouma BE, Kang DH et al. Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound. J Am Coll Cardiol 2002; 39(4):604-9. 48. Johnston PW, Fort S, Cohen FA. Noncritical disease of the left main coronary artery: Limitations of angiography and the role of intravascular ultrasound. Can J Cardiol.;15(3):297-302. 49. Jude, EB, Oyibo, SO, Chalmers, N, et al. (2001). Peripheral arterial disease in diabetic and nondiabetic patients: a comparison of severity and outcome. Diabetes Care 24.8: 1433-7. 50. Kawasaki, D, Tsujino, T, Fujii, K, et al. (2008). Novel use of ultrasound guidance for recanalization of iliac, femoral, and popliteal arteries. Catheter Cardiovasc Interv 71.6: 727-33. 51. Kimura S, Sugiyama T, Hishikari K, et al. Association of intravascular ultrasound- and optical coherence tomography-assessed coronary plaque morphology with periprocedural myocardial injury in patients with stable angina pectoris. Circ J. 2015;79(9):1944-1953. 52. Klauss V, Mudra H, Uberfuhr P, et al. (1995). Intraindividual variability of cardiac allograft vasculopathy as assessed by intravascular ultrasound. Am J Cardiol.;76:463-466. 53. Kubo T, Nakamura N, Matsuo Y et al. Virtual histology intravascular ultrasound compared with optical coherence tomography for identification of thin-cap fibroatheroma. Int Heart J 2011; 52(3):175-9. 54. L'Allier, PL. (2007) Angiography vs. IVUS Pearls and Pitfalls. Institut de Cardiologie de Montreal. Available: http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&ved=0CC0QFjAB&url=http%3A%2F%2Fwww.cardioso urce.org%2F~%2Fmedia%2FImages%2FACC%2FScience%2520and%2520Quality%2FClinical%2520Collections%2FCollecti on%2520Media%2520Content%2Ff%2FFB_Angiography_vs_IVUS_Pearls_and_Pitfalls.ashx&ei=VV17T9GcGuHi0QH8v5S6B g&usg=AFQjCNGjfIysyxpJ4fzejc5QNnpIeXKqFg&sig2=8c4TwHuubgCeRVdR7F3BKQ. Date Accessed: April 3, 2012. 55. Lau J, Kent D, Tatsioni A, et al. (2004). Vulnerable plaques. A brief review of the concept and proposed approaches to diagnosis and treatment. Prepared by theTufts-New England Medical Center AHRQ Evidence-based Practice Center. Contract No. 290-02-0022, Task Order #1. Rockville, MD: Agency for Healthcare Research and Quality (AHRQ); January 22, 2004. Available at: http://www.ahrq.gov/clinic/ta/placque/placque.pdf. Accessed July 7, 2009 56. Leber AW, Knez A, von Ziegler F, et al. (2005). Quantification of obstructive and nonobstructive coronary lesions by 64-slice computed tomography: a comparative study with quantitative coronary angiography and intravascular ultrasound. J Am Coll Cardiol 46.1: 147-54. 57. Lowe, GD, Fowkes, FG, Dawes, J, et al. (1993). Blood viscosity, fibrinogen, and activation of coagulation and leukocytes in peripheral arterial disease and the normal population in the Edinburgh Artery Study. Circulation 87.6: 1915-20. 58. Matthews BD, Joels CS, LeQuire MH. (2003). Inferior vena cava filter placement: Preinsertion inferior vena cava imaging. Am Surg.;69(8):649-653. 59. McDermott, MM, Hahn, EA, Greenland, P, et al. (2002). Atherosclerotic risk factor reduction in peripheral arterial diseasea: results of a national physician survey. J Gen Intern Med 17.12: 895-904. 60. Medical Services Advisory Committee (MSAC). (2001). Intravascular ultrasound. Assessment Report. MSAC application 1032. Canberra, ACT: Department of Health and Ageing. 61. Mintz GS, Nissen SE, Anderson WD, et al. (2001). American College of Cardiology Clinical Expert Consensus Document on Standards for Acquisition, Measurement and Reporting of Intravascular Ultrasound Studies (IVUS). A report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol.;37(5):1478-1492. 62. Miyamoto Y, Okura H, Kume T et al. Plaque characteristics of thin-cap fibroatheroma evaluated by OCT and IVUS. JACC Cardiovasc Imaging 2011; 4(6):638-46. 63. Mohler, ER. (2012) Clinical features, diagnosis, and natural history of lower extremity peripheral artery disease. August 3, 2010. Up to Date. Available: http://www.uptodate.com/contents/clinical-features-diagnosis-and-natural-history-of-lower- extremity-peripheral-artery-disease?source=search_result&search=peripheral+artery+disease&selectedTitle=1~150. Date Accessed: March 29, 2012. 64. Moriuchi M, Gordon IL, Bergman A, et al. (1992). Anatomic and functional assessment of stenosis severity with intravascular ultrasound imaging in vitro. Am J Card Imaging.;6(2):109-116. 65. Murabito, JM, D'Agostino, RB, Silbershatz, H, et al. (1997). Intermittent claudication. A risk profile from The Framingham Heart Study. Circulation 96.1: 44-9. 66. Nakamura S, Conroy RM, Gordon IL, et al. A randomized trial of transcutaneous extraction atherectomy in femoral arteries: Intravascular ultrasound observations. J Clin Ultrasound. 1995; 23:461-471. 67. Neglen, P, Hollis, KC, Olivier, J, et al. (2007). Stenting of the venous outflow in chronic venous disease: long-term stent-related outcome, clinical, and hemodynamic result. J Vasc Surg 46.5: 979-990. 68. Nishioka T, Amanullah AM, Luo H, et al. (1999). Clinical validation of intravascular ultrasound imaging for assessment of coronary stenosis severity: Comparison with stress myocardial perfusion imaging. J Am Coll Cardiol.;33(7):1870-1878. 69. Nissen SE. (2002). Application of intravascular ultrasound to characterize coronary artery disease and assess the progression or regression of atherosclerosis. Am J Cardiol.;89(4A):24B-31B.

Cardiovascular Policies, Continued

Intravascular Imaging (i.e., Intravascular Ultrasound [IVUS] and Optical Coherence Tomography [OCT]), continued

70. Nomura M, Kurokawa H, Ishii J, et al. (1999). The role of angioscopy and intravascular ultrasound imaging in acute coronary syndrome. J Cardiol;33 Suppl 1:17-21. 71. Oemrawsingh PV, Mintz GS, Schalij MJ, et al. (2003). Thrombocyte activity evaluation and effects of Ultrasound guidance in Long Intracoronary stent Placement. Intravascular ultrasound guidance improves angiographic and clinical outcome of stent implantation for long coronary artery stenoses: final results of a randomized comparison with angiographic guidance (TULIP Study). Circulation. Jan 7;107(1):62-7. 72. Ontario Ministry of Health and Long-Term Care, Medical Advisory Secretariat (MAS). Intravascular ultrasound to guide percutaneous coronary interventions. Health Technology Literature Review. Toronto, ON: MAS; April 2006. 73. Orford JL, Lerman A, Holmes DR. (2004). Routine intravascular ultrasound guidance of percutaneous coronary intervention: a critical reappraisal. J Am Coll Cardiol;43(8):1335-1342. 74. Park, SJ, Kim, YH, Park, DW, et al. (2009). Impact of intravascular ultrasound guidance on long-term mortality in stenting for unprotected left main coronary artery stenosis. Circ Cardiovasc Interv 2.3: 167-77. 75. Passman MA, Dattilo JB, Guzman RJ, Naslund TC. (2005). Bedside placement of inferior vena cava filters by using transabdominal duplex ultrasonography and intravascular ultrasound imaging. J Vasc Surg;42(5):1027-1032. 76. Perry, JT, Statler, JD. (2007). Advances in vascular imaging. Surg Clin North Am 87.5: 975-93, vii. 77. Pinto, FJ. (1999). The value of intravascular ultrasound in interventional cardiology. Rev Port Cardiol.;18 Suppl 1: I97-I104. 78. Rakel, D. (2007) Integrative Medicine. Saunders Elsevier. Available: http://www.mdconsult.com/books/page.do?eid=4-u1.0- B978-1-4160-2954-0.50033-8&isbn=978-1-4160-2954-0&uniqId=326732792-3#4-u1.0-B978-1-4160-2954-0.50033-8--f1. Date Accessed: March 29, 2012. 79. Rybicki, FJ, Nallamshetty, L, Yucel, EK, et al. (2008). ACR appropriateness criteria on recurrent symptoms following lower- extremity angioplasty. J Am Coll Radiol 5.12: 1176-80. 80. Sacks, D, Bakal, CW, Beatty, PT, et al. (2002). Position statement on the use of the ankle-brachial index in the evaluation of patients with peripheral vascular disease: a consensus statement developed by the standards division of the society of cardiovascular & interventional radiology. J Vasc Interv Radiol 13.4: 353. 81. Schwartz L, Bui S. (2003). The role of intravascular ultrasound in the diagnosis and treatment of patients with coronary artery disease. Compr Ther.;29(1):54-65. 82. Selvin, E, Erlinger, TP. (2004). Prevalence of and risk factors for peripheral arterial disease in the United States: results from the National Health and Nutrition Examination Survey, 1999-2000. Circulation 110.6: 738-43. 83. Starksen NF, Yock PG. Clinical applications of intravascular ultrasound imaging. Am J Card Imaging. 1991;5(1):54-59. 84. Stephens, E. (2012) Peripheral Vascular Disease Workup. March 15, 2010. Medscape. Available: http://emedicine.medscape.com/article/761556-workup#a0720. Date Accessed: April 2, 2012. 85. Stone GW, Hodgson JM, St Goar FG, et al. (1997). Improved procedural results of coronary angioplasty with intravascular ultrasound-guided balloon sizing: The CLOUT Pilot Trial. Clinical Outcomes With Ultrasound Trial Investigators. Circulation. 1997; 95:2044-2052. 86. Tsuchida K, Serruys PW, Bruining N, et al. (2007). Two-year serial coronary angiographic and intravascular ultrasound analysis of in-stent angiographic late lumen loss and ultrasonic neointimal volume from the TAXUS II trial. Am J Cardiol;99(5):607-615. 87. Tuzcu EM, Schoenhagen P. (2004). Atherosclerosis imaging: Intravascular ultrasound. Drugs;64 Suppl 2:1-7. 88. Uemura S, Ishigami K, Soeda T et al. Thin-cap fibroatheroma and microchannel findings in optical coherence tomography correlate with subsequent progression of coronary atheromatous plaques. Eur Heart J 2012; 33(1):78-85. 89. Vaz VD, Abizaid AC, Abizaid AA, et al. (2006). The usefulness of intracoronary ultrasound in the treatment decision-making of patients with ambiguous lesions in the left main coronary artery. Arq Bras Cardiol. Dec;87(6):681-7. 90. Vitale, E, Zuliani, G, Baroni, L, et al. (1990). Lipoprotein abnormalities in patients with extra-coronary arteriosclerosis. Atherosclerosis 81.2: 95-102. 91. Vogelberg, KH, Berchtold, P, Berger, H, et al. (1975). Primary hyperlipoproteinemias as risk factors in peripheral artery disease documented by arteriography. Atherosclerosis 22.2: 271-85. 92. von Segesser, LK, Marty, B, Ruchat, P, et al. (2002). Routine use of intravascular ultrasound for endovascular aneurysm repair: angiography is not necessary. Eur J Vasc Endovasc Surg 23.6: 537-42. 93. Weissman, NJ. (2010). Technique and interpretation of intravascular (intracoronary) ultrasonography. UpToDate 18.1. Available: http://www.utdol.com.xlib1.intermountain.net/online/content/topic.do?topicKey=chd/34626&selectedTitle=1%7E93&source=sea rch_result. Date Accessed: June 2, 2010. 94. Wellons ED, Rosenthal D, Shuler FW, et al. (2004). Real-time intravascular ultrasound-guided placement of a removable inferior vena cava filter. J Trauma;57(1):20-23; discussion 23-25. 95. Wilson, EP, White, RA. (1998). Intravascular ultrasound. Surg Clin North Am 78.4: 561-74. 96. Wykrzykowska JJ, Diletti R, Gutierrez-Chico JL et al. Plaque sealing and passivation with a mechanical self-expanding low outward force nitinol vShield device for the treatment of IVUS and OCT-derived thin cap fibroatheromas (TCFAs) in native coronary arteries: report of the pilot study vShield Evaluated at Cardiac hospital in Rotterdam for Investigation and Treatment of TCFA (SECRITT). EuroIntervention 2012; 8(8):945-54. 97. Yonetsu T, Kakuta T, Lee T et al. In vivo critical fibrous cap thickness for rupture-prone coronary plaques assessed by optical coherence tomography. Eur Heart J 2011; 32(10):1251-9. 98. Ziada KM, Kapadia SR, Tuzcu EM, et al. (1999). The current status of intravascular ultrasound imaging. Curr Probl Cardiol.;24(9):541-566.

Cardiovascular Policies, Continued

Intravascular Imaging (i.e., Intravascular Ultrasound [IVUS] and Optical Coherence Tomography [OCT]), continued

SelectHealth® makes no representations and accepts no liability with respect to the content of any external information cited or relied upon in this policy. SelectHealth updates its Coverage Policies regularly, and reserves the right to amend these policies without notice to healthcare providers or SelectHealth members. Members may contact Customer Service at the phone number listed on their member identification card to discuss their benefits more specifically. Providers with questions about this Coverage Policy may call SelectHealth Provider Relations at (801) 442-3692. No part of this publication may be reproduced, stored in a retrieval system or transmitted, in any form or by any means, electronic, mechanical, photocopying, or otherwise, without permission from SelectHealth. ”Intermountain Healthcare” and its accompanying logo, the marks of “SelectHealth” and its accompanying marks are protected and registered trademarks of the provider of this Service and or Intermountain Health Care, Inc., IHC Health Services, Inc., and SelectHealth, Inc. Also, the content of this Service is proprietary and is protected by copyright. You may access the copyrighted content of this Service only for purposes set forth in these Conditions of Use. © CPT Only – American Medical Association

Cardiovascular Policies, Continued

MEDICAL POLICY

INTRAVASCULAR LITHOTRIPSY (IVL)

Policy # 647 Implementation Date: 4/23/21 Review Dates: Revision Dates:

Description Intravascular lithotripsy (IVL) is a technology derived from renal lithotripsy, in which multiple emitters mounted on a traditional balloon catheter provide circumferential pulsatile energy to disrupt calcified plaque and improve acute gain while minimizing vessel injury. Over the last 40 years, despite multiple advancements in percutaneous coronary interventions, calcifed lesions remain a challenge for even the most experienced operators leading to an increase in morbidity and mortality. Most recently, intravascular lithotripsy (IVL) has been shown to be an innovative technology that is designed to address heavily calcifed lesions.

The Shockwave Medical Peripheral IVL System (Shockwave Medical, Fremont, CA) received U.S. Food and Drug Administration (FDA) approval in 2016. This system is a single-use sterile disposable catheter that contains multiple lithotripsy emitters enclosed in an integrated balloon. The emitters create sonic pressure waves in the shape of a sphere, creating a field effect to treat circumferential vascular calcium. These sonic pressure waves selectively disrupt and fracture calcium in situ, altering vessel compliance, while minimizing injury and maintaining the integrity of the fibro-elastic components of the vessel wall.

Commercial Plan Policy/CHIP (Children’s Health Insurance Program)

For groups selecting this benefit, SelectHealth covers Intravascular Lithotripsy (IVL) only for patients undergoing transfemoral aortic valve replacement (TAVR) with calcified peripheral arterial disease; all other indications of IVL are considered investigational/experimental.

SelectHealth Advantage (Medicare/CMS)

SelectHealth Community Care (Medicaid)

Intravascular Lithotripsy (IVL), continued

coverage, please visit their website http://health.utah.gov/medicaid/manuals/directory.php or the Utah Medicaid code Look-Up tool

Summary of Medical Information IVL, by disrupting intimal and medial calcification, alters vessel compliance to allow for the safe passage of large-bore delivery sheaths. This expands the patient cohort that could be eligible for transfemoral access for TAVR procedures. IVL-enabled transfemoral access offers several advantages. First, it preserves the established benefits of TAVR: decreased morbidity and mortality, fewer hospital days, and reduced cost. Second, although alternative access options exist, they are more invasive and have a significant learning curve (1,5). IVL leverages the familiarity of a balloon-based intervention, minimizing the learning curve, regardless of a center’s volume.

IVL may represent a straightforward technique to preserve the benefits of reduced morbidity and mortality of transfemoral TAVR in patients with calcified peripheral arterial disease.

Billing/Coding Information CPT CODES

C9764 Revascularization, endovascular, open or percutaneous, lower extremity artery(ies), except tibial/peroneal; with intravascular lithotripsy, includes angioplasty within the same vessel(s), when performed

C9765 Revascularization, endovascular, open or percutaneous, lower extremity artery(ies), except tibial/peroneal; with intravascular lithotripsy, and transluminal stent placement(s), includes angioplasty within the same vessel(s), when performed

C9766 Revascularization, endovascular, open or percutaneous, lower extremity artery(ies), except tibial/peroneal; with intravascular lithotripsy and atherectomy, includes angioplasty within the same vessel(s), when performed

C9767 Revascularization, endovascular, open or percutaneous, lower extremity artery(ies), except tibial/peroneal; with intravascular lithotripsy and transluminal stent placement(s), and atherectomy, includes angioplasty within the same vessel(s), when performed

C9772 Revascularization, endovascular, open or percutaneous, tibial/peroneal artery(ies), with intravascular lithotripsy, includes angioplasty within the same vessel(s), when performed

C9773 Revascularization, endovascular, open or percutaneous, tibial/peroneal artery(ies); with intravascular lithotripsy, and transluminal stent placement(s), includes angioplasty within the same vessel(s), when performed

C9774 Revascularization, endovascular, open or percutaneous, tibial/peroneal artery(ies); with intravascular lithotripsy and atherectomy, includes angioplasty within the same vessel(s), when performed

C9775 Revascularization, endovascular, open or percutaneous, tibial/peroneal artery(ies); with the intravascular lithotripsy and transluminal stent placement(s), and atherectomy, includes angioplasty within same vessel(s), when performed

Key References 1. Aksoy, A., et al. Intravascular Lithotripsy in Calcified Coronary Lesions. (2019). https://doi.org/10.1161/CIRCINTERVENTIONS.119.008154 PMID: 31707803 2. Di Mario, C., et al. A Prospective Registry of Intravascular Lithotripsy-Enabled Vascular Access for Transfemoral Transcatheter Aortic Valve Replacement. JACC: Cardiovascular Interventions. (2019). 12(5). doi: 10.1016/j.jcin.2019.01.211

Disclaimer 2

Cardiovascular Policies, Continued

Intravascular Lithotripsy (IVL), continued

This document is for informational purposes only and should not be relied on in the diagnosis and care of individual patients. Medical and Coding/Reimbursement policies do not constitute medical advice, plan preauthorization, certification, an explanation of benefits, or a contract. Members should consult with appropriate healthcare providers to obtain needed medical advice, care, and treatment. Benefits and eligibility are determined before medical guidelines and payment guidelines are applied. Benefits are determined by the member’s individual benefit plan that is in effect at the time services are rendered. The codes for treatments and procedures applicable to this policy are included for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member. SelectHealth® makes no representations and accepts no liability with respect to the content of any external information cited or relied upon in this policy. SelectHealth updates its Coverage Policies regularly, and reserves the right to amend these policies without notice to healthcare providers or SelectHealth members. Members may contact Customer Service at the phone number listed on their member identification card to discuss their benefits more specifically. Providers with questions about this Coverage Policy may call SelectHealth Provider Relations at (801) 442-3692. No part of this publication may be reproduced, stored in a retrieval system or transmitted, in any form or by any means, electronic, mechanical, photocopying, or otherwise, without permission from SelectHealth. ”Intermountain Healthcare” and its accompanying logo, the marks of “SelectHealth” and its accompanying marks are protected and registered trademarks of the provider of this Service and or Intermountain Health Care, Inc., IHC Health Services, Inc., and SelectHealth, Inc. Also, the content of this Service is proprietary and is protected by copyright. You may access the copyrighted content of this Service only for purposes set forth in these Conditions of Use. © CPT Only – American Medical Association

Cardiovascular Policies, Continued

MEDICAL POLICY

LDL APHERESIS (LIPOSORBER DEVICE, HELP SYSTEM)

Policy # 207 Implementation Date: 12/9/03 Review Dates: 2/9/05, 2/16/06, 5/17/07, 4/24/08, 4/23/09, 4/12/12, 6/20/13, 4/17/14, 5/7/15, 4/14/16, 4/27/17, 8/16/18, 4/27/19, 4/15/20 Revision Dates: 2/18/10, 4/21/11, 8/19/15, 5/9/19

Disclaimer: 1. Policies are subject to change without notice. 2. Policies outline coverage determinations for SelectHealth Commercial, SelectHealth Advantage (Medicare), and SelectHealth Community Care (Medicaid) plans. Refer to the “Policy” section for more information.

Description Heart disease is the number one cause of morbidity and mortality in the adult US population. Lowering total and LDL cholesterol has been shown to reduce the development and recurrence of heart disease. Consequently, great emphasis is placed on the treatment of elevated total and LDL cholesterol by many physicians. Treatment including diet and multiple medications are used to reach goals published by the National Cholesterol Education Program (NCEP). However, some patients, primarily those with familial hypercholesterolemia (FH), may require additional therapy. The dextran sulfate cellulose adsorption system (LipoSorber) uses columns containing dextran sulfate immobilized on cellulose beads to remove LDL from the plasma. Typically, there are 2 such columns in the plasma circuit, which are regenerated automatically during LDL apheresis. The system has a high selectivity for the removal of apolipoprotein B (apo B)-containing lipoproteins, removing LDL, very low- density lipoprotein, and lipoprotein (a). Binding of LDL appears to depend on electrostatic interaction between dextran sulfate and apo B and is inhibited by acetylation of LDL. Interestingly, dextran sulfate columns can remove LDL of patients with familial defective apo B-100 with equal efficacy. Although some molecules with similar properties are absorbed to the column, this is not associated with any adverse clinical consequences. The columns are discarded after each apheresis procedure, and this contributes to the high running costs of this system.

Commercial Plan Policy

SelectHealth covers LDL apheresis in limited circumstances when certain criteria have been met.

Patients must meet ONE of the following criteria: 1. Patient has one of the following diagnoses and associated LDL Cholesterol levels: a. Patients with homozygous FH and LDL-chol > 500mg/dl; b. Patients with heterozygous FH with an LDL-chol > 300mg/dl; c. Patients with heterozygous FH with an LDL-chol > 200mg/dl and failed to reach NCEP targets on maximal medical therapy. 2. Patient has documented medical nutritional therapy consultation and has shown active efforts at appropriate lifestyle modifications. 3. Supporting documentation demonstrates the patient to have attempted or is currently on maximal medical therapy. Maximal medical therapy is defined as the following:

Cardiovascular Policies, Continued

LDL Apheresis (Liposorber Device, Help System), continued

a. Maximal doses of high-potency HMG-CoA reductase inhibitor (statin) therapy (unless intolerant or detrimental side effects are documented) with ezetmibe and a PCSK-9 agent with compliance to that therapy.

In addition to the above criteria, the following will apply: a. Patients with familial heterozygous traits with LDL cholesterol > 200 must have documented atherosclerosis. The patient should have known coronary artery disease, cerebrovascular disease, or peripheral vascular disease documented prior to apheresis therapy. b. Discontinuation/avoidance of ACE inhibitor medications (due to the greater risk of hypotension induced by bradykinin release). c. Avoidance of smoking for > 6 months prior to the start of apheresis therapy. d. Absence of other severe co-morbid conditions such as end-stage renal disease, emphysema, or other life-threatening conditions. e. LDL apheresis is to be performed on an FDA approved device. f. The patient is in active case management with SelectHealth and demonstrates compliance with therapies. g. The therapy must be performed by a board-certified Lipidologist at a formal Lipid management clinic.

SelectHealth Advantage (Medicare/CMS)

SelectHealth Community Care (Medicaid/CHIP)

Summary of Medical Information The evidence permits the conclusion that lipid apheresis consistently reduces total cholesterol and LDL cholesterol. Three randomized, controlled trials (RCTs) report that the reductions in LDL cholesterol are clinically and statistically significantly greater than those achieved by medication alone for patients with refractory hypercholesterolmeia. The evidence suggests that lipid apheresis may reduce arterial morphologic change and improve hemodynamic flow in diseased arteries; however, this has not been consistently demonstrated in RCTs. The RCTs are insufficient to provide direct evidence that lipid apheresis reduces adverse cardiovascular events as compared to maximal medical management. The results of these RCTs are also limited by the fact that 2 of the 3 trials included some patients who may have been responsive to medical management, rather than limiting the population to those patients who are truly refractory to maximal medical management. In most of the nonrandomized studies, the patients had failed diet and drug therapy, and correspond more closely to the target group of refractory patients. The efficacy of LDL lowering is of similar magnitude in these studies as compared to the RCTs. In uncontrolled studies using pre-and post- treatment coronary angiography, the reductions in cholesterol appear to be associated with non- 2

Cardiovascular Policies, Continued

LDL Apheresis (Liposorber Device, Help System), continued

progression of atherosclerosis. Therefore, the evidence supports the effectiveness of lipid apheresis for providing a long-term lipid-lowering benefit and suggests that lipid apheresis may be associated with non- progression of coronary artery disease. Given the established causal relationship between LDL cholesterol and cardiac events, it is likely that lipid apheresis will reduce cardiovascular events for patients with hypercholesterolemia who are refractory or intolerant to maximal drug therapy. Lipid apheresis improves health outcomes by lowering cholesterol in patients with refractory hypercholesterolemia, leading to a reduction in adverse cardiovascular events. However, the available evidence has not quantified the magnitude of this benefit. Given that the magnitude of LDL lowering by apheresis is large, 50%−70% or greater, the magnitude of reduction in adverse cardiovascular events is also likely to be clinically meaningful. Lipid apheresis is a relatively safe treatment, although it occasionally may be associated with significant hypotension and anaphylactic reactions. Most adverse effects are minor. Hypotension may be more likely with dextran sulfate chemo adsorption, especially in patients receiving concomitant angiotensin- converting enzyme (ACE) inhibitors. There are no adequate trials of direct comparison of the techniques to quantitatively determine treatment or safety advantages. All 3 techniques are relatively selective for LDL cholesterol but may remove some other molecules non-selectively. The clinical effect of removal of other factors such as HDL, fibrinogen, and bradykinin are unclear at this time, but there is no evidence to suggest that adverse effects have resulted from this phenomenon. For the indicated patient group with refractory hypercholesterolemia despite maximal medical therapy, the alternatives are very limited. Radical treatments such as portocaval shunt or liver transplantation have been tried but are not yet established in clinical practice. Intensification of medical therapy is an option as newer and more potent cholesterol lowering agents are introduced, but only a minority of patients will remain refractory. Lipid apheresis is likely the best option for many of these patients.

Billing/Coding Information Covered: For the conditions outlined above CPT CODES 36516 Therapeutic apheresis; with extracorporeal selective adsorption or selective filtration and plasma reinfusion

HCPCS CODES S2120 Low density lipoprotein (LDL) apheresis using heparin-induced extracorporeal LDL precipitation

E88.89 Other specified metabolic disorders Key References 1. BCBS TEC ― Lipid apheresis in the treatment of patients with severe, refractory hypercholesterolemia. 4/1999. 2. Bambauer R, Schiel R, Latza R. Low-density lipoprotein apheresis: an overview. Therap Apher Dial. 2003 Aug;7(4):382-90. 3. Thompson GR. LDL apheresis. Atherosclerosis. 2003 Mar;167(1):1-13. Review. 4. Bambauer R, Schneidewind JM, Latza R. Apheresis technologies for prevention and regression of atherosclerosis: clinical results. ASAIO J. 1999 Sep-Oct;45(5):403-7. PMID: 10503615 5. Nishimura S, Sekiguchi M, Kano T, Ishiwata S, Nagasaki F, Nishide T, Okimoto T, Kutsumi Y, Kuwabara Y, Takatsu F, Nishikawa H, Daida H, Yamaguchi H. Effects of intensive lipid lowering by low-density lipoprotein apheresis on regression of coronary atherosclerosis in patients with familial hypercholesterolemia: Japan Low-density Lipoprotein Apheresis Coronary Atherosclerosis Prospective Study (L-CAPS). Atherosclerosis. 1999 Jun;144(2):409-17. PMID: 10407502 6. Matsuzaki M, Hiramori K, Imaizumi T, Kitabatake A, Hishida H, Nomura M, Fujii T, Sakuma I, Fukami K, Honda T, Ogawa H, Yamagishi M. Intravascular ultrasound evaluation of coronary plaque regression by low density lipoprotein-apheresis in familial hypercholesterolemia: the Low Density Lipoprotein-Apheresis Coronary Morphology and Reserve Trial (LACMART). J Am Coll Cardiol. 2002 Jul 17;40(2):220-7. PMID: 12106923 7. Jovin IS, Taborski U, Muller-Berghaus G. Analysis of the long-term efficacy and selectivity of immunoadsorption columns for low density lipoprotein apheresis. ASAIO J. 2000 May-Jun;46(3):298-300. PMID: 10826740 8. Mabuchi H, Koizumi J, Shimizu M, Kajinami K, Miyamoto S, Ueda K, Takegoshi T. Long-term efficacy of low-density lipoprotein apheresis on coronary heart disease in familial hypercholesterolemia. Hokuriku-FH-LDL-Apheresis Study Group. Am J Cardiol. 1998 Dec 15;82(12):1489-95. PMID: 9874053 9. Borberg H. Results of an open, longitudinal multicenter LDL-apheresis trial. Transfus Sci. 1999 Feb;20(1):83-94. PMID: 10621566 10. Bambauer R, Schiel R, Latza R, Klinkmann J, Schneidewind JM. LDL apheresis in clinical practice: long-term treatment of severe hyperlipidemia. Ther Apher. 1997 Feb;1(1):49-54. PMID: 10225781 11. Robinson JG, Farnier M, Krempf M, Bergeron J, Luc G, Averna M, Stroes ES, Langslet G, Raal FJ, El Shahawy M, Koren MJ, Lepor NE, Lorenzato C, Pordy R, Chaudhari U, Kastelein JJ; ODYSSEY LONG TERM Investigators. Efficacy and safety of

Cardiovascular Policies, Continued

Acute Inpatient Rehabilitation LDL Apheresis (Liposorber Device, Help System), continued

alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015 Apr 16;372(16):1489-99. doi: 10.1056/NEJMoa1501031. Epub 2015 Mar 15. PMID:25773378 12. Kereiakes DJ, Robinson JG, Cannon CP, Lorenzato C, Pordy R, Chaudhari U, Colhoun HM. Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: The ODYSSEY COMBO I study. Am Heart J. 2015 Jun;169(6):906-915.e13. doi: 10.1016/j.ahj.2015.03.004. Epub 2015 Mar 13. 13. Robinson JG1, Colhoun HM, Bays HE, Jones PH, Du Y, Hanotin C, Donahue S. Efficacy and safety of alirocumab as add-on therapy in high-cardiovascular-risk patients with hypercholesterolemia not adequately controlled with atorvastatin (20 or 40 mg) or rosuvastatin (10 or 20 mg): design and rationale of the ODYSSEY OPTIONS Studies. Clin Cardiol. 2014 Oct;37(10):597- 604. doi: 10.1002/clc.22327. Epub 2014 Sep 30.

Cardiovascular Policies, Continued

MEDICAL POLICY

LEFT ATRIAL APPENDAGE CLOSURE (LAAC) DEVICES (E.G., WATCHMAN®)

Policy # 430 Implementation Date: 12/28/09 Review Dates: 5/19/11, 6/19/14, 10/20/16, 10/19/17, 10/3/18, 10/15/19 Revision Dates: 6/21/12, 4/13/13, 8/6/15

Description Atrial fibrillation (AF) is a common dysrhythmia. It is characterized as paroxysmal if the duration is less than 1 week, persistent if the duration is between 7 days, and 1 year and permanent if greater than 1 year in duration with failure of conversion. AF can have adverse consequences related to a reduction in cardiac output and thrombus formation that can lead to systemic embolization and strokes. Most embolized thrombi are felt to develop in the left atrial appendage (LAA). In patients with atrial fibrillation, blood tends to pool and form clots in this appendage. To prevent clot formation and subsequent embolization in patients with AF, current guidelines recommend anticoagulation with warfarin. Management of anticoagulation with warfarin is cumbersome due to the need for frequent monitoring as warfarin is subject to significant drug-drug and drug-food interactions which can result in excessive or inadequate anticoagulation. Though warfarin is the long-term oral antithrombotic of choice in patients at high risk of embolism in association with non-valvular atrial fibrillation, especially after an ischemic cerebrovascular event, many patients cannot achieve anticoagulation targets. It is estimated that therapeutic INRs are reached less than 60% of the time, and only 50% of high-risk atrial fibrillation patients are treated with warfarin. In some of these instances, alternative treatment with medications such as aspirin or clodipogrel are used, though, studies have shown these therapies to be inferior to warfarin. To overcome many of the alternative issues surrounding anticoagulation therapy, the WATCHMAN® LAA Closure Technology (Boston Scientific Corporation, Maple Grove, MN) consists of a delivery catheter and a device that is permanently implanted in the left atrial appendage (LAA) of the heart. The device, often referred to as the WATCHMAN, which received FDA approval on March 13, 2015, prevents LAA blood clots from entering the bloodstream and potentially causing a stroke. It is made of a self-expanding, nickel-titanium (Nitinol) frame with an attached woven plastic cap. The physician inserts the delivery catheter into the body through a vein in the leg. The catheter is advanced through the bloodstream until it reaches the upper right chamber of the heart (right atrium). The physician makes a small hole through the wall between the two upper chambers of the heart (atrial septum) so that the catheter reaches the LAA. The physician then pushes the WATCHMAN through the delivery catheter into the LAA where it opens up like an umbrella and is permanently implanted. Once the WATCHMAN is in place, a thin layer of tissue grows over it in about 45 days. This keeps blood clots in the LAA from entering the bloodstream.

Commercial Plan Policy (No Preauthorization Required but criteria must be met)

SelectHealth covers left atrial appendage closure (e.g., WATCHMAN®) in limited circumstances as outlined below.

Criteria for coverage (Must meet 1, 2 and either 3, 4, or 5)

1. Patients with CHA2DS2VAsc > 2 who have contraindications to anticoagulation therapy

Cardiovascular Policies, Continued

Left Atrial Appendage Closure (LAAC) Devices (e.g., Watchman®), continued

2. Patient does not rheumatic valvular heart disease 3. Patients are unable to take long term oral anticoagulation occupational or intolerance of anticoagulation due to side effects or prior bleeding experience 4. Patients in whom administering oral anticoagulation long-term is deemed clinically high risk or contraindicated because of fall risk or other predisposition to bleeding complications 5. Patients in need of secondary prevention who had a therapeutic INR or verified medication compliance with novel oral anticoagulation (NOAC) medications at the time of their embolic event

SelectHealth does NOT cover any other left atrial closure device.

SelectHealth Advantage (Medicare/CMS) (Preauthorization Required)

SelectHealth Community Care (Medicaid/CHIP) (Preauthorization Required)

Summary of Medical Information The WATCHMAN was evaluated in four clinical studies, in which two studies compared the WATCHMAN to warfarin. Many patients with atrial fibrillation take warfarin or other FDA approved blood thinning medicines to prevent a stroke caused by a blood clot in the brain. However, warfarin can increase the risk of bleeding anywhere in the body. If bleeding happens in the brain, this can also cause a stroke. These two clinical studies suggested that warfarin was better than the WATCHMAN in preventing strokes caused by a blocked blood vessel in the brain. However, the number of strokes caused by bleeding in the brain was lower in the WATCHMAN patients compared to the warfarin patients. The overall rate of serious bleeding was similar in the WATCHMAN and warfarin patients. Within several months after the device was implanted, the rate of serious bleeding was higher in the WATCHMAN patients as compared to warfarin patients. However, beginning six months after the device implant procedure, the rate of serious bleeding was lower in WATCHMAN patients. In one of the clinical studies that evaluated the WATCHMAN, 226 out of 246 WATCHMAN patients (approximately 92%) were able to stop taking their warfarin 45 days after the device was implanted. Within a year after the implant procedure, 231 out of 234 patients remaining in the study (over 99%) were able to stop taking warfarin. To prevent strokes, most atrial fibrillation patients can safely take blood thinning medicines (like warfarin) without serious side effects. However, in some patients, blood thinning medicines can be difficult to use due to bleeding concerns. In choosing a treatment, physicians should consider the risks and benefits of blood thinning medicines compared to the WATCHMAN for each individual patient. This includes the risk that either kind of stroke (caused by a blocked blood vessel or by bleeding) might occur.

Cardiovascular Policies, Continued

Left Atrial Appendage Closure (LAAC) Devices (e.g., Watchman®), continued

Billing/Coding Information Covered: For the conditions outlined above CPT CODES 33340 Percutaneous transcatheter closure of the left atrial appendage with endocardial implant, including fluoroscopy, transseptal puncture, catheter placement(s), left atrial angiography, left atrial appendage angiography, when performed, and radiological supervision and interpretation

HCPCS CODES No specific codes identified

Key References 1. Arnsdorf M, Podrid. Overview of the evaluation and management of atrial fibrillation. 17.2. February 4, 2009 2009. UpToDate. Available: http://www.utdol.com/online/content/topic.do?topicKey=carrhyth/4832&selectedTitle=1~150&source=search_result. Date Accessed: November 9, 2009. 2. Arnsdorf M. Electrocardiographic and electrophysiologic features of atrial fibrillation. 17.2. June 12, 2009 2009. UpToDate. Available: http://www.utdol.com/online/content/topic.do?topicKey=carrhyth/4532&selectedTitle=1~150&source=search_result. Date Accessed: November 9, 2009. 3. Arnsdorf M. Patient information: atrial fibrillation. 17.2. August 28, 2009 2009. UpToDate. Available: http://www.utdol.com/online/content/topic.do?topicKey=hrt_dis/4882&selectedTitle=1~150&source=search_result. Date Accessed: November 9, 2009. 4. Atritech. The WATCHMAN System. 2008 2009. Atritech. Available: http://www.atritech.net/device.aspx?id=107. Date Accessed: November 9, 2009. 5. Bayard YL, Ostermayer SH, Sievert H. "Transcatheter occlusion of the left atrial appendage for stroke prevention." Expert Rev Cardiovasc Ther 3.6 (2005): 1003-8. 6. Block PC, Burstein S, Casale PN, et al. "Percutaneous left atrial appendage occlusion for patients in atrial fibrillation suboptimal for warfarin therapy: 5-year results of the PLAATO (Percutaneous Left Atrial Appendage Transcatheter Occlusion) Study." JACC Cardiovasc Interv 2.7 (2009): 594-600. 7. Calkins H, Brugada J, Packer DL, et al. "HRS/EHRA/ECAS expert Consensus Statement on catheter and surgical ablation of atrial fibrillation: recommendations for personnel, policy, procedures and follow-up. A report of the Heart Rhythm Society (HRS) Task Force on catheter and surgical ablation of atrial fibrillation." Heart Rhythm 4.6 (2007): 816-61. 8. Cheng J, Arnsdorf M. Surgical approaches to prevent recurrent atrial fibrillation. 17.2. July 17, 2008 2009. UpToDate. Available: http://www.utdol.com/online/content/topic.do?topicKey=carrhyth/55314&selectedTitle=1~150&source=search_result. Date Accessed: November 9, 2009. 9. Cheng J, Hijazi Z. Left atrial appendage amputation, ligation, or occulsion in patients with atrial fibrillation. 17.2. April 19, 2007 2009. UpToDate. Available: http://www.utdol.com/online/content/topic.do?topicKey=carrhyth/20022&selectedTitle=1~45&source=search_result. Date Accessed: November 9, 2009. 10. Chiam PT, Ruiz CE. "Percutaneous transcatheter left atrial appendage exclusion in atrial fibrillation." J Invasive Cardiol 20.4 (2008): E109-13. 11. Crandall MA, Bradley DJ, Packer DL, Asirvatham SJ. "Contemporary management of atrial fibrillation: update on anticoagulation and invasive management strategies." Mayo Clin Proc 84.7 (2009): 643-62. 12. Food and Drug Administration. Summary from the Circulatory System Meeting - April 23, 2009. June 18. 2009 2009. FDA. Available: http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/Circ ulatorySystemDevicesPanel/ucm142895.htm. Date Accessed: November 9, 2009. 13. Fountain R, Holmes DR, Jr., Hodgson PK, Chandrasekaran K, Van Tassel R, Sick P. "Potential applicability and utilization of left atrial appendage occlusion devices in patients with atrial fibrillation." Am Heart J 152.4 (2006): 720-3. 14. Friedman PA, Asirvatham SJ, Dalegrave C, et al. "Percutaneous epicardial left atrial appendage closure: preliminary results of an electrogram guided approach." J Cardiovasc Electrophysiol 20.8 (2009): 908-15. 15. Fuster V, Ryden LE, Cannom DS, et al. "ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society." Circulation 114.7 (2006): e257-354. 16. Holmes DR, Reddy VY, Turi ZG, et al. "Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial." Lancet 374.9689 (2009): 534-42. 17. Kanderian AS, Gillinov AM, Pettersson GB, Blackstone E, Klein AL. "Success of surgical left atrial appendage closure: assessment by transesophageal echocardiography." J Am Coll Cardiol 52.11 (2008): 924-9. 18. Lerakis S, Synetos A. "Left atrial appendage exclusion system for stroke prevention in atrial fibrillation: a percutaneous device delivery approach." Minerva Cardioangiol 56.6 (2008): 667-70. 19. Lerakis S, Synetos A. "WATCHMAN((R)) left atrial appendage system for stroke prevention in atrial fibrillation: a percutaneous- device delivery approach." Future Cardiol 3.5 (2007): 507-9. 20. Mannin W, Singer D, Lip G, Hart R. Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation. 17.2. June 19, 2009 2009. UpToDate. Available: http://www.utdol.com/online/content/topic.do?topicKey=carrhyth/50724&selectedTitle=1~150&source=search_result. Date Accessed: November 9, 2009. 21. Manning W, Singer D, Hart R. Risk stratification for embolization in atrial fibrillation. 17.2. October 24, 2008 2009. UpToDate. Available: http://www.utdol.com/online/content/topic.do?topicKey=carrhyth/61906. Date Accessed: November 9, 2009.

Cardiovascular Policies, Continued

Left Atrial Appendage Closure (LAAC) Devices (e.g., Watchman®), continued

22. Matsuo Y, Sandri M, Mangner N et al. Interventional Closure of the Left Atrial Appendage for Stroke Prevention. Circ J 2014; 78(3):619-24. https://www.jstage.jst.go.jp/article/circj/78/3/78_CJ-13-0828/_pdf 23. Mobius-Winkler S, Schuler GC, Sick PB. "Interventional treatments for stroke prevention in atrial fibrillation with emphasis upon the WATCHMAN device." Curr Opin Neurol 21.1 (2008): 64-9. 24. Onalan O, Crystal E. "Left atrial appendage exclusion for stroke prevention in patients with nonrheumatic atrial fibrillation." Stroke 38.2 Suppl (2007): 624-30. 25. Reddy VY, Homes D, Doshi HK, et al. (2011). Safety of percutaneous left atrial appendage closure: results from the Watchman Left Atrial Appendage System for Embolic Protection in Patients with AF (PROTECT AF) clinical trial and the Continued Access Registry. Circulation. Feb 1;123(4):417-24. 26. Reddy VY, Möbius-Winkler S, Miller MA et al. Left Atrial Appendage Closure With the Watchman Device in Patients With a Contraindication for Oral AnticoagulationThe ASAP Study (ASA Plavix Feasibility Study With Watchman Left Atrial Appendage Closure Technology). J Am Coll Cardiol 2013; 61(25):2551-56. http://www.sciencedirect.com/science/article/pii/S0735109713014150 27. Sick PB, Schuler G, Hauptmann KE, et al. "Initial worldwide experience with the WATCHMAN left atrial appendage system for stroke prevention in atrial fibrillation." J Am Coll Cardiol 49.13 (2007): 1490-5. 28. Ussia GP, Mule M, Cammalleri V, et al. "Percutaneous closure of left atrial appendage to prevent embolic events in high-risk patients with chronic atrial fibrillation." Catheter Cardiovasc Interv 74.2 (2009): 217-22. 29. Weimar C, Weber R, Diener HC. "Antithrombotic medication for stroke prevention." Expert Rev Cardiovasc Ther 7.10 (2009): 1245-54.

Cardiovascular Policies, Continued

MEDICAL POLICY

MAGNETIC RESONANCE IMAGING (MRI) FOR CARDIOVASCULAR INDICATIONS

Policy # 154 Implementation Date: 4/20/03 Review Dates: 10/23/03, 4/18/05, 4/27/06, 5/17/07, 6/23/08, 4/21/11, 6/21/12, 8/15/13, 6/19/14, 6/11/15, 6/16/16, 6/15/17, 7/20/18, 6/18/19 Revision Dates: 5/1/04, 4/28/09, 4/22/10, 1/16/15, 8/1/19 Related Medical Policies: #528 PET Scans for Cardiac Indications

Description Magnetic resonance imaging (MRI) is a non-invasive imaging procedure used to study various organs including the brain, spine, bones, heart, and other soft tissues. MRI uses pulsed radiofrequency waves in the presence of a high magnetic field to produce high-quality images in any plane. These studies are performed with or without IV contrast. MRI use in the field of cardiology has evolved into a mature modality. However, echocardiography, i.e., transthoracic (TTE) remains the generally accepted modality to evaluate cardiac anatomy and function for many routine applications, given its greater ease of application and interpretation, lower cost, and real- time interpretation. However, 20–30%of the population cannot be adequately imaged with an echocardiogram or have adequate diagnostic information provided. Additionally, the details provided by MRIs are of greater utility for preoperative planning.

Commercial Plan Policy

SelectHealth covers cardiac MRI in limited conditions. Coverage is allowed in the following situations: • Congenital or acquired disease of the thoracic aorta • Tumor staging of the organs of the chest • Congenital heart disease • Constrictive pericarditis • Evaluation of anomalous coronary arteries • Aortic and pulmonary artery disease: To define the dimensions and extent of aortic aneurysms, false aneurysms, dissection flaps, periaortic abscess, aortic arch abnormalities, coarctation, valvular and supravalvular aortic stenosis, or abnormalities of the pulmonary artery and great neck vessels • Cardiac masses: MRI is useful in the assessment of cardiac tumors and paracardiac masses (to assess for cardiac invasion)

Cardiovascular Policies, Continued

Magnetic Resonance Imaging (MRI) for Cardiovascular Indications, continued

• As planning for patients undergoing ablative procedures for atrial fibrillation, supraventricular tachycardia, or other dysrhythmias found to be amenable to ablative therapies • For post-ablative follow-up of cardiac dysrhythmia involving the pulmonary vein or right ventricular (RV) outflow tract (limited to once in the first 6 months post-ablation for asymptomatic patients)

Coverage is allowed in any of the following situations when standard cardiovascular testing has been done and is felt to be inadequate to determine appropriate management by the ordering physician • Ischemic heart disease and post-myocardial infarction status • Measurement of left and right ventricular function and volumes • Assess mitral regurgitation and ventricular septal defects (mechanical complications of acute MI) • Assess thrombus formation • Assess left ventricular aneurysm • Detect regional wall motion abnormalities • Initial and serial evaluations of pericardial disease, including pericarditis, pericardial effusions, and pericardial masses • Assess viability of the infarcted myocardium utilizing delayed hyperenhancement (contrast studies) • Assess perfusion, function, and viability when all 3 parameters are required for predictive or decision-making purposes: o Evaluate patients with suspected anomalous coronary arteries o Assess microvascular angina (Syndrome X) in patients without epicardial coronary artery occlusive disease • Cardiomyopathy: o Dilated o Hypertrophic o Infiltrative or restrictive o Myocarditis • As an initial assessment of cardiac dysrhythmias to discern potential etiology including atrial fibrillation, supraventricular tachycardia, or other dysrhythmias • Assess regional wall-thickening and tissue classification in variants of hypertrophic cardiomyopathy • Diagnosis of infiltrative cardiomyopathies such as those associated with hemachromatosis, sarcoidosis, and amyloidosis • Distinguish between restrictive and constrictive disease • Serial assessment of volumes and function during medical or surgical therapy when more precise, reproducible values are clinically required than provided by echocardiography • Valvular heart disease: To assess valvular regurgitation or stenosis when echocardiographic studies are technically inadequate • Right ventricular lesions to evaluate for the presence of arrhythmogenic right ventricular cardiomyopathy (ARVC) and for other right ventricular diseases when echocardiographic studies are technically inadequate • To evaluate cardiotoxicity in members who are undergoing treatment with cardiotoxic medications 2

Cardiovascular Policies, Continued

Magnetic Resonance Imaging (MRI) for Cardiovascular Indications, continued

SelectHealth does NOT cover MRI of the cardiovascular system, particularly of the coronary arteries, when used as a screening study in asymptomatic individuals.

SelectHealth Advantage (Medicare/CMS)

SelectHealth Community Care (Medicaid/CHIP)

Summary of Medical Information Magnetic resonance imaging (MRI) is a non-invasive imaging procedure used frequently for studying intracranial and intraspinal pathology, and for evaluating abnormalities of the musculoskeletal system, the heart, and pelvis. It is also used to evaluate abdominal visceral problems. Magnetic resonance imaging uses a pulsed radiofrequency wave in the presence of a high magnetic field to produce high-quality images of the body in any plane. Magnetic resonance imaging may be preferred to a CT scan because of its established capability to depict soft tissue, often without the need for contrast material and absence of ionizing radiation. During a MRI examination, the patient is placed inside a very strong hollow magnet. A fraction of the hydrogen atoms within the patient's body align themselves with the magnetic field. The body area being examined is exposed to radio waves that are first absorbed and then emitted. The emitted waves become the MRI signal. The signal is analyzed by computer and processed into images of the body. The images are usually in the form of slices through the body. The slices can be taken in any plane. Magnetic resonance imaging also has the ability to acquire 2-, 3- or 4-dimensional data. Images with high-signals appear white (e.g., fat) and those with low-signals appear black (e.g., air in the lungs). Magnetic resonance imaging is sometimes performed with the use of contrast agents for specific indications in order to achieve a desired image. Contrast enhancement agents approved by the Federal Drug Administration (FDA) for use with MRI include Magnevist, (gadopentetate dimeglumine), ProHance, (gadoteritol), Omniscan, (gadodiomode), Ultravist, (iopromide), and Ferumoxsil (feroxide). Magnetic resonance imaging has been shown to have several technical advantages in comparison to other standard diagnostic testing procedures such as CT scan and X-ray. Magnetic resonance imaging is a non-invasive technique that uses no ionizing radiation, and according to available literature, there are no known clinically significant side effects. The literature indicates magnetic resonance imaging can be used during the first trimester of pregnancy when it has been shown to offer an advantage over other modalities. Magnetic resonance imaging does not always require contrast agents in order to achieve a high degree of resolution. The literature indicates there is some increased risk of administering MRI contrast agents to patients with asthma or iodine allergy, but administration of these agents is still performed with caution. Magnetic resonance imaging soft tissue contrast has been shown to be superior to that of other imaging modalities, and there are no image artifacts from bone. The literature indicates magnetic resonance imaging has greater inherent contrast between different types of normal body tissues and between pathological tissues and normal tissues. Magnetic resonance imaging clarity is equal in any

Cardiovascular Policies, Continued

Magnetic Resonance Imaging (MRI) for Cardiovascular Indications, continued

view: axial, sagittal, coronal, or oblique. Magnetic resonance imaging also has the ability to acquire two dimensional, three-dimensional, and four-dimensional data. Magnetic resonance imaging has been shown to have several disadvantages. It requires more patient cooperation than other tests. Imaging time is longer than CT or x-ray. Exposure time of MRI is between 100 and 1,000 times as long as the time required for a CT slice. Installation and operation of MRI equipment is costly. It has limitations in the acute trauma setting due to its incompatibility with various medical and life-support devices. Transient biological effects have been noted, such as cardiac T-wave changes. Overheating may result from the alternating magnetic transmissions of the radiofrequency coils. The literature indicates that care should be exercised when using MRI with infants, elderly patients, and hyper-pyrexic individuals. There is a forceful attraction of ferromagnetic objects to the magnet. Many aneurysm clips, intracranial or intraocular metal, shrapnel, cardiac pacemakers or pacemaker wires and cochlear implants are absolute or relative contraindications for MRI. Magnetic resonance imaging has somewhat less spatial resolution than CT scan. According to the literature, incidental anatomic discrepancies, such as non-specific white matter abnormalities, may be misinterpreted as causing the patient's symptoms. Magnetic resonance imaging in the field of cardiology has evolved at a rapid pace. However, echocardiography, i.e., transthoracic (TTE) and transesophageal echocardiogram (TEE) remains the generally accepted modality for the evaluation of cardiac anatomy and functions, most of the time, because of greater ease of acquisition, lower cost, and real-time imaging. According to the literature, 20– 30% of the population cannot be adequately imaged with an echocardiogram or get adequate diagnostic information. For these patients, MRI has been shown to be particularly important. Magnetic resonance imaging has the following important attributes that make it effective for the evaluation of the cardiovascular system: • It can produce high-resolution images of the cardiac chambers and large vessels without the need of contrast agents; • It is a three-dimensional imaging technique; • It produces images of cardiovascular structures without the interference from adjacent bone or air; • Fast gradient echo techniques can be used to assess global and regional ventricular contractile function; • Velocity-encoded techniques permit measurement of blood flow; • It has high tissue contrast; • It does not have the weakness of geometric assumptions as does angiography and echocardiography in the assessment of ventricular volumes; and • It does not have difficulties in evaluating right ventricular function. Since MRI can usually not be brought to the bedside like the TEE, it usually is not the first test used in an emergency situation, but it may be used later to better define the diagnosis. Under established guidelines, magnetic resonance imaging is used as the diagnostic test for the following indications: diseases of the aorta, diseases of the pericardium, external and internal masses, pathology involving surrounding structures, congenital heart disease, and ventricular dysplasia. Magnetic resonance imaging is increasingly being used in the assessment of cardiac function, morphology, structure, perfusion, and viability. When echocardiography does not provide enough information, in these circumstances, the literature suggests MRI may be warranted. A February 2009 Medical Technology review found that MRI is equivalent, and in some cases superior, to alternative procedures for measuring cardiac parameters. Indeed, in some cases, cardiac MRI appears to have become the gold standard of care such as in the case for diagnosing cardiomyopathy or for estimating ejection fraction. No studies could be located that estimated the cost-effectiveness of CMRI relative to standard diagnostic tests, which remains an important limitation in the literature. Moreover, the validity of testing in individuals with a low probability of heart disease is poorly understood. Thus, its use as a screening test is not supported in the literature. However, for diagnosing heart conditions in patients in whom such conditions are likely to be present, CMRI appears to be a useful test. A literature reviewed performed in June 2012 identified a British trial Clinical evaluation of Magnetic Resonance imaging in Coronary heart disease (CE MARC) representing a 2012 update in use of CMR for stress perfusion testing. In this prospective trial, 752 patients with suspected angina underwent 4

Cardiovascular Policies, Continued

Magnetic Resonance Imaging (MRI) for Cardiovascular Indications, continued

adenosine stress CMR, adenosine SPECT (radionucleotide) and x-ray coronary angiography testing. By coronary angiography, 39% had significant CAD. The sensitivity (87% vs. 67%) and negative predictive value (91% vs. 79%) differed in favor of CMR vs. SPECT (p < 0.001) whereas specificity (83% vs. 83%) and positive predictive value (77% vs. 71%) were similar. These results argue for broader application of stress CMR in the investigation of CAD. The diagnostic and prognostic utility of myocardial delayed (late) gadolinium enhancement (MDE) as a marker of myocardial scar/fibrosis continues to build. MDE has well-established prognostic value after MI, and to determine reproducibility of with revascularization (viability) in hypertrophic cardiomyopathy, the degree of MDE contributes to the risk of sudden death and may be considered in resolving decision- making for implantation of an implantable defibrillator. Additional emerging applications of MDE include atrial fibrosis and stroke risk midwall fibrosis and cardiomyopathy risk, RV fibrosis, and arrythmogenic RV cardiomyopathy diagnosis, detection of silent MI and prognosis in constrictive pericarditis. Increasingly, CMR is recognized as an ideal one-stop-shop for non-invasive assessment of complex cardiac conditions.

Billing/Coding Information CPT CODES 75557 Cardiac magnetic resonance imaging for morphology and function without contrast material; 75559 ; with stress imaging 75561 Cardiac magnetic resonance imaging for morphology and function without contrast material(s) followed by contrast material(s) and further sequences; 75563 ; with stress imaging 75565 Cardiac magnetic resonance imaging for velocity flow mapping (List separately in addition to code for primary procedure)

HCPCS CODES A9576 Injection, gadoteridol, (ProHance multipack), per ml A9577 Injection, gadobenate dimeglumine (MultiHance), per ml A9578 Injection, gadobenate dimeglumine (MultiHance multipack), per ml A9579 Injection, gadolinium-based magnetic resonance contrast agent, not otherwise specified (NOS), per ml A9581 Injection, gadoxetate disodium, 1 ml Q9953 Injection, iron-based magnetic resonance contrast agent, per ml Q9954 Oral magnetic resonance contrast agent, per 100 ml

Key References 1. ACC/AHA Guidelines for the management of patients with valvular heart disease. (1998). A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Heart Valve Dis. 7(6):672-707. 2. Akinboboye O, Nichols K, Wang Y, Dim UR, Reichek N. (2005). Accuracy of radionuclide ventriculography assessed by magnetic resonance imaging in patients with abnormal left ventricles. J Nucl Cardiol 12.4: 418-27. 3. Allison JD, Flickinger FW, Wright JC, et al. (1993). Measurement of left ventricular mass in hypertrophic cardiomyopathy using MRI: comparison with echocardiography. Magn Reson Imaging 11.3:329-34. 4. Baer FM, Theissen P, Schneider CA, et al. (1999). MRI assessment of myocardial viability: comparison with other imaging techniques. Rays 24.1: 96-108. 5. Baer FM, Voth E, LaRosee K, et al. (1996). Comparison of dobutamine transesophageal echocardiography and dobutamine magnetic resonance imaging for detection of residual myocardial viability. Am J Cardiol 78.4: 415-9. 6. Barclay JL, Egred M, Kruszewski K, et al. (2007). The relationship between transmural extent of infarction on contrast enhanced magnetic resonance imaging and recovery of contractile function in patients with first myocardial infarction treated with thrombolysis. Cardiology 108.4: 217-22. 7. Bellenger NG, Burgess MI, Ray SG, et al. (2000). Comparison of left ventricular ejection fraction and volumes in heart failure by echocardiography, radionuclide ventriculography and cardiovascular magnetic resonance; are they interchangeable? Eur Heart J 21.16: 1387-96. 8. Bernhardt P, Levenson B, Engels T, Strohm O. (2006). Contrast-enhanced adenosine-stress magnetic resonance imaging-- feasibility and practicability of a protocol for detection or exclusion of ischemic heart disease in an outpatient setting. Clin Res Cardiol 95.9: 461-7. 5

Cardiovascular Policies, Continued

Magnetic Resonance Imaging (MRI) for Cardiovascular Indications, continued

9. Bodi V, Sanchis J, Lopez-Lereu MP, et al. (2007). Prognostic value of dipyridamole stress cardiovascular magnetic resonance imaging in patients with known or suspected coronary artery disease. J Am Coll Cardiol 50.12: 1174-9. 10. Cain PA, Ugander M, Palmer J, Carlsson M, et al. (2005). Quantitative polar representation of left ventricular myocardial perfusion, function and viability using SPECT and cardiac magnetic resonance: initial results. Clin Physiol Funct Imaging 25.4: 215-22. 11. Carrozza JP, Baim DS. (2006). Complications of diagnostic cardiac catheterization. UpToDate Online http://www.utdol.com/. 12. Caruthers SD, Lin SJ, Brown P, et al. (2003). Practical value of cardiac magnetic resonance imaging for clinical quantification of aortic valve stenosis: comparison with echocardiography. Circulation 108.18:2236-43. 13. Catalano O, Antonaci S, Moro G, et al. (2005). Contrast-enhanced magnetic resonance imaging assessment of scar size in patients with chronic myocardial infarction. Ital Heart J 6.2. 133-7. 14. Chan J, Jenkins C, Khafagi F, Du L, Marwick TH. (2006). What is the optimal clinical technique for measurement of left ventricular volume after myocardial infarction? A comparative study of 3-dimensional echocardiography, single photon emission computed tomography, and cardiac magnetic resonance imaging. J Am Soc Echocardiogr 19.2:192-201. 15. Chuang ML, Hibberd MG, Salton CJ, et al. (2000). Importance of imaging method over imaging modality in noninvasive determination of left ventricular volumes and ejection fraction: assessment by two- and three-dimensional echocardiography and magnetic resonance imaging. J Am Coll Cardiol 35.2:477-84. 16. Corsi C, Coon P, Goonewardena S, et al. (2006). Quantification of regional left ventricular wall motion from real-time 3- dimensional echocardiography in patients with poor acoustic windows: effects of contrast enhancement tested against cardiac magnetic resonance. J Am Soc Echocardiogr 19.7:886-93. 17. Cury RC, Shash K, Nagurney JT, et al. (2008). Cardiac magnetic resonance with T2-weighted imaging improves detection of patients with acute coronary syndrome in the emergency department. Circulation 118.8:837-44. 18. Debl K, Djavidani B, Seitz J, et al. (2005). Planimetry of aortic valve area in aortic stenosis by magnetic resonance imaging. Invest Radiol 40.10:631-6. 19. Demir H, Tan YZ, Kozdag G, et al. (2007). Comparison of gated SPECT, echocardiography and cardiac magnetic resonance imaging for the assessment of left ventricular ejection fraction and volumes. Ann Saudi Med 27.6:415-20. 20. Devlin AM, Moore NR, Ostman-Smith I. (1999). A comparison of MRI and echocardiography in hypertrophic cardiomyopathy. Br J Radiol 72.855:258-64. 21. Dewilde W, Boersma L, Delanote J, et al. (2008). Symptomatic arrhythmogenic right ventricular dysplasia/cardiomyopathy. A two-centre retrospective study of 15 symptomatic ARVD/C cases and focus on the diagnostic value of MRI in symptomatic ARVD/C patients. Acta Cardiol 63.2:181-9. 22. Djavidani B, Debl K, Lenhart M, et al. (2005). Planimetry of mitral valve stenosis by magnetic resonance imaging. J Am Coll Cardiol 45.12:2048-53. 23. Doesch C, Seeger A, Hoevelborn T, et al. (2008). Adenosine stress cardiac magnetic resonance imaging for the assessment of ischemic heart disease. Clin Res Cardiol. 24. Dornier C, Somsen GA, Ivancevic MK, et al. (2004). Comparison between tagged MRI and standard cine MRI for evaluation of left ventricular ejection fraction. Eur Radiol 14.8):1348-52. 25. Faber TL, Vansant JP, Pettigrew RI, et al. (2001). Evaluation of left ventricular endocardial volumes and ejection fractions computed from gated perfusion SPECT with magnetic resonance imaging: comparison of two methods. J Nucl Cardiol 8.6:645- 51. 26. Fischbach R, Juergens KU, Ozgun M, et al. (2007). Assessment of regional left ventricular function with multidetector-row computed tomography versus magnetic resonance imaging. Eur Radiol 17.4:1009-17. 27. Friedrich MG, Schulz-Menger J, Poetsch T, et al. (2002). Quantification of valvular aortic stenosis by magnetic resonance imaging. Am Heart J 144.2:329-34. 28. Fuisz AR, Pohost GM. (2008). Clinical utility of cardiovascular magnetic resonance imaging.. UpToDate. Available: http://www.utdol.com/online/content/topic.do?topicKey=noninvas/2111&selectedTitle=1~88&source=search_result. Date Accessed: September 10, 2008. 29. Garber AM, Solomon NA. (1999). Cost-effectiveness of alternative test strategies for the diagnosis of coronary artery disease. Ann Intern Med 130.9:719-28. 30. Gersh BJ, Maron BJ, Bonow RO, et al. (2011). 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. Dec 13;124(24):2761-96. 31. Greenwood JP, Maredia N, Younger JF, et al. (2012). Cardiovascular magnetic resonance and single-photon emission computed tomography for diagnosis of coronary heart disease (CE-MARC): a prospective trial. Lancet. Feb 4;379(9814):453- 60. 32. Grothues F, Smith GC, Moon JC, et al. (2002). Comparison of interstudy reproducibility of cardiovascular magnetic resonance with two-dimensional echocardiography in normal subjects and in patients with heart failure or left ventricular hypertrophy. Am J Cardiol 901:29-34. 33. Gunning MG, Anagnostopoulos C, Davies G, et al. (1999). Simultaneous assessment of myocardial viability and function for the detection of hibernating myocardium using ECG-gated 99Tcm-tetrofosmin emission tomography: a comparison with 201Tl emission tomography combined with cine magnetic resonance imaging. Nucl Med Commun 20.3:209-14. 34. Gutberlet M, Frohlich M, Mehl S, et al. (2005). Myocardial viability assessment in patients with highly impaired left ventricular function: comparison of delayed enhancement, dobutamine stress MRI, end-diastolic wall thickness, and TI201-SPECT with functional recovery after revascularization. Eur Radiol 15.5:872-80. 35. Haghi D, Suselbeck T, Fluechter S, et al. (2006). A hybrid approach for quantification of aortic valve stenosis using cardiac magnetic resonance imaging and echocardiography: comparison to right heart catheterization and standard echocardiography. Clin Res Cardiol 95.3:162-7. 36. Hedstrom E, Palmer J, Ugander M, Arheden H. (2004). Myocardial SPECT perfusion defect size compared to infarct size by delayed gadolinium-enhanced magnetic resonance imaging in patients with acute or chronic infarction. Clin Physiol Funct Imaging 24.6:380-6. 37. Hillenbrand HB, Sandstede J, Lipke C, et al. (2003). Detection of myocardial viability in acute infarction using contrast- enhanced (1)H magnetic resonance imaging. Magma 16.3:129-34. 38. Hoffmann R, von Bardeleben S, Kasprzak JD, et al. (2006). Analysis of regional left ventricular function by cineventriculography, cardiac magnetic resonance imaging, and unenhanced and contrast-enhanced echocardiography: a multicenter comparison of methods. J Am Coll Cardiol 47.1:121-8. 6

Cardiovascular Policies, Continued Magnetic Resonance Imaging (MRI) for Cardiovascular Indications, continued

39. Hoffmann R, von Bardeleben S, ten Cate F, et al. (2005). Assessment of systolic left ventricular function: a multi-centre comparison of cineventriculography, cardiac magnetic resonance imaging, unenhanced and contrast-enhanced echocardiography. Eur Heart J 26.6:607-16. 40. Hundley WG, Hillis LD, Hamilton CA, et al. (2000). Assessment of coronary arterial restenosis with phase-contrast magnetic resonance imaging measurements of coronary flow reserve. Circulation 101.20:2375-81. 41. Hundley WG, Li HF, Willard JE, et al. (1995). Magnetic resonance imaging assessment of the severity of mitral regurgitation. Comparison with invasive techniques. Circulation 92.5:1151-8. 42. Ibrahim T, Bulow HP, Hackl T, et al. (2007). Diagnostic value of contrast-enhanced magnetic resonance imaging and single- photon emission computed tomography for detection of myocardial necrosis early after acute myocardial infarction. J Am Coll Cardiol 49.2:208-16. 43. Ioannidis JP, Trikalinos TA, Danias PG. (2002). Electrocardiogram-gated single-photon emission computed tomography versus cardiac magnetic resonance imaging for the assessment of left ventricular volumes and ejection fraction: a meta-analysis. J Am Coll Cardiol 39.12:2059-68. 44. Ishida N, Sakuma H, Motoyasu M, et al. (2003). Noninfarcted myocardium: correlation between dynamic first-pass contrast- enhanced myocardial MR imaging and quantitative coronary angiography. Radiology 229.1 209-16. 45. Iwase M, Kondo T, Hasegawa K, et al. (1997). Three-dimensional echocardiography by semi-automatic border detection in assessment of left ventricular volume and ejection fraction: comparison with magnetic resonance imaging. J Cardiol 30.2:97- 105. 46. Jahnke C, Nagel E, Gebker R, et al. (2007). Prognostic value of cardiac magnetic resonance stress tests: adenosine stress perfusion and dobutamine stress wall motion imaging. Circulation 115.13:1769-76. 47. Jenkins C, Chan J, Bricknell K, et al. (2007). Reproducibility of right ventricular volumes and ejection fraction using real-time three-dimensional echocardiography: comparison with cardiac MRI. Chest 131.6:1844-51. 48. Jerosch-Herold M, Vazquez G, Wang L, et al. (2008). Variability of myocardial blood flow measurements by magnetic resonance imaging in the multi-ethnic study of atherosclerosis. Invest Radiol 43.3:155-61. 49. Kaandorp TA, Lamb HJ, Poldermans D, et al. (2007). Assessment of right ventricular infarction with contrast-enhanced magnetic resonance imaging. Coron Artery Dis 18.1:39-43. 50. Kefer J, Coche E, Legros G, et al. (2005). Head-to-head comparison of three-dimensional navigator-gated magnetic resonance imaging and 16-slice computed tomography to detect coronary artery stenosis in patients. J Am Coll Cardiol 46.1:92-100. 51. Keijer JT, van Rossum AC, van Eenige MJ, et al. (2000) Magnetic resonance imaging of regional myocardial perfusion in patients with single-vessel coronary artery disease: quantitative comparison with (201)Thallium-SPECT and coronary angiography. J Magn Reson Imaging 11.6:607-15. 52. Kim RJ, Albert TS, Wible JH, et al. (2008). Performance of delayed-enhancement magnetic resonance imaging with gadoversetamide contrast for the detection and assessment of myocardial infarction: an international, multicenter, double- blinded, randomized trial. Circulation 117.5:629-37. 53. Kim RJ, Wu E, Rafael A, et al. (2000). The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. N Engl J Med 343.20:1445-53. 54. Kjaer A, Lebech AM, Hesse B, Petersen CL. (2005). Right-sided cardiac function in healthy volunteers measured by first-pass radionuclide ventriculography and gated blood-pool SPECT: comparison with cine MRI. Clin Physiol Funct Imaging 25:344-9. 55. Klein C, Nekolla SG, Bengel FM, et al. (2002). Assessment of myocardial viability with contrast-enhanced magnetic resonance imaging: comparison with positron emission tomography. Circulation 105.2:162-7. 56. Klumpp B, Fenchel M, Hoevelborn T, et al. (2006). Assessment of myocardial viability using delayed enhancement magnetic resonance imaging at 3.0 Tesla. Invest Radiol 41.9:661-7. 57. Kuhl HP, Schreckenberg M, Rulands D, et al. (2004). High-resolution transthoracic real-time three-dimensional echocardiography: quantitation of cardiac volumes and function using semi-automatic border detection and comparison with cardiac magnetic resonance imaging. J Am Coll Cardiol 43.11:2083-90. 58. Leber AW, Knez A, von Ziegler F, et al. (2005). Quantification of obstructive and nonobstructive coronary lesions by 64-slice computed tomography: a comparative study with quantitative coronary angiography and intravascular ultrasound. J Am Coll Cardiol 46.1:147-54. 59. Lee DC, Simonetti OP, Harris KR, et al. (2004). Magnetic resonance versus radionuclide pharmacological stress perfusion imaging for flow-limiting stenoses of varying severity. Circulation 110.1:58-65. 60. Lenstrup M, Kjaergaard J, Petersen CL, et al. (2006). Evaluation of left ventricular mass measured by 3D echocardiography using magnetic resonance imaging as gold standard. Scand J Clin Lab Invest 66.8:647-57. 61. Lidegran M, Odhner L, Jacobsson LA, Greitz D, Lundell B. (2000). Magnetic resonance imaging and echocardiography in assessment of ventricular function in atrially corrected transposition of the great arteries. Scand Cardiovasc J 34.4:384-9. 62. Lipke C, Katoh M, Franke A, et al. (2007). The value of non-contrast harmonic transthoracic echocardiography for the detection of left ventricular thrombi in patients with cardiomyopathy: comparison with contrast-enhanced magnetic resonance imaging. Int J Cardiovasc Imaging 23.4:479-87. 63. Lipke CS, Kuhl HP, Nowak B, et al. (2004). Validation of 4D-MSPECT and QGS for quantification of left ventricular volumes and ejection fraction from gated 99mTc-MIBI SPET: comparison with cardiac magnetic resonance imaging. Eur J Nucl Med Mol Imaging 31.4:482-90. 64. Lissin LW, Li W, Murphy DJ, Jr., et al. (2004). Comparison of transthoracic echocardiography versus cardiovascular magnetic resonance imaging for the assessment of ventricular function in adults after atrial switch procedures for complete transposition of the great arteries. Am J Cardiol 93.5:654-7. 65. Mahnken AH, Koos R, Katoh M, et al. (2005). Assessment of myocardial viability in reperfused acute myocardial infarction using 16-slice computed tomography in comparison to magnetic resonance imaging. J Am Coll Cardiol 45.12:2042-7. 66. Mahrholdt H, Wagner A, Holly TA, et al. (2002). Reproducibility of chronic infarct size measurement by contrast-enhanced magnetic resonance imaging. Circulation 106.18:2322-7. 67. Malm S, Frigstad S, Sagberg E, Steen PA, Skjarpe T. (2006). Real-time simultaneous triplane contrast echocardiography gives rapid, accurate, and reproducible assessment of left ventricular volumes and ejection fraction: a comparison with magnetic resonance imaging. J Am Soc Echocardiogr 19.12:1494-501. 68. McCrohon JA, Lyne JC, Rahman SL, et al. (2005) Adjunctive role of cardiovascular magnetic resonance in the assessment of patients with inferior attenuation on myocardial perfusion SPECT. J Cardiovasc Magn Reson 7.2:377-82. 69. Medical Technology Directory. (2005). Cardiac Magnetic Resonance Angiography. Winifred S. Hayes, Inc. Date Accessed: September 10, 2008. 7

Cardiovascular Policies, Continued

Magnetic Resonance Imaging (MRI) for Cardiovascular Indications, continued

70. Medical Technology Directory. (2004). Magnetic Resonance Imaging for Myocardial Viability.. Winifred S. Hayes, Inc. Date Accessed: September 10, 2008. 71. Medline Plus. (2005) Coronary Heart Disease. Medical Encyclopedia http://www.nlm.nih.gov/medlineplus/ency. 72. Merck Manual Online. Arteriosclerosis. Eds. Beers M, Berkow M. 17 ed. Vol. http://www.merck.com. 73. Misko J, Dziuk M, Skrobowska E, et al. (2006). Co-registration of cardiac MRI and rest gated SPECT in the assessment of myocardial perfusion, function and viability. J Cardiovasc Magn Reson 8.2):389-97. 74. Muehling O, Jerosch-Herold M, Cyran C, et al. (2007). Assessment of collateralized myocardium with Cardiac Magnetic Resonance (CMR): transmural extent of infarction but not angiographic collateral vessel filling determines regional function and perfusion in collateral-dependent myocardium. Int J Cardiol 120.1:38-44. 75. Muellerleile K, Barmeyer A, Groth M, Lund GK. (2008). Assessment of myocardial viability in ischemic heart disease by cardiac magnetic resonance imaging. Minerva Cardioangiol 56.2:237-49. 76. Murtagh J, Foerster V, Warburton R, et al. (2006). Clinical and cost effectiveness of CT and MRI for selected clinical disorders: results of two systematic reviews. Canadian Agency for Drugs and Technologies in Health (CADTH). Date Accessed: October 1, 2008. 77. Nagel E, Bornstedt A, Hug J, et al. (1999). Noninvasive determination of coronary blood flow velocity with magneticresonance imaging: comparison of breath-hold and navigator techniques with intravascular ultrasound. Magn Reson Med;41(3):544-9. 78. Nagel E, Fleck E. (1999). Functional MRI in ischemic heart disease based on detection of contraction abnormalities. J Magn Reson Imaging;10(3):411-417. 79. Nagel E, Klein C, Paetsch I, et al. (2003). Magnetic resonance perfusion measurements for the noninvasive detection of coronary artery disease. Circulation 108.4:432-7. 80. Nagel E, Lehmkuhl HB, Bocksch W, et al. (1999). Noninvasive diagnosis of ischemia-induced wall motion abnormalities with the use of high-dose dobutamine stress MRI: comparison with dobutamine stress echocardiography. Circulation 99.6:763-70. 81. Nagel E, Lehmkuhl HB, Bocksch W, et al. (1999). Noninvasive diagnosis of ischemia-induced wall motion abnormalities with the use of high-dose dobutamine stress MRI: comparison with dobutamine stress echocardiography. Circulation.99(6):763-70. 82. Nandalur KR, Dwamena BA, Choudhri AF, Nandalur MR, Carlos RC. (2007). Diagnostic performance of stress cardiac magnetic resonance imaging in the detection of coronary artery disease: a meta-analysis. J Am Coll Cardiol 50.14):1343-53. 83. Nazarian S, Roguin A, Zviman MM, et al. (2006). Clinical utility and safety of a protocol for noncardiac and cardiac magnetic resonance imaging of patients with permanent pacemakers and implantable-cardioverter defibrillators at 1.5 tesla. Circulation 114.12:1277-84. 84. Ontario Ministry of Health and Long-Term Care. (2003). Functional cardiac magnetic resonance imaging in the assessment of myocardial viability and perfusion.. Medical Advisory Secretariat. Available: http://www.health.gov.on.ca/english/providers/program/ohtac/tech/reviews/pdf/rev_cardmri_110103.pdf. Date Accessed: September 15, 2008. 85. Paetsch I, Jahnke C, Ferrari VA, et al. (2006). Determination of interobserver variability for identifying inducible left ventricular wall motion abnormalities during dobutamine stress magnetic resonance imaging. Eur Heart J 27.12:1459-64. 86. Pereira RS, Wisenberg G, Prato FS, Yvorchuk K. (2000). Clinical assessment of myocardial viability using MRI during a constant infusion of Gd-DTPA. Magma 11.3:104-13. 87. Pilz G, Bernhardt P, Klos M, Ali E, Wild M, Hofling B. (2006). Clinical implication of adenosine-stress cardiac magnetic resonance imaging as potential gatekeeper prior to invasive examination in patients with AHA/ACC class II indication for coronary angiography. Clin Res Cardiol 95.10:531-8. 88. Pilz G, Jeske A, Klos M, et al. (2008). Prognostic value of normal adenosine-stress cardiac magnetic resonance imaging. Am J Cardiol 101.10:1408-12. 89. Pilz G, Klos M, Ali E, Hoefling B, Scheck R, Bernhardt P. (2008). Angiographic correlations of patients with small vessel disease diagnosed by adenosine-stress cardiac magnetic resonance imaging. J Cardiovasc Magn Reson 10.1:8. 90. Plumhans C, Muhlenbruch G, Rapaee A, et al. (2008). Assessment of global right ventricular function on 64-MDCT compared with MRI. AJR Am J Roentgenol 190.5:1358-61. 91. Pohost GM, et al. (1984). Nuclear Magnetic Resonance - Potential applications in clinical cardiology. JAMA. 251:1304-1309. 92. Qi X, Cogar B, Hsiung MC, et al. (2007). Live/real time three-dimensional transthoracic echocardiographic assessment of left ventricular volumes, ejection fraction, and mass compared with magnetic resonance imaging. Echocardiography 24.2:166-73. 93. Radiology Info. Cardiac MRI. (2007). Radiological Society of North America, Inc. Available: http://www.radiologyinfo.org/en/info.cfm?PG=cardiacmr&bhcp=1. Date Accessed: September 10, 2008. 94. RadiologyInfo. (2006). Available: http://www.radiologyinfo.org/content/ct-angiography.htm. Date Accessed: January 25, 2006. 95. Reddy DB, Jena A, Venugopal P. (1994). Magnetic resonance imaging (MRI) in evaluation of left atrial masses: an in vitro and in vivo study. J Cardiovasc Surg (Torino) 35.4:289-94. 96. Sato A, Nozato T, Hikita H, et al. (2012). Prognostic value of myocardial contrast delayed enhancement with 64-slice multidetector computed tomography after acute myocardial infarction. J Am Coll Cardiol. Feb 21;59(8):730-8. 97. Schaefer WM, Lipke CS, Nowak B, et al. (2003). Validation of an evaluation routine for left ventricular volumes, ejection fraction and wall motion from gated cardiac FDG PET: a comparison with cardiac magnetic resonance imaging. Eur J Nucl Med Mol Imaging 30.4:545-53. 98. Schaefer WM, Lipke CS, Nowak B, et al. (2004). Validation of QGS and 4D-MSPECT for quantification of left ventricular volumes and ejection fraction from gated 18F-FDG PET: comparison with cardiac MRI. J Nucl Med 45.1:74-9. 99. Schmidt M, Voth E, Schneider CA, et al. (2004). F-18-FDG uptake is a reliable predictory of functional recovery of akinetic but viable infarct regions as defined by magnetic resonance imaging before and after revascularization. Magn Reson Imaging 22.2:229-36. 100. Schwitter J, Wacker CM, van Rossum AC, et al. (2008). MR-IMPACT: comparison of perfusion-cardiac magnetic resonance with single-photon emission computed tomography for the detection of coronary artery disease in a multicentre, multivendor, randomized trial. Eur Heart J 29.4:480-9. 101. Selvanayagam JB, Kardos A, Francis JM, et al. (2004). Value of delayed-enhancement cardiovascular magnetic resonance imaging in predicting myocardial viability after surgical revascularization. Circulation. 110.12:1535-41. 102. Sen-Chowdhry S, Prasad SK, Syrris P, et al. (2006). Cardiovascular magnetic resonance in arrhythmogenic right ventricular cardiomyopathy revisited: comparison with task force criteria and genotype. J Am Coll Cardiol. 48.10:2132-40. 103. Setser RM, Fischer SE, Lorenz CH. (2000). Quantification of left ventricular function with magnetic resonance images acquired in real time. J Magn Reson Imaging 12.3:430-8.

Cardiovascular Policies, Continued

Magnetic Resonance Imaging (MRI) for Cardiovascular Indications, continued

104. Sievers B, Kirchberg S, Franken U, et al. (2005). Visual estimation versus quantitative assessment of left ventricular ejection fraction: a comparison by cardiovascular magnetic resonance imaging. Am Heart J. 150.4:737-42. 105. Slomka PJ, Fieno D, Thomson L, et al. (2005). Automatic detection and size quantification of infarcts by myocardial perfusion SPECT: clinical validation by delayed-enhancement MRI. J Nucl Med. 46.5:728-35. 106. Soriano BD, Hoch M, Ithuralde A, et al. (2008). Matrix-array 3-dimensional echocardiographic assessment of volumes, mass, and ejection fraction in young pediatric patients with a functional single ventricle: a comparison study with cardiac magnetic resonance. Circulation. 117.14:1842-8. 107. Steen H, Nasir K, Flynn E, et al. (2007). Is magnetic resonance imaging the 'reference standard' for cardiac functional assessment? Factors influencing measurement of left ventricular mass and volumes. Clin Res Cardiol. 96.10:743-51. 108. Steiner RE. (1986). Present and future clinical position of magnetic resonance imaging. Magn Reson Med. 487. 109. Sugeng L, Mor-Avi V, Weinert L, et al. (2006). Quantitative assessment of left ventricular size and function: side-by-side comparison of real-time three-dimensional echocardiography and computed tomography with magnetic resonance reference. Circulation. 114.7:654-61. 110. Task Force of the European Society of Cardiology. (1998). The clinical role of magnetic resonance in cardiovascular disease. Association of European Paediatric Cardiologists. Eur Heart J.19(1):19-39. 111. Thorley PJ, Plein S, Bloomer TN, Ridgway JP, Sivananthan UM. (2003). Comparison of 99mTc tetrofosmin gated SPECT measurements of left ventricular volumes and ejection fraction with MRI over a wide range of values. Nucl Med Commun. 24.7:763-9. 112. Tse HF, Cheung BM, Ng W, et al. (2003). Regression of left ventricular hypertrophy after treatment of hypertension: comparison of directed M-echocardiography with magnetic resonance imaging in quantification of serial mass changes. J Card Fail. 9.2:122-7. 113. van der Vleuten PA, Willems TP, Gotte MJ, et al. (2006). Quantification of global left ventricular function: comparison of multidetector computed tomography and magnetic resonance imaging. A meta-analysis and review of the current literature. Acta Radiol. 47.10:1049-57. 114. Wilson W, Culleton M. (2005). Overview of the risk factors for cardiovascular disease. UpToDate Online http://www.utdol.com. 115. Yan AT, Shayne AJ, Brown KA, et al. (2006). Characterization of the peri-infarct zone by contrast-enhanced cardiac magnetic resonance imaging is a powerful predictor of post-myocardial infarction mortality. Circulation. 114.1:32-9. 116. Yang PC, Nguyen P, Shimakawa A, et al. (2004). Spiral magnetic resonance coronary angiography--direct comparison of 1.5 Tesla vs. 3 Tesla. J Cardiovasc Magn Reson. 6.4:877-84. 117. Zerhouni EA. (1994). Magnetic Resonance Imaging of Acquired Heart Disease. In: Haaga JR, Sartoris DJ, Lanzieri DF, et al, eds. Computed Tomography and Magnetic Resonance Imaging of the Whole Body. Vol 1. St. Louis, MO: Mosby:788-818. 118. Tezuka, D., et al. (2015). "Clinical characteristics of definite or suspected isolated cardiac sarcoidosis: application of cardiac magnetic resonance imaging and 18F-Fluoro-2-deoxyglucose positron-emission tomography/computerized tomography." J Card Fail 21(4): 313-322. 119. Zipse, M. M. and W. H. Sauer (2014). "Cardiac sarcoidosis." Curr Cardiol Rep 16(8): 514.

Cardiovascular Policies, Continued

MEDICAL POLICY

NON-INVASIVE FRACTIONAL FLOW RESERVE USING CT ANGIOGRAPHY

Policy # 617 Implementation Date: 8/1/17 Review Dates: 7/25/18, 6/13/19, 6/18/20 Revision Dates:

Description Invasively measured fractional flow reserve (FFR) evaluates the severity of ischemia caused by coronary artery obstructions and can predict when revascularization is beneficial. FFR is not a diagnostic test for ischemic heart disease, but evaluates ischemia resulting from a stenosis. It is now possible to obtain FFR noninvasively, using computed tomography angiography (CTA), also called FFR-CT (HeartFlow software termed FFRCT; Siemens cFFR) using routinely collected CTA imaging data. The process involves constructing a digital model of coronary anatomy and calculating FFR across the entire vascular tree using computational fluid dynamics. FFR-CT can also be used for “virtual stenting” to simulate how stent placement would be predicted to improve vessel flow. Only the HeartFlow FFR-CT software has been cleared by the U.S. Food and Drug Administration. Imaging analyses require transmitting data to a central location, taking 1 to 3 days to complete. Other prototype software is workstation-based with onsite analyses. FFR-CT cannot be calculated when images lack sufficient quality (11% to 13% in recent studies); for example, in obese individuals (e.g., body mass index, > 35 kg/m2).

Commercial Plan Policy

SelectHealth does NOT cover noninvasive fractional flow reserve testing using computed tomography angiography (FFR-CT) preceding invasive coronary angiography in patients with suspected stable ischemic heart disease; it is considered investigational.

SelectHealth Advantage (Medicare/CMS) (Preauthorization Required)

SelectHealth Community Care (Medicaid/CHIP) (Preauthorization Required)

Cardiovascular Policies, Continued

Non-Invasive Fractional Flow Reserve Using CT Angiography, continued

coverage, please visit their website http://health.utah.gov/medicaid/manuals/directory.php or the Utah Medicaid code Look-Up tool

Summary of Medical Information For individuals who have suspected stable ischemic heart disease and planned invasive coronary angiography (ICA) who receive fractional flow reserve using computed tomography angiography (FFR- CT), the evidence includes studies on test technical performance, meta-analyses of diagnostic accuracy, and 2 studies of patient outcomes [one non-randomized study and one retrospective cohort study (Phase III), with no post-adoption use/safety studies (Phase IV) identified]. Relevant outcomes are test accuracy and validity, morbid events, quality of life, resource utilization, and treatment-related mortality and morbidity. Randomized controlled trials and observational studies have demonstrated that FFR-guided revascularization can improve cardiovascular outcomes, reduce revascularizations, and decrease costs. For example, the Fractional Flow Reserve versus Angiography for Multivessel Evaluation (FAME) trial randomized 1,005 patients with multivessel disease and planned percutaneous coronary intervention (PCI). At 1 year, compared with PCI guided by angiography alone, FFR-guided PCI reduced the number of stents placed by approximately 30%, followed by lower rates (13.2% vs 18.3%) of major cardiovascular adverse events (myocardial infarction, death, repeat revascularization) and at a lower cost. The clinical benefit persisted through 2 years, although by 5 years, event rates were similar between groups. European guidelines for stable coronary artery disease recommend FFR be used: “… to identify hemodynamically relevant coronary lesion(s) when evidence of ischemia is not available” (class 1A), and “[r]evascularization of stenoses with FFR < 0.80 is recommended in patients with angina symptoms or a positive stress test.” Guidelines also recommend using: “FFR to identify hemodynamically relevant coronary lesion(s) in stable patients when evidence of ischemia is not available” (class 1A recommendation). U.S guidelines state that an FFR of 0.80 or less provides level 1A evidence for revascularization for significant stenosis amenable to revascularization and unacceptable angina despite guideline-directed medical therapy. FFR-CT may offer an effective means to reduce unnecessary ICA with a rationale for a potential role in decision making. Test performance characteristics are consistent with a negative test reducing the probability of significant obstructive disease (e.g., vessels with FFR < 0.80) and potentially altering a decision to perform ICA. However, outcome data are limited and obtained entirely from non-randomized studies with comparisons only to usual care. Limitations and uncertainties in body of evidence examining FFR-CT prevent conclusions concerning the net health outcome. The evidence is insufficient to determine the effects of the technology on health outcomes.

Billing/Coding Information CPT CODES 93799 Unlisted cardiovascular service or procedure Effective 1/1/18 0501T Noninvasive estimated coronary fractional flow reserve (FFR) derived from coronary computed tomography angiography data using computation fluid dynamics physiologic simulation software analysis of functional data to assess the severity of coronary artery disease; data preparation and transmission, analysis of fluid dynamics and simulated maximal coronary hyperemia, generation of estimated FFR model, with anatomical data review in comparison with estimated FFR model to reconcile discordant data, interpretation and report 0502T data preparation and transmission 0503T analysis of fluid dynamics and simulated maximal coronary hyperemia, and generation of estimated FFR model 0504T anatomical data review in comparison with estimated FFR model to reconcile discordant data, interpretation and report (Report 0501T, 0502T, 0503T, 0504T one time per coronary CT angiogram) (Do not report 0501T in conjunction with 0502T, 0503T, 0504T)

Cardiovascular Policies, Continued

Non-Invasive Fractional Flow Reserve Using CT Angiography, continued

HCPCS CODES No specific codes identified

Key References 1. Coenen A, Lubbers MM, Kurata A, et al. Fractional flow reserve computed from noninvasive CT angiography data: diagnostic performance of an on-site clinician-operated computational fluid dynamics algorithm. Radiology. Mar 2015;274(3):674-683. PMID 25322342 2. Danad I, Szymonifka J, Twisk JW, et al. Diagnostic performance of cardiac imaging methods to diagnose ischaemia-causing coronary artery disease when directly compared with fractional flow reserve as a reference standard: a meta-analysis. Eur Heart J. May 2, 2016. PMID 27141095 3. de Bruyne B, Bartunek J, Sys SU, et al. Simultaneous coronary pressure and flow velocity measurements in humans. Feasibility, reproducibility, and hemodynamic dependence of coronary flow velocity reserve, hyperemic flow versus pressure slope index, and fractional flow reserve. Circulation. Oct 15, 1996;94(8):1842-1849. PMID 8873658 4. De Geer J, Sandstedt M, Bjorkholm A, et al. Software-based on-site estimation of fractional flow reserve using standard coronary CT angiography data. Acta Radiol. Oct 2016;57(10):1186-1192. PMID 26691914 5. Douglas PS, De Bruyne B, Pontone G, et al. 1-year outcomes of FFRCT-guided care in patients with suspected coronary disease: the PLATFORM Study. J Am Coll Cardiol. Aug 2, 2016;68(5):435-445. PMID 27470449 6. Douglas PS, Pontone G, Hlatky MA, et al. Clinical outcomes of fractional flow reserve by computed tomographic angiography- guided diagnostic strategies vs. usual care in patients with suspected coronary artery disease: the prospective longitudinal trial of FFR(CT): outcome and resource impacts study. Eur Heart J. Dec 14, 2015;36(47):3359-3367. PMID 26330417 7. Fearon WF, Shilane D, Pijls NH, et al. Cost-effectiveness of percutaneous coronary intervention in patients with stable coronary artery disease and abnormal fractional flow reserve. Circulation. Sep 17, 2013;128(12):1335-1340. PMID 23946263 8. Fihn SD, Gardin JM, Abrams J, et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. Dec 18, 2012;60(24): e44-e164. PMID 23182125 9. Gaur S, Bezerra HG, Lassen JF, et al. Fractional flow reserve derived from coronary CT angiography: variation of repeated analyses. J Cardiovasc Comput Tomogr. Jul-Aug 2014;8(4):307-314. PMID 25151923 10. HeartFlow. DEN130045, FFRct V. 1.4. 2013; http://www.accessdata.fda.gov/cdrh_docs/reviews/DEN130045.pdf. Accessed September 11, 2016. 11. Hlatky MA, De Bruyne B, Pontone G, et al. Quality-of-life and economic outcomes of assessing fractional flow reserve with computed tomography angiography: PLATFORM. J Am Coll Cardiol. Dec 1, 2015;66(21):2315-2323. PMID 26475205 12. Hulten E, Di Carli MF. FFRCT: Solid PLATFORM or thin ice? J Am Coll Cardiol. Dec 1 2015;66(21):2324-2328. PMID 26475206 13. Johnson NP, Johnson DT, Kirkeeide RL, et al. Repeatability of fractional flow reserve despite variations in systemic and coronary hemodynamics. JACC Cardiovasc Interv. Jul 2015;8(8):1018-1027. PMID 26205441 14. Koo BK, Erglis A, Doh JH, et al. Diagnosis of ischemia-causing coronary stenoses by noninvasive fractional flow reserve computed from coronary computed tomographic angiograms. Results from the prospective multicenter DISCOVER-FLOW (Diagnosis of Ischemia-Causing Stenoses Obtained Via Noninvasive Fractional Flow Reserve) study. J Am Coll Cardiol. Nov 1, 2011;58(19):1989-1997. PMID 22032711 15. Macaskill P, Gatsonis C, Deeks JJ, et al. Chapter 10: Analysing and Presenting Results. In: Deeks JJ, Bossuyt PM, Gatsonis C (editors). Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy Version 1.0. The Cochrane Collaboration, 2010. 2010; http://srdta.cochrane.org/. Accessed September 2016. 16. Min JK, Berman DS, Budoff MJ, et al. Rationale and design of the DeFACTO (Determination of Fractional Flow Reserve by Anatomic Computed Tomographic AngiOgraphy) study. J Cardiovasc Comput Tomogr. Sep-Oct 2011;5(5):301-309. PMID 21930103 17. Min JK, Koo BK, Erglis A, et al. Effect of image quality on diagnostic accuracy of noninvasive fractional flow reserve: results from the prospective multicenter international DISCOVER-FLOW study. J Cardiovasc Comput Tomogr. May-Jun 2012;6(3):191-199. PMID 22682261 18. Min JK, Leipsic J, Pencina MJ, et al. Diagnostic accuracy of fractional flow reserve from anatomic CT angiography. JAMA. Sep 26, 2012;308(12):1237-1245. PMID 22922562 19. Nakazato R, Park HB, Berman DS, et al. Noninvasive fractional flow reserve derived from computed tomography angiography for coronary lesions of intermediate stenosis severity: results from the DeFACTO study. Circ Cardiovasc Imaging. Nov 2013;6(6):881-889. PMID 24081777 20. Nørgaard BL, Hjort J, Gaur S, et al. Clinical Use of Coronary CTA-Derived FFR for Decision-Making in Stable CAD. JACC Cardiovasc Imaging. Apr 7 2016. PMID 27085447 21. Nørgaard BL, Leipsic J, Gaur S, et al. Diagnostic performance of noninvasive fractional flow reserve derived from coronary computed tomography angiography in suspected coronary artery disease: the NXT trial (Analysis of Coronary Blood Flow Using CT Angiography: Next Steps). J Am Coll Cardiol. Apr 1, 2014;63(12):1145-1155. PMID 24486266 22. Nørgaard BL, Gaur S, Leipsic J, et al. Influence of coronary calcification on the diagnostic performance of CT angiography derived FFR in coronary artery disease: a substudy of the NXT Trial. JACC Cardiovasc Imaging. Sep 2015;8(9):1045-1055. PMID 26298072 23. Patel MR, Peterson ED, Dai D, et al. Low diagnostic yield of elective coronary angiography. N Engl J Med. Mar 11, 2010;362(10):886-895. PMID 20220183 24. Reitsma JB, Glas AS, Rutjes AW, et al. Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews. J Clin Epidemiol. Oct 2005;58(10):982-990. PMID 16168343 25. Renker M, Schoepf UJ, Wang R, et al. Comparison of diagnostic value of a novel noninvasive coronary computed tomography angiography method versus standard coronary angiography for assessing fractional flow reserve. Am J Cardiol. Nov 1, 2014;114(9):1303-1308. PMID 25205628 26. Task Force Members, Montalescot G, Sechtem U, et al. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. Oct 2013;34(38):2949-3003. PMID 23996286 3

Cardiovascular Policies, Continued

Non-Invasive Fractional Flow Reserve Using CT Angiography, continued

27. Thompson AG, Raju R, Blanke P, et al. Diagnostic accuracy and discrimination of ischemia by fractional flow reserve CT using a clinical use rule: results from the Determination of Fractional Flow Reserve by Anatomic Computed Tomographic Angiography study. J Cardiovasc Comput Tomogr. Mar-Apr 2015;9(2):120-128. PMID 25819194 28. Tonino PA, De Bruyne B, Pijls NH, et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med. Jan 15, 2009;360(3):213-224. PMID 19144937 29. Whiting PF, Rutjes AW, Westwood ME, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. Oct 18, 2011;155(8):529-536. PMID 22007046 30. Wu W, Pan DR, Foin N, et al. Noninvasive fractional flow reserve derived from coronary computed tomography angiography for identification of ischemic lesions: a systematic review and meta-analysis. Sci Rep. 2016; 6:29409. PMID 27377422

Cardiovascular Policies, Continued

MEDICAL POLICY

NUCLEAR MAGNETIC RESONANCE (NMR) OF LDL PARTICLE NUMBERS TO ASSESS CARDIOVASCULAR RISK

Policy # 498 Implementation Date: 3/17/12 Review Dates: 4/25/13, 6/19/14, 6/11/15, 6/16/16, 6/15/17, 7/25/18, 6/13/19, 6/18/20 Revision Dates:

Description Cardiovascular disease (CVD) is the leading cause of morbidity and mortality for both men and women in the US. Atherosclerosis is an important risk factor in the development of CVD. Multiple factors contribute to atherosclerosis, including endothelial dysfunction, dyslipidemia, inflammatory and immunologic factors, plaque rupture, and smoking. Advanced obstructive CVD can exist with minimal or no symptoms and can progress rapidly. The first clinical manifestation is often catastrophic: heart attack, stroke, unstable angina, or sudden cardiac death. Many tests are performed to assess CV risk. These include blood tests such as hsCRP, lipid profile measurement, Apolipoprotein B assessment, PLAC testing, vertical autoprofiling (VAP), and others. Imaging tests such as intima-media thickness, CT calcium scoring, CT coronary angiography, and others are also used to screen for CV risk. Perhaps the most relied upon test or metric for determining CVD risk is the Framingham risk score. The first Framingham risk score (1998) incorporated age, gender, LDL- cholesterol, total cholesterol, HDL-cholesterol, blood pressure (including whether the patient is treated or not), diabetes, and smoking to derive an estimated risk of developing CHD (MI, coronary death, and angina) within 10 years. A validation study found that the Framingham CHD predictor performed well for prediction of CHD events in black and white women and men. Nuclear magnetic resonance (NMR) has been proposed as a means of measuring LDL and HDL cholesterol levels and particle numbers in patient plasma samples. The sample is subjected to a short pulse of radio energy within a strong magnetic field. The resonant sound that is broadcast by the lipoproteins in the sample is recorded and analyzed to determine the number and size of lipoproteins present. Each type of lipoprotein broadcasts a signal that is characteristically distinct from the others. A computer algorithm separates the signals into groups and then quantifies the number of lipoprotein particles in that group.

Commercial Plan Policy

SelectHealth does NOT cover nuclear magnetic resonance (NMR) or similar tests to assess low density lipoprotein particle (LDL-P) numbers. Patient selection criteria and benefits have not been established. The currently available tests for CV risk assessment provide accurate data and suggest a clinical benefit. This meets the plan’s definition of investigational/experimental and is not medically necessary.

SelectHealth Advantage (Medicare/CMS) (No Preauthorization Required but criteria may apply if appropriate)

Coverage is determined by the Centers for Medicare and Medicaid Services (CMS); if a coverage determination has not been adopted by CMS, and InterQual criteria

Cardiovascular Policies, Continued

Nuclear Magnetic Resonance (NMR) of LDL Particle Numbers to Assess Cardiovascular Risk, continued

SelectHealth Community Care (Medicaid/CHIP)

Summary of Medical Information A Medical Technology Assessment performed in December 2011 identified 2 systematic reviews and 9 primary articles meeting criteria for nuclear magnetic resonance (NMR) testing. It is notable that most of the primary published literature was from Dr. Otvos, the Chief Science Officer for LipoScience. Selecting the correct patient who is at risk for CVD and treating them to target levels of cholesterol is the goal of lipoprotein subfractions and particle number assessment. Most articles support a select number of patients, especially those with dysmetabolic syndrome; there is discordance between LDL cholesterol (LDL-C) and LDL particles (LDL-P) levels. In these individuals, LDL-P improves prediction to clinical outcomes. This statement is highlighted in the Multi-Ethnic Study of Atherosclerosis (MESA). This NIH funded study included 5,598 participants without cardiovascular disease. The study was conducted for 5.5 years and tracked intima media thickness (IMT) and cardiovascular events. In both areas, LDL-P predicted events with better sensitivity. The article by Otvos et al., a retrospective study of the VA-HIT study, attempted to explain the improved clinical outcomes despite minimal changes in LDL-C in a secondary prevention study population with low LDL-C levels. This 394-patient group was randomized to gemfibrizol or a placebo. The study group had both low HDL concentration and low LDL-C. NMR was used to determine LDL-P. This study demonstrated improved outcomes in cardiovascular events were more likely in patients with reduced LDL-P. This is the only article demonstrating improvement in health outcomes after treatment and correlated to LDL-P and not LDL-C. Further, clinical information concerning the utility of NMR testing for LDL-P and other lipoprotein subunits is contained in guidelines from review groups. Most studies support that either Apolipoprotein B (apoB/apoB-100) or LDL-P can be utilized to more accurately reflect cardiovascular risk, especially in patients who have metabolic syndrome, diabetes, abdominal obesity, hypertriglyceridemia, or low HDL-C. This applies to both apoB and LDL-P. The consensus panel noted apoB may not be as robust a predictor of risk compared with non-HDL-C as LDL-C., and suggested it appears that: “… more studies are needed to better define risk in discordant patients whose apoB or LDL-P levels is higher or lower than would be predicted based on measurement of lipoprotein cholesterol concentration (LDL-C). ApoB treatment levels have also not been established. Because of this data experts state that until: “… the appropriate large scale clinical outcomes trials are completed, each clinician must use his or her clinical judgment as to whether further lowering of LDL burden is warranted in a particular patient.” These same concepts apply to LDL-P. Cost effectiveness of either test has not been established. There are also questions that address which test, apoB or LDL-P, may assess or manage risk the best. All concepts for treatment goals, either for apoB or LDL-P, are unknown. Some experts recommend using the same criteria as LDL-C, which is to reach 20th percentile for very high-risk patients, and 50th percentile for moderate-risk patients. In summary, despite improved prediction of risk of cardiovascular disease using apoB or LDL-P, the optimal patient who should receive testing, or what should be the goal of treatment, have not been established, calling into question to the true clinical utility of this testing.

Cardiovascular Policies, Continued

Nuclear Magnetic Resonance (NMR) of LDL Particle Numbers to Assess Cardiovascular Risk, continued

Billing/Coding Information Not covered: Investigational/Experimental/Unproven for this indication CPT CODES 83704 Lipoprotein, blood; quantitation of lipoprotein particle numbers and lipoprotein particle subclasses (e.g., by nuclear magnetic resonance spectroscopy)

HCPCS CODES No specific codes identified

Key References 1. Ala-Korpela, M, Lankinen, N, Salminen, A, et al. (2007). The inherent accuracy of 1H NMR spectroscopy to quantify plasma lipoproteins is subclass dependent. Atherosclerosis. 190. 2:352-8. 2. Arsenault, BJ, Despres, JP, Stroes, ES, et al. (2010). Lipid assessment, metabolic syndrome and coronary heart disease risk. Eur J Clin Invest. 40. 12:1081-93. 3. Ballantyne, CM, Grundy, SM, Oberman, A, et al. (2000). Hyperlipidemia: diagnostic and therapeutic perspectives. J Clin Endocrinol Metab. 85. 6:2089-112. 4. Bastuji-Garin, S, Deverly, A, Moyse, D, et al. (2002). The Framingham prediction rule is not valid in a European population of treated hypertensive patients. J Hypertens. 20. 10:1973-80. 5. Besse, JL, Colombier, JA, Asencio, J, et al. (2010). Total ankle arthroplasty in France. Orthop Traumatol Surg Res. 96. 3:291- 303. 6. Blake, GJ, Otvos, JD, Rifai, N, et al. (2002). Low-density lipoprotein particle concentration and size as determined by nuclear magnetic resonance spectroscopy as predictors of cardiovascular disease in women. Circulation. 106. 15:1930-7. 7. Bonnefont-Rousselot, D, Bittar, R, Atassi, M, et al. (2008). [Contribution of NMR to the assessment of dyslipidemia-related cardiovascular risk]. Ann Pharm Fr. 66. 3:123-8. 8. Brindle, P, Emberson, J, Lampe, F, et al. (2003). Predictive accuracy of the Framingham coronary risk score in British men: prospective cohort study. BMJ. 327. 7426:1267. 9. Brunzell, JD, Davidson, M, Furberg, CD, et al. (2008). Lipoprotein management in patients with cardiometabolic risk: consensus conference report from the American Diabetes Association and the American College of Cardiology Foundation. J Am Coll Cardiol. 51. 15:1512-24. 10. Contois, JH, McConnell, JP, Sethi, AA, et al. (2009). Apolipoprotein B and cardiovascular disease risk: position statement from the AACC Lipoproteins and Vascular Diseases Division Working Group on Best Practices. Clin Chem. 55. 3:407-19. 11. Courville, XF, Hecht, PJ, Tosteson, AN. (2011). Is total ankle arthroplasty a cost-effective alternative to ankle fusion? Clin Orthop Relat Res. 469. 6:1721-7. 12. Cromwell, WC, Otvos, JD, Keyes, MJ, et al. (2007). LDL Particle Number and Risk of Future Cardiovascular Disease in the Framingham Offspring Study - Implications for LDL Management. J Clin Lipidol. 1. 6:583-92. 13. D'Agostino, RB, Sr., Grundy, S, Sullivan, LM, et al. (2001). Validation of the Framingham coronary heart disease prediction scores: results of a multiple ethnic groups investigation. JAMA. 286. 2:180-7. 14. Davidson, MH, Ballantyne, CM, Jacobson, TA, et al. (2011). Clinical utility of inflammatory markers and advanced lipoprotein testing: Advice from an expert panel of lipid specialists. J Clin Lipidol. 5. 5:338-67. 15. Ford, ES, Giles, WH, Mokdad, AH. (2004). The distribution of 10-Year risk for coronary heart disease among US adults: findings from the National Health and Nutrition Examination Survey III. J Am Coll Cardiol. 43. 10:1791-6. 16. Freedman, DS, Otvos, JD, Jeyarajah, EJ, et al. (2004). Sex and age differences in lipoprotein subclasses measured by nuclear magnetic resonance spectroscopy: the Framingham Study. Clin Chem. 50. 7:1189-200. 17. Gougoulias, N, Khanna, A, Maffulli, N. (2010). How successful are current ankle replacements?: a systematic review of the literature. Clin Orthop Relat Res. 468. 1:199-208. 18. Grundy, SM, Cleeman, JI, Merz, CN, et al. (2004). Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Arterioscler Thromb Vasc Biol. 24. 8: e149-61. 19. Helfand, M, Carson, S. (2008). 20. LipoScience. (2011) Cardiovascular Disease. LipoScience. Last Update: 2010. Available: http://www.liposcience.com/cardiovasculardisease/. Date Accessed: November 22, 2011. 21. Liu, J, Hong, Y, D'Agostino, RB, Sr., et al. (2004). Predictive value for the Chinese population of the Framingham CHD risk assessment tool compared with the Chinese Multi-Provincial Cohort Study. JAMA. 291. 21:2591-9. 22. Naal, FD, Impellizzeri, FM, Loibl, M, et al. (2009). Habitual physical activity and sports participation after total ankle arthroplasty. Am J Sports Med. 37. 1:95-102. 23. National Cholesterol Education Program (NCEP). (2002). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 106. 25:3143-421. 24. Otvos, JD, Mora, S, Shalaurova, I, et al. (2011). Clinical implications of discordance between low-density lipoprotein cholesterol and particle number. J Clin Lipidol. 5. 2:105-13. 25. Rakel, RE. (2011) Textbook of Family Medicine. Elseiver Saunders. Last Update: Available: http://www.mdconsult.com/books/page.do?eid=4-u1.0-B978-1-4377-1160-8.10027-2--s0015&isbn=978-1-4377-1160- 8&uniqId=303413701-4#4-u1.0-B978-1-4377-1160-8.10027-2--s0015. Date Accessed: November 21, 2011. 26. Ridker, PM, Danielson, E, Fonseca, FA, et al. (2008). Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 359. 21:2195-207. 27. Rosenson, RS. (2011) HDL metabolism and approach to the patient with abnormal HDL-cholesterol levels. Up to Date. Last Update: June 3, 2011. Available: http://www.uptodate.com/contents/hdl-metabolism-and-approach-to-the-patient-with- abnormal-hdl-cholesterol-levels?source=search_result&search=nmr+lipid&selectedTitle=1~150. Date Accessed: November 22, 2011. 3

Cardiovascular Policies, Continued

Nuclear Magnetic Resonance (NMR) of LDL Particle numbers to Assess Cardiovascular Risk, continued

28. Rosenson, RS. (2011) Screening guidelines for dyslipidemia. Up to Date. Last Update: April 25, 2011. Available: http://www.uptodate.com/contents/screening-guidelines-for- dyslipidemia?source=search_result&search=lipid+profile&selectedTitle=2~150. Date Accessed: November 21, 2011. 29. Toth, PP. (2001). High-density lipoprotein: epidemiology, metabolism, and antiatherogenic effects. Dis Mon. 47. 8:369-416. 30. Toth, PP. (2003). Reverse cholesterol transport: high-density lipoprotein's magnificent mile. Curr Atheroscler Rep. 5. 5:386-93. 31. Toth, PP. (2004). High-density lipoprotein and cardiovascular risk. Circulation. 109. 15:1809-12. 32. Toth, PP. (2009). Novel therapies for increasing serum levels of HDL. Endocrinol Metab Clin North Am. 38. 1:151-70. 33. Tufts Evidence-based Practice Center (EPC). (2008) Low Density Lipoprotein Subfractions: Systematic Review of Measurement Methods and Association with Cardiovascular Outcomes. Agency for Healthcare Research and Quality (AHRQ). June 16. 34. Walsh, J. (2008) LDL Particle Number as Assessed by NMR Spectroscopy. California Technology Assessment Forum (CTAF). October 15. 35. Wilson, P. (2011) Estimation of cardiovascular risk in an individual patient without known cardiovascular disease. Up to Date. Last Update: June 16, 2010. Available: http://www.uptodate.com/contents/estimation-of-cardiovascular-risk-in-an-individual- patient-without-known-cardiovascular-disease?source=search_result&search=framingham+risk+score&selectedTitle=1~40. Date Accessed: November 21, 2011. 36. Wilson, P. (2011) Overview of the risk equivalents and established risk factors for cardiovascular disease. Up to Date. Last Update: October 6, 2011. Available: http://www.uptodate.com/contents/overview-of-the-risk-equivalents-and-established-risk- factors-for-cardiovascular-disease?source=search_result&search=cardiovascular+disease&selectedTitle=1~150. Date Accessed: November 21, 2011. 37. Wilson, PW, D'Agostino, RB, Levy, D, et al. (1998). Prediction of coronary heart disease using risk factor categories. Circulation. 97. 18:1837-47.

Cardiovascular Policies, Continued

MEDICAL POLICY

PECTUS EXCAVATUM SURGERY

Policy # 160 Implementation Date: 4/22/02 Review Dates: 6/25/03, 6/24/04, 5/20/05, 5/4/06, 7/12/07, 6/19/08, 6/11/09, 5/19/11, 7/18/13, 6/19/14, 6/11/15, 6/16/16, 6/15/17, 6/21/18, 6/19/19, 6/18/20 Revision Dates: 4/22/02, 7/24/06, 1/12/10

Description Pectus excavatum deformity is a congenitally acquired deformity of the front portion of the chest wall caused by the backward displacement of the xiphoid cartilage. In this condition, the anterior chest wall cartilages develop abnormally, leaving a "dent" in the chest wall. Though it causes a cosmetic deformity, it can also cause reduced function of an individual if the depression in the chest wall impairs the ability of the lungs or heart to work normally. Surgery can be done to correct the deformity while the child is still growing. Surgery is usually done prior to puberty with its associated bone growth and maturing of the child's skeletal structure. The degree of anticipated functional impairment a patient with pectus excavatum deformity may expect is measured indirectly with the Haller Index. This value reflects the ratio of the transverse diameter (the horizontal distance of the inside of the ribcage) to the anterior-posterior diameter (the shortest distance between the vertebrae and sternum) of the chest and is calculated from a single CT scan of the chest performed through the deepest portion of a pectus excavatum deformity.

Commercial Plan Policy

SelectHealth covers repair of pectus excavatum deformities when the following criteria are met: 1. Patient is > 7 years of age; AND one of the following: 2. Haller index > 3.25; OR 3. Serial lateral chest x-rays taken at mid-respiration and at least 6 months apart revealing a persistent ratio of the external skeletal AP diameter of the chest at the angle of Lewis compared to the distance between the anterior surface of the vertebral body and the gladiolar-xiphoid junction is < 0.3; OR 4. Serial lateral chest x-rays taken at mid-respiration and at least 6 months apart revealing a persistent ratio of the external skeletal AP diameter of the chest at the angle of Lewis compared to the distance between the anterior surface of the vertebral body and the gladiolar-xiphoid junction is < 0.5 and > 0.3, AND either of the following: a) Pulmonary function tests consistent with restrictive lung disease without other underlying lung disease which explains the abnormalities; OR b) An echocardiogram performed with in the last 3 months reveals reduced cardiovascular function attributable to the chest wall deformity

Cardiovascular Policies, Continued

Pectus Excavatum Surgery, continued

SelectHealth Advantage (Medicare/CMS)

SelectHealth Community Care (Medicaid/CHIP)

Summary of Medical Information Patients with chest wall deformities often have poor body image and self-esteem. Some individuals attempt to cover the defect with clothing and avoid activities that may require exposure of the chest. Indications for surgical correction are controversial and vary widely. Surgical repair is offered primarily as a method of improving cosmesis and psychological factors but may be necessary to improve cardiopulmonary function in some patients, as the disfigurement may be accompanied by physiologic impairment. The scientific literature is controversial as to whether pectus excavatum is primarily cosmetic or whether it results in actual physiological impairment of function. Patients with mild pectus excavatum deformity may be treated with posture and exercise. Most surgical corrections are performed for cosmetic reasons, and in some cases to improve functional impairment. Authors agree that if patients with severe deformities do not undergo surgical repair in childhood, their symptoms worsen in adulthood. If surgical repair is performed at an early age it has been reported there is a high recurrence rate due to periods of rapid bone growth. While the optimal age for surgical repair is generally between the ages of 11 and 18 years, each case must be reviewed individually for the presence of impaired cardiopulmonary symptoms. In some cases, surgery may be performed in adults to correct pectus deformities. Adults who have uncorrected pectus excavatum deformity and experience symptoms of activity limitation may undergo surgical repair with low morbidity, short-term limitation of activities, and improvement of symptoms. Surgery for pectus excavatum may be performed using any of several techniques, including a sternal osteotomy (i.e., a modified osteotomy that involves supporting, removing and repositioning the sternum) or implantation of a Silastic mold in the subcutaneous space to fill the defect without altering the thoracic cage. Surgical correction often employs a metal bar behind the sternum; the bar may be removed in 1−2 years, after remolding has occurred. The standard surgical procedure is the open Ravitch procedure, which involves extensive dissection, cartilage resection, and sternal osteotomy. More recently, minimally invasive techniques, including the Nuss procedure (i.e., a minimally invasive repair of pectus excavatum [MIRpectus excavatum]), have been utilized that involve the insertion of a convex steel bar beneath the sternum through small thoracic incisions. These recently developed minimally invasive methods do not require cartilage resection or osteotomy.

Billing/Coding Information CPT CODES 21740 Reconstructive repair of pectus excavatum or carinatum; open 21742 ; minimally invasive approach (Nuss procedure), without thoraoscopy 21743 ; minimally invasive approach (Nuss procedure), with thoracoscopy

Cardiovascular Policies, Continued

Pectus Excavatum Surgery, continued

HCPCS CODES No specific codes identified

Key References 1. Stedman's Medical Dictionary, 26th Edition 2. Haller, Alex J., Journal of Pediatric Surgery, Vol 22, No 10 (October), 1887: pp 904-906. 3. Haller, et al., Journal of Thoracic and Cardiovascular Surgery, Vol 60, No 3 (September), 1970: pp. 375−383. 4. Haller, Alex J., Turner, Charles S. Diagnosis and Operative Management of Chest Wall Deformities in Children, Surgical Clinics of North America, Vol. 61, No. 5, (October) 1981. 5. Welch, Kenneth J., Satisfactory Surgical Correction of Pectus Excavation Deformity in Childhood, A Limited Opportunity. J. Thoracic Surgery, Vol. 36, No 5 (November), 1958: pp. 697−713.

Cardiovascular Policies, Continued

MEDICAL POLICY

PERCUTANEOUS MITRAL VALVE REPAIR (MITRACLIP®)

Policy # 464 Implementation Date: 10/19/10 Review Dates: 12/15/11, 10/20/16, 10/19/17, 10/3/18, 10/15/19 Revision Dates: 5/30/13, 1/10/14, 1/23/14

Description The mitral valve insufficiency occurs when the mitral valve fails to close properly causing blood to flow backward into the atrium (regurgitation), leaving the left ventricle, the heart's primary pumping chamber, with too little blood. To compensate, the ventricle stretches and overworks. Over time, it becomes enlarged, distorted, and weak. Historically, 3 options have been available to treat symptomatic mitral valve regurgitation: medications (such as diuretics to alleviate fluid retention), valve repair, and valve replacement. Valve surgery is a highly invasive procedure which many fragile patients may not be able to undertake due to their associated comorbidities. Consequently, new approaches to mitral valve repair/replacement are under development. One such development is the MitraClip® (Abbott Laboratories, Chicago, IL). The MitraClip procedure is performed in a cardiac catheterization laboratory with the patient under general anesthesia. A thin catheter is inserted through a small incision in the groin and guided through the femoral vein to the affected area of the heart. A smaller catheter holding the clip is slipped through the first catheter. After the clip is attached to the valve leaflets, the catheters are removed. The patient is released from the hospital within a day or two. If the clip is not placed ideally on the first attempt, it can be reset. If it does not sufficiently correct the regurgitation, surgical repair or replacement of the valve remains an option. The MitraClip system received FDA approval on October 24, 2013, for use in the United States. The FDA approved indication is for the percutaneous reduction of significant symptomatic mitral regurgitation (MR is for the percutaneous reduction of significant symptomatic mitral regurgitation (> 3+) due to primary abnormality of the mitral apparatus [degenerative MR] in patients who have been determined to be at a prohibitive risk for mitral valve surgery by a heart team. This team includes a cardiac surgeon experienced in mitral valve surgery and a cardiologist experienced in mitral valve disease, and this procedure is intended for patients in whom existing comorbidities would not preclude the expected benefit from the reduction of the mitral regurgitation.

Commercial Plan Policy (No Preauthorization Required but criteria must be met)

SelectHealth covers percutaneous mitral valve repair (MitraClip®) for patients who have been determined to be at a prohibitive risk for mitral valve surgery and meet other specific coverage criteria.

Coverage criteria (must meet ALL the following):

1. Patients is determined to be at a prohibitive risk for mitral valve surgery by a heart team, which included a cardiac surgeon experienced in mitral valve surgery and a cardiologist experienced in mitral valve disease

Cardiovascular Policies, Continued

Percutaneous Mitral Valve Repair (Mitraclip®), continued

2. Symptomatic* Mitral regurgitation is > 3+ on echocardiography or cardiac catheterization

3. Mitral regurgitation is due to degenerative** mitral valve disease

4. Existing comorbidities would not preclude the expected benefit from the reduction in the mitral regurgitation

*Symptomatic is defined as patients experiencing chest pain, shortness of breath at rest or with exertion, orthopnea or PND requiring medical intervention and directly related to the mitral regurgitation.

**Degenerative mitral valve disease is classified as degeneration of the mitral valve due to changes in the connective tissue of the valve or mitral chordae causing weakness and redundancy of the leaflets and their supporting structures. Degenerative mitral valve disease does not include infective causes, or mitral regurgitation due to ischemia or problems intrinsic with the left ventricle causing the mitral annulus to dilate and creating the mitral insufficiency. The most common finding in patients with degenerative valve disease is leaflet prolapse due to elongation or rupture of the chordal apparatus.

SelectHealth Advantage (Medicare/CMS) (Preauthorization Required)

SelectHealth Community Care (Medicaid/CHIP) (Preauthorization Required)

Summary of Medical Information In December 2013, an updated review of this technology was undertaken. This review identified one systematic review and 41 primary literature articles which met the inclusion criteria for review. Most of the authors conducted and published their results after the EVEREST I Trial, EVEREST II RCT, EVEREST II HRR, and REALISM HR trials were completed. The only systematic review included only 12 studies and stated that no RCTs comparing MitraClip to non-surgical therapies were identified. This is the same finding illustrated in this report. They also noted that only one paper published between 2000 and 2013 reported outcomes beyond 12 months; however, 11 papers identified for this review followed-up with patients after 12 months between only 2010 and 2013; with regards to the primary literature articles, 5,575 patients have been enrolled in published studies in the last three years. Outcomes from the studies showed successful implantation ranging from 85% to 100% with reduction in mitral regurgitation ranging from a low 41.4% to 65%. These studies also showed improvement in NYHA categorization of at least 1 grade, ranging from 34.4% to 66.7%. In the 9 studies which assessed patients out to at least 12 months post-procedure, survival ranged from 71.1% to 87.5%. Similar to the findings reported in the systematic review, the average follow-up time was just over a year in the primary literature. Dissimilar to that review, however, 5 papers followed patients for 2 years and one paper followed patients out to 4 years. An important observation from the studies relates to the number of MitraClips used. 11 of the 41 studies used either more than 2 clips or no clip at all in each procedure. Paranskaya et al., for example, reported that 19 patients (22.3%) received 3 clips, 4 patients (4.7%) received 4 clips, and 1 patient (1.2%) received 5 clips. For studies where clips had to be removed because of perioperative complications, the authors reported that zero clips were used. Also, some of the 11 studies did not report what number of clips over 2 were used during the procedure so it is difficult to estimate what number of procedures used 3, 4, or 5 clips. 2

Cardiovascular Policies, Continued

Percutaneous Mitral Valve Repair (Mitraclip®), continued

Feldman et al. and Mauri et al. were the only two to have randomized their surgical repair patients from their MitraClip patients. This is important to note as the remaining three studies explicitly note that MitraClip patients were significantly older, had lower LVEF, had a higher EuroSCORE I, had higher LV diameter, and had more comorbidities in general. Five studies compared MitraClip surgery to standard valvular surgery. Feldman et al. and Mauri et al. were the only two to have randomized their surgical repair patients from their MitraClip patients. This is important to note, as the remaining three studies explicitly note that MitraClip patients were significantly older, had lower LVEF, had a higher EuroSCORE I, had higher LV diameter, and had more comorbidities in general. These studies did not demonstrate a statistically significant difference between percutaneous MitraClip procedures to valvular surgery for endpoints which included 30-day survival, longer term mortality, and improvement in cardiovascular function. In conclusion, the current body of evidence regarding MitraClip demonstrates that MitraClip may reasonably improve patient outcomes, especially for patients who otherwise could not undergo surgery. Though only a few papers thoroughly examine patient outcomes in the long-term (> 2 years), what evidence does exist, shows similar outcomes as compared to standard surgical methods in appropriately selected patients. (GRADE 1B).

Billing/Coding Information CPT CODES 0483T Transcatheter mitral valve implantation/replacement (TMVI) with prosthetic valve; percutaneous approach, including transseptal puncture, when performed 0484T Transcatheter mitral valve implantation/replacement (TMVI) with prosthetic valve; transthoracic exposure (eg, thoracotomy, transapical) 33418 Transcatheter mitral valve repair, percutaneous approach, including transseptal puncture when performed; initial prosthesis 33419 ; additional prosthesis (es) during the same session (List separately in addition to code for primary procedure) Not Covered/Considered investigational: 93590 Percutaneous transcatheter closure of paravalvular leak; initial occlusion device, mitral valve 93592 Percutaneous transcatheter closure of paravalvular leak; each additional occlusion device (List separately in addition to code for primary procedure)

HCPCS CODES No specific codes identified

Key References 1. Vascular, A. (2013) MitraClip Percutaneous Mitral Valve Repair System. Abbott Vascular. Available: http://www.abbottvascular.com/int/mitraclip.html#about-mitral-regurgitation. Date Accessed: November 29, 2013. 2. Mayo Clinic. (2010) Mitral Valve Regurgitation. Mayo Clinic. Available: http://www.mayoclinic.com/health/mitral-valve- regurgitation/DS00421. Date Accessed: August 11, 2010. 3. Cedars-Sinai. (2010) Cedars-Sinai Heart Institute And The Evalve Mitraclip: Clinical Trial Of Non-Surgical Repair For Severe Mitral Valve Regurgitation. Cedars-Sinai. Available: http://www.cedars-sinai.edu/About-Us/News/News-Releases-2008/Cedars- Sinai-Heart-Institute-And-The-Evalve-Mitraclip-Clinical-Trial-Of-Non-Surgical-Repair-For-Severe-Mitral-Valve-Regurgitation- .aspx. Date Accessed: August 11, 2010. 4. Zoghbi, WA, Enriquez-Sarano, M, Foster, E, et al. (2003). Recommendations for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr 16.7: 777-802. 5. Otto, CM, Salerno, CT. (2005). Timing of surgery in asymptomatic mitral regurgitation. N Engl J Med 352.9: 928-9. 6. Foster, E. (2010). Clinical practice. Mitral regurgitation due to degenerative mitral-valve disease. N Engl J Med 363.2: 156-65. 7. Grigioni, F, Avierinos, JF, Ling, LH, et al. (2002). Atrial fibrillation complicating the course of degenerative mitral regurgitation: determinants and long-term outcome. J Am Coll Cardiol 40.1: 84-92. 8. Gaasch, WH. (2013) Functinoal mitral regurgitation. September 17, 2012. Up to Date. Available: http://www.uptodate.com/contents/functional-mitral-regurgitation. Date Accessed: November 29, 2013. 9. Colucci, WS. (2013) Predictors of survival in heart failure due to systolic dysfunction. Up to Date. Available: http://www.uptodate.com/contents/predictors-of-survival-in-heart-failure-due-to-systolic- dysfunction?source=search_result&search=nyha&selectedTitle=1~150#H3. Date Accessed: December 5, 2013. 10. Hanson, I. (2013) Mitral Regurgiatation Medication,Medscape. Available: http://emedicine.medscape.com/article/155618- medication#showall. Date Accessed: December 5, 2013. 3

Cardiovascular Policies, Continued

Percutaneous Mitral Valve Repair (Mitraclip®), continued

11. Seneviratne, B, Moore, GA, West, PD. (1994). Effect of captopril on functional mitral regurgitation in dilated heart failure: a randomised double blind placebo controlled trial. Br Heart J 72.1: 63-8. 12. Capomolla, S, Febo, O, Gnemmi, M, et al. (2000). Beta-blockade therapy in chronic heart failure: diastolic function and mitral regurgitation improvement by carvedilol. Am Heart J 139.4: 596-608. 13. Rosenthal, L. (2013) Atrial Fibrillation Medication. December 3, 2013. Medscape. Available: http://emedicine.medscape.com/article/151066-medication. Date Accessed: December 5, 2013. 14. Food and Drug Administration. (2013) MitraClip Clip Delivery System Labelling. November 15, 2013. US Department of Health & Human Services. Available: http://www.accessdata.fda.gov/cdrh_docs/pdf10/P100009c.pdf. Date Accessed: November 28, 2013. 15. Gaasch, WH. (2013) Overview of the management of chronic mitral regurgitation. August 12, 2013. Up to Date. Available: http://www.uptodate.com/contents/overview-of-the-management-of-chronic-mitral- regurgitation?source=search_result&search=mitraclip&selectedTitle=1~2. Date Accessed: November 28, 2013. 16. Feldman, T, Foster, E, Glower, DD, et al. (2011). Percutaneous repair or surgery for mitral regurgitation. N Engl J Med 364.15: 1395-406. 17. Lim, DS, Reynolds, MR, Feldman, T, et al. (2013). Improved Functional Status and Quality of Life in Prohibitive Surgical Risk Patients With Degenerative Mitral Regurgitation Following Transcatheter Mitral Valve Repair with the MitraClip(R) System. J Am Coll Cardiol. 18. Ussia, GP, Cammalleri, V, Sarkar, K, et al. (2012). Quality of life following percutaneous mitral valve repair with the MitraClip System. Int J Cardiol 155.2: 194-200 19. Alegria-Barrero, E, Chan, PH, Foin, N, et al. (2013). Concept of the central clip: when to use one or two MitraClips(R). EuroIntervention. 20. Conradi, L, Treede, H, Franzen, O, et al. (2011). Impact of MitraClip therapy on secondary mitral valve surgery in patients at high surgical risk. Eur J Cardiothorac Surg 40.6: 1521-6. 21. Guarracino, F, Ferro, B, Baldassarri, R, et al. (2013). Non invasive evaluation of cardiomechanics in patients undergoing MitrClip procedure. Cardiovasc Ultrasound 11: 13. 22. Mauri, L, Foster, E, Glower, DD, et al. (2013). 4-year results of a randomized controlled trial of percutaneous repair versus surgery for mitral regurgitation. J Am Coll Cardiol 62.4: 317-28. 23. Schillinger, W, Hunlich, M, Baldus, S, et al. (2013). Acute outcomes after MitraClip therapy in highly aged patients: results from the German TRAnscatheter Mitral valve Interventions (TRAMI) Registry. EuroIntervention 9.1: 84-90. 24. Auricchio, A, Schillinger, W, Meyer, S, et al. (2011). Correction of mitral regurgitation in nonresponders to cardiac resynchronization therapy by MitraClip improves symptoms and promotes reverse remodeling. J Am Coll Cardiol 58.21: 2183- 9. 25. Franzen, O, van der Heyden, J, Baldus, S, et al. (2011). MitraClip(R) therapy in patients with end-stage systolic heart failure. Eur J Heart Fail 13.5: 569-76. 26. Gaemperli, O, Biaggi, P, Gugelmann, R, et al. (2013). Real-time left ventricular pressure-volume loops during percutaneous mitral valve repair with the MitraClip system. Circulation 127.9: 1018-27. 27. Paranskaya, L, D'Ancona, G, Bozdag-Turan, I, et al. (2013). Percutaneous mitral valve repair with the MitraClip system: perioperative and 1-year follow-up results using standard or multiple clipping strategy. Catheter Cardiovasc Interv 81.7: 1224- 31. 28. Paranskaya, L, D'Ancona, G, Bozdag-Turan, I, et al. (2013). Residual mitral valve regurgitation after percutaneous mitral valve repair with the MitraClip(R) system is a risk factor for adverse one-year outcome. Catheter Cardiovasc Interv 81.4: 609-17. 29. Paranskaya, L, D'Ancona, G, Bozdag-Turan, I, et al. (2013). Percutaneous vs surgical repair of mitral valve regurgitation: single institution early and midterm outcomes. Can J Cardiol 29.4: 452-9. 30. Rudolph, V, Knap, M, Franzen, O, et al. (2011). Echocardiographic and clinical outcomes of MitraClip therapy in patients not amenable to surgery. J Am Coll Cardiol 58.21: 2190-5. 31. Surder, D, Pedrazzini, G, Gaemperli, O, et al. (2013). Predictors for efficacy of percutaneous mitral valve repair using the MitraClip system: the results of the MitraSwiss registry. Heart 99.14: 1034-40. 32. Teufel, T, Steinberg, DH, Wunderlich, N, et al. (2012). Percutaneous mitral valve repair with the MitraClip(R) system under deep sedation and local anaesthesia. EuroIntervention 8.5: 587-90. 33. Munkholm-Larsen, S, Wan, B, Tian, DH, et al. (2013). A systematic review on the safety and efficacy of percutaneous edge-to- edge mitral valve repair with the MitraClip system for high surgical risk candidates. Heart. 34. Armoiry, X, Brochet, E, Lefevre, T, et al. (2013). Initial French experience of percutaneous mitral valve repair with the MitraClip: a multicentre national registry. Arch Cardiovasc Dis 106.5: 287-94. 35. Armstrong, EJ, Rogers, JH, Swan, CH, et al. (2013). Echocardiographic predictors of single versus dual MitraClip device implantation and long-term reduction of mitral regurgitation after percutaneous repair. Catheter Cardiovasc Interv 82.4: 673-9. 36. Chan, PH, She, HL, Alegria-Barrero, E, et al. (2012). Real-world experience of MitraClip for treatment of severe mitral regurgitation. Circ J 76.10: 2488-93. 37. Conradi, L, Treede, H, Rudolph, V, et al. (2013). Surgical or percutaneous mitral valve repair for secondary mitral regurgitation: comparison of patient characteristics and clinical outcomes. Eur J Cardiothorac Surg 44.3: 490-6; discussion 496. 38. Divchev, D, Kische, S, Paranskaya, L, et al. (2012). In-hospital outcome of patients with severe mitral valve regurgitation classified as inoperable and treated with the MitraClip(R) device. J Interv Cardiol 25.2: 180-9. 39. Estevez-Loureiro, R, Franzen, O, Winter, R, et al. (2013). Echocardiographic and clinical outcomes of central versus non- central percutaneous edge-to-edge repair of degenerative mitral regurgitation. J Am Coll Cardiol. 40. Foster, E, Kwan, D, Feldman, T, et al. (2013). Percutaneous mitral valve repair in the initial EVEREST cohort: evidence of reverse left ventricular remodeling. Circ Cardiovasc Imaging 6.4: 522-30. 41. Gaemperli, O, Moccetti, M, Surder, D, et al. (2012). Acute haemodynamic changes after percutaneous mitral valve repair: relation to mid-term outcomes. Heart 98.2: 126-32. 42. Glower, D, Ailawadi, G, Argenziano, M, et al. (2012). EVEREST II randomized clinical trial: predictors of mitral valve replacement in de novo surgery or after the MitraClip procedure. J Thorac Cardiovasc Surg 143.4 Suppl: S60-3. 43. Herrmann, HC, Gertz, ZM, Silvestry, FE, et al. (2012). Effects of atrial fibrillation on treatment of mitral regurgitation in the EVEREST II (Endovascular Valve Edge-to-Edge Repair Study) randomized trial. J Am Coll Cardiol 59.14: 1312-9. 44. Maisano, F, Franzen, O, Baldus, S, et al. (2013). Percutaneous mitral valve interventions in the real world: early and 1-year results from the ACCESS-EU, a prospective, multicenter, nonrandomized post-approval study of the MitraClip therapy in Europe. J Am Coll Cardiol 62.12: 1052-61. 4

Cardiovascular Policies, Continued

Percutaneous Mitral Valve Repair (Mitraclip®), continued

45. Mealing, S, Feldman, T, Eaton, J, et al. (2013). EVEREST II high risk study based UK cost-effectiveness analysis of MitraClip(R) in patients with severe mitral regurgitation ineligible for conventional repair/replacement surgery. J Med Econ 16.11: 1317-26. 46. Orban, M, Braun, D, Sonne, C, et al. (2013). Dangerous liaison: successful percutaneous edge-to-edge mitral valve repair in patients with end-stage systolic heart failure can cause left ventricular thrombus formation. EuroIntervention. 47. Perl, L, Vaturi, M, Assali, A, et al. (2013). Preliminary experience using the transcatheter mitral valve leaflet repair procedure. Isr Med Assoc J 15.10: 608-12. 48. Pleger, ST, Mereles, D, Schulz-Schonhagen, M, et al. (2011). Acute safety and 30-day outcome after percutaneous edge-to- edge repair of mitral regurgitation in very high-risk patients. Am J Cardiol 108.10: 1478-82. 49. Pleger, ST, Schulz-Schonhagen, M, Geis, N, et al. (2013). One year clinical efficacy and reverse cardiac remodelling in patients with severe mitral regurgitation and reduced ejection fraction after MitraClip implantation. Eur J Heart Fail 15.8: 919- 27. 50. Puls, M, Tichelbacker, T, Bleckmann, A, et al. (2013). Failure of acute procedural success predicts adverse outcome after percutaneous edge-to-edge mitral valve repair with MitraClip. EuroIntervention. 51. Reichenspurner, H, Schillinger, W, Baldus, S, et al. (2013). Clinical outcomes through 12 months in patients with degenerative mitral regurgitation treated with the MitraClip(R) device in the ACCESS-EUrope Phase I trial. Eur J Cardiothorac Surg 44.4: e280-8. 52. Reynolds, M, Galper, B, Apruzzese, P, et al. (2012). TCT-786 Cost Effectiveness of the MitraClip® Compared with Mitral Valve Surgery: 12-month Results from the EVEREST II Randomized Controlled Trial. J Am Coll Cardiol 60.17_S. 53. Rudolph, V, Lubos, E, Schluter, M, et al. (2013). Aetiology of mitral regurgitation differentially affects 2-year adverse outcomes after MitraClip therapy in high-risk patients. Eur J Heart Fail 15.7: 796-807. 54. Scandura, S, Ussia, GP, Capranzano, P, et al. (2012). Left cardiac chambers reverse remodeling after percutaneous mitral valve repair with the MitraClip system. J Am Soc Echocardiogr 25.10: 1099-105. 55. Siegel, RJ, Biner, S, Rafique, AM, et al. (2011). The acute hemodynamic effects of MitraClip therapy. J Am Coll Cardiol 57.16: 1658-65. 56. Smith, T, McGinty, P, Bommer, W, et al. (2012). Prevalence and echocardiographic features of iatrogenic atrial septal defect after catheter-based mitral valve repair with the MitraClip system. Catheter Cardiovasc Interv 80.4: 678-85. 57. Taramasso, M, Denti, P, Buzzatti, N, et al. (2012). Mitraclip therapy and surgical mitral repair in patients with moderate to severe left ventricular failure causing functional mitral regurgitation: a single-centre experience. Eur J Cardiothorac Surg 42.6: 920-6. 58. Taramasso, M, Denti, P, Buzzatti, N, et al. (2012). Mitraclip therapy and surgical mitral repair in patients with moderate to severe left ventricular failure causing functional mitral regurgitation: a single-centre experience. Eur J Cardiothorac Surg 42.6: 920-6. 59. Whitlow, PL, Feldman, T, Pedersen, WR, et al. (2012). Acute and 12-month results with catheter-based mitral valve leaflet repair: the EVEREST II (Endovascular Valve Edge-to-Edge Repair) High Risk Study. J Am Coll Cardiol 59.2: 130-9. 60. Hsieh, LHT. (2013) The MitraClip Miricle. The Globe and Mail. Available: http://www.theglobeandmail.com/life/health-and- fitness/advsunnybrook/sunnybrookfeatures/the-mitraclip-miracle/article12038536/. Date Accessed: December 6, 2013. 61. TCT Daily Staff. (2012) Extended EVEREST II Data Examine Safety, Efficacy of MitraClip as Well as Cost Effectiveness. October 25, 2012. TCT MD. Available: http://www.tctmd.com/show.aspx?id=115915. Date Accessed: December 6, 2013.

Cardiovascular Policies, Continued

MEDICAL POLICY

PERCUTANEOUS TRANSCATHETER CLOSURE FOR THE TREATMENT OF ATRIAL SEPTAL DEFECTS (ASD) AND PATENT FORAMEN OVALE (PFO)

Policy # 174 Implementation Date: 4/21/02 Review Dates: 10/23/03, 11/18/04, 3/25/05, 6/19/08, 6/11/09, 6/17/10, 5/3/11, 7/18/13, 6/19/14, 6/11/15, 6/16/16, 6/15/17, 6/28/18, 6/13/19, 6/18/20 Revision Dates: 11/18/04, 8/4/06, 10/31/06, 2/5/07, 6/30/07, 12/5/11, 8/14/18

Description Atrial septal defect (ASD) is the most common congenital lesion in adults after bicuspid aortic valve. Although the defect is often asymptomatic until adulthood, potential complications of an undetected ASD include right ventricular failure, atrial arrhythmias, paradoxical embolization, cerebral abscess, and pulmonary hypertension that can become irreversible and lead to right-to-left shunting (Eisenmenger syndrome). In approximately 70% of individuals, the primum and secundum septa fuse after birth, creating an intact interatrial septum. However, in a significant proportion of the population, the septae do not fuse. If the foramen ovale is completely covered but not sealed, it is called a "probe patent" or simply "patent" foramen ovale (PFO), indicating that the foramen can be opened by a reversal of the interatrial pressure gradient or by an intracardiac catheter. Less commonly, an open communication persists between the atria after septation. Such a communication is called an atrial septal defect (ASD). The various types of ASDs are classified according to their location and the nature of the embryologic defect. Isolated ASDs include: PFO, ASD at the fossa ovalis (secundum ASD), a defect superior to the fossa ovalis (superior sinus venosus type ASD, superior vena caval defect), a defect inferior to the fossa ovalis (inferior sinus venosus type ASD, inferior vena caval defect), and coronary sinus defects. The standard of care for the treatment of significant or symptomatic ASDs is percutaneous closure using several FDA-approved devices. Recently, this same therapy has been investigated for closure of physiologically significant PFOs. No devices are currently FDA approved that are specific to PFO-closure, however, this therapy is being performed using devices that are FDA approved for ASD-closure in patients with cryptogenic stroke. PFO-closure is also being investigated as a treatment of migraine headaches.

Commercial Plan Policy

SelectHealth covers percutaneous transcatheter closure of symptomatic atrial septal defect (ASD) in secundum position or for the closure of the fenestration in individuals who have undergone a fenestrated Fontan procedure. These procedures are considered medically necessary when using a device that has been FDA approved for that purpose and used according to the labeled indications.

SelectHealth covers percutaneous transcatheter closure of patent foramen ovale (PFO) using FDA approved closure devices in limited circumstances.

Cardiovascular Policies, Continued

Percutaneous Transcatheter Closure for the Treatment of Atrial Septal Defects (ASD) and Patent Foramen Ovale (PFO), continued

Criteria for coverage: 1. Patient has a documented history of recurrent, cryptogenic, and clinically-evident transient ischemic episode or stroke which has been verified by an independent, qualified neurologic specialist. 2. Patient has demonstrated the PFO to be hemodynamically significant as defined by EITHER one of the following: a. Right-sided pressure or volume overload changes on imaging studies along with evidence of a large shunt (typically permanent right-to-left shunt); or b. Documented orthodeoxia-platypnea (resting or exercise induced)

SelectHealth does NOT cover percutaneous transcatheter closure of PFO for migraine prophylaxis or for any other indications because its effectiveness for these indications has not been established. It is considered experimental and investigational in these circumstances.

SelectHealth Advantage (Medicare/CMS)

SelectHealth Community Care (Medicaid/CHIP)

Summary of Medical Information There are a number of devices approved by the FDA for closure of ASDs. These include the AMPLATZER® Septal Occluder, HELEX Septal Occluder, and the NMT Medical CardioSEAL® STARFlex™ Septal Occlusion System. All these devices are inserted via a catheter in collapsed form, then once at the defect, the device opens up and occludes the defect. Prior to October 31, 2006, the FDA approved 2 catheter systems under the Human Device Exemption (HDE) for patients with patent foramen ovale (PFO) and cryptogenic stroke due to presumed paradoxical embolism through a PFO and who have failed conventional drug therapy. The previously approved devices were the NMT Medical CardioSEAL STARFlex Septal Occlusion System and the AGA Medical Amplatzer PFO Occluder. As it was felt that these devices no longer met the criteria for the HDE exemption and needed to prove their efficacy through the PMA approval process, both manufacturers agreed to cease marketing their devices effective October 31, 2006. Though no randomized, controlled trials have proven the PFO specific percutaneous devices to be safe and effective, the literature suggests that currently approved FDA devices are effective in closing both ASD and PFO. Anzola et al., for example, studied 140 patients who underwent percutaneous closure for PFO. At the 12-month follow-up, 91% had not detectable right-to-left shunt and only one CVA-like event had occurred. Bruch et al. reported on 66 patients with ASD, none of whom had residual shunting after 12 months. No evidence of recurrent thromboembolic events was observed in this population.

Cardiovascular Policies, Continued

Percutaneous Transcatheter Closure for the Treatment of Atrial Septal Defects (ASD) and Patent Foramen Ovale (PFO), continued

A 2004 study of 28 patients with ASD by Khositseth et al. found a 7% residual shunt rate at 12 months. A 3.6% recurrence rate for recurrent thromboembolic events was observed at 23 months. Yew et al. reported 5-year data on patients who underwent percutaneous ASD-closure. All patients experienced complete closure. Subsequently, as the questions around the similarity between PFO and ASD physiology have been addressed in the above literature, one may be able to extrapolate that use of ASD-closure approved devices will be effective in PFOs. Supporting this supposition, several conference abstracts provide additional support for ASD-closure devices for treating PFO. In 58 patients, closed with either the Amplatzer PFO device or the Amplatzer Septal Occluder, residual shunt at 3 months was lower in the latter group. In 1000 patients treated with either device, serious adverse events were uncommon and the relative risk of CVA was 0.15 compared with historical controls. It was noted that a Hayes Directory published in 2002 gave percutaneous closure of PFO and ASD a ‘B’ rating indicating a device with some proven benefit (i.e., use of the technology is supported by a moderate level of published evidence but further research is required to fully clarify clinical indications, contraindications, treatment parameters, comparison with other technologies, and/or impact on health outcomes). The report cited a lack of long-term follow-up data as a weakness in the literature. These data suggest that ASD devices are effective at closing PFO and reducing risk for recurrent stroke, at least in the short-term. Long-term data are still lacking as well as comparative trials to examine the relative efficacy between percutaneous devices and medical therapy on stroke outcomes. Ongoing clinical trials may provide additional insight pertinent to this question. In 2011, a literature review was performed, and guidelines provided by the Intermountain Medical Center Heart Institute identified a science advisory from the American College of Cardiology Foundation (ACCF), American Heart Association (AHA), American Stroke Association (ASA), and the American Academy of Neurology published in 2010. The advisory concluded the optimal therapy for prevention of recurrent stroke or transient ischemic attack in patients with cryptogenic stroke and PFO has not been defined. Although numerous observational studies have suggested a strong association between PFO and cryptogenic stroke, a causal relationship has not been convincingly established for the majority of affected patients. Treatment choices include medical therapy with antiplatelet agents or vitamin K antagonists, percutaneous device closure, or open surgical repair. Whereas suture closure of an incidental PFO is performed routinely during an operation undertaken for another indication, primary surgical repair is rarely advocated in the current era. The choice between medical therapy and percutaneous device closure has been the subject of intense debate over the past several years, albeit one that has not been adequately informed by randomized, prospective clinical trial data to permit an objective comparison of the relative safety and efficacy of these respective approaches. Enrollment in clinical trials has lagged considerably despite frequent calls for participation from the US Food and Drug Administration and major professional societies. Completion and peer review of ongoing trials are critical steps to establish an evidence base from which clinicians can make informed decisions regarding the best therapy for individual patients. The present advisory strongly encourages all clinicians involved in the care of appropriate patients with cryptogenic stroke and patent foramen ovale-cardiologists, neurologists, internists, radiologists, and surgeons-to consider referral for enrollment in these landmark trials to expedite their completion and help resolve the uncertainty regarding optimal care for this condition. Based on a guideline for healthcare professionals from the American Heart Association/American Stroke Association published in 2011, the importance of PFO with or without atrial septal aneurysm for a first stroke or recurrent cryptogenic stroke, remains in question. No randomized controlled clinical trials comparing different medical therapies, medical versus surgical closure, or medical versus transcatheter closure, have been reported, although several studies are ongoing. Non-randomized comparisons of various closure techniques with medical therapy have generally shown reasonable complication rates and recurrence risk with closure at or below those reported with medical therapy. One study suggested a particular benefit in patients with > 1 stroke at baseline. There is still debate on the possible mechanism of formation of WMLs in migraine. Subjects with migraine with aura (MA) have a two-fold risk of being a carrier of a cardiac right-to-left shunt (RILES) due to PFO compared with the general population. Patent foramen ovale, which can be detected by transcranial Doppler (TCD), is a risk factor for cryptogenic ischemic stroke in young patients, and its prevalence in patients with MA is about 45%. In 2010, Ueno et al. assessed the contribution of embolic etiologies, PFO and atrial septal aneurysm (ASA), to cerebral white matter lesions (WMLs) in ischemic stroke patients. They enrolled 115 patients 3

Cardiovascular Policies, Continued

Percutaneous Transcatheter Closure for the Treatment of Atrial Septal Defects (ASD) and Patent Foramen Ovale (PFO), continued

(age, 69 +/- 11 years; 41 females); 49 (43%) were in the PFO group, 4 (3%) were in the ASA group, 23 (20%) were in the PFO-ASA group, and 39 (34%) were in the non-SA group. The PFO-ASA group had significantly increased WMLs compared to the other three groups (p = 0.004). On multiple logistic regression analysis, the coexistence of PFO and ASA was significantly associated with the degree of WMLs (odds ratio: 2.40; 95% confidence interval: 1.11-5.17; p = 0.026) when the PFO-ASA and non-SA groups were compared. They concluded that coexistence of PFO with ASA could play an important pathogenic role in WML severity. Adami et al. performed the Shunt Associated Migraine (SAM) study. One hundred eighty-five patients (77% women) underwent a standardized headache and vascular risk factors questionnaire, contrast- enhanced transcranial Doppler, blood coagulation tests, and brain MRI. RLS was categorized into four grades: no shunt, < 10 microbubbles (mb), > 10 mb single spikes pattern, and > 10 mb shower/curtain pattern. Standard and fluid-attenuated inversion recovery T2- weighted MRI sequences were inspected for WMLs by three independent raters blinded to RLS grade. WML load was scored in the periventricular areas (PV-WMLs) with the Fazekas scale and in the deep white matter (D-WMLs) with the Scheltens scale. Interobserver agreement was good to excellent (k = 0.64 to 0.96, p < 0.0001). WML load was then correlated between patients with and without RLS. They concluded that the presence of right-to-left shunt does not increase white matter lesion load in patients who have migraine with aura. In summary, these studies provide new information on options for closure of PFO and generally indicate that short-term complications with these procedures are rare and for the most part minor. Unfortunately, long-term follow-up is lacking. Event rates over 1−2 years after transcatheter closure ranged from 0%− 3.4%. Studies in which closure was compared with medical treatment alone indicate trends toward better outcomes with closure. Windecker et al. reported a very high 3-year event rate of 33.2% in 44 medically treated patients compared with 7.3% in 59 similar patients treated with PFO-closure. The generally low rates of stroke in the closure series, the lack of robust outcome differences in the 3 non-randomized comparison studies, and the overall absence of controlled comparisons of closure strategies with medical treatment alone, reinforce the need to complete randomized clinical trials comparing closure with medical therapy. A 2009 statement from the AHA/ASA/ACC strongly encourages all clinicians involved in the care of appropriate patients with cryptogenic stroke and PFO-cardiologists, neurologists, internists, radiologists, and surgeons, to consider referral for enrollment in these landmark trials to expedite their completion and help resolve the uncertainty regarding optimal care for this condition.

Billing/Coding Information CPT CODES Covered: For the indications outlined above 93580 Percutaneous transcatheter closure of congenital interatrial communication (i.e., Fontan fenestration, atrial septal defect) with implant

HCPCS CODES C1760 Closure device, vascular (implantable/insertable) C1817 Septal defect implant system, intracardiac

Key References 1. Adami A, Rossato G, Cerini R, et al. (2008). Right-to-left shunt does not increase white matter lesion load in migraine with aura patients. Neurol 71; 101-107. 2. Alaeddini J, Feghali G, Jenkins S, Ramee S, White C, Abi-Samra F. Frequency of atrial tachyarrhythmias following transcatheter closure of patent foramen ovale. J Invasive Cardiol 18.8 (2006): 365-8. 3. American Academy of Neurology. Recurrent stroke in patients with patent foramen ovale and atrial septal aneurysm. Available: http://www.aan.com/professionals/practice/pdfs/ClinicianStrokeD3.pdf. Date Accessed: June 14, 2007. 4. Anzai H, Child J, Natterson B, et al. Incidence of thrombus formation on the CardioSEAL and the Amplatzer interatrial closure devices. Am J Cardiol 93.4 (2004): 426-31. 5. Anzola GP, Morandi E, Casilli F, Onorato E. Does transcatheter closure of patent foramen ovale really shut the door? A prospective study with transcranial Doppler. Stroke 35.9 (2004): 2140-4. 6. Aslam F, Iliadis AE, Blankenship JC. Percutaneous closure of patent foramen ovale: success and outcomes of a low-volume procedure at a rural medical center. J Invasive Cardiol 19.1 (2007): 20-4. 7. Bogousslavsky J, Garazi S, Jeanrenaud X, Aebischer N, Van Melle G. Stroke recurrence in patients with patent foramen ovale: the Lausanne Study. Lausanne Stroke with Paradoxal Embolism Study Group. Neurology 46.5 (1996): 1301-5.

Cardiovascular Policies, Continued

Percutaneous Transcatheter Closure for the Treatment of Atrial Septal Defects (ASD) and Patent Foramen Ovale (PFO), continued

8. Brandt RR, Neumann T, Neuzner J, Rau M, Faude I, Hamm CW. Transcatheter closure of atrial septal defect and patent foramen ovale in adult patients using the Amplatzer occlusion device: no evidence for thrombus deposition with antiplatelet agents. J Am Soc Echocardiogr 15.10 Pt 1 (2002): 1094-8. 9. Braun MU, Fassbender D, Schoen SP, et al. Transcatheter closure of patent foramen ovale in patients with cerebral ischemia. J Am Coll Cardiol 39.12 (2002): 2019-25. 10. Bruch L, Parsi A, Grad MO, et al. Transcatheter closure of interatrial communications for secondary prevention of paradoxical embolism: single-center experience. Circulation 105.24 (2002): 2845-8. 11. Burian M, Neumann T, Weber M, et al. Nickel release, a possible indicator for the duration of antiplatelet treatment, from a nickel cardiac device in vivo: a study in patients with atrial septal defects implanted with an Amplatzer occluder. Int J Clin Pharmacol Ther 44.3 (2006): 107-12. 12. Buscheck F, Sievert H, Kleber F, et al. Patent foramen ovale using the Premere device: the results of the CLOSEUP trial. J Interv Cardiol 19.4 (2006): 328-33. 13. Carandang R, Seshadri S, Beiser A, et al. Trends in incidence, lifetime risk, severity, and 30-day mortality of stroke over the past 50 years. JAMA 296.24 (2006): 2939-46. 14. Cardoso CO, Rossi Filho RI, Machado PR, Francois LM, Horowitz ES, Sarmento-Leite R. Effectiveness of the Amplatzer device for transcatheter closure of an ostium secundum atrial septal defect. Arq Bras Cardiol 88.4 (2007): 384-9. 15. Chatterjee T, Petzsch M, Ince H, et al. Interventional closure with Amplatzer PFO occluder of patent foramen ovale in patients with paradoxical cerebral embolism. J Interv Cardiol 18.3 (2005): 173-9. 16. De Castro S, Cartoni D, Fiorelli M, et al. Morphological and functional characteristics of patent foramen ovale and their embolic implications. Stroke 31.10 (2000): 2407-13. 17. De Ridder S, Suttorp MJ, Ernst SM, et al. Percutaneous transcatheter closure of atrial septal defects: initial single-centre experience and follow-up results. Initial experience with three-dimensional echocardiography. Acta Cardiol 60.2 (2005): 171-8. 18. Del Sette M, Dinia L, Bonzano L, et al. (2008). White matter lesions in migraine and right-to-left shunt: a conventional and diffusion MRI study. Ceph28; 376-382. 19. Demkow M, Ruzyllo W, Kepka C, et al. Transcatheter closure of patent foramen ovale in patients with cryptogenic stroke. Kardiol Pol 61.8 (2004): 101-9; discussion 109. 20. Donti A, Giardini A, Salomone L, Formigari R, Picchio FM. Transcatheter patent foramen ovale closure using the premere PFO occlusion system. Catheter Cardiovasc Interv 68.5 (2006): 736-40. 21. Dorenbeck U, Simon B, Skowasch D, et al. Cerebral embolism with interventional closure of symptomatic patent foramen ovale: an MRI-based study using diffusion-weighted imaging. Eur J Neurol 14.4 (2007): 451-4. 22. Du ZD, Cao QL, Joseph A, et al. Transcatheter closure of patent foramen ovale in patients with paradoxical embolism: intermediate-term risk of recurrent neurological events. Catheter Cardiovasc Interv 55.2 (2002): 189-94. 23. El Said HG, McMahon CJ, Mullins CE, et al. Patent foramen ovale morphology and impact on percutaneous device closure. Pediatr Cardiol 26.1 (2005): 62-5. 24. Food and Drug Administration FDA Panel Summary-PFO Trial Design Issues. 2007. Available: http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4284b201.pdf. Date Accessed: May 16, 2007. 25. Food and Drug Administration Information for Physicians and Patients on the Withdrawal of Two Humanitarian Device Exemptions (HDEs) For Patent Foramen Ovale (PFO) Occluders. 2006. Available: http://www.fda.gov/cdrh/ode/h000007- h990011withdraw.html. Date Accessed: December 6, 2006. 26. Furie KL, Kasner SE, Adams RJ, et al. (2011). Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. Jan;42(1):227-76. Epub 2010 Oct 21. 27. Gentile S, Rainero I, Diniele D, et al. (2009). Reversible MRI abnormalities in a patient with recurrent status migrainous. Cephalgia 29. 687-690. 28. Giardini A, Donti A, Formigari R, et al. Comparison of results of percutaneous closure of patent foramen ovale for paradoxical embolism in patients with versus without thrombophilia. Am J Cardiol 94.8 (2004): 1012-6. 29. Goldstein LB, Bushnell CD, Adams RJ, et al. (2011). Guidelines for the primary prevention of stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. Feb;42(2):517-84. Epub 2010 Dec 2. 30. Hara H, Schwartz RS. Patent foramen ovale. 2006. UpToDate. Available: http://www.utdol.com/utd/content/topic.do?topicKey=cong_adu/5471&type=A&selectedTitle=1~26. Date. 31. Hara H, Virmani R, Ladich E, et al. Patent foramen ovale: current pathology, pathophysiology, and clinical status. J Am Coll Cardiol 46.9 (2005): 1768-76. 32. Harms V, Reisman M, Fuller CJ, et al. Outcomes after transcatheter closure of patent foramen ovale in patients with paradoxical embolism. Am J Cardiol 99.9 (2007): 1312-5. 33. Hayes Directory. Transcatheter Closure of Septal Defects. Lansdale, PA: Winifred S. Hayes, Inc., 2002. 34. Herrmann HC, Silvestry FE, Glaser R, et al. Percutaneous patent foramen ovale and atrial septal defect closure in adults: results and device comparison in 100 consecutive implants at a single center. Catheter Cardiovasc Interv 64.2 (2005): 197- 203. 35. Homma S, Sacco RL, Di Tullio MR, Sciacca RR, Mohr JP. Effect of medical treatment in stroke patients with patent foramen ovale: patent foramen ovale in Cryptogenic Stroke Study. Circulation 105.22 (2002): 2625-31. 36. Hong TE, Thaler D, Brorson J, Heitschmidt M, Hijazi ZM. Transcatheter closure of patent foramen ovale associated with paradoxical embolism using the amplatzer PFO occluder: initial and intermediate-term results of the U.S. multicenter clinical trial. Catheter Cardiovasc Interv 60.4 (2003): 524-8. 37. Ilkhanoff L, Naidu SS, Rohatgi S, Ross MJ, Silvestry FE, Herrmann HC. Transcatheter device closure of interatrial septal defects in patients with hypoxia. J Interv Cardiol 18.4 (2005): 227-32. 38. Kannan BR, Francis E, Sivakumar K, Anil SR, Kumar RK. Transcatheter closure of very large (>or= 25 mm) atrial septal defects using the Amplatzer septal occluder. Catheter Cardiovasc Interv 59.4 (2003): 522-7. 39. Khositseth A, Cabalka AK, Sweeney JP, et al. Transcatheter Amplatzer device closure of atrial septal defect and patent foramen ovale in patients with presumed paradoxical embolism. Mayo Clin Proc 79.1 (2004): 35-41. 40. Kiblawi FM, Sommer RJ, Levchuck SG. Transcatheter closure of patent foramen ovale in older adults. Catheter Cardiovasc Interv 68.1 (2006): 136-42; discussion 143-4. 41. Krumsdorf U, Ostermayer S, Billinger K, et al. Incidence and clinical course of thrombus formation on atrial septal defect and patient foramen ovale closure devices in 1,000 consecutive patients. J Am Coll Cardiol 43.2 (2004): 302-9.

Cardiovascular Policies, Continued

Percutaneous Transcatheter Closure for the Treatment of Atrial Septal Defects (ASD) and Patent Foramen Ovale (PFO), continued

42. Lopez K, Dalvi BV, Balzer D, et al. Transcatheter closure of large secundum atrial septal defects using the 40 mm Amplatzer septal occluder: results of an international registry. Catheter Cardiovasc Interv 66.4 (2005): 580-4. 43. Martin F, Sanchez PL, Doherty E, et al. Percutaneous transcatheter closure of patent foramen ovale in patients with paradoxical embolism. Circulation 106.9 (2002): 1121-6. 44. Mas JL, Arquizan C, Lamy C, et al. Recurrent cerebrovascular events associated with patent foramen ovale, atrial septal aneurysm, or both. N Engl J Med 345.24 (2001): 1740-6. 45. Messé SR, Schwartz RS, Perloff JK. Treatment of atrial septal abnormalities (PFO, ASD, and ASA) for prevention of recurrent stroke in adults. 2006. UpToDate. Available: http://www.utdol.com/utd/content/topic.do?topicKey=cva_dise/19543. Date Accessed: May 15, 2007. 46. Messe SR, Silverman IE, Kizer JR, et al. Practice parameter: recurrent stroke with patent foramen ovale and atrial septal aneurysm: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 62.7 (2004): 1042-50. 47. Onorato E, Melzi G, Casilli F, et al. Patent foramen ovale with paradoxical embolism: mid-term results of transcatheter closure in 256 patients. J Interv Cardiol 16.1 (2003): 43-50. 48. Overell JR, Bone I, Lees KR. Interatrial septal abnormalities and stroke: a meta-analysis of case-control studies. Neurology 55.8 (2000): 1172-9. 49. O'Gara PT, Messe SR, Tuzcu EM, et al. (2009). Percutaneous device closure of patent foramen ovale for secondary stroke prevention: a call for completion of randomized clinical trials. A science advisory from the American Heart Association/American Stroke Association and the American College of Cardiology Foundation. J Am Coll Cardiol. May 26;53(21):2014-8. 50. Patel A, Lopez K, Banerjee A, Joseph A, Cao QL, Hijazi ZM. Transcatheter closure of atrial septal defects in adults > or =40 years of age: immediate and follow-up results. J Interv Cardiol 20.1 (2007): 82-8. 51. Post MC, Van Deyk K, Budts W. Percutaneous closure of a patent foramen ovale: single-centre experience using different types of devices and mid-term outcome. Acta Cardiol 60.5 (2005): 515-9. 52. Purcell IF, Brecker SJ, Ward DE. Closure of defects of the atrial septum in adults using the Amplatzer device: 100 consecutive patients in a single center. Clin Cardiol 27.9 (2004): 509-13. 53. Sacco RL, Adams R, Albers G, et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline. Circulation 113.10 (2006): e409-49. 54. Schneider B, Bauer R. Is surgical closure of patent foramen ovale the gold standard for treating interatrial shunts? An echocardiographic follow-up study. J Am Soc Echocardiogr 18.12 (2005): 1385-91. 55. Schwerzmann M, Windecker S, Wahl A, et al. Percutaneous closure of patent foramen ovale: impact of device design on safety and efficacy. Heart 90.2 (2004): 186-90. 56. Silverman IE, Kiernan FJ, Kelsey AM, et al. Initial experience with a transcatheter septal closure system for secondary stroke prevention in patients with interatrial septal defects. Conn Med 67.3 (2003): 135-44. 57. Slavin L, Tobis JM, Rangarajan K, Dao C, Krivokapich J, Liebeskind DS. Five-year experience with percutaneous closure of patent foramen ovale. Am J Cardiol 99.9 (2007): 1316-20. 58. Spies C, Strasheim R, Timmermanns I, Schraeder R. Patent foramen ovale closure in patients with cryptogenic thromboembolic events using the Cardia PFO occluder. Eur Heart J 27.3 (2006): 365-71. 59. Spies C, Timmermanns I, Schrader R. Transcatheter closure of secundum atrial septal defects in adults with the Amplatzer septal occluder: Intermediate and long-term results. Clin Res Cardiol 96.6 (2007): 340-6. 60. Thanopoulos BV, Dardas PD, Karanasios E, Mezilis N. Transcatheter closure versus medical therapy of patent foramen ovale and cryptogenic stroke. Catheter Cardiovasc Interv 68.5 (2006): 741-6. 61. Varma C, Benson LN, Warr MR, et al. Clinical outcomes of patent foramen ovale closure for paradoxical emboli without echocardiographic guidance. Catheter Cardiovasc Interv 62.4 (2004): 519-25. 62. Wang JK, Tsai SK, Wu MH, Lin MT, Lue HC. Short- and intermediate-term results of transcatheter closure of atrial septal defect with the Amplatzer Septal Occluder. Am Heart J 148.3 (2004): 511-7. 63. Wiegers SE, Sutton MGSJ. Pathophysiology and clinical features of atrial septal defects in adults. 2006. UpToDate. Available: http://www.utdol.com/utd/content/topic.do?topicKey=congadu/4835&type=A&selectedTitle=3~42. Date Accessed: June 4, 2007. 64. Windecker S, Wahl A, Nedeltchev K, et al. Comparison of medical treatment with percutaneous closure of patent foramen ovale in patients with cryptogenic stroke. J Am Coll Cardiol 44.4 (2004): 750-8. 65. Woods TD, Patel A. A critical review of patent foramen ovale detection using saline contrast echocardiography: when bubbles lie. J Am Soc Echocardiogr 19.2 (2006): 215-22. 66. Yew G, Wilson NJ. Transcatheter atrial septal defect closure with the Amplatzer septal occluder: five-year follow-up. Catheter Cardiovasc Interv 64.2 (2005): 193-6. 67. Zajarias A, Thanigaraj S, Lasala J, Perez J. Predictors and clinical outcomes of residual shunt in patients undergoing percutaneous transcatheter closure of patent foramen ovale. J Invasive Cardiol 18.11 (2006): 533-7. 68. Lee PH, Song J-K, Kim JS, Heo R, Lee S, Kim D-H, Song J-M, Kang D-H, Kwon SU, Kang D-W, Lee D, Kwon HS, Yun S-C, Sun BJ, Park J-H, Lee J-H, Jeong HS, Song H-J, Kim J, Park S-J, Cryptogenic Stroke and High-Risk Patent Foramen Ovale: The DEFENSE-PFO Trial, Journal of the American College of Cardiology (2018), doi: 10.1016/j.jacc.2018.02.046.

Cardiovascular Policies, Continued

Percutaneous Transcatheter Closure for the Treatment of Atrial Septal Defects (ASD) and Patent Foramen Ovale (PFO), continued

Cardiovascular Policies, Continued

MEDICAL POLICY

PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY STENTING (PTAS) FOR THE TREATMENT OF INTRACEREBRAL DISEASE

Policy # 495 Implementation Date: 12/5/11 Review Dates: 7/18/13, 6/19/14, 6/11/15, 6/16/16, 6/15/17, 9/18/18, 8/7/19 Revision Dates:

Description Cerebrovascular disease (CVD) refers to a group of conditions that affect the circulation of blood to the brain, potentially limiting blood flow to affected areas of the brain. This can manifest itself as either a stroke or transient ischemic attack (TIA). Standard therapy for patients with atherosclerotic disease is antiplatelet therapy with aspirin or other antiplatelet agents and control of other risk factors. Intracerebral stenting of identified atherosclerotic lesions is also offered to some patients. The stent and delivery catheter consist of an expandable stainless-steel device that provides structural support for a blood vessel, helping to keep it open. The stent is a self-expanding, metal (nitinol) mesh in the shape of a tube. It is intended for use in the treatment of patients with recurrent intracranial stroke due to atherosclerotic disease who did not respond to medical therapy.

Commercial Plan Policy

SelectHealth does NOT cover percutaneous transluminal angioplasty stenting (PTAS) in the treatment of intracranial disease. The current evidence has not demonstrated this treatment as a clinical benefit for the initial therapy of intracerebral atherosclerotic disease.

SelectHealth Advantage (Medicare/CMS) (No Preauthorization Required but criteria may apply if appropriate)

SelectHealth Community Care (Medicaid/CHIP) (No Preauthorization Required but criteria may apply if appropriate)

Cardiovascular Policies, Continued

Percutaneous Transluminal Angioplasty Stenting (PTAS) for the Treatment of Intracerebral Disease, continued

Summary of Medical Information A Medical Technology Assessment performed in October 2011 identified 4 systematic reviews. All systematic reviews were published in 2006 or 2007 and no updates are available and long-term outcomes were not presented. Questions concerning durability and success of 2 different stents were raised. All concluded that current evidence at the time of their reviews was insufficient to warrant broad coverage outside an investigational setting. Seventeen peer-reviewed papers studying PTAS were identified. These studies were small in size and supported the use of stenting in patients with > 50% atherosclerotic narrowing of any intracerebral vessel with significant success and relatively low risk of complications. For example, the largest study by Jiang, involved 637 patients and 670 lesions. It was a retrospective study comparing 2 different stents. A relatively low risk of complications, 6.1% within 30 days of the procedure was demonstrated. This study’s limitations include the short duration of follow-up (1 month), and the lack of randomization or blinding. The most recent article on this topic was a randomized controlled multi-centered study published in September 2011 by Chimowitz et al. This study compared percutaneous transluminal angioplasty and stenting (PTAS) with aggressive medial management in patients with 70%–99% narrowing. The 2 groups had similar initial clinical findings, and both achieved similar outcomes to medical management including improved blood pressure control, LDL reduction, and diabetic control. Aspirin and clopidogrel were used. The interventional group developed a much higher rate of complications including hemorrhagic stroke and death within the first 30 days. The medical group also achieved a lower rate of stroke reduction than what was expected compared with previous studies evaluating the role of medical therapy in the prevention of recurrent stroke. “The 30-day rate of stroke or death in the PTAS group (14.7) is substantially higher than the rates previously reported with the use of the Wingspan stent in the Phase I trial and in 2 registries (rates ranging from 4.4-9.6).” The rate of stroke was much lower at 5.5% with expected rate of 10.7%. The expected 1-year rate of stroke or death was 25% and realized rate in this study was 12.2%. These results were carefully analyzed to attempt to explain the difference in realized and expected outcomes. Despite experienced interventional radiologists, similar initial clinical parameters, and similar results in aggressive medical management between the 2 groups, the much higher complication rate within the first 30 days of the procedure which included stroke and death led to the early suspension of this trial. Also discouraging was that 4% of patients (total of 9) who crossed over from the medical group to the PTAS group due to recurrent strokes also had a high rate of complications. Three of the 9 patients suffered a stroke after PTAS within 30 days. Despite attempts from stent manufacturers to minimize restenosis the rate of restenosis occurs “23%-30% within 6 months after intracranial PTAS and could also lead to later stroke.” In conclusion, the most recent large clinical trial, Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS), 14% of patients treated with angioplasty combined with stenting experienced a stroke or died within the first 30 days after enrollment compared with 5.8% of patients treated with medical therapy alone. Even though there have been many studies dating back to 2002, the literature has shown for patients with intracranial arterial stenosis, aggressive medical management was superior to PTAS with the use of either the Wingspan™ or the Neurolink® stent systems. The risks of early stroke after PTAS were high and the risk of stroke with aggressive medical therapy alone was lower than expected. Therefore, the use of PTAS with or without medical management does not seem to be a reliable form of treatment for intracranial stroke.

Billing/Coding Information Not covered: Investigational/Experimental/Unproven for this indication CPT CODES 61635 Transcatheter placement of intravascular stent(s), intracranial (e.g., atherosclerotic stenosis), including balloon angioplasty, if performed

HCPCS CODES C1874 Stent, coated/covered, with delivery system C1875 Stent, coated/covered, without delivery system 2

Cardiovascular Policies, Continued

Percutaneous Transluminal Angioplasty Stenting (PTAS) for the Treatment of Intracerebral Disease, continued

C1876 Stent, non-coated/non-covered, with delivery system C1877 Stent, non-coated/non-covered, without delivery system Key References 1. Abruzzo, TA, Tong, FC, Waldrop, AS, et al. (2007). Basilar artery stent angioplasty for symptomatic intracranial athero- occlusive disease: complications and late midterm clinical outcomes. AJNR Am J Neuroradiol 28.5: 808-15. 2. Albers, GW, Caplan, LR, Easton, JD, et al. (2002). Transient ischemic attack--proposal for a new definition. N Engl J Med 347.21: 1713-6. 3. Australia and New Zealand Horizon Scanning Network (ANZHSN).(2007) Intracranial angioplasty and stenting (WingSpan™) for cerebral atherosclerotic stenosis. 4. Bang, JS, Oh, CW, Jung, C, et al. (2010). Intracranial stent placement for recanalization of acute cerebrovascular occlusion in 32 patients. AJNR Am J Neuroradiol 31.7: 1222-5. 5. Bennett, CL, Connors, JM, Carwile, JM, et al. (2000). Thrombotic thrombocytopenic purpura associated with clopidogrel. N Engl J Med 342.24: 1773-7. 6. Caplan, LR. (2011) Overview of the evaluation of stroke. March 24, 2011. Up to Date. Available: http://www.uptodate.com/contents/overview-of-the-evaluation-of- stroke?source=search_result&search=cerebrovascular+disease&selectedTitle=1~150. Date Accessed: September 28, 2011. 7. Chimowitz, MI, Lynn, MJ, Derdeyn, CP, et al. (2011). Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med 365.11: 993-1003. 8. Creager, MA. (2006) Vascular Medicine: A Companion to Braunwald's Heart Disease. 1. Saunders Elseiver. Available: http://www.mdconsult.com/books/page.do?eid=4-u1.0-B978-0-7216-0284-4.50001-4&isbn=978-0-7216-0284- 4&uniqId=283830556-8#4-u1.0-B978-0-7216-0284-4.50001-4. Date Accessed: September 26, 2011. 9. Cronenwett, JL. (2010) Cronenwett: Rutherford's Vascular Surgery, 7th ed. 7. Saunders Elseiver. Available: http://www.mdconsult.com/books/page.do?eid=4-u1.0-B978-1-4160-5223-4.00092-5--s0015&isbn=978-1-4160-5223- 4&sid=1210424548&uniqId=283830556-5#4-u1.0-B978-1-4160-5223-4..0092-5--s0015. Date Accessed: September 26, 2011. 10. Cruz-Flores, S, Diamond, AL. (2006). Angioplasty for intracranial artery stenosis. Cochrane Database Syst Rev 3: CD004133. 11. Cucchiara, BL, Messé, SR. (2011) Antiplatelet therapy for secondary prevention of stroke. 19.2. April 4, 2011. UToDate. Available: http://www.uptodate.com/contents/antiplatelet-therapy-for-secondary-prevention-of- stroke?source=search_result&search=stroke+prevention&selectedTitle=1%7E150#H17. Date Accessed: October 23, 2011 12. Del Zoppo, GJ, Saver, JL, Jauch, EC, et al. (2009). Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator: a science advisory from the American Heart Association/American Stroke Association. Stroke 40.8: 2945-8. 13. Demarin, V, Lisak, M, Morovic, S, et al. (2010). Low high-density lipoprotein cholesterol as the possible risk factor for stroke. Acta Clin Croat 49.4: 429-39. 14. Endres, M, Heuschmann, PU, Laufs, U, et al. (2011). Primary prevention of stroke: blood pressure, lipids, and heart failure. Eur Heart J 32.5: 545-52. 15. FDA. (2009) NEUROLINK® System - H010004. September 8, 2009. FDA. Available: http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently- ApprovedDevices/ucm083307.htm. Date Accessed: September 30, 2011. 16. FDA. (2009) Wingspan™ Stent System with Gateway™ PTA Balloon Catheter - H50001. June 30, 2009. FDA. Available: http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently- ApprovedDevices/ucm078508.htm. Date Accessed: September 30, 2011. 17. Foundation for Education and Research in Neurological Emergencies. (2011) Efficient ED Neurological Exam, CT Diagnosis, and Documentation. FERNE. Available: http://www.ferne.org/Lectures/acep2005_spring/sloan_acep2005_spring_neuroexam.htm. Date Accessed: October 13, 2011. 18. Gupta, R, Schumacher, HC, Mangla, S, et al. (2003). Urgent endovascular revascularization for symptomatic intracranial atherosclerotic stenosis. Neurology 61.12: 1729-35. 19. Hauth, EA, Gissler, HM, Drescher, R, et al. (2004). Angioplasty or stenting of extra- and intracranial vertebral artery stenoses. Cardiovasc Intervent Radiol 27.1: 51-7. 20. Higashida, RT, Meyers, PM, Connors, JJ, 3rd, et al. (2005). Intracranial angioplasty & stenting for cerebral atherosclerosis: a position statement of the American Society of Interventional and Therapeutic Neuroradiology, Society of Interventional Radiology, and the American Society of Neuroradiology. AJNR Am J Neuroradiol 26.9: 2323-7. 21. International Stroke Trial (IST). (1997).: a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. International Stroke Trial Collaborative Group. Lancet 349.9065: 1569-81. 22. Jeon, P, Kim, BM, Kim, DI, et al. (2010). Emergent self-expanding stent placement for acute intracranial or extracranial internal carotid artery dissection with significant hemodynamic insufficiency. AJNR Am J Neuroradiol 31.8: 1529-32. 23. Jiang, WJ, Cheng-Ching, E, Abou-Chebl, A, et al. (2011). Multi-Center Analysis of Stenting in Symptomatic Intracranial Atherosclerosis. Neurosurgery. 24. Kelly, PJ. Mild-to-moderate hyperhomocystin(e)inemia and risk of stroke. Abstracts of the International Stroke Conference. Presentation at the International Stroke Conference: Stroke; 2000: 366. 25. Life Extension Foundation. (2011) Stroke and cerebrovascular disease stroke and prevention. Life Extension Foundation. Available: http://www.lef.org/protocols/heart_circulatory/stroke_cerebrovascular_disease_01.htm. Date Accessed: September 28, 2011. 26. Lin, R, Aleu, A, Jankowitz, B, et al. (2010). Endovascular Revascularization of Chronic Symptomatic Vertebrobasilar Occlusion. J Neuroimaging. 27. Lylyk, P, Vila, JF, Miranda, C, et al. (2005). Endovascular reconstruction by means of stent placement in symptomatic intracranial atherosclerotic stenosis. Neurol Res 27 Suppl 1: S84-8. 28. Marks, MP, Marcellus, ML, Do, HM, et al. (2005). Intracranial angioplasty without stenting for symptomatic atherosclerotic stenosis: long-term follow-up. AJNR Am J Neuroradiol 26.3: 525-30. 29. Mayo Clinic. (2011) Stroke. Mayo Clinic. Available: http://www.mayoclinic.com/health/stroke/DS00150/DSECTION=prevention. Date Accessed: September 28, 2011. 30. Meyers, PM, Schumacher, HC, Higashida, RT, et al. (2009). Indications for the performance of intracranial endovascular neurointerventional procedures: a scientific statement from the American Heart Association Council on Cardiovascular Radiology and Intervention, Stroke Council, Council on Cardiovascular Surgery and Anesthesia, Interdisciplinary Council on 3

Cardiovascular Policies, Continued

Percutaneous Transluminal Angioplasty Stenting (PTAS) for the Treatment of Intracerebral Disease, continued

Peripheral Vascular Disease, and Interdisciplinary Council on Quality of Care and Outcomes Research. Circulation 119.16: 2235-49. 31. National Institute for Health (NIH). (2011) Clinical Alert: Angioplasty Combined with Stenting Plus Aggressive Medical Therapy vs. Aggressive Medical Therapy Alone for Intracranial Arterial Stenosis: NINDS Stops Trial Enrollment Due to a Higher Risk of Stroke and Death in the Stented Group. June 16, 2011. US National Library of Medicine. Available: http://www.nlm.nih.gov/databases/alerts/intracranial_arterial_stenosis.html. Date Accessed: October 24, 2011. 32. National Institute for Health and Clinical Excellence (NICE).(2007) Endovascular stent insertion for intracranial atherosclerotic disease. 33. National Stroke Association. (2011) High Blood Pressure (Hypertension). National Stroke Association. Available: http://www.stroke.org/site/PageServer?pagename=highbloodpressure. Date Accessed: September 30, 2011. 34. Park, SI, Kim, BM, Kim, DI, et al. (2009). Clinical and angiographic follow-up of stent-only therapy for acute intracranial vertebrobasilar dissecting aneurysms. AJNR Am J Neuroradiol 30.7: 1351-6. 35. Povedano, G, Zuberbuhler, P, Lylyk, P, et al. (2010). Management strategies in posterior circulation intracranial atherosclerotic disease. J Endovasc Ther 17.3: 308-13. 36. Rakel, R. (2011) Rakel: Textbook of Family Medicine, 8th ed. 6. Elseiver Saunders. Available: http://www.mdconsult.com/books/page.do?eid=4-u1.0-B978-1-4377-1160-8.10042-9--s0130&isbn=978-1-4377-1160- 8&uniqId=284399105-13#4-u1.0-B978-1-4377-1160-8..10042-9--s0130. Date Accessed: September 30, 2011. 37. Ridker, PM, Cushman, M, Stampfer, MJ, et al. (1997). Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 336.14: 973-9. 38. Riedel, CH, Tietke, M, Alfke, K, et al. (2009). Subacute stent thrombosis in intracranial stenting. Stroke 40.4: 1310-4. 39. Roth, C, Papanagiotou, P, Behnke, S, et al. (2010). Stent-assisted mechanical recanalization for treatment of acute intracerebral artery occlusions. Stroke 41.11: 2559-67. 40. Sacco, RL, Prabhakaran, S, Thompson, JL, et al. (2006). Comparison of warfarin versus aspirin for the prevention of recurrent stroke or death: subgroup analyses from the Warfarin-Aspirin Recurrent Stroke Study. Cerebrovasc Dis 22.1: 4-12. 41. Sainani, GS, Sainani, R. (2002). Homocysteine and its role in the pathogenesis of atherosclerotic vascular disease. J Assoc Physicians India 50 Suppl: 16-23. 42. Saver, JL, Kalaft, M. (2011) Thrombolytic Therapy in Stroke March 29, 2011. Medscape Reference. Available: http://emedicine.medscape.com/article/1160840-overview. Date Accessed: October 18, 2011. 43. Suh, DC, Kim, JK, Choi, JW, et al. (2008). Intracranial stenting of severe symptomatic intracranial stenosis: results of 100 consecutive patients. AJNR Am J Neuroradiol 29.4: 781-5. 44. Technology Assessment Committee. (2006) Carotid, Vertebral and Intracranial Artery Angioplasty and Stenting TA #93. 45. Toole, JF, Malinow, MR, Chambless, LE, et al. (2004). Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA 291.5: 565-75. 46. Vajda, Z, Miloslavski, E, Guthe, T, et al. (2010). Treatment of intracranial atherosclerotic arterial stenoses with a balloon- expandable cobalt chromium stent (Coroflex Blue): procedural safety, efficacy, and midterm patency. Neuroradiology 52.7: 645-51. Wald, DS, Law, M, Morris, JK. (2002). Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ 325.7374: 1202. 47. Wehrschuetz, M, Wehrschuetz, E, Augustin, M, et al. (2011). Early single center experience with the solitaire thrombectomy device for the treatment of acute ischemic stroke. Interv Neuroradiol 17.2: 235-40. 48. Zhang, J, Zhang, R, Wu, Z, et al. (2010). Results of endovascular management for mid-basilar artery aneurysms. Interv Neuroradiol 16.3: 249-54. 49. Kernan, W. N., B. Ovbiagele, H. R. Black, D. M. Bravata, M. I. Chimowitz, M. D. Ezekowitz, M. C. Fang, M. Fisher, K. L. Furie, D. V. Heck, S. C. Johnston, S. E. Kasner, S. J. Kittner, P. H. Mitchell, M. W. Rich, D. Richardson, L. H. Schwamm, J. A. Wilson, C. o. C. American Heart Association Stroke Council, C. o. C. C. Stroke Nursing and D. Council on Peripheral Vascular (2014). "Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association." Stroke 45(7): 2160-2236.

Cardiovascular Policies, Continued

MEDICAL POLICY

SUBCUTANEOUS IMPLANTABLE DEFIBRILLATOR

Policy # 535 Implementation Date: 8/9/13 Review Dates: 8/28/14, 8/20/15, 8/25/16, 8/17/17, 7/25/18, 6/13/19, 6/18/20, 8/11/21 Revision Dates: 8/23/21

Description Tachyarrhythmias are broadly characterized as supraventricular tachycardia (SVT), defined as a tachycardia in which the driving circuit or focus originates, at least in part, in tissue above the level of the ventricle (i.e., sinus node, atria, AV node, or the bundle of His) and ventricular tachycardia (VT), defined as a tachycardia in which the driving circuit or focus solely originates in ventricular tissue or Purkinje f ibers. Sustained arrhythmias are an important cause of sudden death. Ventricular arrhythmias that occur in the absence of structural heart disease or a defined ion channel abnormality are referred to as idiopathic and are usually benign. Ventricular arrhythmias are responsible for most of the 150,000 to 350,000 sudden deaths that occur annually in the United States and account for approximately 13% of all mortality. Without immediate action, ventricular tachycardia can degenerate to ventricular fibrillation and lead to sudden death. Short-term goals of treatment are to stabilize hemodynamically unstable patients, transfer them to a hospital immediately, and stop ventricular tachycardia. Transvenous implantable cardiac defibrillators (ICDs) have been used for years and are designed to detect a life-threatening, rapid heartbeat emanating from the lower chamber of the heart, and then deliver an electrical discharge intended to terminate the rhythm so that it is converted back to normal. Conventional ICDs consist of a generator, which is usually implanted in a pocket in the pectoral region below the left shoulder. The transvenous right ventricular lead contains the shock coils and pacing electrode. Additional leads may be connected for right atrial or left ventricular pacing, sensing, and defibrillation. The ICD can be implanted under local anesthesia with the leads inserted through an incision into a vein and guided to the heart under fluoroscopy. The lead is attached to the heart muscle, while the other end of the lead is attached to the pulse generator. Subcutaneous implantable defibrillators (S-ICD) have recently been approved in an effort to reduce morbidity and procedure-related complications. The S-ICD consists of an electrically active pulse generator, which is implanted near the left mid-axillary line and a subcutaneous lead, consisting of sensing electrodes and a shocking coil, which is tunneled 1 to 2 cm to the left of the mid-sternal line. The current FDA approved S-ICD weighs 145 grams and has a lithium battery with a projected life of 5 years; therapy consists of 80-joule biphasic transthoracic shocks and 30 seconds of post-shock pacing.

Commercial Plan Policy/CHIP (Children’s Health Insurance Program)

SelectHealth covers subcutaneous implantable defibrillator for members 10 years of age and older who would require a transvenous cardiac defibrillator for ventricular tachyarrhythmias for the treatment of life-threatening ventricular tachyarrhythmias.

SelectHealth does not cover subcutaneous implantable defibrillators for patients who have symptomatic bradycardia, incessant ventricular tachycardia, or spontaneous, frequently recurring ventricular tachycardia that is reliably terminated with antitachycardia pacing.

Cardiovascular Policies, Continued

Subcutaneous Implantable Defibrillator, continued

SelectHealth Advantage (Medicare/CMS)

SelectHealth Community Care (Medicaid)

Summary of Medical Information A recent review of subcutaneous implantable cardiac defibrillators (S-ICDs) identified eight peer-reviewed published studies that met inclusion criteria for this report. No systematic reviews on the safety, efficacy, or cost-effectiveness of subcutaneous implantable defibrillators have been published. These studies had a mean duration ranging from 7.2 to 22.3 months. The studies documented efficacy of 89.6% to 100% in aborting dysrhythmias. These studies also identified inappropriate shocks occurring from 0% to 22% of the time. These numbers compare favorably to historical rates for efficacy and inappropriate shocks for transvenous ICDs which have demonstrated inappropriate shock rates as high as 30%. In general, single shocks, whether preceded by symptoms or not, are most often caused by the appropriate detection and treatment of a ventricular tachyarrhythmia. Conversely, multiple transvenous ICD discharges often result from the detection of other arrhythmias or signals that are inaccurately classified as a ventricular tachyarrhythmia. Thus, transvenous ICD therapy often is inappropriately delivered for sinus tachycardia, or other supraventricular tachycardias with rapid AV conduction. To this point, Jarman et al., Kobe et al., and Olde Nordkamp et al., all noted that inappropriate shocks (5.6% of all shocks) were associated with T-wave oversensing in patients with S-ICDs. During the MADIT II Trial of transvenous ICDs, Daubert et al. found that one or more inappropriate shocks occurred in 11.5% of the 719 patients enrolled. No cost-effectiveness studies have been completed comparing S-ICD to either transvenous ICD or to medical treatment. Using the Grade evidence system, which rates the body of evidence as either Grade 1−3, with additional ranking of A−C, the current body of evidence has a Grade evidence level of 2B. This is primarily due to the limitations in evidence, where risks and magnitude of benefits appear to be finely balanced in comparison to medical treatment or conventional ICD placement and where the quality of evidence is moderate (cohort studies with short follow-up times).

Billing/Coding Information CPT CODES 33240 Insertion of implantable defibrillator pulse generator only; with existing single lead 33241 Removal of implantable defibrillator pulse generator only 33262 Removal of implantable defibrillator pulse generator with replacement of implantable defibrillator pulse generator; single lead system 33263 Removal of implantable defibrillator pulse generator with replacement of implantable defibrillator pulse generator; dual lead system 33264 Removal of implantable defibrillator pulse generator with replacement of implantable defibrillator pulse generator; multiple lead system 2

Cardiovascular Policies, Continued

Subcutaneous Implantable Defibrillator, continued

33270 Insertion or replacement of permanent subcutaneous implantable defibrillator system, with subcutaneous electrode, including defibrillation threshold evaluation, induction of arrhythmia, evaluation of sensing for arrhythmia termination, and programming or reprogramming of sensing or therapeutic parameters, when performed 33271 Insertion of subcutaneous implantable defibrillator electrode 33272 Removal of subcutaneous implantable defibrillator electrode 33273 Repositioning of previously implanted subcutaneous implantable defibrillator electrode 93260 Programming device evaluation (in person) with iterative adjustment of the implantable device to test the function of the device and select optimal permanent programmed values with analysis, review and report by a physician or other qualified health care professional; implantable subcutaneous lead defibrillator system 93261 Interrogation device evaluation (in person) with analysis, review and report by a physician or other qualified health care professional, includes connection, recording and disconnection per patient encounter; implantable subcutaneous lead defibrillator system

HCPCS CODES C1721 Cardioverter-defibrillator, dual chamber (implantable)

C1722 Cardioverter-defibrillator, single chamber (implantable)

C1882 Cardioverter-defibrillator, other than single or dual chamber (implantable)

C1899 Lead, pacemaker/cardioverter-defibrillator combination (implantable)

G0448 Insertion or replacement of a permanent pacing cardioverter-defibrillator system with transvenous lead(s), single or dual chamber with insertion of pacing electrode, cardiac venous system, for left ventricular pacing

Key References 1. Medicine, HDAToC. (2012) Heart Disease: A Textbook of Cardiovascular Medicine. 9. Elsevier. Available: https://www.clinicalkey.com/#!/ContentPlayerCtrl/doPlayContent/3-s2.0- B9781437703986000391/{"scope":"all","query":"Ventricular Tachycardia"}. Date Accessed: April 17, 2013. 2. Compton, SJ. (2013) Ventricular Tachycardia Clinical Presentation. February 25, 2013. Medscape. Available: http://emedicine.medscape.com/article/159075-clinical. Date Accessed: May 20, 2013. 3. Goldman, L. (2012) Cecil Medicine. 24. Elseiver. Available: https://www.clinicalkey.com/#!/ContentPlayerCtrl/doPlayContent/3- s2.0-B9781437716047000658/{"scope":"all","query":"Ventricular Tachycardia"}. Date Accessed: April 17, 2013. 4. Borek, PP. (2011) Ventricular Tachycardia. October 7, 2011. Elsevier. Available: https://www.clinicalkey.com/#!/ContentPlayerCtrl/doPlayContent/21-s2.0-1011028/{"scope":"all","query":"ventricular tachyarrhythmia"}. Date Accessed: April 17, 2013. 5. (1997). A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. The Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators. N Engl J Med 337.22: 1576-83. 6. Greene, HL, Roden, DM, Katz, RJ, et al. (1992). The Cardiac Arrhythmia Suppression Trial: first CAST ... then CAST-II. J Am Coll Cardiol 19.5: 894-8. 7. Waldo, AL, Camm, AJ, deRuyter, H, et al. (1996). Effect of d-sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction. The SWORD Investigators. Survival With Oral d-Sotalol. Lancet 348.9019: 7-12. 8. EuroScan International Network. (2013) Subcutaneous Implantable Cardioverter-defibrillator (ICD). EuroScan International Network. Available: http://euroscan.org.uk/technologies/technology/view/1704. Date Accessed: May 24, 2013. 9. Bardy, GH, Hofer, B, Johnson, G, et al. (1993). Implantable transvenous cardioverter-defibrillators. Circulation 87.4: 1152-68. 10. Hauser, RG. (2013). The subcutaneous implantable cardioverter-defibrillator: should patients want one? J Am Coll Cardiol 61.1: 20-2. 11. Hohnloser, SH, Kuck, KH, Dorian, P, et al. (2004). Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction. N Engl J Med 351.24: 2481-8. 12. Jarman, JW, Todd, DM. (2013). United Kingdom national experience of entirely subcutaneous implantable cardioverter- defibrillator technology: important lessons to learn. Europace. 13. W., S. (2012) Subcutaneous Implantable Cardiac Defibrillator FDA Approved. October 1, 2012. MedGadget. Available: http://www.medgadget.com/2012/10/subcutaneous-implantable-cardiac-defibrillator-fda-approved.html. Date Accessed: April 19, 2013. 14. Cameron Health. (2013) About the Procedure. Cameron Health. Available: http://www.cameronhealth.com/understand-your- options/about-the-procedure/. Date Accessed: May 31, 2013.

Cardiovascular Policies, Continued

Subcutaneous Implantable Defibrillator, continued

15. Administration, USFaD. (2012) Subcutaneous Implantable Defibrillator (S-ICD) System - P110042. November 7, 2012. U.S. Department of Health & Human Services. Available: http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently- ApprovedDevices/ucm326541.htm. Date Accessed: April 19, 2013. 16. Boston Scientific. (2013) Introducing the S-ICD® System, the world's first and only Subcutaneous Implantable Defibrillator. Boston Scientific. Available: http://www.bostonscientific.com/cardiac-rhythm-resources/cameron-health/sicd-system.html. Date Accessed: April 19, 2013. 17. Aydin, A, Hartel, F, Schluter, M, et al. (2012). Shock efficacy of subcutaneous implantable cardioverter-defibrillator for prevention of sudden cardiac death: initial multicenter experience. Circ Arrhythm Electrophysiol 5.5: 913-9. 18. Bardy, GH, Smith, WM, Hood, MA, et al. (2010). An entirely subcutaneous implantable cardioverter-defibrillator. N Engl J Med 363.1: 36-44. 19. Dabiri Abkenari, L, Theuns, DA, Valk, SD, et al. (2011). Clinical experience with a novel subcutaneous implantable defibrillator system in a single center. Clin Res Cardiol 100.9: 737-44. 20. Griksaitis, MJ, Rosengarten, JA, Gnanapragasam, JP, et al. (2013). Implantable cardioverter defibrillator therapy in paediatric practice: a single-centre UK experience with focus on subcutaneous defibrillation. Europace 15.4: 523-30. 21. Kaltman, JR, Gaynor, JW, Rhodes, LA, et al. (2007). Subcutaneous array with active can implantable cardioverter defibrillator configuration: a follow-up study. Congenit Heart Dis 2.2: 125-9. 22. Kobe, J, Reinke, F, Meyer, C, et al. (2013). Implantation and follow-up of totally subcutaneous versus conventional implantable cardioverter-defibrillators: a multicenter case-control study. Heart Rhythm 10.1: 29-36. 23. Olde Nordkamp, LR, Dabiri Abkenari, L, Boersma, LV, et al. (2012). The entirely subcutaneous implantable cardioverter- defibrillator: initial clinical experience in a large Dutch cohort. J Am Coll Cardiol 60.19: 1933-9. 24. Callans, DJ, Hook, BG, Marchlinski, FE. (1991). Use of bipolar recordings from patch-patch and rate sensing leads to distinguish ventricular tachycardia from supraventricular rhythms in patients with implantable cardioverter defibrillators. Pacing Clin Electrophysiol 14.11 Pt 2: 1917-22. 25. Saksena, S. (2012) Electrophysiological Disorders of the Heart, Second Edition. 2. Elsevier. Available: https://www.clinicalkey.com/#!/ContentPlayerCtrl/doPlayContent/3-s2.0- B9781437702859000879/{"scope":"onlyThisSpecificBookChapter","query":"effectiveness"}. Date Accessed: May 23, 2013. 26. Daubert, JP, Zareba, W, Cannom, DS, et al. (2008). Inappropriate implantable cardioverter-defibrillator shocks in MADIT II: frequency, mechanisms, predictors, and survival impact. J Am Coll Cardiol 51.14: 1357-65. 27. British Cardiovascular Society. (2013) The Entirely Subcutaneous ICD (S-ICD). January 11, 2013. British Cardiovascular Society. Available: http://www.bcs.com/pages/news_full.asp?NewsID=19792120. Date Accessed: April 10, 2013. 28. Russo, AM, Stainback, RF, Bailey, SR, et al. (2013). ACCF/HRS/AHA/ASE/HFSA/SCAI/SCCT/SCMR 2013 appropriate use criteria for implantable cardioverter-defibrillators and cardiac resynchronization therapy: a report of the American College of Cardiology Foundation appropriate use criteria task force, Heart Rhythm Society, American Heart Association, American Society of Echocardiography, Heart Failure Society of America, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance. J Am Coll Cardiol 61.12: 1318-68. 29. ACCF/HRS/AHA/ASE/HFSA/SCAI/SCCT/SCMR. (2013). Appropriate use criteria for implantable cardioverter-defibrillators and cardiac resynchronization therapy. American College of Cardiology.

Cardiovascular Policies, Continued

MEDICAL POLICY

TOTAL ARTIFICIAL HEART

Policy # 436 Implementation Date: 3/22/10 Review Dates: 8/16/11, 8/15/13, 8/28/14, 8/20/15, 8/25/16, 12/15/16, 8/17/17, 7/20/18, 6/13/19, 6/18/20 Revision Dates: 8/16/12, 10/19/15

Description Heart failure (HF) is a common complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood. Heart failure is classified based upon the history, including assessment of New York Heart Association (NYHA) functional class, and physical examination in conjunction with certain diagnostic tests. Both establish the primary cause of the heart failure and provide a reasonable estimate of its severity. The NYHA classification system most commonly used to quantify the degree of functional limitation imposed by HF was first developed by the New York Heart Association (NYHA). This system assigns patients to one of four functional classes, depending on the degree of effort needed to elicit symptoms. • Class I - symptoms of HF only at activity levels that would limit normal individuals • Class II - symptoms of HF with ordinary exertion • Class III - symptoms of HF with less than ordinary exertion • Class IV - symptoms of HF at rest Additionally, heart failure has 4 stages (Stage A – Stage D) that reflect the development and progression of the condition. Treatment depends on the stage of heart failure. The first 2 stages (Stage A and B) are technically not heart failure but indicate that a patient is at high risk for developing it. Lifestyle and risk factor modification are the key components to the treatment of these stages. Patients with Stage C heart failure have a structural abnormality and current or previous symptoms of heart failure, including shortness of breath, fatigue, and difficulty exercising. In addition to the treatment undertaken for Stage A and B, these patients may be placed on a number of additional treatments, medications, or procedures. In addition to left ventricular assist devices, total artificial heart transplants (TAH-t) are used in patients with end-stage heart disease who need a heart transplant, who have failed optimal medical therapy, and for who no other reasonable medical or surgical treatment options are available. TAH-t is typically chosen in patients with biventricular failure rather than left ventricular failure only or who are ineligible for other ventricular devices when a donor organ is not immediately available. Total artificial hearts have been used as a bridge to transplant (temporary) or as a destination therapy (permanent). The SynCardia™ Total Artificial Heart (SynCardia Systems Inc., Tucson, AZ) is a pulsating bi-ventricular device that is implanted into the chest to replace the lower portion of the patient’s heart. Patients are connected by tubes from the heart through their chest wall to a large power-generating console, which operates and monitors the device. A smaller portable controller, the Freedom Driver, is available through clinical trial and patients may be discharged to home while waiting for transplantation. The AbioCor® Implantable Replacement Heart (Abiomed, Inc., Danvers, MA) is an electrically powered pump (pulsatile electrohydraulic device) used to replace the main pumping chambers (the ventricles) of the human heart. The device consists of a “Thoracic Unit” containing 2 sealed blood pumps, separated by an energy converter. After the lower chambers are removed, the unit is connected to the heart’s 2 upper collecting chambers. The energy converter moves hydraulic fluid from one side of the device to the other,

Cardiovascular Policies, Continued

Total Artificial Heart, continued

squeezing a sac containing the blood in one side of the pump to force the blood through the connected outgoing vessel. Simultaneously, blood is actively drawn into the pump on the opposite side, filling it for the next cycle, which will discharge blood to the other outgoing vessel. This device is totally implanted, including a regulator and an externally rechargeable battery. Both artificial hearts continue to be studied extensively, as both a bridge to transplant and a destination therapy in patients with intractable (stage 4) heart failure, failing on medication therapy alone.

Commercial Plan Policy (Preauthorization Required)

SelectHealth covers the SynCardia™ total artificial heart as a bridge to transplant in limited circumstances. Members must meet ALL the following criteria: 1. Intractable biventricular failure unresponsive to maximal medical therapy; AND 2. Member is an approved candidate for donor heart transplantation and has been registered as a transplant candidate; AND 3. Member is NOT a candidate for left ventricular assist device (LVAD) implantation; AND 4. Member has adequate space in the chest area where the ventricles will be removed. This is generally defined as a body surface area (BSA) > 1.7 m2 and a distance between the sternum and the 10th anterior vertebral body measured by CT is > or = 10 cm.

SelectHealth does NOT cover any other total artificial heart device (e.g., AbioCor®). The lack of evidence does not support adequate safety or efficacy. This meets the plan’s definition of investigational/experimental.

SelectHealth does NOT cover ANY total artificial heart device as destination therapy. The lack of evidence does not support adequate safety or efficacy. This meets the plan’s definition of investigational/experimental.

SelectHealth Advantage (Medicare/CMS) (Preauthorization Required)

SelectHealth Community Care (Medicaid/CHIP)

Summary of Medical Information The number of studies available assessing total artificial heart transplant (TAH-t) as a bridge to transplant or destination therapy is quite limited. Only 3 studies met the inclusion criteria for review and none were randomized to include an arm comparing the efficacy and safety of TAH-t to left ventricular assist device (LVAD) implantation. None of the reviews assessed the AbioCor device.

Cardiovascular Policies, Continued

Total Artificial Heart, continued

These studies, as expected, tended to have small study numbers, though, the largest by Platis et al. published in 2009 assessed the outcomes of 715 SynCardia transplants over 16 years. Overall, the studies demonstrated improved mortality as compared to watchful waiting but also demonstrated significant complications. From the studies included in this report, the table below provides a parallel comparison of the various trials and the outcomes as they compare to LVAD used as a bridge to transplant. Total Artificial Left Ventricular Characteristic Heart Device Assist Device Survival to transplant post-implantation 71.5%–79% 69%–86.9% 1-year survival post donor heart transplant 57%–90% 63%–66.6% 5-year survival post donor heart transplant 34%–81% Re-exploration for bleeding 47% 15.6%–33.3% Respiratory failure 4.7%–44% Renal failure requiring temporary dialysis 40% Infection 33%–85% 8%–19% Neurological event 7%–16% 4.8%-8.0% GI bleeding 15.6% Device failure 2.3% 0%–3.1% Though difficult to directly compare, parallel analysis of LVAD to TAH-t therapy suggests similar outcomes in appropriately selected patients.

Billing/Coding Information Covered: For the conditions outlined above CPT CODES 33927 Implantation of a total replacement heart system (artificial heart) with recipient cardiectomy 33928 Removal and replacement of total replacement heart system (artificial heart) 33929 Removal of a total replacement heart system (artificial heart) for heart transplantation (List separately in addition to code for primary procedure)

HCPCS CODES No specific codes identified

Key References 1. Colucci WS. Evaluation of the patient with heart failure or cardiomyopathy. 17.3. October 8, 2009. UpToDate. Available: http://www.uptodate.com/online/content/topic.do?topicKey=hrt_fail/20066&source=preview&anchor=H3#H3. Date Accessed: February 2, 2010. 2. Copeland JG, Smith RG, Arabia FA, et al. "Cardiac replacement with a total artificial heart as a bridge to transplantation." N Engl J Med 351.9 (2004): 859-67. 3. Copeland JG, Smith RG, Bose RK, Tsau PH, Nolan PE, Slepian MJ. "Risk factor analysis for bridge to transplantation with the CardioWest total artificial heart." Ann Thorac Surg 85.5 (2008): 1639-44. 4. El-Hamamsy I, Jacques F, Perrault LP, et al. "Results following implantation of mechanical circulatory support systems: the Montreal Heart Institute experience." Can J Cardiol 25.2 (2009): 107-10. 5. FDA. AbioCor® Implantable Replacement Heart - H040006. June 30, 2009. Food and Drug Administration. Available: http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently- ApprovedDevices/ucm077536.htm. Date Accessed: January 30, 2010. 6. FDA. Syncardia Temporary CardioWest Total Artificial Heart (TAH-t) - P030011. June 29, 2009. Food and Drug Administration. Available: http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently- ApprovedDevices/ucm080816.htm. Date Accessed: January 30, 2010. 7. Hayes Inc. Total Artificial Heart, Temporary or Permanent Biventricular Support Device. Lansdale: Hayes Inc., 2005. 8. HeartReplacement.com. The AbiCor System. 2009. AbioMed. Available: http://www.heartreplacement.com/abiocore.html. Date Accessed: January 10, 2010. 9. Hutchinson J, Scott DA, Clegg AJ, et al. "Cost-effectiveness of left ventricular-assist devices in end-stage heart failure." Expert Rev Cardiovasc Ther 6.2 (2008): 175-85. 10. John R, Kamdar F, Liao K, Colvin-Adams M, Boyle A, Joyce L. "Improved survival and decreasing incidence of adverse events with the HeartMate II left ventricular assist device as bridge-to-transplant therapy." Ann Thorac Surg 86.4 (2008): 1227-34; discussion 1234-5. 11. Lahpor J, Khaghani A, Hetzer R, et al. "European results with a continuous-flow ventricular assist device for advanced heartfailure patients." Eur J Cardiothorac Surg. (2009). 3

Cardiovascular Policies, Continued

Total Artificial Heart, continued

12. Loforte A, Montalto A, Ranocchi F, et al. "Long-term mechanical support with the HeartMate II LVAS." Transplant Proc 41.4 (2009): 1357-9. 13. MD Consult. Heart Failure. 5/13/2009. A.D.A.M. Inc. Available: http://www.mdconsult.com/das/patient/body/183362523- 4/952480291/10041/9436.html. Date Accessed: January 30, 2010. 14. Platis A, Larson DF. "CardioWest temporary total artificial heart." Perfusion 24.5 (2009): 341-6. 15. Roussel JC, Senage T, Baron O, et al. "CardioWest (Jarvik) total artificial heart: a single-center experience with 42 patients." Ann Thorac Surg 87.1 (2009): 124-9; discussion 130. 16. Slaughter MS, Rogers JG, Milano CA, et al. "Advanced heart failure treated with continuous-flow left ventricular assist device." N Engl J Med 361.23 (2009): 2241-51. 17. Slaughter MS, Tsui SS, El-Banayosy A, et al. "Results of a multicenter clinical trial with the Thoratec Implantable Ventricular Assist Device." J Thorac Cardiovasc Surg 133.6 (2007): 1573-80. 18. Struber M, Sander K, Lahpor J, et al. "HeartMate II left ventricular assist device; early European experience." Eur J Cardiothorac Surg 34.2 (2008): 289-94. 19. SynCardia. SynCardia Total Artificial Heart. 2009. Available: http://www.syncardia.com/SynCardia-Total-Artificial-Heart.html. Date Accessed: January 30, 2010.

Cardiovascular Policies, Continued

MEDICAL POLICY

TRANSCATHETER AORTIC VALVE IMPLANT (TAVI) TRANSCATHETER AORTIC VALVE REPLACEMENT (TAVR)

Policy # 444 Implementation Date: 5/26/10 Review Dates: 4/21/11, 12/18/14, 10/20/16, 9/19/18, 12/1/18, 12/18/19 Revision Dates: 8/5/13, 11/06/13, 4/3/15, 7/10/15, 12/9/16, 1/20/17, 12/21/17, 9/24/18, 8/23/19

Disclaimer: 1. Policies are subject to change without notice. 2. Policies outline coverage determinations for SelectHealth Commercial, SelectHealth Advantage (Medicare/CMS) and SelectHealth Community Care (Medicaid/CHIP) plans. Refer to the “Policy” section for more information.

Description There are 3 primary causes of valvular aortic stenosis (AS): a congenitally abnormal valve with superimposed calcification (unicuspid or bicuspid), calcific disease of a trileaflet valve, and rheumatic valve disease. In North America and Europe, aortic valve disease is primarily due to calcific disease of a native trileaflet or a congenital bicuspid valve. Worldwide, rheumatic valve disease is most common; mitral valve involvement invariably accompanies rheumatic aortic valve disease. Many patients do not develop symptoms until severe valve obstruction (valve area < 1.0 cm2) is present, while some patients become symptomatic when the stenosis is less severe (1.5−2.0 cm2), particularly, if there is coexisting aortic regurgitation. Replacement of the aortic valve is the only effective treatment for severe AS. Standard aortic valve replacement surgery involves the patient undergoing a sternotomy and being placed on cardio bypass. Not all patients can tolerate such an extensive procedure. Less invasive transcatheter techniques for aortic valve replacements have been developed. Currently, FDA approved transcatheter valves include the balloon expandable Sapien® valve and self-expandable CoreValve® systems. Both Sapien and CoreValve consist of metal frames which support tissue valves. In June 2015, the first repositionable transcatheter valve, the CoreValve Evolut R™ received FDA approval. This is the first valve which can be repositioned after initial deployment, so as to reduce valve leakage or other issues. Approaches to transcatheter aortic valve replacement include retrograde delivery with transfemoral, transaortic, and subclavian access, as well as antegrade delivery with the transapical approach.

Commercial Plan Policy (No Preauthorization Required but criteria must be met)

SelectHealth covers FDA approved transcatheter aortic valve implants/replacements in limited circumstances.

Criteria for Coverage (Must meet ALL): 1. Device has been approved by the FDA [PMA or 510(k)] 2. Patient has one of the following conditions: a. Severe native calcific aortic stenosis demonstrated by at least 1 of the following: 1) An aortic valve area ≤ 0.8cm2 2) A mean aortic valve gradient greater than 40mmHg 3) A jet velocity greater than 4.0m/sec b. Failure (stenosed, insufficient, or combined) of a surgical bioprosthetic aortic valve c. Severe aortic regurgitation with justification from a cardiothoracic surgeon

Cardiovascular Policies, Continued

Transcatheter Aortic Valve Implant (TAVI), Transcatheter Aortic Valve Replacement (TAVR), continued

3. Patient has documented New York Heart Association (NYHA) functional class II or greater 4. Patient has been evaluated face-to-face for open heart surgery by at least 1 cardiologist and 1 cardiothoracic surgeon, with full documentation, and determined to be a candidate for TAVR based on any one of the following: a. STS Risk Score > 3 b. Predicted surgical AVR irreversible morbidity > 40% c. Previous heart surgery d. Previous radiation to the chest e. Systemic steroids f. Severely calcified aorta (i.e., a porcelain aorta) g. Severe COPD (defined as FEV1 < 50% and FEV1/FVC of < 70) h. Significant comorbidities are present, which create at least moderate surgical risk, which has been determined by the cardiologist and the cardiothoracic surgeons’ documentation

5. Patient does not have any of the following exclusions: a. Aortic valve is a congenital unicuspid valve; or is non-calcified b. Hypertrophic cardiomyopathy with or without obstruction c. Echocardiographic evidence of intracardiac mass, thrombus or vegetation d. A known hypersensitivity or contraindication to aspirin, heparin, ticlopidine, or clopidogrel, or sensitivity to contrast media, which cannot be adequately pre- medicated e. Life expectancy < 12 months due to non-cardiac co-morbid conditions 6. TAVR must be furnished in a hospital with the appropriate infrastructure that includes but is not limited to: a. A cohesive, multi-disciplinary team of medical professionals with representatives from cardiology, cardiothoracic surgery, and critical care medicine b. On-site heart valve surgery program c. Cardiac catheterization lab or hybrid operating room/catheterization lab equipped with a fixed radiographic imaging system with flat-panel fluoroscopy d. Appropriate volume requirement per the applicable qualifications below 7. Operating facility has experience with TAVI/TAVR and maintains the following criteria: a. The hospital program must maintain the following: • ≥ 50 AVRs in the year prior to TAVR, including > 10 high-risk patients • ≥ 2 physicians with cardiac surgery privileges; and • ≥ 1,000 catheterizations per year, including ≥ 400 percutaneous coronary interventions (PCIs) per year b. The heart team must include: 1) Cardiovascular surgeon with > 100 career AVRs or > 25 AVRs in 1 year 2) Interventional cardiologist with 100 structural heart disease procedures lifetime or 30 left side structural procedures per year excluding septal defect closures 3) A cardiovascular surgeon and an interventional cardiologist whose combined experience maintains the following: • ≥ 20 TAVR procedures in the prior year, or • ≥ 40 TAVR procedures in the prior 2 years, and 2

Cardiovascular Policies, Continued

Transcatheter Aortic Valve Implant (TAVI), Transcatheter Aortic Valve Replacement (TAVR), continued

4) Additional members, such as echocardiographers, imaging specialists, heart failure specialists, cardiac anesthesiologists, intensivists, nurses, and social workers

SelectHealth covers transcatheter valve-in-valve aortic valve replacement when the above criteria are met.

SelectHealth Advantage (Medicare/CMS) (Preauthorization Required)

SelectHealth Community Care (Medicaid/CHIP) (Preauthorization Required)

Summary of Medical Information TAVR for Aortic Stenosis: A May 2010 Medical Technology Assessment found the published literature available on this topic was limited. Only 1 technology assessment and 4 primary studies were identified. However, it is important to note the 1 technology assessment was published in June 2006 and was performed by a highly respected organization—the National Institute for Health and Clinical Excellence (NICE) out of the U.K. This technology assessment aimed to provide conclusions concerning current evidence of transcatheter aortic valve implantation. Aortic regurgitation and transvalvular gradient both appeared to decrease significantly in postoperative follow-up. Most of the literature focused on the implementation of these 2 devices. These are 2 major indicators/complications associated with diseased aortic valves. A Medical Technology Assessment performed in June 2012 identified 23 new papers published since the last review in 2010, reflecting data at least 2 years post-procedure. In February 2012, Bleiziffer et al. reported 2-year results in 227 patients who received TAVI/TAVR. Clinical and echocardiographic investigations were performed at 6 months, 1 year, and 2 years. Survival was 88.5% at 30 days, 75.9% at 6 months, 74.5% at 1 year, and 64.4% at 2 years. Patients improved significantly in New York Heart Association class after 6 months (from 3.2 +/- 0.5 to 1.7 +/- 0.7, p < .001) and up to 2 years (1.9 +/- 0.7). Cumulative incidences of myocardial infarction, stroke, and life-threatening or major bleeding were 2.7%, 6.2%, and 16.2% at 2 years, respectively. Moderate or severe prosthetic regurgitation was present in 8% of patients at 2 years. In 6% of patients, the paravalvular or valvular regurgitation grade increased significantly over time. They concluded transcatheter aortic valve implantation may be considered the treatment of choice for aortic valve stenosis in elderly patients with an increased risk for surgery with a heart-lung machine. A prospective multicenter observational study published in 2011 by D’Onofrio et al. assessed early and 2- year outcomes after TAVI/TAVR in 179 patients. Patients underwent clinical and echocardiographic follow-up visits at hospital discharge, 3 and 6 months after TAVI/TAVR, and every 6 months thereafter. Seventeen severe intraoperative complications occurred in 13 (7.3%) patients. Thirty-day mortality was 3.9% (7 patients). Mean follow-up was 9.2 +/- 6.5 months. Late mortality occurred in 9 patients. Two-year survival was 88% +/- 3%. An intraoperative severe complication was identified as the only significant independent predictor of 1-year mortality. A significant benefit was found when comparing 2-year survival of the second versus the first 50% patients at each center (93% +/- 2% vs. 84% +/- 3 %; p = 0.046). A

Cardiovascular Policies, Continued

Transcatheter Aortic Valve Implant (TAVI), Transcatheter Aortic Valve Replacement (TAVR), continued

significant reduction of both mean and peak gradients from the preoperative to the postoperative period, which remained stable during follow-up, was found. In May 2012, the Centers for Medicare and Medicaid (CMS) issued a national coverage determination (NCD) outlining criteria under which it would provide coverage of TAVR/TAVI. Current evidence demonstrates improved mortality for patients who are ineligible for standard AVR, though, some increased morbidity risks exist especially for early stroke problems. Nonetheless, several studies identify this therapy to meet current standards for cost-effectiveness as defined by QALY’s. Transcatheter aortic valve replacement (TAVR) has emerged as a therapeutic alternative for patients with severe aortic stenosis whose surgical risk is very high or prohibitively high, in part due to findings of the PARTNER trials (inoperable patients: NEJM JW Cardiology May 2012 and N Engl J Med 2012; 366:1696; high-risk patients: NEJM JW Cardiology May 2012 and N Engl J Med 2012; 366:1686). Two manufacturer-sponsored analyses from PARTNER provide insights into the long-term survival patterns of such patients. Kapadia and colleagues focused on 358 patients with severe aortic stenosis (mean age, 83; mean Society of Thoracic Surgeons estimated risk of 30-day mortality after operative AVR [STS], 11.7%; women, 54%) who were deemed inoperable because of mortality risk or anatomical factors. Individuals were randomized to TAVR or nonoperative standard therapy. At 5 years, mortality was 71.8% in the TAVR group and 93.6% in the standard therapy group. There were six standard-therapy survivors with follow-up data; five received AVR outside the study. Of 49 survivors in the TAVR group, 86% had modest symptom burden (New York Heart Association class I or II symptoms). Prosthetic valve deterioration was not evident in the TAVR group. Mack and colleagues followed 699 patients with severe aortic stenosis (mean age, 84; mean STS score, 11.7%; women, 43%) who were considered at high but not prohibitive risk for surgery. Individuals were randomized to TAVR or surgical AVR (SAVR). At 5 years, the two groups had statistically similar mortality—67.8% with TAVR and 62.4% with SAVR. No postprocedural events requiring repeat valve replacement were reported. Moderate-to-severe aortic regurgitation 30 days after the procedure occurred in 14% of the TAVR group and 1% of the SAVR group (P < 0.0001) and was identified as a risk factor for death. Aortic Stenosis with Aortic Insufficiency: A literature review completed in November 2016 reviewed the evidence as it relates to TAVR use in aortic insufficiency. This review identified one systematic review and 3 primary studies were identified which met inclusion criteria. In all, 159 patients were studied, of which, 92 (57.9%) received TAVR for aortic insufficiency. The systematic review by Phan et al., though, specific to AI, investigated the use of TAVR in patients with a left ventricular assist device. Though the report showed promise for the procedure, it does not generally address the question of the procedure’s clinical utility in most patients with traditional AI symptoms. The 3 primary studies were all published since 2013. They consist of multi-center, prospective, or retrospective patient populations. No long-term data has been published to date on the use of this intervention for the treatment of AI. Only 1 of the 3 (33%, Wilder et al.) compared outcomes to other surgical methods. Survival outcomes from studies by Roy et al. and Testa et al. varied widely even with use of the same device (CoreValve) likely due to differing patient populations and inclusion criteria. Mortality from AI/AR in symptomatic patients is > 10% per year. The assessed studies show greater than double the mortality rate in patients treated with TAVR for AI than previously published outcomes from patients not undergoing surgical management for the treatment of AI. One obvious limitation of this conclusion is the lack of randomized, controlled published data regarding TAVR in patients with primary symptomatic AI. Though the evidence regarding TAVR in aortic insufficiency is weak, it demonstrates net benefit in high risk patients who are otherwise not surgical candidates. In addition, the FDA has approved the Edwards Sapien XT for use in aortic insufficiency in patients with a bioprosthetic valve (valve-in-valve procedure). As experience with TAVR continues to grow, potential candidates for TAVR continue to be explored. Whereas initial candidates were either ineligible for surgery or have serious surgery risk for post-operative morbidity or mortality. A body of literature has been published related to performing TAVR in patients with intermediate surgical risk (STS score > 3 and < 10). A review of the published literature recently completed identified four systematic reviews and 14 primary studies related to patients with intermediate surgical risk undergoing TAVR. All 4 systematic reviews were published in 2016 and the primary studies

Cardiovascular Policies, Continued

Transcatheter Aortic Valve Implant (TAVI), Transcatheter Aortic Valve Replacement (TAVR), continued

have all been published since 2012. These studies represent assessment of > 17,000 intermediate risk patients, of which, > 8,800 received TAVR. The four systematic reviews by Arora et al., Khan et al., Siemieniuk et al., and Zhou et al., reached similar conclusions that all-cause mortality rates did not differ to a statistically significant degree between SAVR and TAVR-treated intermediate-risk patients. From the primary literature studies by Abdul-Jawad Altisent et al., D'Errigo et al., Fanning et al., Kodali et al., Leon et al., and Thourani et al., it was also suggested the rate of stroke was lower in TAVR than in SAVR. One concern noted from the studies was related to the need for permanent cardiac pacemaker placement. Nine of the primary studies and the four systematic reviews reported on pacemaker implantation. All the systematic reviews reported an increased incidence of pacemaker implantation in TAVR vs. SAVR patients. This rate varied in the studies, from 2 to 15 times the incidence of pacemaker placement TAVR compared to SAVR. Conclusions drawn from the recently published data on TAVR for intermediate risk patients from 2012 has illustrated mortality and pacemaker implantation rates in nearly 8,000 patients. Most of the literature compared TAVR to SAVR and illustrated comparable mortality rates at follow-up periods between 1 and 24 months. However, substantially more pacemakers are implanted in TAVR patients than in those receiving standard surgical treatment.

Billing/Coding Information Covered: For the circumstances outlined above: CPT CODES 33361 Transcatheter aortic valve replacement (TAVR/TAVI) with prosthetic valve; percutaneous femoral artery approach 33362 Transcatheter aortic valve replacement (TAVR/TAVI) with prosthetic valve; open femoral artery approach 33363 Transcatheter aortic valve replacement (TAVR/TAVI) with prosthetic valve; open axillary artery approach 33364 Transcatheter aortic valve replacement (TAVR/TAVI) with prosthetic valve; open iliac artery approach 33365 Transcatheter aortic valve replacement (TAVR/TAVI) with prosthetic valve; transaortic approach (eg, median sternotomy, mediastinotomy) 33366 Transcatheter aortic valve replacement (TAVR/TAVI) with prosthetic valve; transapical exposure (eg, left thoracotomy 33367 Transcatheter aortic valve replacement (TAVR/TAVI) with prosthetic valve; cardiopulmonary bypass support with percutaneous peripheral arterial and venous cannulation (eg, femoral vessels) (List separately in addition to code for primary procedure) 33368 Transcatheter aortic valve replacement (TAVR/TAVI) with prosthetic valve; cardiopulmonary bypass support with open peripheral arterial and venous cannulation (eg, femoral, iliac, axillary vessels) (List separately in addition to code for primary procedure) 33369 Transcatheter aortic valve replacement (TAVR/TAVI) with prosthetic valve; cardiopulmonary bypass support with central arterial and venous cannulation (eg, aorta, right atrium, pulmonary artery) (List separately in addition to code for primary procedure) 33405 Replacement, aortic valve, with cardiopulmonary bypass; with prosthetic valve other than homograft or stentless valve 93355 Echocardiography, transesophageal (TEE) for guidance of a transcatheter intracardiac or great vessel(s) structural intervention(s) (eg,TAVR, transcatheter pulmonary valve replacement, mitral valve repair, paravalvular regurgitation repair, left atrial appendage occlusion/closure, ventricular septal defect closure) (peri-and intra-procedural), real-time image acquisition and documentation, guidance with quantitative measurements, probe manipulation, interpretation, and report, including diagnostic transesophageal

Cardiovascular Policies, Continued

Transcatheter Aortic Valve Implant (TAVI), Transcatheter Aortic Valve Replacement (TAVR), continued

echocardiography and, when performed, administration of ultrasound contrast, Doppler, color flow, and 3D Not Covered: Considered investigational: 93591 Percutaneous transcatheter closure of paravalvular leak; initial occlusion device, aortic valve

HCPCS CODES No specific codes identified

Key References 1. Al-Attar N, Ghodbane W, Himbert D, et al. (2009). Unexpected complications of transapical aortic valve implantation. Ann Thorac Surg 88.1: 90-4. 2. Amat-Santos, IJ, Rodes-Cabau, J, Urena, M, et al. (2012). Incidence, predictive factors, and prognostic value of new-onset atrial fibrillation following transcatheter aortic valve implantation. J Am Coll Cardiol 59.2: 178-88. 3. Bleiziffer, S, Mazzitelli, D, Opitz, A, et al. (2012). Beyond the short-term: clinical outcome and valve performance 2 years after transcatheter aortic valve implantation in 227 patients. J Thorac Cardiovasc Surg 143.2: 310-7. 4. CardiacHealth.org. (2012) Cardiac Risk STS Calculator. Cardiachealth.org. Available: http://www.cardiachealth.org/app/sts.php. Date Accessed: May 29, 2012. 5. Conradi, L, Seiffert, M, Treede, H, et al. (2012). Transcatheter aortic valve implantation versus surgical aortic valve replacement: a propensity score analysis in patients at high surgical risk. J Thorac Cardiovasc Surg 143.1: 64-71. 6. D'Onofrio, A, Fusari, M, Abbiate, N, et al. (2011). Transapical aortic valve implantation in high-risk patients with severe aortic valve stenosis. Ann Thorac Surg 92.5: 1671-7. 7. Edwards Life Sciences LLC. (2010) Edwards SAPIEN Transcatheter Heart Valve. Available: Edwards SAPIEN Transcatheter Heart Valve. Date Accessed: March 1, 2010. 8. ElBardissi, AW, Shekar, P, Couper, GS, et al. (2011). Minimally invasive aortic valve replacement in octogenarian, high-risk, transcatheter aortic valve implantation candidates. J Thorac Cardiovasc Surg 141.2: 328-35. 9. Erkapic, D, S, DER, Kelava, A, et al. (2012). Risk for permanent pacemaker after transcatheter aortic valve implantation: a comprehensive analysis of the literature. J Cardiovasc Electrophysiol 23.4: 391-7. 10. Ewe, SH, Delgado, V, Ng, AC, et al. (2011). Outcomes after transcatheter aortic valve implantation: transfemoral versus transapical approach. Ann Thorac Surg 92.4: 1244-51. 11. Fairbairn, TA, Meads, DM, Mather, AN, et al. (2012). Serial change in health-related quality of life over 1 year after transcatheter aortic valve implantation: predictors of health outcomes. J Am Coll Cardiol 59.19: 1672-80. 12. Fraccaro C, Napodano M, Tarantini G, et al. (2009). Expanding the eligibility for transcatheter aortic valve implantation the trans-subclavian retrograde approach using: the III generation CoreValve revalving system. JACC Cardiovasc Interv 2.9: 828- 33. 13. Gaasch, WH. (2009) Indications for valve replacement in aortic stenosis in adults. August 28, 2009. Up to Date. Available: http://www.utdol.com/online/content/topic.do?topicKey=valve_hd/3020&selectedTitle=1%7E85&source=search_result#. Date Accessed: March 2, 2010, 2010. 14. Gaasch, WH. (2009) Methods of valve replacement in aortic stenosis in adults. February 2, 2009. Up To Date. Available: http://www.utdol.com/online/content/topic.do?topicKey=valve_hd/21421&selectedTitle=1%7E150&source=search_result. Date Accessed: February 24, 2010, 2010. 15. Gada, H, Kapadia, SR, Tuzcu, EM, et al. (2012). Markov model for selection of aortic valve replacement versus transcatheter aortic valve implantation (without replacement) in high-risk patients. Am J Cardiol 109.9: 1326-33. 16. Gilard, M, Eltchaninoff, H, Iung, B, et al. (2012). Registry of transcatheter aortic-valve implantation in high-risk patients. N Engl J Med 366.18: 1705-15. 17. Grube E, Laborde JC, Gerckens U, et al. (2006). Percutaneous implantation of the CoreValve self-expanding valve prosthesis in high-risk patients with aortic valve disease: the Siegburg first-in-man study. Circulation 114.15: 1616-24. 18. Grube E, Schuler G, Buellesfeld L, et al. (2007). Percutaneous aortic valve replacement for severe aortic stenosis in high-risk patients using the second- and current third-generation self-expanding CoreValve prosthesis: device success and 30-day clinical outcome. J Am Coll Cardiol 50.1: 69-76. 19. Hammermeister K, Sethi GK, Henderson WG, et al. (2000). Outcomes 15 years after valve replacement with a mechanical versus a bioprosthetic valve: final report of the Veterans Affairs randomized trial. J Am Coll Cardiol 36.4: 1152-8. 20. Hayashida, K, Morice, MC, Chevalier, B, et al. (2012). Sex-related differences in clinical presentation and outcome of transcatheter aortic valve implantation for severe aortic stenosis. J Am Coll Cardiol 59.6: 566-71. 21. Holmes, DR, Jr., Mack, MJ, Kaul, S, et al. (2012). 2012 ACCF/AATS/SCAI/STS expert consensus document on transcatheter aortic valve replacement: developed in collaboration with the American Heart Association, American Society of Echocardiography, European Association for Cardio-Thoracic Surgery, Heart Failure Society of America, Mended Hearts, Society of Cardiovascular Anesthesiologists, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance. Ann Thorac Surg 93.4: 1340-95. 22. Kalavrouziotis, D, Rodes-Cabau, J, Bagur, R, et al. (2011). Transcatheter aortic valve implantation in patients with severe aortic stenosis and small aortic annulus. J Am Coll Cardiol 58.10: 1016-24. 23. Latsios, G, Gerckens, U, Grube, E. (2009). Transaortic transcatheter aortic valve implantation: A novel approach for the truly "no-access option" patients. Catheter Cardiovasc Interv. 24. Leon, MB, Kodali, S, Williams, M, et al. (2006). Transcatheter aortic valve replacement in patients with critical aortic stenosis: rationale, device descriptions, early clinical experiences, and perspectives. Semin Thorac Cardiovasc Surg 18.2: 165-74. 25. Lichtenstein SV, Cheung A, Ye J, et al. (2006). Transapical transcatheter aortic valve implantation in humans: initial clinical experience. Circulation 114.6: 591-6. 26. Makkar, RR, Fontana, GP, Jilaihawi, H, et al. (2012). Transcatheter aortic-valve replacement for inoperable severe aortic stenosis. N Engl J Med 366.18: 1696-704.

Cardiovascular Policies, Continued

Transcatheter Aortic Valve Implant (TAVI), Transcatheter Aortic Valve Replacement (TAVR), continued

27. Medtronic. (2009) Medtronic CoreValve System 60. Available: http://www.medtronic.com/corevalve/other.html. Date Accessed: April 28, 2010 28. Moat, NE, Ludman, P, de Belder, MA, et al. (2011). Long-term outcomes after transcatheter aortic valve implantation in high- risk patients with severe aortic stenosis: the U.K. TAVI (United Kingdom Transcatheter Aortic Valve Implantation) Registry. J Am Coll Cardiol 58.20: 2130-8. 29. Motloch, LJ, Reda, S, Rottlaender, D, et al. (2012). Postprocedural atrial fibrillation after transcatheter aortic valve implantation versus surgical aortic valve replacement. Ann Thorac Surg 93.1: 124-31. 30. NICE. (2008) http://www.nice.org.uk/nicemedia/live/11914/41020/41020.pdf. London: National Institute for Health and Clinical Excellence. 31. Otto, CM. (2010). Pathophysiology and clinical features of valvular aortic stenosis in adults. 18.1. Available: http://www.uptodate.com/online/content/topic.do?topicKey=valve_hd/7401&selectedTitle=2%7E150&source=search_result. April 4 Access Date, Access 2010. 32. Otto, CM. (2012) Estimating the mortality risk of valvular surgery. April 11, 2012. Up to Date. Available: http://www.uptodate.com/contents/estimating-the-mortality-risk-of-valvular- surgery?source=search_result&search=sts+score&selectedTitle=1~150. Date Accessed: June 4, 2012. 33. Piazza N, Grube E, Gerckens U, et al. (2008). Procedural and 30-day outcomes following transcatheter aortic valve implantation using the third generation (18 Fr) corevalve revalving system: results from the multicentre, expanded evaluation registry 1-year following CE mark approval. EuroIntervention 4.2: 242-9. 34. Piazza N, Grube E, Gerckens U, et al. (2010). A clinical protocol for analysis of the structural integrity of the Medtronic CoreValve System(R) frame and its application in patients with 1-year minimum follow-up. EuroIntervention 5.6: 680-6. 35. Reynolds, MR, Magnuson, EA, Lei, Y, et al. (2011). Health-related quality of life after transcatheter aortic valve replacement in inoperable patients with severe aortic stenosis. Circulation 124.18: 1964-72. 36. Smith, CR, Leon, MB, Mack, MJ, et al. (2011). Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med 364.23: 2187-98. 37. Society for Cardiothoracic Surgery. (2008) A position statement of the British Cardiovascular Intervention Society (BCIS) and the Society for Cardiothoracic Surgery (SCTS). December 18, 2008. Society for Cardiothoracic Surgery in Great Britain and England. 58. Available: http://www.scts.org/documents/PDF/BCISTAVIDec2008.pdf. Date Accessed: March 3, 2010 38. Stortecky, S, Brinks, H, Wenaweser, P, et al. (2011). Transcatheter aortic valve implantation or surgical aortic valve replacement as redo procedure after prior coronary artery bypass grafting. Ann Thorac Surg 92.4: 1324-30; discussion 1230-1. 39. Swinkels, BM, Plokker, HW. (2010). Evaluating operative mortality of cardiac surgery: first define operative mortality. Neth Heart J 18.7-8: 344-5. 40. Tchetche D, Dumonteil N, Sauguet A, et al. (2010). Thirty-day outcome and vascular complications after transarterial aortic valve implantation using both Edwards Sapien and Medtronic CoreValve(R) bioprostheses in a mixed population. EuroIntervention 5.6: 659-65. 41. The Society of Thoracic Surgeons. (2012) Explanation of Quality Rating, Composite Score, and Star Ratings. The Society of Thoracic Surgeons. Available: http://www.sts.org/quality-research-patient-safety/sts-public-reporting-online/explanation-quality- rating-composite-sco. Date Accessed: June 1, 2012. 42. TheHeart.org. (2012) PARTNER CAP data show transapical outcomes improve with practice. January 31, 2012. Interventional and Surgery. Available: http://www.theheart.org/article/1348117.do. Date Accessed: June 5, 2012. 43. Unbehaun, A, Pasic, M, Dreysse, S, et al. (2012). Transapical aortic valve implantation: incidence and predictors of paravalvular leakage and transvalvular regurgitation in a series of 358 patients. J Am Coll Cardiol 59.3: 211-21. 44. Ussia, GP, Scarabelli, M, Mule, M, et al. (2011). Dual antiplatelet therapy versus aspirin alone in patients undergoing transcatheter aortic valve implantation. Am J Cardiol 108.12: 1772-6. 45. Watt, M, Mealing, S, Eaton, J, et al. (2012). Cost-effectiveness of transcatheter aortic valve replacement in patients ineligible for conventional aortic valve replacement. Heart 98.5: 370-6. 46. Webb, JG, Chandavimol, M, Thompson, CR, et al. (2006). Percutaneous aortic valve implantation retrograde from the femoral artery. Circulation 113.6: 842-50. 47. Ye, J, Cheung, A, Lichtenstein, SV, et al. (2007). Six-month outcome of transapical transcatheter aortic valve implantation in the initial seven patients. Eur J Cardiothorac Surg 31.1: 16-21. 48. Zierer, A, Wimmer-Greinecker, G, Martens, S, et al. (2008). The transapical approach for aortic valve implantation. J Thorac Cardiovasc Surg 136.4: 948-53. 49. Food and Drug Administration (2013). "Edwards SAPIEN Transcatheter Heart Valve (THV)-P100041." Retrieved 11/07, 2013. 50. Barbanti, M., et al. (2012). "Transcatheter aortic valve implantation in patients with mitral prosthesis." J Am Coll Cardiol 60(18): 1841-1842. 51. Beller, C. J., et al. (2011). "Transcatheter aortic valve implantation after previous mechanical mitral valve replacement: expanding indications?" Heart Surg Forum 14(3): E166-170. 52. Garcia, E., et al. (2011). "[Transcatheter aortic valve implantation in patients with a mechanical mitral valve]." Rev Esp Cardiol 64(11): 1052-1055. 53. Bunc, M. (2012). "Successful Tavi in Patients with Previous Mitral Valve Replacement " Scietific Research 3((7)). 54. Kapadia SR et al. 5-year outcomes of transcatheter aortic valve replacement compared with standard treatment for patients with inoperable aortic stenosis (PARTNER 1): A randomised controlled trial. Lancet 2015 Mar 15; [e-pub]. (http://dx.doi.org/10.1016/S0140-6736(15)60290-2) 55. Mack MJ et al. 5-year outcomes of transcatheter aortic valve replacement or surgical aortic valve replacement for high surgical risk patients with aortic stenosis (PARTNER 1): A randomised controlled trial. Lancet 2015 Mar 15; [e-pub]. (http://dx.doi.org/10.1016/S0140-6736(15)60308-7 56. Kappetein, A.P. PARTNERs in the future of surgical aortic valve replacement. Lancet 2015 Mar 15; [e-pub]. (http://dx.doi.org/10.1016/S0140-6736(15)60568-2) 57. Medtronic (2015). "Medtronic Announces FDA Approval for New TAVR System, Introduces First and Only Recaturable Heart Valve in U.S.". Retrieved 06/23/2015, 2015, from http://newsroom.medtronic.com/phoenix.zhtml?c=251324&p=irol- newsArticle&ID=2061818. 58. Gaasch, W.H. Clinical manifestations and diagnosis of chronic aortic regurgitation in adults. 2016 April 10 [cited 2016 November 11]; Available from: https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-chronic-aortic- regurgitation-in-adults?source=search_result&search=aortic%20insufficiency&selectedTitle=1~150#H5.

Cardiovascular Policies, Continued

Transcatheter Aortic Valve Implant (TAVI), Transcatheter Aortic Valve Replacement (TAVR), continued

59. Gaasch, W.H. Natural history and management of chronic aortic regurgitation in adults. 2016 July 29, 2015 [cited 2016 November 11]; Available from: https://www.uptodate.com/contents/natural-history-and-management-of-chronic-aortic- regurgitation-in- adults?source=search_result&search=aortic%20regurgitation%20treatment&selectedTitle=1~150#H1411845277. 60. Wang, S.S. Aortic Regurgitation. 2016 February 12, 2014 [cited 2016 November 11]; Available from: http://emedicine.medscape.com/article/150490-overview#a7. 61. UnitedHealthcare. Transcatheter Heart Valve Procedures. 2016 September 1, 2016 [cited 2016 November 1, 2016]; Available from: https://www.unitedhealthcareonline.com/ccmcontent/ProviderII/UHC/en_US/Assets/ProviderStaticFiles/ProviderStaticFilesPdf/ Tools%20and%20Resources/Policies%20and%20Protocols/Medical%20Policies/Medical%20Policies/TranscatheterHeartValve _Procedures.pdf 62. Phan, K., et al., Percutaneous transcatheter interventions for aortic insufficiency in continuous-flow left ventricular assist device patients: A systematic review and meta-analysis. ASAIO J, 2016. 63. Roy, D.A., et al., Transcatheter aortic valve implantation for pure severe native aortic valve regurgitation. J Am Coll Cardiol, 2013. 61(15): p. 1577-84. 64. Testa, L., et al., CoreValve implantation for severe aortic regurgitation: a multicentre registry. EuroIntervention, 2014. 10(6): p. 739-45. 65. Wilder, T.J., et al., Aortic valve repair for insufficiency in older children offers unpredictable durability that may not be advantageous over a primary Ross operationdagger. Eur J Cardiothorac Surg, 2016. 49(3): p. 883-92. 66. Nishimura, R.A., et al., 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation, 2014. 129(23): p. 2440-92. 67. Food and Drug Administration. Edwards SAPIEN XT Transcatheter Heart Valve. 2015 October 9, 2015 [cited 2016 November 23]; Available from: http://www.accessdata.fda.gov/cdrh_docs/pdf13/P130009S034A.pdf. 68. Food and Drug Administration. Edwards SAPIEN 3 Transcatheter Heart Valve. 2016 August 18, 2016 [cited 2016 November 23]; Available from: http://www.accessdata.fda.gov/cdrh_docs/pdf14/P140031S010a.pdf. Intermediate Risk References 69. Gaasch, W.H. Clinical manifestations and diagnosis of chronic aortic regurgitation in adults. 2016 April 10 [cited 2016 November 11]; Available from: https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-chronic-aortic- regurgitation-in-adults?source=search_result&search=aortic%20insufficiency&selectedTitle=1~150#H5. 70. Gaasch, W.H. Indications for valve replacement in aortic stenosis in adults. 2009 August 28, 2009 [cited 2010 March 2, 2010]; Available from: http://www.utdol.com/online/content/topic.do?topicKey=valve_hd/3020&selectedTitle=1%7E85&source=search_result#. 71. Van Mieghem, N. The Art of Risk Stratification in TAVI. 2013 [cited 2016 December 13]; Available from: http://www.medscape.com/viewarticle/807418_3. 72. Wenaweser, P., et al., Clinical outcomes of patients with estimated low or intermediate surgical risk undergoing transcatheter aortic valve implantation. Eur Heart J, 2013. 34(25): p. 1894-905. 73. Van Mieghem, N.M. and P.W. Serruys, The art of risk stratification in TAVI. Eur Heart J, 2013. 34(25): p. 1859-61. 74. Gaasch, W.H. Natural history and management of chronic aortic regurgitation in adults. 2016 July 29, 2015 [cited 2016 November 11]; Available from: https://www.uptodate.com/contents/natural-history-and-management-of-chronic-aortic- regurgitation-in- adults?source=search_result&search=aortic%20regurgitation%20treatment&selectedTitle=1~150#H1411845277. 75. Wang, S.S. Aortic Regurgitation. 2016 February 12, 2014 [cited 2016 November 11]; Available from: http://emedicine.medscape.com/article/150490-overview#a7. 76. Gaasch, W.H. Methods of valve replacement in aortic stenosis in adults. [Methods of valve replacement in aortic stenosis in adults] 2009 February 2, 2009 [cited 2010 February 24, 2010]; Available from: http://www.utdol.com/online/content/topic.do?topicKey=valve_hd/21421&selectedTitle=1%7E150&source=search_result. 77. Hammermeister, K., et al., Outcomes 15 years after valve replacement with a mechanical versus a bioprosthetic valve: final report of the Veterans Affairs randomized trial. J Am Coll Cardiol, 2000. 36(4): p. 1152-8. 78. Groh, M.A., et al., Is Surgical Intervention the Optimal Therapy for the Treatment of Aortic Valve Stenosis for Patients With Intermediate Society of Thoracic Surgeons Risk Score? Ann Thorac Surg, 2016. 79. Leon, M.B., et al., Transcatheter aortic valve replacement in patients with critical aortic stenosis: rationale, device descriptions, early clinical experiences, and perspectives. Semin Thorac Cardiovasc Surg, 2006. 18(2): p. 165-74. 80. Webb, J.G., et al., Percutaneous aortic valve implantation retrograde from the femoral artery. Circulation, 2006. 113(6): p. 842- 50. 81. Zierer, A., et al., The transapical approach for aortic valve implantation. J Thorac Cardiovasc Surg, 2008. 136(4): p. 948-53. 82. UnitedHealthcare. Transcatheter Heart Valve Procedures. 2016 September 1, 2016 [cited 2016 November 1, 2016]; Available from: https://www.unitedhealthcareonline.com/ccmcontent/ProviderII/UHC/en- US/Assets/ProviderStaticFiles/ProviderStaticFilesPdf/Tools%20and%20Resources/Policies%20and%20Protocols/Medical%20 Policies/Medical%20Policies/Transcatheter_Heart_Valve_Procedures.pdf. 83. Abdul-Jawad Altisent, O., et al., Neurological damage after transcatheter aortic valve implantation compared with surgical aortic valve replacement in intermediate risk patients. Clin Res Cardiol, 2016. 105(6): p. 508-17. 84. Barbash, I.M., et al., Outcomes of Patients at Estimated Low, Intermediate, and High Risk Undergoing Transcatheter Aortic Valve Implantation for Aortic Stenosis. Am J Cardiol, 2015. 116(12): p. 1916-22. 85. Castrodeza, J., et al., Propensity score matched comparison of transcatheter aortic valve implantation versus conventional surgery in intermediate and low risk aortic stenosis patients: A hint of real-world. Cardiol J, 2016. 86. D'Errigo, P., et al., Transcatheter aortic valve implantation versus surgical aortic valve replacement for severe aortic stenosis: results from an intermediate risk propensity-matched population of the Italian OBSERVANT study. Int J Cardiol, 2013. 167(5): p. 1945-52. 87. Fanning, J.P., et al., Neurological Injury in Intermediate-Risk Transcatheter Aortic Valve Implantation. J Am Heart Assoc, 2016. 5(11). 88. Fraccaro, C., et al., Early and Midterm Outcome of Propensity-Matched Intermediate-Risk Patients Aged >/=80 Years With Aortic Stenosis Undergoing Surgical or Transcatheter Aortic Valve Replacement (from the Italian Multicenter OBSERVANT Study). Am J Cardiol, 2016. 117(9): p. 1494-501. 8

Cardiovascular Policies, Continued

Transcatheter Aortic Valve Implant (TAVI), Transcatheter Aortic Valve Replacement (TAVR), continued

89. Kodali, S., et al., Early clinical and echocardiographic outcomes after SAPIEN 3 transcatheter aortic valve replacement in inoperable, high-risk and intermediate-risk patients with aortic stenosis. Eur Heart J, 2016. 37(28): p. 2252-62. 90. Latib, A., et al., Transcatheter vs surgical aortic valve replacement in intermediate-surgical-risk patients with aortic stenosis: a propensity score-matched case-control study. Am Heart J, 2012. 164(6): p. 910-7. 91. Leon, M.B., et al., Transcatheter or Surgical Aortic-Valve Replacement in Intermediate-Risk Patients. N Engl J Med, 2016. 374(17): p. 1609-20. 92. Muneretto, C., et al., A comparison of conventional surgery, transcatheter aortic valve replacement, and sutureless valves in "real-world" patients with aortic stenosis and intermediate- to high-risk profile. J Thorac Cardiovasc Surg, 2015. 150(6): p. 1570-7; discussion 1577-9. 93. Osnabrugge, R.L., et al., Costs of transcatheter versus surgical aortic valve replacement in intermediate-risk patients. Ann Thorac Surg, 2012. 94(6): p. 1954-60. 94. Piazza, N., et al., A 3-center comparison of 1-year mortality outcomes between transcatheter aortic valve implantation and surgical aortic valve replacement on the basis of propensity score matching among intermediate-risk surgical patients. JACC Cardiovasc Interv, 2013. 6(5): p. 443-51. 95. Thourani, V.H., et al., Transcatheter aortic valve replacement versus surgical valve replacement in intermediate-risk patients: a propensity score analysis. Lancet, 2016. 387(10034): p. 2218-25. 96. Arora, S., et al., Transcatheter versus surgical aortic valve replacement in intermediate risk patients: a meta-analysis. Cardiovasc Diagn Ther, 2016. 6(3): p. 241-9. 97. Khan, A.R., et al., Efficacy and safety of transcatheter aortic valve replacement in intermediate surgical risk patients: A systematic review and meta-analysis. Catheter Cardiovasc Interv, 2016. 88(6): p. 934-944. 98. Siemieniuk, R.A., et al., Transcatheter versus surgical aortic valve replacement in patients with severe aortic stenosis at low and intermediate risk: systematic review and meta-analysis. BMJ, 2016. 354: p. i5130. 99. Zhou, Y., et al., Transcatheter versus surgical aortic valve replacement in low to intermediate risk patients: A meta-analysis of randomized and observational studies. Int J Cardiol, 2016. 228: p. 723-728. 100. National Guideline Clearinghouse, 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2014. 101. Food and Drug Administration. Edwards SAPIEN 3 Transcatheter Heart Valve. 2016 August 18, 2016 [cited 2016 November 23]; Available from: http://www.accessdata.fda.gov/cdrh_docs/pdf14/P140031S010a.pdf. 102. Food and Drug Administration. Edwards SAPIEN XT Transcatheter Heart Valve. 2015 October 9, 2015 [cited 2016 November 23]; Available from: http://www.accessdata.fda.gov/cdrh_docs/pdf13/P130009S034A.pdf. 103. Yoon SH, Schmidt T, Bleiziffer S, et al. Transcatheter Aortic Valve Replacement in Pure Native Aortic Valve Regurgitation. J Am Coll Cardiol. 2017 Dec 5;70(22):2752-2763. doi: 10.1016/j.jacc.2017.10.006

Cardiovascular Policies, Continued

MEDICAL POLICY

TRANSCATHETER PULMONARY VALVE REPLACEMENT

Policy # 483 Implementation Date: 4/11/11 Review Dates: 6/21/12, 6/20/13, 4/17/14, 5/7/15, 4/14/16, 4/27/17, 7/25/18, 4/27/19, 11/11/19, 5/26/21 Revision Dates: 5/21/16, 2/13/20, 6/17/21

DESCRIPTION The pulmonary valve is made up of 3 thin pieces of tissue called leaflets that are arranged in a circle, much like a 3-piece pie. With each heartbeat, the valve opens in the direction of blood flow, into the pulmonary artery and continuing to the lungs, and then closes to prevent blood from flowing backward into the right ventricle of the heart. In pulmonary valve stenosis, 1 or more of the leaflets may be defective or too thick, or the leaflets may not separate from each other properly. If this happens, the valve doesn't open correctly, restricting blood flow. Pulmonary valve stenosis usually occurs when the pulmonary valve doesn't grow properly during fetal development. It's not known what causes the valve to develop abnormally. Adults occasionally have the condition as a complication of another illness, but most of the time pulmonary valve stenosis develops before birth. As the condition advances, patients may develop symptoms of shortness of breath or fluid retention. In these instances, medications may be prescribed to control shortness of breath, reduce the heart's workload, or regulate the heart's rhythm. For most people, medication alone cannot slow the progression of pulmonary valve disease. Once severe or moderately severe stenosis develops, patients will often require surgical intervention. The 2006 ACC/AHA guidelines recommend balloon valvotomy in symptomatic patients with a peak systolic gradient > 30 mmHg and in asymptomatic patients with peak systolic gradient > 40 mmHg (moderate-to-severe disease). Standard surgery involves open sternotomy with inherent risks to cardiovascular, pulmonary, and infectious complications. A newer approach has been developed which avoids the necessity of open-heart surgery. Transcatheter valve implantation involves placement of an artificial valve in the affected valve via a catheter inserted through a vein such as the femoral vein or jugular vein. Currently, only two valves have obtained FDA approval, the Medtronic Melody® Transcatheter Pulmonary Valve (Medtronic, Inc., Santa Ana, CA) and the Edwards SAPIEN XT Transcatheter Heart Valve (Edwards Lifesciences Corporation Irvine, CA). With both these valves, the heart valve is first crimped down onto the catheter’s balloon and then is fished through a vein in the groin and into the right side of the heart where it is placed into position within the pulmonary valve. The small balloon is then inflated to open the valve into position, the catheter is removed from the body, and then immediately becomes the new pulmonary valve.

Harmony™ TPV is the first FDA-approved transcatheter valve system specifically designed to treat severe pulmonary regurgitation in patients with a native or surgically-repaired right ventricular outflow tract (RVOT) — offering your patients a minimally invasive treatment option.

The Harmony TPV was designed in an effort to offer a treatment alternative for patients with Congenital Heart Disease (CHD), specifically the 80 percent of CHD patients born with right ventricular outflow tract anomalies who undergo a surgical repair early in life. For these patients, the Harmony TPV provides a less invasive option to restore normal valve function later in life. The minimally invasive TPV therapy builds off of the proven Melody TPV technology, the first transcatheter heart valve available anywhere in the world, which has been implanted in more than 10,000 patients worldwide. Cardiovascular Policies, Continued

Transcatheter Pulmonary Valve Replacement, continued

Commercial Plan Policy/CHIP (Children’s Health Insurance Program)

Application of coverage criteria is dependent upon an individual’s benefit coverage at the time of the request.

SelectHealth covers Transcatheter Pulmonary Valve Replacement with an FDA approved device when either A or B are met:

A. Will be approved If recommended by Intermountain Healthcare Cardiovascular Clinical Program,

B. For all other clinicians, will be approved when EITHER of the following criteria are met:

1. SelectHealth covers Transcatheter Pulmonary Valve Replacement with an FDA approved device (e.g., Harmony valve) for pediatric and adult patients who meet the following conditions: i) Severe pulmonary regurgitation (i.e., severe pulmonary regurgitation as determined by echocardiography and/or pulmonary regurgitant fraction ≥ 30% as determined by cardiac magnetic resonance imaging) ii) Who have a native or surgically-repaired right ventricular outflow tract and are clinically indicated for surgical pulmonary valve replacement; or

2. SelectHealth covers Transcatheter Pulmonary Valve Replacement with an FDA approved device (e.g., Melody® Transcatheter Pulmonary Valve or Sapien XT) for the management of pediatric and adult patients with prior surgical valve replacement when the following criteria are met:

i) Dysfunctional RVOT conduits with a clinical indication for intervention, and either of the following:

a) ≥ Moderate pulmonary stenosis, or

b) ≥ Moderate pulmonary regurgitation

SelectHealth Advantage (Medicare/CMS)

Cardiovascular Policies, Continued

Transcatheter Pulmonary Valve Replacement, continued

SelectHealth Community Care (Medicaid)

Summary of Medical Information A Medical Technology Assessment performed in March 2011 identified 3 systematic reviews and 8 peer- reviewed journal articles related to percutaneous transcatheter pulmonary valve implantation. Notable, is the fact that the 3 systematic reviews were completed by well-respected organizations: Hayes, NICE, and the Australia and New Zealand Horizon Scanning Network. Though the Hayes systematic review completed in 2010 was a “Prognosis Notes” rather than a “Directory Report,” this reflects the limited evidence currently available on the Melody device; it provided insight into the current state of the evidence, specifically regarding the Melody device. It reported: “PPVI with the Melody Valve system is feasible and may delay open heart surgery in selected patients with failing RVOT conduits, but the long-term efficacy of this intervention to reduce the lifetime risk for exposure to multiple pulmonary valve surgeries is still being evaluated.“ It also noted, importantly, that long-term durability remains unknown and the appropriate patient selection criteria remain undefined. The NICE guidance, though completed in 2007, holds remarkably similar findings to that of Hayes’ “Prognosis Notes.” It notes most of the evidence was derived from a small number of patients, but short- term efficacy was good. It too, noted little evidence related to long-term efficacy; safety was also noted to not be a concern. The Australia and New Zealand Horizon Scanning Network compared bare-metal stenting (BMS) to percutaneous pulmonary valve implantation (PPVI). Though use of BMS to treat pulmonary stenosis is not commonly performed in the US, this review noted no major complications for BMS or PPVI in the perioperative period, and a complication rate of 9% over the median 28.4-month follow-up period. Additionally, it observed the mean pulmonary artery diastolic pressure increased significantly after PPVI compared to BMS, indicating that pulmonary valvular competence was restored (9 mmHg before BMS vs. 11 mmHg after PPVI; p = 0.048). Pulmonary regurgitation was virtually eliminated following PPVI as indicated by measurements of pulmonary regurgitation fraction (41.4% after BMS vs. 3.6% after PPVI; p < 0.001). Right ventricular end diastolic volume was also significantly lower (98.3 mL/m2 vs. 85.3 mL/m2, p = 0.021) and there was a significant improvement in effective right ventricular stroke volume after PPVI, compared with the post-BMS state (32.6 mL/m2 vs. 41.0 mL/m2; p = 0.004). All indications were for correction of the underlying hemodynamic issues related to the pulmonary valve stenosis. Again, a lack of long-term outcomes was noted. Seven of these were considered major complications: device instability in 5 patients, which included dislodgement of the device (n = 2) and homograft rupture (n = 3); compression of the left main coronary artery (n = 1); and obstruction of the origin of the right pulmonary artery (n = 1). Five of the patients with major complications required surgical RVOT revision. During the follow-up period, 5 patients were diagnosed with endocarditis, a median 4.9 months after PPVI, which led to valve removal in 3 patients. A stent fracture led to stent embolization in the right pulmonary valve in 1 patient, requiring surgical removal of the Melody valve. BMS achieved significant reduction in mean right ventricular systolic pressure, mean pulmonary artery to right ventricular pullback gradient, and the mean ratio of right ventricular to systemic pressure. However, PPVI did not produce any statistically significant changes in these measurements. The primary studies, as could be imagined (as they are the basis for the systematic reviews), demonstrate the same outcomes. They show adequate safety and good short-term efficacy. These studies all suffer from the lack of randomization and short-term endpoints, and for the most part, are small in size. One large case series study indicated that PPVI is a feasible procedure (in a select group of patients) and that most patients who underwent PPVI avoided surgical RVOT revision. Nevertheless, the proportion of patients who required re-do procedures (surgical or transcatheter) was quite substantial and increased over time. The results also indicated that patient outcomes improved substantially with operator experience.

Cardiovascular Policies, Continued

Transcatheter Pulmonary Valve Replacement, continued

In conclusion, current evidence supports transcatheter pulmonary valve implantation to be safe and efficacious, at least in the short-term. Long-term evidence is lacking related to efficacy and durability of the procedure and the optimal patient candidates are poorly defined.

Billing/Coding Information Covered: For the indications outlined above CPT CODES 33477 Transcatheter pulmonary valve implantation, percutaneous approach, including pre- stenting of the valve delivery site, when performed

HCPCS CODES No specific codes identified

Key References 1. Australia and New Zealand Horizon Scanning Network (ANZHSN). (2009) Horizon scanning technology prioritising summary: Percutaneous pulmonary valve implantation. Australian Safety and Efficacy Register of New Interventional Procedures - Surgical. November 2009 2. Bittl, JA. (2010) Natural history and treatment of pulmonic stenosis. 18.3. Last Update: March 23, 2010. UpToDate. Available: http://www.uptodate.com/contents/natural-history-and-treatment-of-pulmonic- stenosis?source=preview&selectedTitle=2%7E42&anchor=H9#H9. Date Accessed: March 12, 2011. 3. Boone, RH, Webb, JG, Horlick, E, et al. (2010). Transcatheter pulmonary valve implantation using the Edwards SAPIEN transcatheter heart valve. Catheter Cardiovasc Interv 75.2: 286-94. 4. Food and Drug Administration (FDA). (2010) Medtronic Melody® Transcatheter Pulmonary Valve - H080002 New Humanitarian Device Approval. Last Update: January 29, 2010. US Department of Health & Human Services. Available: http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently- ApprovedDevices/ucm199258.htm. Date Accessed: February 4, 2011. 5. Interventional Procedures Programme. (2007) IPG237 Percutaneous pulmonary valve implantation for right ventricular outflow tract dysfunction: guidance. The National Institute for Health and Clinical Excellence (NICE). November 2007 6. Lurz, P, Coats, L, Khambadkone, S, et al. (2008). Percutaneous pulmonary valve implantation: impact of evolving technology and learning curve on clinical outcome. Circulation 117.15: 1964-72. 7. Mayo Clinic Staff. (2011) Pulmonary Valve Stenosis. Last Update: December 11, 2009. Mayo Clinic. Available: http://www.mayoclinic.com/health/pulmonary-valve-stenosis/DS00610. Date Accessed: February 14, 2011. 8. McElhinney, DB, Hellenbrand, WE, Zahn, EM, et al. (2010). Short- and medium-term outcomes after transcatheter pulmonary valve placement in the expanded multicenter US melody valve trial. Circulation 122.5: 507-16. 9. Medtronic. (2011) Melody. Last Update. Medtronic. Available: http://www.medtronic.com/melody/probable-benefits-and- risks.html. Date Accessed: February 14, 2011, 10. Moiduddin, N, Asoh, K, Slorach, C, et al. (2009). Effect of transcatheter pulmonary valve implantation on short-term right ventricular function as determined by two-dimensional speckle tracking strain and strain rate imaging. Am J Cardiol 104.6: 862- 7. 11. Raikou, M, McGuire, A, Lurz, P, et al. (2011). An assessment of the cost of percutaneous pulmonary valve implantation (PPVI) versus surgical pulmonary valve replacement (PVR) in patients with right ventricular outflow tract dysfunction. J Med Econ 14.1: 47-52. 12. Ruzyllo, W, Demkow, M, Wlodarska, EK, et al. (2009). [POL-PAVTI--Polish report on transcatheter pulmonary artery valve implantation of Melody-Medtronic prosthesis in the first 14 patients in Poland]. Kardiol Pol 67.10: 1155-61. 13. U.S. Food and Drug Administration. FDA News Release. FDA Approves First in the World Device to Treat Patients with Congenital Heart Disease. March 26, 2021. Available: https://www.fda.gov/news-events/press-announcements/fda-approves- first-world-device-treat-patients-congenital-heart-disease?utm_medium=email&utm_source=govdelivery 14. Vezmar, M, Chaturvedi, R, Lee, KJ, et al. (2010). Percutaneous pulmonary valve implantation in the young 2-year follow-up. JACC Cardiovasc Interv 3.4: 439-48. 15. Zahn, EM, Hellenbrand, WE, Lock, JE, et al. (2009). Implantation of the melody transcatheter pulmonary valve in patients with a dysfunctional right ventricular outflow tract conduit early results from the U.S. Clinical trial. J Am Coll Cardiol 54.18: 1722-9.

Cardiovascular Policies, Continued

Transcatheter Pulmonary Valve Replacement, continued

No part of this publication may be reproduced, stored in a retrieval system or transmitted, in any form or by any means, electronic, mechanical, photocopying, or otherwise, without permission from SelectHealth. ”Intermountain Healthcare” and its accompanying logo, the marks of “SelectHealth” and its accompanying marks are protected and registered trademarks of the provider of this Service and or Intermountain Health Care, Inc., IHC Health Services, Inc., and SelectHealth, Inc. Also, the content of this Service is proprietary and is protected by copyright. You may access the copyrighted content of this Service only for purposes set forth in these Conditions of Use. © CPT Only – American Medical Association

Cardiovascular Policies, Continued

MEDICAL POLICY

TRANSTHORACIC ELECTRICAL BIOIMPEDANCE (TEB) TESTING

Policy # 335 Implementation Date: 12/21/06 Review Dates: 12/20/07, 12/18/08, 12/19/09, 12/16/10, 12/15/11, 7/18/13, 6/19/14, 6/11/15, 6/16/16, 6/15/17, 7/20/18, 6/13/19, 6/18/20 Revision Dates: 1/17/14

Description Transthoracic electrical bioimpedance (TEB), also referred to as plethysmography or bioimpedance cardiography, has been investigated as a non-invasive method for the determination of cardiac output. TEB relies on the conductivity of blood and the fact that resistance to electrical current in the thorax varies in relation to the amount of blood in the aorta. Blood pumped into the aorta causes a decrease in electrical impedance (resistance) that is inversely proportional to the volume of blood pumped. Transthoracic electrical bioimpedance measures cardiac output by introducing a low voltage alternating current between 2 sets of electrodes placed on the skin over the thorax. The outer sensors, attached to the neck and chest, transmit a high-frequency, low-amplitude electric current through the thoracic cavity. The inner sensors, placed adjacent to the first set, detect impedance of the electric current in the thoracic cavity. The difference between the initial voltage and that which the device senses moving through the thorax provides a measure of electrical impedance. The magnitude of the decrease in impedance in conjunction with electrocardiographic results allows stroke volume to be estimated, which can be used to calculate cardiac output. Multiple uses for TEB have been proposed: these include non-invasive diagnosis or monitoring of hemodynamics in patients with suspected or known cardiovascular disease, differentiation of cardiogenic from pulmonary causes of acute dyspnea, optimization of atrioventricular interval for patients with A/V sequential cardiac pacemakers, patients with need of determination for intravenous inotropic therapy, early identification of rejection in post-heart transplant myocardial biopsy patients, cardiac patients with a need for fluid management (excluding patients on dialysis and with cirrhosis of the liver), and management of hypertension.

Commercial Plan Policy

SelectHealth does NOT cover transthoracic electrical bioimpedance (TEB) testing. This testing is not found to be medically necessary to manage patients with various cardiac conditions in an outpatient setting.

SelectHealth Advantage (Medicare/CMS) (No Preauthorization Required but criteria may apply if appropriate)

Cardiovascular Policies, Continued

Transthoracic Electrical Bioimpedance (TEB) Testing, continued

coverage-database/overview-and-quick-search.aspx?from2=search1.asp& or the manual website

SelectHealth Community Care (Medicaid/CHIP) (No Preauthorization Required but criteria may apply if appropriate)

Summary of Medical Information In a 2003 Hayes Review, Thoracic Electrical Bioimpedance was given a rating of ‘C,’ reflecting a technology with potential but unproven benefit. The review concluded that the literature suggests that TEB provides accurate measurement of cardiac output in properly selected patients, but that the appropriate clinical role of cardiac output measurement in patient management and its impact on clinical outcomes were poorly defined. Similarly, the Agency for Healthcare Research and Quality’s (AHRQ) 2002 review concluded that TEB may have potential value in patient care. However, the accuracy of TEB relative to other measures of hemodynamic parameters could not be evaluated because limited literature and that a focus on clinical outcomes of TEB measurement was needed to evaluate its role in clinical care. The literature published since 2003 is fairly consistent with the observations made in these two reviews, and TEB measurements of hemodynamic parameters also correlate fairly well with those from other invasive or noninvasive techniques, though one study by Leslie et al., found poor agreement between TEB and thermodilution on measures of cardiac output. A few studies provide some data to address the question of the clinical role of TEB and the impact of measuring cardiac output on changing patient outcomes. Several of these have application to outpatient uses. In Packer et al. for example, 212 patients with chronic heart failure attributable to an ischemic or non-ischemic cause underwent clinical assessment and TEB every 2 weeks for 26 weeks. Three clinical variables (patient visual analog rating of symptoms, NYHA functional class, and systolic blood pressure) and three TEB parameters (thoracic fluid content index, velocity index, and left ventricular ejection time) were independently associated with the occurrence of a heart failure event within 14 days following their measurement. A composite ICG score based on these 3 variables grouped patients into low- (0–3), intermediate- (4–6), and high-risk categories (7–10). Patients in the high-risk group had an 8.4% event rate compared with vs. 3.5% and 1.0% for intermediate- and low-risk patients, respectively. High-risk patients accounted for 41.6% of heart-failure events. While the study suggests that TEB may provide some prognostic information pertinent to treatment planning in this population, the authors caution that TEB parameters should not be used to titrate therapeutic agents or to monitor therapy. Moreover, they noted that the study could not determine whether TEB contributed any unique information to the clinical data already available to clinicians. They indicate that large-scale trials are needed to evaluate whether treatment guided by TEB would have any impact on clinical outcomes. Peacock et al. examined the use of TEB with patients presenting with dyspnea to an emergency department. After conducting their routine history and physical, and indicating their working diagnosis, physicians reviewed each patient’s TEB data and reconsidered their working diagnosis. Of the 89 patients evaluated, the initial diagnosis for 12 (13%) was changed after the physician had reviewed the TEB data. Physicians made changes to the medication plan in 35 patients (39%) after the initial assessment and review of TEB. A 2004 study by Sharman et al. enrolled 21 patients with uncontrolled hypertension on a treatment protocol that was guided by TEB measurements of hemodynamic parameters. After 215 ± 85 days, average blood pressure had declined from approximately 157/78 mmHg to 142/77 mmHg. Moreover, 57% of participants achieved sustained blood pressure control. A prospective randomized controlled trial in 2006 by Smith et al. also evaluated use of TEB to inform treatment in patients with essential hypertension. Patients (n = 164) underwent a 2-week anti-hypertensive medication washout period and were randomized to a standard care or TEB-informed treatment group. Physicians treating patients in the standard group prescribed anti-hypertensives according to published guidelines, usual practice patterns, and patient characteristics. Physicians treating patients in the TEB-informed group were also provided

Cardiovascular Policies, Continued

Transthoracic Electrical Bioimpedance (TEB) Testing, continued

TEB measurements about their patients and were encouraged to use a hemodynamic treatment algorithm to guide decisions about pharmacologic agents and dosing. Compared with standard care, patients in the TEB group were more likely to achieve blood pressure reduction at or below the target goal of < 140/90 mmHg (77% vs. 57%). A greater percentage of TEB patients also achieved reductions below 130/85mmHg (55% vs. 27%). These studies suggest some novel clinical applications for TEB in the outpatient setting and that TEB may impact physicians’ treatment decisions. However, small sample sizes and lack of replication suggest that these findings should be considered preliminary. Future research is needed to define specific TEB- informed treatment protocols in addition to replicating these findings in larger patient samples. Literature reviews performed in December 2008, 2009, and 2010 did not identify any new information.

Billing/Coding Information Not Covered: Investigational/Experimental/Unproven for this indication CPT CODES 93701 Bioimpedance-derived physiologic cardiovascular analysis

HCPCS CODES No specific codes identified

Key References 1. Hayes Directory. Electrical Bioimpedance for the Measurement of Cardiac Output. 2003. Winifred S. Hayes, Inc. Available: https://www.hayesinc.com/subscribers/displaySubscriberArticle.do?articleId=1896&targetList=searchArticles.do&query=bioimp edance&icdQuery=&sd1=asearchRelevance&sd2=dtransformdatesort&sd3=atransformdoctype&sd4=atransformsort. Date Accessed: November 7, 2006. 2. Jordan HS, Ioannidis JPA, Goudas LC, et al. Thoracic Electrical Bioimpedance. 2002. Agency for Health Care Research and Quality and Centers for Medicare and Medicaid Services. Available: http://www.cms.hhs.gov/mcd/viewtechassess.asp?id=23. Date Accessed: November 7, 2006. 3. Centers for Medicare and Medicaid Services. Decision Memo for Electrical Bioimpedance for Cardiac Output Monitoring. 2003. Available: http://www.cms.hhs.gov/mcd/viewdecisionmemo.asp?id=23. Date Accessed: November 7, 2006. 4. Braunwald E. "Disorders of the Cardiovascular System." Harrison's Principles of Internal Medicine. Eds. Fauci A, Braunwald E, Isselbacher K, et al. 14th ed. New York: McGraw Hill, 1998. 5. "Effect of prophylactic amiodarone on mortality after acute myocardial infarction and in congestive heart failure: meta-analysis of individual data from 6500 patients in randomised trials. Amiodarone Trials Meta-Analysis Investigators." Lancet 350.9089 (1997): 1417-24. 6. Colucci WS. Overview of the therapy of heart failure due to systolic dysfunction. 2006. UpToDate. Available: http://www.utdol.com/utd/content/topic.do?topicKey=hrt_fail/6883. Date Accessed: November 6, 2006. 7. Ventura HO, Taler SJ, Strobeck JE. "Hypertension as a hemodynamic disease: the role of impedance cardiography in diagnostic, prognostic, and therapeutic decision making." Am J Hypertens 18.2 Pt 2 (2005): 26S-43S. 8. Cardiodynamics Website. CardioDynamics International Corporation. Available: http://www.cardiodynamics.com/index.html. Date Accessed: November 7, 2006. 9. Leslie SJ, McKee S, Newby DE, Webb DJ, Denvir MA. "Non-invasive measurement of cardiac output in patients with chronic heart failure." Blood Press Monit 9.5 (2004): 277-80. 10. Packer M, Abraham WT, Mehra MR, et al. "Utility of impedance cardiography for the identification of short-term risk of clinical decompensation in stable patients with chronic heart failure." J Am Coll Cardiol 47.11 (2006): 2245-52. 11. Peacock WF, Summers RL, Vogel J, Emerman CE. "Impact of impedance cardiography on diagnosis and therapy of emergent dyspnea: the ED-IMPACT trial." Acad Emerg Med 13.4 (2006): 365-71. 12. Sharman DL, Gomes CP, Rutherford JP. "Improvement in blood pressure control with impedance cardiography-guided pharmacologic decision making." Congest Heart Fail 10.1 (2004): 54-8. 13. Smith RD, Levy P, Ferrario CM. "Value of noninvasive hemodynamics to achieve blood pressure control in hypertensive subjects." Hypertension 47.4 (2006): 771-7. 14. Stout CL, Van de Water JM, Thompson WM, et al. "Impedance cardiography: can it replace thermodilution and the pulmonary artery catheter?" Am Surg 72.8 (2006): 728-32; discussion 733-4. 15. Parry MJ, McFetridge-Durdle J. "Ambulatory impedance cardiography: a systematic review." Nurs Res 55.4 (2006): 283-91. 16. Wynne JL, Ovadje LO, Akridge CM, Sheppard SW, Vogel RL, Van de Water JM. "Impedance cardiography: a potential monitor for hemodialysis." J Surg Res 133.1 (2006): 55-60. 17. Goedhart AD, Kupper N, Willemsen G, Boomsma DI, de Geus EJ. "Temporal stability of ambulatory stroke volume and cardiac output measured by impedance cardiography." Biol Psychol 72.1 (2006): 110-7. 18. Braun MU, Schnabel A, Rauwolf T, Schulze M, Strasser RH. "Impedance cardiography as a noninvasive technique for atrioventricular interval optimization in cardiac resynchronization therapy." J Interv Card Electrophysiol 13.3 (2005): 223-9. 19. Bougault V, Lonsdorfer-Wolf E, Charloux A, Richard R, Geny B, Oswald-Mammosser M. "Does thoracic bioimpedance accurately determine cardiac output in COPD patients during maximal or intermittent exercise?" Chest 127.4 (2005): 1122-31. 20. Scherhag A, Kaden JJ, Kentschke E, Sueselbeck T, Borggrefe M. "Comparison of impedance cardiography and thermodilution-derived measurements of stroke volume and cardiac output at rest and during exercise testing." Cardiovasc Drugs Ther 19.2 (2005): 141-7.

Cardiovascular Policies, Continued

Transthoracic Electrical Bioimpedance (TEB) Testing, continued

21. Treister N, Wagner K, Jansen PR. "Reproducibility of impedance cardiography parameters in outpatients with clinically stable coronary artery disease." Am J Hypertens 18.2 Pt 2 (2005): 44S-50S. 22. Abdelhammed AI, Smith RD, Levy P, Smits GJ, Ferrario CM. "Noninvasive hemodynamic profiles in hypertensive subjects." Am J Hypertens 18.2 Pt 2 (2005): 51S-59S. 23. Bhalla V, Isakson S, Bhalla MA, et al. "Diagnostic ability of B-type natriuretic peptide and impedance cardiography: testing to identify left ventricular dysfunction in hypertensive patients." Am J Hypertens 18.2 Pt 2 (2005): 73S-81S. 24. Yung GL, Fedullo PF, Kinninger K, Johnson W, Channick RN. "Comparison of impedance cardiography to direct Fick and thermodilution cardiac output determination in pulmonary arterial hypertension." Congest Heart Fail 10.2 Suppl 2 (2004): 7-10. 25. Springfield CL, Sebat F, Johnson D, Lengle S, Sebat C. "Utility of impedance cardiography to determine cardiac vs. noncardiac cause of dyspnea in the emergency department." Congest Heart Fail 10.2 Suppl 2 (2004): 14-6. 26. Santos JF, Parreira L, Madeira J, Fonseca N, Soares LN, Ines L. "Non invasive hemodynamic monitorization for AV interval optimization in patients with ventricular resynchronization therapy." Rev Port Cardiol 22.9 (2003): 1091-8. 27. Van De Water JM, Miller TW, Vogel RL, Mount BE, Dalton ML. "Impedance cardiography: the next vital sign technology?" Chest 123.6 (2003): 2028-33. 28. Vijayaraghavan K, Crum S, Cherukuri S, Barnett-Avery L. "Association of impedance cardiography parameters with changes in functional and quality-of-life measures in patients with chronic heart failure." Congest Heart Fail 10.2 Suppl 2 (2004): 22-7. 29. Tordi N, Mourot L, Matusheski B, Hughson RL. "Measurements of cardiac output during constant exercises: comparison of two non-invasive techniques." Int J Sports Med 25.2 (2004): 145-9. 30. Karakitsos DN, Patrianakos AP, Paraskevopoulos A, et al. "Impedance cardiography derived cardiac output in hemodialysis patients: a study of reproducibility and comparison with echocardiography." Int J Artif Organs 29.6 (2006): 564-72. 31. Shochat M, Charach G, Meyler S, et al. "Internal thoracic impedance monitoring: a novel method for the preclinical detection of acute heart failure." Cardiovasc Revasc Med 7.1 (2006): 41-5. 32. DeMarzo AP, Calvin JE, Kelly RF, Stamos TD. "Using impedance cardiography to assess left ventricular systolic function via postural change in patients with heart failure." Prog Cardiovasc Nurs 20.4 (2005): 163-7. 33. Yu CM, Wang L, Chau E, et al. "Intrathoracic impedance monitoring in patients with heart failure: correlation with fluid status and feasibility of early warning preceding hospitalization." Circulation 112.6 (2005): 841-8. 34. Scherhag A, Pfleger S, Garbsch E, Buss J, Sueselbeck T, Borggrefe M. "Automated impedance cardiography for detecting ischemic left ventricular dysfunction during exercise testing." Kidney Blood Press Res 28.2 (2005): 77-84. 35. Hunt SA. "ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure)." J Am Coll Cardiol 46.6 (2005): e1-82.

Cardiovascular Policies, Continued

MEDICAL POLICY

VENTRICULAR ASSIST DEVICES

Policy # 187 Implementation Date: 7/98 Review Dates: 1/4/00, 2/27/01, 4/16/02, 10/23/03, 11/18/04, 3/25/05, 4/20/06, 10/18/07, 10/22/09, 10/22/10, 2/16/12, 4/25/13, 2/20/14, 3/19/15, 2/11/16, 2/16/17, 2/15/18, 2/5/19, 2/11/20 Revision Dates: 8/22/06, 10/30/06, 10/23/08

Description A ventricular assist device (VAD) is a mechanical pump that relieves the native left ventricle by pumping blood through the body. The VAD requires a control system and a power source that are maintained outside the body. The VAD pump may be placed internally or externally but the control system and power source are maintained outside the body. Sometimes called, “bridge-to-transplant” (BTT), VADs were originally intended for use in patients awaiting heart transplant who required additional assistance for survival. As VAD technology has improved and the supply of transplantable hearts remains limited, VADs are now sometimes used for long-term (destination) therapy in severe heart-failure patients. The first FDA approval of a VAD for this indication was in 1994. A variety of devices have received approval from the U.S. Food and Drug Administration (FDA), encompassing both biventricular and left ventricular devices, as well as devices that are intended to be used in the hospital setting alone and those that can be used as an outpatient. Devices that can be used in an outpatient setting while the patient awaits a human donor heart include Thoratec’s® HeartMate XVE, HeartMate II LVAS, and the Ventricular Assist Device (VAD) System. In these systems, the device is surgically placed entirely within the thoracic and abdominal cavity and connected to the power source by a percutaneous drive line.

Commercial Plan Policy

SelectHealth covers all FDA approved* ventricular assist devices in the following limited circumstances. 1. Members with post-cardiotomy ventricular dysfunction on maximum inotropic volume and support and intra-aortic balloon pump where indicated; or 2. As a bridge to transplant for members who are awaiting heart transplantation; or 3. As destination therapy for members with severe (NYHA Class IV) heart failure, and who are ineligible for heart transplantation due to age or co-morbidities.

*FDA approved is defined as devices that have been granted approval through a Pre-Marketing Approval (PMA) process or have gained FDA approval as Investigational Exempt Devices (IDE) and are categorized as Category “B” devices by the FDA.

SelectHealth Advantage (Medicare/CMS)

Coverage is determined by the Centers for Medicare and Medicaid Services (CMS); if a coverage determination has not been adopted by CMS, and InterQual criteria

Cardiovascular Policies, Continued

Ventricular Assist Devices, continued

SelectHealth Community Care (Medicaid/CHIP)

Summary of Medical Information Destination Therapy Support The Thoratec HeartMate XVE LVAS is also FDA approved for use as a long-term permanent implant, (i.e., for destination therapy) as an alternative to optimal medical therapy for end-stage HF patients who are not eligible for cardiac transplantation (patients with NYHA Class IV end-stage left ventricular failure who have received optimal medical therapy for at least 60 of the last 90 days, have a life expectancy of < 2 years, and are not eligible for cardiac transplantation). The device system is approved for use both inside and outside of the hospital. FDA approval of this device system is based on the results of the REMATCH (Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure) trial, which compared the experience of patients supported by the HeartMate SNAP VE LVAS with those being treated with optimal medical management. The Thoratec HeartMate II LVAS is approved by the FDA for use in a DT clinical trial evaluating efficacy as an alternative to optimal medical therapy for end-stage heart failure patients not eligible for cardiac transplantation. The basic design of available VADs is similar. Usually, the pump is implanted into the upper part of the abdominal wall or the peritoneal lining, and, for left ventricular assist devices (LVADs), a tube from the pump fits into the left ventricle, draining blood from the ventricle into the pump, which then sends the blood into the aorta. Another tube from the implanted pump extends outside the body through the skin and is attached to a beeper-sized control system that is worn on a belt; the computerized control unit is powered by a console or battery pack that is worn on a shoulder holster or belt. For right ventricular assist devices (RVADs), a tube shunts blood from the right ventricle through the pump and into the pulmonary artery. VADs have activity sensors to increase the pump output when activity increases, and backup mechanisms are available in case of pump failure. Patients who receive VADs with a wearable power source can be fully ambulatory after implantation, and, if their condition permits, live at home, although a 24-hour companion is necessary in the event of equipment malfunction. There are several different types of VADs currently in use; the devices can be broadly subdivided into continuous flow/centrifugal or pulsatile pumps. Continuous flow/centrifugal pumps operate on the principle of a cyclone. Blood is diverted through cannulae placed in the right or left heart to an external chamber with a centrifugal pump. Continuous flow/centrifugal pumps include the Thoratec HeartMate II LVAS, Biopump, the Sarns-3M, and the Hemopump. Pulsatile pumps are subdivided into pneumatic and electromechanical types. Each type can be operated in several different modes including a synchronous mode triggered by the EKG (similar to an intra-aortic balloon pump) and an asynchronous mode. Placement of the inflow and outflow cannulae is variable. Pulsatile pumps include the Abiomed, Thoratec (Pierce Donachy), Novacor, and HeartMate XVE devices. Bridge to Transplant (BTT) Support: VADs have also been used as a bridge to transplant. Several clinical studies have demonstrated the success of VADs in improving survival rates to heart transplantation. In addition, VADs have been shown to significantly improve patients' functional status prior to heart transplantation such that patients are overall better surgical candidates. More than 5 million people in the United States live with heart failure, and the incidence of heart failure continues to increase, due in part to the expanded aging population and advances in therapeutic management of cardiovascular disease. Transplantation has become the standard treatment for eligible patients with irreversible severe biventricular failure unresponsive to 2

Cardiovascular Policies, Continued

Ventricular Assist Devices, continued

medical or surgical treatment. The supply of donor hearts has decreased in recent years, however, while the demand has increased, as patients become more hemodynamically compromised, there is an increased risk of death prior to transplantation, as well as a less favorable outcomes following transplantation. Timely VAD use may restore hemodynamic stability and end-organ function, and allow nutritional support and rehabilitation prior to transplantation. VAD implant surgery carries risks of severe complications, including bleeding, development of blood clots, the most common causes of early morbidity and mortality after placement of a VAD have been bleeding, right-sided heart failure, air embolism, and progressive multisystem organ failure. In the late postoperative period, the most common complications have been infection, thromboembolism, and failure of the device. Early investigators reported that approximately 50% of patients required reoperation for bleeding; however, the risk of major hemorrhage decreased to approximately 30% with the use of aprotinin. In patients who do not have major bleeding in the perioperative period, right-sided HF rarely develops. Additionally, the use of textured blood-contacting surfaces (e.g., in the HeartMate LVAD) has decreased the incidence of thromboembolic events. The REMATCH trial, a multicenter randomized controlled clinical trial, involved 129 adults with end-stage heart failure who were not eligible for a heart transplant. Participants had NYHA class IV heart failure for at least 90 days despite attempted therapy with an ACE inhibitor, diuretics, and digoxin; an ejection fraction ≤ 25%%; and an exercise peak O2 uptake ≤ 14 mL/kg per minute or a continued need for intravenous inotropic therapy because of symptomatic hypotension, decreasing renal function, or worsening pulmonary congestion. After 18 months of enrollment, entry criteria were relaxed to include patients with symptoms of NYHA class III or IV heart failure for 28 days and 14 days of support with an intra-aortic balloon pump or with a dependence on intravenous inotropic agents with 2 failed weaning attempts. 61 patients received optimal medical management, including intravenous inotropic therapy, and 68 patients received LVADs. Survival at 1 year was significantly improved from 25% at 1 year in the medical therapy group to 52% in the LVAD group (relative risk, 0.52 (95% confidence interval 0.34−0.78)). Median length of survival for patients implanted with the HeartMate LVAD was 408 days compared to 108 days for patients in the medical therapy group. At 2 years, 23% of LVAD patients had survived compared to 8% in the medical group (p = 0.09). Serious adverse events were 2.35 times as frequent in the LVAD group, predominately caused by infection, bleeding, neurological dysfunction, and device malfunction. A 2005 Hayes review concluded the following regarding Ventricular Assist Devices: There is substantial evidence that LVADs can provide effective circulatory support for patients with end-stage HF, and that the improved hemodynamics that these devices provide, can help to stabilize and possibly reverse damage to myocardial tissue and secondary organs in patients waiting for transplantation, improving survival, both before, and after transplantation. There also is evidence to support the use of LVADs as intermediate- term support for HF patients who may subsequently recover sufficient function of the native heart to allow explantation. In addition, there is recent evidence to support the use of LVADs as permanent, or destination, therapy for end-stage HF patients who are not suitable candidates for transplantation. Additional research is necessary to determine optimal timing for implantation, to define criteria for weaning and explantation in patients with reversible cardiac dysfunction, and to determine methods of reducing the occurrence of complications such as bleeding and sepsis. Therefore, the following Hayes Ratings have been assigned: A for LVAD use as a bridge to cardiac transplantation in patients with end- stage HF; B for LVAD use as a bridge to recovery for those patients meeting hemodynamic criteria who have potentially reversible left ventricular dysfunction; B for LVAD use as destination therapy for patients who are not eligible for transplantation and in whom no return of cardiac function is anticipated. A rating of D has been assigned for LVAD use in patients with specific contraindications, including irreversible multiple organ dysfunction, HIV seropositivity, age > 70, stroke, systemic infection, cancer, severely restricted pulmonary function, major neurological deficit, blood clotting disorders, or long-term high-dose corticosteroid use. This rating reflects the lack of evidence that LVAD use improves outcomes in patients with these conditions. A 2007 Update Search showed efficacy and safety remained the same. In 2007, the HeartMate II BTT Pivotal trial reported that principal outcomes occurred in 75% of patients; the median duration of support was 126 days. The survival rate during support was 75% at 6 months and 68% at 12 months. At 23 months, therapy was associated with significant improvement in functional status and in quality of life. The trial concluded that a continuous-flow left VAD can provide effective hemodynamic support for a period of at least 6 months in patients awaiting heart transplantation with improved functional status and quality of life.

Cardiovascular Policies, Continued

Ventricular Assist Devices, continued

A Hayes review published in August 2010 concluded in their analyses of several moderate-size to large groups of patients implanted with ventricular assist devices (VADs) for bridge to transplantation (BTT) suggested that most patients survive until transplantation, but the lack of comparative data for patients treated with optimal medical management (OMM) precludes any conclusion regarding the causal effect of VADs on survival to transplantation. A large volume of comparative evidence strongly suggests that patients supported by VAD as BTT have survival following cardiac transplant similar to that of patients supported with OMM while waiting for transplant. Evidence pertaining to overall survival from the time of left ventricular assist device (LVAD) implantation for BTT until death is sparse and comparisons with OMM groups reported conflicting results. Evidence pertaining to the impact of LVADs BTT on quality of life (QoL) and function was insufficient to allow conclusions. A small percentage of patients implanted with LVAD as BTT can be expected to recover, but patient characteristics associated with bridge to recovery (BTR) have not been identified. A single randomized controlled trial and a nonrandomized trial have demonstrated that LVADs as destination therapy (DT) substantially improve survival and disease-related functional status and have modest positive effects on QoL. Serious adverse events in patients who have an implanted LVAD are common; LVAD has been shown to cause an increase in nonfatal adverse events when used as DT, but the causal link between LVAD and adverse events when the device is used as BTT is unknown. Three LVADs have received FDA approval for short-term use as a BTT in cardiac transplant candidates at risk of imminent death from nonreversible left ventricular failure. These include the HeartMate® System and its enhanced version, the HeartMate® Extended Lead, as well as earlier versions, such as the HeartMate® Implantable Pneumatic (IP) LVAS and the HeartMate® VE LVAS, the Thoratec® Ventricular Assist Device (VAD) System and the Novacor® LVAS. In addition to approval for use as BTT, 3 Thoratec devices have been approved for use as DT: the HeartMate SNAP VE LVA, the HeartMate XVE LVAS, and the HeartMate II. The HeartMate VE/XVE, DT is indicated as an alternative to optimal medical therapy for end-stage HF patients who are not eligible for cardiac transplantation (patients with NYHA Class IV end-stage left ventricular failure who have received optimal medical management (OMM) for at least 60 of the last 90 days, have a life expectancy of < 2 years, and are not eligible for cardiac transplantation).

Billing/Coding Information Covered: For the conditions outlined above CPT CODES 0451T Insertion or replacement of a permanently implantable aortic counterpulsation ventricular assist system, endovascular approach, and programming of sensing and therapeutic parameters; complete system (counterpulsation device, vascular graft, implantable vascular hemostatic seal, mechano-electrical skin interface and subcutaneous electrodes) 0452T ; aortic counterpulsation device and vascular hemostatic seal 0455T Removal of permanently implantable aortic counterpulsation ventricular assist system; complete system (aortic counterpulsation device, vascular hemostatic seal, mechano- electrical skin interface and electrodes) 0456T ; aortic counterpulsation device and vascular hemostatic seal 0458T ; subcutaneous electrode 0459T Relocation of skin pocket with replacement of implanted aortic counterpulsation ventricular assist device, mechano-electrical skin interface and electrodes 0460T Repositioning of previously implanted aortic counterpulsation ventricular assist device; subcutaneous electrode 0461T ; aortic counterpulsation device 0463T Interrogation device evaluation (in person) with analysis, review and report, includes connection, recording and disconnection per patient encounter, implantable aortic counterpulsation ventricular assist system, per day 33975 Insertion of ventricular assist device; extracorporeal, single ventricle 33976 ; extracorporeal, biventricular 4

Cardiovascular Policies, Continued

Ventricular Assist Devices, continued

33977 Removal of ventricular assist device; extracorporeal, single ventricle 33978 ; extracorporeal, biventricular 33979 Insertion of ventricular assist device, implantable intracorporeal, single ventricle 33980 Removal of ventricular assist device, implantable intracorporeal, single ventricle 33981 Replacement of extracorporeal ventricular assist device, single or biventricular, pump(s), single or each pump 33990 Insertion of ventricular assist device, percutaneous including radiological supervision and interpretation; arterial access only 33991 Insertion of ventricular assist device, percutaneous including radiological supervision and interpretation; both arterial and venous access, with transseptal puncture 33992 Removal of percutaneous ventricular assist device at separate and distinct session from insertion 33993 Repositioning of percutaneous ventricular assist device with imaging guidance at separate and distinct session from insertion 33999 Unlisted procedure, cardiac surgery 92970 Cardioassist-method of circulatory assist; internal 92971 ; external 93750 Interrogation of ventricular assist device (VAD), in person, with physician or other qualified health care professional analysis of device parameters (eg, drivelines, alarms, power surges), review of device function (eg, flow and volume status, septum status, recovery), with programming, if performed, and report

HCPCS CODES Q0480 Driver for use with pneumatic ventricular assist device, replacement only Q0481 Microprocessor control unit for use with pneumatic ventricular assist device, replacement only Q0482 Microprocessor control unit for use with electric/pneumatic combination ventricular assist device, replacement only Q0483 Monitor/display module for use with pneumatic ventricular assist device, replacement only Q0484 Monitor/display module for use with electric or electric/pneumatic ventricular assist device, replacement only Q0485 Monitor control cable for use with pneumatic ventricular assist device, replacement only Q0486 Monitor control cable for use with electric/pneumatic ventricular assist device, replacement only Q0487 Leads (pneumatic/electrical) for use with any type electric/pneumatic ventricular assist device, replacement only Q0488 Power pack base for use with pneumatic ventricular assist device, replacement only Q0489 Power pack base for use with electric/pneumatic ventricular assist device, replacement only Q0490 Emergency power source for use with pneumatic ventricular assist device, replacement only Q0491 Emergency power source for use with electric/pneumatic ventricular assist device, replacement only Q0492 Emergency power supply cable for use with pneumatic ventricular assist device, replacement only

Cardiovascular Policies, Continued

Ventricular Assist Devices, continued

Q0493 Emergency power supply cable for use with electric/pneumatic ventricular assist device, replacement only Q0494 Emergency hand pump for use with electric/pneumatic ventricular assist device, replacement only Q0495 Battery power pack charger for use with electric or electric/pneumatic ventricular assist device, replacement only Q0496 Battery for use with electric or electric/pneumatic ventricular assist device, replacement only Q0497 Battery clip for use with electric or electric/pneumatic ventricular assist device, replacement only Q0498 Holster for use with electric or electric/pneumatic ventricular assist device, replacement only Q0499 Belt/vest for use with electric or electric/pneumatic ventricular assist device, replacement only Q0500 Filters for use with electric or electric/pneumatic ventricular assist device, replacement only Q0502 Mobility cart for pneumatic ventricular assist device, replacement only Q0503 Battery for pneumatic ventricular assist device, replacement only, each Q0506 Battery, lithium-ion, for use with electric or electric/pneumatic ventricular assist device, replacement only Q0507 Miscellaneous supply or accessory for use with an external ventricular assist device Q0508 Miscellaneous supply or accessory for use with an implanted ventricular assist device

Key References 1. Kanter KR, McBride LR, Pennington G. Bridging to cardiac transplantation with pulsatile ventricular assist devices. Ann Thorac Surg. 1988;46:134-140. 2. Portner PM, Oyer PE, Pennington DG, et al. Implantable electrical left ventricular assist system: Bridge to transplantation and the future. Ann Thorac Surg. 1989;47:142-150. 3. McCarthy PM. HeartMate implantable left ventricular assist device: Bridge to transplantation and future applications. Ann Thoarc Surg. 1995;59:S46-S51. 4. Pennington DG, McBride LR, Swartz MT, et al. Use of the Pierce-Donachy ventricular assist device in patients with cardiogenic shock after cardiac operation. Ann Thorac Surg. 1989;47:130-135. 5. Abou-Awdi NL, Frazier OH. The HeartMate: A left ventricular assist device as a bridge to cardiac transplantation. Transplant Proc. 1992;24(5):2002-2003. 6. Wessex Institute for Health Research and Development, Development and Evaluation Committee. Left ventricular assist devices (LVADs) for end stage heart failure. Southampton, UK: Wessex Institute; 1999. 7. 2001 Heart and stroke statistical update. Dallas: American Heart Association, 2000. 8. O’Connell JB, Birstow MR. Economic impact of heart failure in the United States: time for a different approach. J Heart Lung Transplant 1994;13:S107-S112. 9. www.clinicaltrials.gov. search term “ventricular assist device.” Accessed 5/4/2006. 10. Rose EA, Gelijns AC, Moskowitz AJ, et al. Long term use of a left ventricular assist device for end-stage heart failure. N Engl J Med. 2001 Nov 15;345(20):1435-43. 11. Hunt SA. Comment--the REMATCH trial: Long-term use of a left ventricular assist device for end-stage heart failure. J Card Fail. 2002;8(2):59-60. 12. Summary of Safety and Effectiveness Data Novacor Left Ventricular Assist System. 1998. Baxter Healtcare. pp 2-3. 13. HeartMate XVE LVAS Instructions for Use. Thoratec Corporation. 2003. pp 2. 14. Bank AJ, Mir SH, Nguyen DQ, et al. Effects of left ventricular assist devices on outcomes in patients undergoing heart transplantation. Ann Thorac Surg. 2000;69(5):1369-1374. 15. L'Agence Nationale d'Accreditation d'Evaluation en Sante (ANAES). Evaluation of ventricular assist as a bridge to heart transplant or as destination therapy. Paris, France: ANAES; 2001. 16. Institute for Clinical Systems Improvement (ICSI). Left ventricular assist devices as permanent implants. Bloomington, MN: ICSI; 2002. 17. Alpert JS. Left ventricular assist devices reduced the risk for death and increased 1-year survival in chronic end-stage heart failure. ACP J Club. 2002;136(3):88. 18. Kherani AR, Oz MC. Ventricular assistance to bridge to transplantation. Surg Clin North Am. 2004;84(1):75-89, viii-ix. 19. Westaby S. Ventricular assist devices as destination therapy. Surg Clin North Am. 2004;84(1):91-123. 20. Ontario Ministry of Health and Long-Term Care, Medical Advisory Secretariat. Left ventricular assist devices. Health Technology Scientific Literature Review. Toronto, ON: Ontario Ministry of Health and Long-Term Care; updated March 2004. 21. BlueCross BlueShield Association (BCBSA), Technology Evaluation Center (TEC). Special report: Cost-effectiveness of left- ventricular assist devices as destination therapy for end-stage heart failure. TEC Assessment Program. Chicago, IL: BCBSA; April 2004;19(2). Available at: http://www.bcbs.com/tec/vol19/19_02.html. Accessed October 3, 2005. 6

Cardiovascular Policies, Continued

Ventricular Assist Devices, continued

22. Hayes Directory. Ventricular Assist Devices. Lansdale, PA, Winifred S. Hayes, Inc. 2005. Update 2007.

Cardiovascular Policies, Continued

MEDICAL POLICY

VERTICAL AUTOPROFILING (VAP™) CHOLESTEROL TEST

Policy # 298 Implementation Date: 2/15/06 Review Dates: 5/17/07, 4/24/08, 4/23/09, 2/18/10, 5/19/11, 6/21/12, 6/20/13, 4/17/14, 5/7/15, 4/14/16, 4/27/17, 7/20/18, 4/27/19, 4/15/20 Revision Dates:

Disclaimer: 1. Policies are subject to change without notice. 2. Policies outline coverage determinations for SelectHealth Commercial, SelectHealth Advantage (Medicare/CMS) and SelectHealth Community Care (Medicaid/CHIP) plans. Refer to the “Policy” section for more information.

Description Coronary heart disease (CHD) affects about 14 million men and women in the United States. Atherosclerosis is an important risk factor in the development of CHD. Routine cholesterol screening, which measures HDL, LDL (calculated), and triglycerides is a major component of CHD risk management. The Vertical Auto Profile (VAP) cholesterol test from Atherocare not only includes these standard tests, but also, measures atherogenic remnant lipids (VLDL and IDL), Lp(a), LDL pattern density, and HDL subtypes. This additional testing purports to improve CHD risk stratification by measuring these additional risk factors along with the traditional cholesterol panel. By measuring these lipid factors, the test also provides a screen for metabolic syndrome, a constellation of metabolic risk factors that increase risk for CHD. The VAP test is the only commercially available test that measures possible cardiovascular risk factors Lp(a), LDL particle size, lipoprotein remnants, and HDL subfractions at the same time. Alternatively, providers can order each test individually. Additionally, many other tests are available to assess cardiovascular risk. Tests covered by SelectHealth include fasting lipid profiles, PLACTM testing, and hs- CRP. Other risk factors for CHD can be assessed through a variety of methods including the Framingham Risk Assessment tool.

Commercial Plan Policy

SelectHealth does NOT cover vertical autoprofiling (VAP™) cholesterol testing for assessment of cardiovascular risk. This testing meets the plan’s definition of investigational/experimental.

SelectHealth Advantage (Medicare/CMS) (No Preauthorization Required but criteria may apply if appropriate)

Cardiovascular Policies, Continued

Vertical Autoprofiling (VAP™) Cholesterol Test, continued

SelectHealth Community Care (Medicaid/CHIP) (No Preauthorization Required but criteria may apply if appropriate)

Summary of Medical Information The extant literature is somewhat equivocal on the prognostic value of the risk factors the VAP test adds to the traditional lipid panel: Remnant lipoproteins: Fukushima et al.’s 2004 2-year follow-up study of 240 diabetes patients with or without CAD found remnant lipoproteins to be a strong independent risk factor for CAD. Inoue et al. reported similar findings in their 2004 study of 188 CAD patients and 68 controls. In contrast, Imke et al.’s study of 1,156 Japanese-American men over 7 years found that remnant lipoproteins levels did not improve the prediction of future CHD incidence beyond that already provided by total triglycerides. Lp(a): Ariyo et al. studied 5,888 adults over 7.5 years (median) and concluded that Lp(a) level is an independent risk factor of future vascular events in men, but not in women. Danesh et al.’s meta-analysis of 27 studies supported the association between CHD and Lp(a) but called for additional research to determine the extent to which this relationship is causal. Moliterno et al.’s study of 140 African American subjects concluded that Lp(a) is not an independent risk factor for CAD in that population. LDL particle size: Berneis et al. studied LDL size in 38 type II diabetics and concluded that, among other lipid parameters, LDL particle size is the strongest predictor of CHD and atherosclerosis. Mykkanen et al., in contrast, studied 86 patients who were MI-free over 3.5 years and observed that LDL particle size was not an independent risk factor of CHD events once controlling for diabetes status. St-Pierre et al.’s study of 2,072 men over 13 years demonstrated that accumulation of small LDL particles was primarily responsible for the risk attributable to LDL size. HDL subtypes: Lamarche et al.’s 1990 study of 1,169 men followed over 11 years found a statistical association between HDL2 and CHD but concluded that that in the clinical setting, measurement of HDL subtypes provides no additional information about CHD risk over traditional lipid risk markers. Sweetnam et al. followed 4,860 men between 3−5 years and observed an inverse association between HDL2 and HDL3 cholesterol and the incidence of CHD. They further noted that the predicting adding HDL subtype measurement to traditional HDL did not improve predication of CHD risk. Only 2 studies located for this literature review examined the impact of treating these risk factors on future atherosclerosis or CHD events. Campos et al. administered pravastatin or placebo to 837 MI survivors and matched controls with similarly elevated LDL and tracked outcomes over 5 years. In patients taking placebo, large LDL predicted coronary events, but this association was not present in patients taking pravastatin. However, the authors concluded that identifying LDL size 5, not to be very useful clinically since elevated LDL cholesterol and large LDL are both effectively treated in the same manner. Miller et al. prospectively followed 213 men enrolled in a cardiac risk reduction program that included lipid-altering therapies with counseling and training in the modification of diet, exercise, and other lifestyle factors. After four years, patients with higher dense LDL levels showed significant benefit from the program while subjects with higher buoyant (less dense) LDL had no benefit from the intervention. ATP-III identifies lipoprotein remnants, Lp(a), LDL particle size, and HDL subtypes as “emerging risk factors”, suggesting that their association with CHD and the impact of modifying them on CHD risk is not well understood. Additional prospective trials are needed to more fully explain the relationship between these risk factors and atherosclerosis and future CHD events. Research is particularly needed to determine whether adding these emerging risk factors to traditional lipid panels adds any value to the prediction of CHD. The interaction between these emerging risk factors and other lipid and non-lipid risk factors in producing CHD risk must also be examined. Finally, research is needed to determine whether measuring these risk factors would have any unique impact on treatment decisions, whether treatments can be sufficiently tailored for specific lipid profiles, and whether patients with particular lipid parameters respond differently to lipid lowering therapies.

Cardiovascular Policies, Continued

Vertical Autoprofiling (VAP™) Cholesterol Test, continued

A June 2012 literature review identified the 2010 ACCF/AHA Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults and does not recommend lipid/lipoprotein subfraction. Similarly, the 2011 National Lipid Association Expert Panel did not recommend HDL and LDL subfraction measurements for clinical assessment. However, Apo-B or LDL particle measurement and LPa are endorsed by NLA reasonable for many subjects at intermediate risk, those with a positive family history, and those with recurrent events, and selectively in those with coronary heart disease and CHD equivalents. These recommendations follow recent studies and metaanalyses that indicate that LDL particle number (measured by NML or as Apo-B) may be a letter indicator of CHD risk than LDLc or non-HDLc.

Billing/Coding Information Not Covered: Investigational/Experimental/Unproven for this indication (when used in this combination) CPT CODES 3011F Lipid panel results documented and reviewed (must include total cholesterol, HDL-C, triglycerides and calculated LDL-C) (CAD) 80050 General health panel This panel must include the following: Comprehensive metabolic panel (80053) Blood count, complete (CBC), automated and automated differential WBC count (85025 or 85027 and 85004) OR Blood count, complete (CBC), automated (85027) and appropriate manual differential WBC count (85007 or 85009) Thyroid stimulating hormone (TSH) (84443) 80061 Lipid panel. This panel must include the following: Cholesterol, serum, total (82465) Lipoprotein, direct measurement, high density cholesterol (HDL cholesterol) (83718) Triglycerides (84478) 82465 Cholesterol, serum or whole blood, total 83698 Lipoprotein-associated phospholipase A2 (Lp-PLA2) 83701 Lipoprotein, blood; high-resolution fractionation and quantitation of lipoproteins including lipoprotein subclasses when performed (e. electrophoresis, ultracentrifugation) 83718 Lipoprotein, direct measurement; high density cholesterol (HDL cholesterol) 83719 Lipoprotein, direct measurement; VLDL cholesterol 83721 Lipoprotein, direct measurement; LDL cholesterol 84478 Triglycerides

HCPCS CODES No specific codes identified

Key References 1. Segrest JP. Lipids: classifications and understandings. 2005. 2. Coronary heart disease overview. http://www.emedicinehealth.com/Articles/10951-1.asp. 2005. 3. Medline Plus. Coronary Heart Disease. Medical Encyclopedia. 2005; http://www.nlm.nih.gov/medlineplus/ency 4. Merck Manual Online. Arteriosclerosis. 17 ed. Vol. http://www.merck.com. (Berkow M, ed. 5. Wilson W, Culleton M. Overview of the risk factors for cardiovascular disease. UpToDate Online. 2005; http://www.utdol.com. 6. Rosenson RS. Lipoprotein classification; metabolism; and role in atherosclerosis. UpToDate Online. 2005; http://www.utdol.com/. 7. National Cholesterol Education Program. (National Institutes of Health). Detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). 2002. 8. Rosenson RS. HDL metabolism and approach to the patient with low HDL-cholesterol. UpToDate Online. 2005; http://www.utdol.com/. 9. Adams J, Apple F. Cardiology patient page. New blood tests for detecting heart disease. Circulation. 2004; 109(3): E12-4. 10. Atherotech. The VAP™ Cholesterol Test as a Replacement for the Traditional Lipid Profile. 2005. 11. Atherotech Website. http://www.atherotech.com. 2005 12. Fukushima H, Sugiyama S, Honda O, et al. Prognostic value of remnant-like lipoprotein particle levels in patients with coronary artery disease and type II diabetes mellitus. J Am Coll Cardiol. 2004; 43(12):2219-24. 13. Inoue T, Uchida T, Kamishirado H, et al. Remnant-like lipoprotein particles as risk factors for coronary artery disease in elderly patients. Horm Metab Res. 2004; 36(5):298-302. 14. Imke C, Rodriguez BL, Grove JS, et al. Are remnant-like particles independent predictors of coronary heart disease incidence? The Honolulu Heart study. Arterioscler Thromb Vasc Biol. 2005; 25(8):1718-22. 15. Ariyo AA, Thach C, Tracy R. Lp(a) lipoprotein, vascular disease, and mortality in the elderly. N Engl J Med. 2003; 349(22):2108-15. 3

Cardiovascular Policies, Continued

Vertical Autoprofiling (VAP™) Cholesterol Test, continued

16. Danesh J, Collins R, Peto R. Lipoprotein(a) and coronary heart disease. Meta-analysis of prospective studies. Circulation. 2000; 102(10):1082-5. 17. Moliterno DJ, Jokinen EV, Miserez AR, et al. No association between plasma lipoprotein(a) concentrations and the presence or absence of coronary atherosclerosis in African-Americans. Arterioscler Thromb Vasc Biol. 1995; 15(7):850-5. 18. Berneis K, Jeanneret C, Muser J, Felix B, Miserez AR. Low-density lipoprotein size and subclasses are markers of clinically apparent and non-apparent atherosclerosis in type 2 diabetes. Metabolism. 2005; 54(2):227-34. 19. Mykkanen L, Kuusisto J, Haffner SM, Laakso M, Austin MA. LDL size and risk of coronary heart disease in elderly men and women. Arterioscler Thromb Vasc Biol. 1999; 19(11):2742-8. 20. St-Pierre AC, Cantin B, Dagenais GR, et al. Low-density lipoprotein subfractions and the long-term risk of ischemic heart disease in men: 13-year follow-up data from the Quebec Cardiovascular Study. Arterioscler Thromb Vasc Biol. 2005; 25(3):553-9. 21. Lamarche B, Moorjani S, Cantin B, Dagenais GR, Lupien PJ, Despres JP. Associations of HDL2 and HDL3 subfractions with ischemic heart disease in men. Prospective results from the Quebec Cardiovascular Study. Arterioscler Thromb Vasc Biol. 1997; 17(6):1098-105. 22. Sweetnam PM, Bolton CH, Yarnell JW, et al. Associations of the HDL2 and HDL3 cholesterol subfractions with the development of ischemic heart disease in British men. The Caerphilly and Speedwell Collaborative Heart Disease Studies. Circulation. 1994; 90(2):769-74. 23. Campos H, Moye LA, Glasser SP, Stampfer MJ, Sacks FM. Low-density lipoprotein size, pravastatin treatment, and coronary events. Jama. 2001; 286(12):1468-74. 24. Miller BD, Alderman EL, Haskell WL, Fair JM, Krauss RM. Predominance of dense low-density lipoprotein particles predicts angiographic benefit of therapy in the Stanford Coronary Risk Intervention Project. Circulation. 1996; 94(9):2146-53. 25. Hayes Technology Directory. High-density lipoprotein subclass testing for screening, diagnosis, and management of dyslipidemia and cardiovascular disease. 2000. 26. Kulkarni KR, Garber DW, Jones MK, Segrest JP. Identification and cholesterol quantification of low density lipoprotein subclasses in young adults by VAP-II methodology. J Lipid Res. 1995; 36(11):2291-302. 27. Kulkarni KR, Marcovina SM, Krauss RM, Garber DW, Glasscock AM, Segrest JP. Quantification of HDL2 and HDL3 cholesterol by the Vertical Auto Profile-II (VAP-II) methodology. J Lipid Res. 1997; 38(11):2353-64. 28. Kulkarni KR, Markovitz JH, Nanda NC, Segrest JP. Increased prevalence of smaller and denser LDL particles in Asian Indians. Arterioscler Thromb Vasc Biol. 1999; 19(11):2749-55. 29. Tzou WS, Douglas PS, Srinivasan SR, Chen W, Berenson G, Stein JH. Advanced lipoprotein testing does not improve identification of subclinical atherosclerosis in young adults: the Bogalusa Heart Study. Ann Intern Med. 2005; 142(9):742-50. 30. Alaupovic P, Mack WJ, Knight-Gibson C, Hodis HN. The role of triglyceride-rich lipoprotein families in the progression of atherosclerotic lesions as determined by sequential coronary angiography from a controlled clinical trial. Arterioscler Thromb Vasc Biol. 1997; 17(4):715-22. 31. Rallidis LS, Pitsavos C, Panagiotakos DB, Sinos L, Stefanadis C, Kremastinos DT. Non-high density lipoprotein cholesterol is the best discriminator of myocardial infarction in young individuals. Atherosclerosis. 2005; 179(2):305-9. 32. Sacks FM, Alaupovic P, Moye LA, et al. VLDL, apolipoproteins B, CIII, and E, and risk of recurrent coronary events in the Cholesterol and Recurrent Events (CARE) trial. Circulation. 2000; 102(16):1886-92. 33. Budde T, Fechtrup C, Bosenberg E, et al. Plasma Lp(a) levels correlate with number, severity, and length-extension of coronary lesions in male patients undergoing coronary arteriography for clinically suspected coronary atherosclerosis. Arterioscler Thromb. 1994; 14(11):1730-6. 34. Evans RW, Shpilberg O, Shaten BJ, Ali S, Kamboh MI, Kuller LH. Prospective association of lipoprotein(a) concentrations and apo(a) size with coronary heart disease among men in the Multiple Risk Factor Intervention Trial. J Clin Epidemiol. 2001; 54(1):51-7. 35. Imhof A, Rothenbacher D, Khuseyinova N, et al. Plasma lipoprotein Lp(a), markers of haemostasis and inflammation, and risk and severity of coronary heart disease. Eur J Cardiovasc Prev Rehabil. 2003; 10(5):362-70. 36. Luc G, Bard JM, Arveiler D, et al. Lipoprotein (a) as a predictor of coronary heart disease: the PRIME Study. Atherosclerosis. 2002; 163(2):377-84. 37. Nishino M, Malloy MJ, Naya-Vigne J, Russell J, Kane JP, Redberg RF. Lack of association of lipoprotein(a) levels with coronary calcium deposits in asymptomatic postmenopausal women. J Am Coll Cardiol. 2000; 35(2):314-20. 38. Seman LJ, DeLuca C, Jenner JL, et al. Lipoprotein(a)-cholesterol and coronary heart disease in the Framingham Heart Study. Clin Chem. 1999; 45(7):1039-46. 39. Gardner CD, Fortmann SP, Krauss RM. Association of small low-density lipoprotein particles with the incidence of coronary artery disease in men and women. Jama. 1996; 276(11):875-81. 40. Sherrard B, Simpson H, Cameron J, Wahi S, Jennings G, Dart A. LDL particle size in subjects with previously unsuspected coronary heart disease: relationship with other cardiovascular risk markers. Atherosclerosis. 1996; 126(2):277-87. 41. Nowicka G, Jarosz A. LpAI in HDL subfractions: serum levels in men and women with coronary heart disease and changes under hypolipemic therapy. Clin Chim Acta. 2001; 306(1-2):43-9. 42. Yu S, Yarnell JW, Sweetnam P, Bolton CH. High density lipoprotein subfractions and the risk of coronary heart disease: 9- years follow-up in the Caerphilly Study. Atherosclerosis. 2003; 166(2):331-8. 43. Greenland P, Alpert JS, Beller GA, et al. (2010). 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. Dec 14;56(25): e50-103. 44. Davidson MH, Ballantyne CM, Jacobson TA, et al. (2011). Clinical utility of inflammatory markers and advanced lipoprotein testing: advice from an expert panel of lipid specialists. J Clin Lipidol. Sep-Oct;5(5):338-67. 45. Cromwell WC, Otvos JD, Keyes MJ, et al. (2011). LDL Particle Number and Risk of Future Cardiovascular Disease in the Framingham Offspring Study - Implications for LDL Management. J Clin Lipidol. 2007 Dec;1(6):583-92. 46. Sniderman AD, Williams K, Contois JH. (2011). A meta-analysis of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk. Circ Cardiovasc Qual Outcomes. May;4(3):337- 45. Epub 2011 Apr 12.

Cardiovascular Policies, Continued

Vertical Autoprofiling (VAP™) Cholesterol Test, continued

Members should consult with appropriate healthcare providers to obtain needed medical advice, care, and treatment. Benefits and eligibility are determined before medical guidelines and payment guidelines are applied. Benefits are determined by the member’s individual benefit plan that is in effect at the time services are rendered. The codes for treatments and procedures applicable to this policy are included for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member. SelectHealth® makes no representations and accepts no liability with respect to the content of any external information cited or relied upon in this policy. SelectHealth updates its Coverage Policies regularly, and reserves the right to amend these policies without notice to healthcare providers or SelectHealth members. Members may contact Customer Service at the phone number listed on their member identification card to discuss their benefits more specifically. Providers with questions about this Coverage Policy may call SelectHealth Provider Relations at (801) 442-3692. No part of this publication may be reproduced, stored in a retrieval system or transmitted, in any form or by any means, electronic, mechanical, photocopying, or otherwise, without permission from SelectHealth. ”Intermountain Healthcare” and its accompanying logo, the marks of “SelectHealth” and its accompanying marks are protected and registered trademarks of the provider of this Service and or Intermountain Health Care, Inc., IHC Health Services, Inc., and SelectHealth, Inc. Also, the content of this Service is proprietary and is protected by copyright. You may access the copyrighted content of this Service only for purposes set forth in these Conditions of Use. © CPT Only – American Medical Association

Cardiovascular Policies, Continued

MEDICAL POLICY

WEARABLE CARDIOVERTER-DEFIBRILLATOR

Policy # 406 Implementation Date: 8/1/08 Review Dates: 6/11/09, 9/15/11, 11/29/12, 2/20/14, 3/19/15, 2/16/17, 2/15/18, 2/5/19, 2/17/20 Revision Dates: 6/17/10, 2/29/16, 2/15/18

Description The term "sudden cardiac death" (SCD) is used to describe cardiac arrest with cessation of cardiac function, whether resuscitation or spontaneous reversion occurs. This definition of SCD is misleading because not all affected individuals die, and the use of SCD in this sense has been challenged. The implantable cardioverter defibrillator (ICD) is considered a cornerstone of modern cardiology practice for reducing the incidence of sudden cardiac death related to ventricular fibrillation (VF) or ventricular tachycardia (VT). However, several factors limit the prophylactic implantation of the ICD, mainly the inability of invasive and noninvasive laboratory investigations to predict sudden death accurately in a patient population bearing the risk of dying suddenly. As a result, a substantial portion of the at-risk population does not receive adequate preventive therapy and others with lower risk will have the ICD implanted. A potential solution to this problem could be the use of an external, wearable cardioverter defibrillator (vest) that has defibrillation features similar to those of the ICD (i.e., no operator required to defibrillate), providing protection to the patient until it is determined that the implantation of the ICD is warranted, or another strategy pursued (e.g., heart transplant). A device used a “bridge” to ICD implantation must be capable of reliably terminating episodes of VF/VT, have a highly sensitive and specific algorithm for the detection of VT/VF, and be user-friendly, thereby, ensuring patient compliance. The vest-like device consists of a chest garment with electrode belt, monitor/defibrillator, patient base station, and physician programming console. The belt is strapped under the heart directly onto the patient’s skin to continuously sense electrical activity. If a life-threatening arrhythmia is detected and no response to device alarms is noted, the patient is presumed to be unconscious and the device delivers a shock to restore normal rhythm. Additional treatment may be delivered if the initial shock is not effective. The device weighs approximately 3 pounds. It is worn continuously, but it is not waterproof. For proper use, patients are trained to connect the device to an external modem and send data over the phone to the physician’s computer for medical evaluation.

Commercial Plan Policy (Preauthorization Required)

SelectHealth covers wearable cardioverter-defibrillators in limited circumstances. Criteria for coverage include: 1. The patient is at high risk for sudden cardiac death and meets criteria for implantable cardioverter defibrillator (ICD) placement but is not currently a suitable candidate for ICD placement because of 1 of the following: • Awaiting heart transplantation • Awaiting ICD reimplantation following infection-related explantation • Systemic infectious process or other temporary medical condition precludes implantation

Cardiovascular Policies, Continued

Wearable Cardioverter-Defibrillator, continued

2. As a bridge to ICD risk stratification and possible implantation for patients: • Had ventricular tachycardia (VT) or ventricular fibrillation (VF) within 48 hours of a myocardial infarction (MI), OR • The first 40 days after myocardial infarction (MI) in patients with an ejection fraction (EF) < 35%, OR • Within 3 months of CABG or PCI with ejection fraction (EF) < 35%, OR • With non-ischemic cardiomyopathy and EF of < 35%

SelectHealth Advantage (Medicare/CMS) (Preauthorization Required)

SelectHealth Community Care (Medicaid/CHIP)

Summary of Medical Information The U.S. Food and Drug Administration (FDA) approved the Lifecor Wearable Cardioverter Defibrillator 2000 system via 510(k) approval in December 2001, based on clinical data submitted to the FDA by the manufacturer, which has subsequently been published in the peer-reviewed literature, and referred to as the BIROAD and WEARIT studies. The trials consisted of prospective, non-randomized studies, which compared the outcomes of the WCD with historical controls of patients suffering sudden cardiac arrest who called 911 emergency services. While this study demonstrated that the WCD could detect arrhythmias and appropriately deliver a counter shock, its long-term efficacy will depend on patient compliance, and from a practical perspective, the WCD cannot be continuously worn. For example, the BIROAD and WEARIT studies included 289 patients; there were 12 deaths reported, and 50% occurred in patients either not wearing the device or wearing it inappropriately. Additionally, 68 of the 289 patients discontinued wearing the device due to comfort issues or adverse reactions. Therefore, an implantable cardiac defibrillator (ICD) is considered the gold standard, and, as such, a WCD would be considered an alternative to an ICD only in the small subset of patients who have co-morbidities or other contraindications for an ICD. Patients with an infected ICD requiring removal may benefit from a WCD worn during the limited interim period until an ICD can be re-implanted. Additionally, a small subset of patients awaiting heart transplantation may be considered at high risk for arrhythmia, but are not candidates for an ICD due to co-morbidities. A WCD may be considered an alternative to an ICD in these patients while they are on the heart transplant waiting list. There has been interest in offering WCDs to patients in the immediate post myocardial infarction (MI) period, when patients are considered at high risk of arrhythmia. However, the DINAMIT trial demonstrated that an ICD is not indicated during this period, thus, the WCD cannot be considered an alternative to an ICD in this setting. The DINAMIT trial randomized 674 patients to receive either an ICD or no ICD within 40 days of a myocardial infarction. All patients had reduced ejection fractions (ejection fraction ≤ 35%) and impaired cardiac autonomic function. There was no difference in overall mortality between the two groups. While the nonrandomized BIROAD study investigated patients treated with a WCD in the immediate post MI period, the results of the large randomized DINAMIT study provide a higher level of evidence, which may be extrapolated to WCD.

Cardiovascular Policies, Continued

Wearable Cardioverter-Defibrillator, continued

A 2009 technology assessment published by the California Technology Assessment Forum (CTAF), concluded that the use of a wearable cardioverter defibrillator (WCD) for patients at risk for sudden cardiac arrest and who are not candidates for or refuse an ICD does not meet the CTAF criteria. The assessment included uncontrolled case series by Auricchio (1998, n = 15), and Reek (2003, n = 12) that evaluated the ability of the device to detect and terminate tachyarrhythmias induced in the controlled setting of the electrophysiology laboratory. The author concluded that the limited scientific evidence, consisting of one pivotal trial with a precursor device and a small number of events, does not permit conclusions regarding the effectiveness of the WCD regarding health outcomes. A multicenter cohort study evaluating the impact of the WCD on mortality and quality of life in patients who meet criteria for, but are unable or unwilling to have an ICD, is needed before definitive conclusions can be made regarding safety and effectiveness. For patients who do not meet criteria for an ICD, but who are considered to be at increased risk of SCD (e.g., post-acute MI with reduced EF), a randomized controlled trial with mortality data is recommended before the safety and efficacy of the device can be evaluated for use in clinical practice.

Billing/Coding Information Covered: For the conditions outlined above CPT CODES 93292 Interrogation device evaluation (in person) with analysis, review and report by a physician or other qualified health care professional, includes connection, recording and disconnection per patient encounter; wearable defibrillator system 93745 Initial set-up and programming by a physician of wearable cardioverter-defibrillator, includes initial programming of system, establishing baseline electronic ECG, transmission of data to data repository, patient instruction in wearing system and patient reporting of problems or events

HCPCS CODES K0606 Automatic external defibrillator, with integrated electrocardiogram analysis, garment type K0607 Replacement battery for automated external defibrillator, garment type only, each K0608 Replacement garment for use with automated external defibrillator, each K0609 Replacement electrodes for use with automated external defibrillator, garment type only, each E0617 External defibrillator with integrated electrocardiogram analysis

Key References 1. Auricchio A, Klein H, Geller CJ, et al. (1998). Clinical efficacy of the wearable cardioverter defibrillator in acutely terminating episodes of ventricular fibrillation. Am J Cardiol. 1998; 81(10):1253-1256. 2. Beauregard LA. (2004). Personal security: clinical applications of the wearable defibrillator. Pacing Clin Electrophysiol. 27(1):1- 3. 3. Bigger JT. (1997). Prophylactic use of implanted cardiac defibrillators in patients at high risk for ventricular arrhythmias after coronary artery bypass surgery. The CABG-PATCH Trial Investigators. N Engl J Med. 337(22):1569-1575. 4. Boehmer JP. (2003). Device therapy for heart failure. Am J Cardiol. 91(suppl):53D-59D. 5. Feldman AM, Klein H, Tchou P, et al. (2004). Use of a wearable defibrillator in terminating tachyarrhythmias in patients at high risk for sudden death: Results of the WEARIT/BIROAD. Pacing Clin Electrophysiol. 27(1):4-9. 6. Feldman MD. (2009). Wearable cardioverter defibrillator for patients at risk for sudden cardiac arrest. California Technology Assessment Forum (CTAF). March 11. Available: http://www.ctaf.org/content/assessment/detail/987. Date Accessed: June 29, 2010. 7. Hohnloser SH, Kuck KH, Dorian P, et al. (2004). Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction. N Engl J Med. 351(24):2481-2488. 8. Podrid, PJ, Arnsdorf, MF, Cheng, J, et al. (2008). Acute therapy of sudden cardiac arrest. UpToDate. Available: http://www.utdol.com/online/content/topic.do?topicKey=carrhyth/49765&selectedTitle=2~150&source=search_result. Accessed July 21, 2008. 9. Reek S, Geller JC, Meltendorf U, et al. (2003). Clinical efficacy of a wearable defibrillator in acutely terminating episodes of ventricular fibrillation using biphasic shocks. Pacing Clin Electrophysiol. 26(10):2016-2022. 10. Reek S, Meltendorf U, Geller JC, et al. (2002). The wearable cardioverter defibrillator (WCD) for the prevention of sudden cardiac death - a single center experience. Z Kardiol. 91(12):1044-1052 (abstract available in English; article in German). 11. Al-Khatib, S. M., W. G. Stevenson, M. J. Ackerman, W. J. Bryant, D. J. Callans, A. B. Curtis, B. J. Deal, T. Dickfeld, M. E. Field, G. C. Fonarow, A. M. Gillis, M. A. Hlatky, C. B. Granger, S. C. Hammill, J. A. Joglar, G. N. Kay, D. D. Matlock, R. J. Myerburg and R. L. Page (2017). "2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society." Heart Rhythm. 3

Cardiovascular Policies, Continued

Wearable Cardioverter-Defibrillator, continued

MEDICAL POLICY

WIRELESS CARDIAC MONITORING (E.G., CARDIOMEMS)

Policy # 642 Implementation Date: 9/28/20 Review Dates: Revision Dates:

Description Heart failure (HF) is a chronic condition that develops over time due to circumstances that overwork and damage the heart. The primary causes include coronary heart disease, high blood pressure, and diabetes. HF is characterized by the inability of the heart to pump blood efficiently. HF is estimated to affect approximately 5.7 million people in the United States. Currently, there is no cure for HF. It can affect both children and adults, although it most commonly occurs in adults 65 years of age or older.

The CardioMEMS (CM) Heart Failure (HF) System (Abbott) is a wireless implantable hemodynamic monitor (IHM), for use at home in patients with HF. The CM-IHM system includes an implantable pulmonary artery pressure (PAP) sensor, a transvenous catheter delivery system, a patient home- monitoring electronic system, and a secure Internet-accessible database that allows clinicians to access patient data. The CM-IHM system provides measurement of the systolic, diastolic, and mean PAP, intending to allow for adjustment of HF medical therapy based on pressure trends and specified pressure goals. Once implanted, the patient will take a wireless reading from their PAP sensor once a day from home. Pressure data from this daily reading is then transmitted to a secure website for the physician and clinical team to review and make any necessary adjustments to HF treatment.

Commercial Plan Policy (Preauthorization Required)

SelectHealth covers the CardioMEMS wireless cardiac monitor for heart failure patients, if either A or B are documented:

A. Recommended by Intermountain Healthcare Cardiovascular Clinical Program, OR

B. All the following criteria are met:

1. Left-sided heart failure diagnosis (preserved or reduced ejection fraction) for at least 3 months 2. History of ≥ 1 heart failure hospitalizations/events in the past year 3. HFrEF patients must be on optimal heart failure medications (GDMT at best- tolerated doses 4. NYHA class III heart failure symptoms 5. The patient is an outpatient, and actively being monitored by a cardiologist specializing in heart failure with the capability of daily monitoring of the CardioMEMS data 6. The patient agrees to the patient training and home measurement schedule

Cardiovascular Policies, Continued

Wireless Cardiac Monitoring (e.g., Cardiomems), continued

Absolute Contraindications to CardioMEMS: a. Non-adherence with medication use, and/or laboratory follow-up recommendations b. The patient has refused CRT c. Inability to take dual antiplatelet therapy or anticoagulation for one-month post-implantation d. Patient cannot tolerate a right heart catheterization e. Mechanical tricuspid or pulmonic valve f. BMI > 35 with chest circumference (at axillary level) > 165cm

Relative Contraindications to CardioMEMS:

g. Patients with an active but treatable infection h. Patients with a history of recurrent (> 1) pulmonary embolism or deep vein thrombosis i. Patients with a GFR < 25 ml/min who are non-responsive to diuretic therapy. j. Patients with ESRD on dialysis k. Patients with congenital heart disease l. Patients with known coagulation disorders m. Patients with a hypersensitivity or allergy to aspirin, and/or clopidogrel n. CRT implantation in the past 3 months (as these patients may clinically improve post-CRT) o. Recent pacemaker, ICD, or CRT implantation (risk of lead dislodgement and would need to discuss timing with electrophysiology) p. Tricuspid valve clip (would need to be discussed with structural heart team)

SelectHealth Advantage (Medicare/CMS) (Preauthorization Required)

SelectHealth Community Care (Medicaid/CHIP) (Preauthorization Required)

Summary of Medical Information CardioMEMS pulmonary artery monitoring device has been approved by the US Food and Drug Administration to monitor pulmonary artery pressure and heart rate in patients with NYHA class III HF who have been hospitalized during the previous year. Further study is needed to determine the efficacy and safety of this device. The 2016 ESC HF guidelines included only a very weak recommendation

Cardiovascular Policies, Continued

Wireless Cardiac Monitoring (e.g., Cardiomems), continued

stating that this device may be considered in symptomatic patients with HF with previous HF hospitalization.

The CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes In NYHA Class III Heart Failure Patients (CHAMPION) randomized single-blind trial of 550 patients found that transmission of pulmonary artery pressure data from the device reduced HF-related hospitalizations at six months (31 versus 44 percent, HR 0.70, 95% CI 0.60−0.84). There was a 1.5 percent rate of device- or system- related complications. An exploratory subgroup analysis found that device-guided management reduced HF-related hospitalization in patients with preserved LVEF (LVEF ≥ 40 percent or LVEF ≥ 50 percent), as well as in patients with LVEF < 40 percent. Another exploratory analysis found that device-guided management reduced respiratory hospitalization rates as well as HF hospitalization rates in the entire cohort, as well as in a subgroup of 187 patients with chronic obstructive pulmonary disease.

A later analysis reported sustained reduction in HF-related hospitalization in the device-guided management group compared with the control at 18-month average follow-up (46 versus 68 percent, HR 0.67, 95% CI 0.55 to 0.80). During a subsequent open access period (mean duration 13 months), pulmonary artery pressure information was made available to guide therapy in the former control group; the rate of admission was reduced compared with that in the control group during the randomized access period (36 versus 68 percent; HR 0.52, 95% CI 0.40 to 0.69). The rate of device- or system-related complications was 1 percent and the rate of procedure-related adverse events was 1 percent.

However, the efficacy of the CardioMEMS device is uncertain given concerns raised about potential bias introduced in the conduct of the CHAMPION trial (including interaction between the trial sponsor and clinical investigators on certain treatment group subjects) and the analysis of data.

Billing/Coding Information

CPT CODES 33289 Transcatheter implantation of wireless pulmonary artery pressure sensor for long-term hemodynamic monitoring, including deployment and calibration of the sensor, right heart catheterization, selective pulmonary catheterization, radiological supervision and interpretation, and pulmonary artery angiography, when performed

93264 Remote monitoring of a wireless pulmonary artery pressure sensor for up to 30 days, including at least weekly downloads of pulmonary artery pressure recordings, interpretation(s), trend analysis, and report(s) by a physician or other qualified health care

HCPCS CODES

C2624 Implantable wireless pulmonary artery pressure sensor with delivery catheter, including all system components

Key References 1. Colucci, W. S. (2019). Investigational and emerging strategies of heart failure. UpToDate. Retrieved from: https://www.uptodate.com/contents/investigational-and-emerging-strategies-for-management-of-heartfailure/print?search=cardiomems&source=search_result&selectedTitle=2~2&usage_type=default&display_rank=2 2. Hayes Brief. (2019). CardioMEMS Implantable Hemodynamic Monitor (Abbott) for Managing Patients with Heart Failure.

Cardiovascular Policies, Continued

Wireless Cardiac Monitoring (e.g., Cardiomems), continued