JERSEY SHORE UNIVERSITY MEDICAL CENTER Cardiovascular Catheterization Laboratory Alcohol Septal Ablation Protocol Purpose

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disorder with a global burden and prevalence of about 1:500. It is characterized by unexplained cardiac hypertrophy involving a non-dilated left in the absence of other identifiable cardiac or systemic causes. HCM generally results from mutations in the sarcomere (Myosin Heavy Chain, Myosin Binding Protein C, etc). It is an autosomal dominant disease with variable penetrance and can manifest at almost any age. The location and extent of myocardial hypertrophy is also variable. Among patients with HCM the most common phenotype involves asymmetric septal hypertrophy of the basal that may be accompanied by dynamic obstruction of the left ventricular outflow tract (LVOT) as well as systolic anterior motion (SAM) of the anterior leaflet of the mitral valve with and without coexistent and clinically significant mitral regurgitation. Not all patients have the dynamic obstructive phenotype and patients may independently experiences symptoms of congestive failure (CHF) or exercise intolerance from diastolic dysfunction (ranging from mild to restrictive). However, the presence of resting and dynamic LVOT obstruction has been related to symptom status, progression of CHF, and risk of death.

In patients with appropriate anatomic features and significant dynamic LVOT obstruction associated with severe and limiting symptoms refractory to medical therapy, septal reduction therapy may be considered to improve quality of life. Therapy resistant obstruction can be treated surgically or percutaneously with substantial symptomatic (NYHA Class, quality of life) and hemodynamic improvement. While there may be a survival advantage to septal reduction in appropriately selected patients that data is from large observations/registries and has not been proven in a randomized way.

The purpose of this document is to demonstrate the credentialing for the performance of transcatheter alcohol septal ablation as an alternative to septal reduction by surgical myectomy in patients with symptomatic hypertrophic cardiomyopathy with obstruction refractory to medical therapy. Appropriate candidates should have asymmetric septal hypertrophy with adequate septal thickness (>15-18 mm), NYHA Class III or IV symptoms and documented resting or provocable outflow tract gradient of 50 mm Hg or greater that is caused by asymmetric septal hypertrophy and SAM of the mitral valve (and not from systolic cavity obliteration), and suitable septal artery anatomy. These features will have been delineated prior to any procedure by a multimodality and multidisciplinary approach. The decision to offer percutaneous rather than surgical septal reduction therapy is a complex one beyond the scope of this document and will have been documented by the multidisciplinary team prior to proceeding with a -based approach. All patient should undergo risk factor stratification for sudden cardiac death, the need for implantable cardiac defibrillator, and the need for pacemaker prior to proceeding with septal reduction.

Policy

Alcohol septal ablation is a percutaneous transcatheter procedure that involves, under fluoroscopic and echocardiographic guidance, the injection of 100% ethanol into a septal perforator to create a controlled infarction of the portion of the hypertrophic septum causing LVOT obstruction.

Procedure Indications (Gersh B, et al. 2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: Executive Summary. JACC. 2011;58:2703-38.)

Invasive Therapies—Recommendations CLASS I 1. Septal reduction therapy should be performed only by experienced operators in the context of a comprehensive HCM clinical program and only for the treatment of eligible patients with severe drug-refractory symptoms and LVOT obstruction (Level of Evidence: C)

CLASS IIa 1. Consultation with centers experienced in performing both surgical and alcohol septal ablation is reasonable when discussing treatment options for eligible patients with HCM with severe drug-refractory symptoms and LVOT obstruction. (Level of Evidence: C) 2. Surgical septal myectomy, when performed in experienced centers, can be beneficial and is the first consideration for the majority of eligible patients with HCM with severe drug refractory symptoms and LVOT obstruction. (Level of Evidence: B) 3. Surgical septal myectomy, when performed at experienced centers, can be beneficial in symptomatic children with HCM and severe resting obstruction (>50 mm Hg) for whom standard medical therapy has failed. (Level of Evidence: C) 4. When surgery is contraindicated or the risk is considered unacceptable because of serious comorbidities or advanced age, alcohol septal ablation, when performed in experienced centers, can be beneficial in eligible adult patients with HCM with LVOT obstruction and severe drug-refractory symptoms usually NYHA functional classes III or IV). (Level of Evidence: B)

CLASS IIb 1. Alcohol septal ablation, when performed in experienced centers, may be considered as an alternative to surgical myectomy for eligible adult patients with HCM with severe drug-refractory symptoms and LVOT obstruction when, after a balanced and thorough discussion, the patient expresses a preference for septal ablation. (Level of Evidence: B) 2. The effectiveness of alcohol septal ablation is uncertain in patients with HCM with marked (i.e., >30 mm) septal hypertrophy, and therefore the procedure is generally discouraged in such patients. (Level of Evidence: C)

CLASS III: HARM 1. Septal reduction therapy should not be done for adult patients with HCM who are asymptomatic with normal exercise tolerance or whose symptoms are controlled or minimized on optimal medical therapy. (Level of Evidence: C) 2. Septal reduction therapy should not be done unless performed as part of a program dedicated to the longitudinal and multidisciplinary care of patients with HCM. (Level of Evidence: C) 3. Mitral for relief of LVOT obstruction should not be performed in patients with HCM in whom septal reduction therapy is an option. (Level of Evidence: C) 4. Alcohol septal ablation should not be done in patients with HCM with concomitant disease that independently warrants surgical correction (e.g., coronary artery bypass grafting for CAD, for ruptured chordae) in whom surgical myectomy can be performed as part of the operation. (Level of Evidence: C) 5. Alcohol septal ablation should not be done in patients with HCM who are less than 21 years of age and is discouraged in adults less than 40 years of age if myectomy is a viable option. (Level of Evidence: C)

Treatment algorithm. ACE indicates angiotensin-converting enzyme; ARB, angiotensin receptor blocker; DM, diabetes mellitus; EF, ejection fraction; GL, guidelines; HCM, hypertrophic cardiomyopathy; HTN, ; and LV, left ventricular.

Alcohol Septal Ablation Procedure Details

-Standard informed consent + consent for ETOH septal ablation will be separately described and documented. -Standard laboratory radial/femoral/internal jugular prep and drape -Standard cardiac catheterization laboratory wires, sheaths, diagnostics, guides, transducers (2) with ADDITION of 6F Langston Multi-purpose dual lumen catheter. -Intravenous moderate sedation managed by interventional cardiologist -Standard cardiac catheterization lab staff/team with ADDITION of transthoracic echocardiogram instrument in the room with a sonographer present in the room in lead protection. -Inpatient Pharmacy to supply dose of 100% denatured ethanol for injection

1) Perform limited transthoracic echocardiogram (assess LV wall motion and LVEF, rule out pericardial effusion, assess degree of SAM and mitral regurgitation, measure LVOT +/- mid cavitary gradients (CW Doppler and PW Doppler) at rest and with Valsalva. 2) Proceed with right internal jugular vein cannulation under ultrasound and fluoroscopic guidance with introduction of a 6F sheath. Introduce a 5F balloon tipped pacing electrode catheter through the sheath and advance under fluoroscopic guidance to the RV septum. Confirm reliable capture and record capture threshold. Secure the sheath and pacing electrode in place. 3) Proceed with radial or femoral arterial cannulation with a 6F sheath under ultrasound and fluoroscopic guidance. 4) Proceed with left heart catheterization in the following manner. Over a 0.035” j tipped guidewire, advance a 6F pigtail catheter across the aortic valve under fluoroscopic guidance. 5) Exchange the pigtail catheter in the left ventricle over a 260 cm 0.035” J tipped guidewire for a 6F Langston Multipurpose dual lumen catheter. 6) Measure simultaneous LV and aortic root pressures at rest, with Valsalva and post PVC. This will often already have been performed during a previous diagnostic catheterization to confirm the classic hemodynamic findings of obstructive cardiomyopathy. 7) Pull the Langston Multipurpose catheter back across the aortic valve and exchange over a 260 cm 0.035” J tipped guidewire for an appropriately sized 6F left main coronary guide catheter. 8) Engage the left main coronary. 9) Proceed with left circulation coronary angiography. (previous coronary angiography should have already been performed including left main and right coronary to rule out fistulas and exclude large right PDA septal contributors/anomalies). 10) Initiate therapeutic anticoagulation with unfractionated heparin. Document ACT >300. 11) De-air the coronary guide catheter and tuohy borst, advance a 300 cm 0.014” Coronary guidewire (for example a Choice PT or Whisper) into the LAD and direct the coronary wire into the candidate septal perforator. 12) Advance an appropriately sized over the wire balloon catheter into the proximal portion of the candidate septal (generally 1.0-2.0 mm diameter, 10-12 mm in length). If the candidate septal takes off at >90 degrees, this may prove difficulty and a stiffer guidewire may be used for extra support. 13) Inflate balloon to an occlusive pressure (total atmosphere on a case by case basis) to complete occlude flow down the candidate septal. 14) Perform coronary angiography through the guide to demonstrate no flow down the occluded septal vessel. 15) Remove the coronary guidewire. 16) Selective inject contrast through the septal OTW balloon to demonstrate no backflow reflux into LAD and no passage by way of collaterals or fistula to another vessel. 17) Under continuous transthoracic echocardiographic guidance (apical 4 chamber view) inject agitated saline mixture into the OTW balloon. If the septal branch subtends the correct area of the intraventricular septum, then on the subtended area of hypertrophic septum at the SAM point will become echo-bright/enhanced. 18) Proceed with ETOH septal ablation. 19) Inject 1-3 cc of 100% denatured ethanol into the inflated OTW balloon catheter over 1-5 minutes followed by adequate flush of heparinized normal saline to clear the lumen of the catheter. 20) Monitor patient for AV block or new bundle branch block. Assure continued reliable pacemaker capture. 21) Monitor patient with balloon inflated for an additional 10 minutes. 22) Repeat limited TTE for re-assessment of effect (Perform limited transthoracic echocardiogram (assess LV wall motion and LVEF, rule out pericardial effusion, assess degree of SAM and mitral regurgitation, measure LVOT +/- mid cavitary gradients (CW Doppler and PW Doppler) at rest. 23) Re-advance the 300 cm 0.014” coronary wire through the balloon catheter into the ablated septal and deflate the balloon. Remove the balloon catheter from the patient. 24) Repeat left circulation coronary angiography with wire in place, to assure that flow down the candidate septal is now impaired or absent, and flow down remainder of the LM/LAD system is stable/unchanged for prior. 25) Disengaged guide catheter from left main and exchange over a 0.035” 260 cm J wire for 6F Langston Multipurpose dual lumen catheter. 26) Perform repeat left heart catheterization with measurement of simultaneous LV and aortic root pressures at rest, with Valsalva and post PVC. 27) Pullback across aortic valve, record pressure, and then remove arterial catheter over a 0.035” J tipped guide wire 28) Remove right radial arterial sheath and obtain patent hemostasis with a TR band per protocol 29) Suture the RIJ temporary pacing electrode catheter to the neck and secure the sheath and pacing catheter with several occlusive dressings (Tegaderm, etc). Assure reliable capture and test capture thresholds. 30) Transfer to CCU for continued observation.

Post-Operative Care

Following uncomplicated ETOH-septal ablation, all patients will remain in CCU on telemetry for at least 24-48 hours. There EKG and creatinine phosphokinase (CK) levels should be obtained every 6 hours and it will be critical to record the peak CK level which correlates with the size of the . Pacemaker capture threshold should be documented each shift. The patient should remain on bedrest with head of bed elevated while device is in place. In the absence of significant heart block or brady-arrhythmias, the temporary pacemaker can be removed after 48 hours only at discretion of performing interventionalist. The patient generally spends an additional 48-72 hours on telemetry floor for continued monitoring for complications including but not limited to sudden cardiac death, ventricular tachycardia, ventricular fibrillation, ventricular septal defect/rupture, cardiac perforation, bundle branch block, heart block, tamponade, myocardial infarction. Over this time period medication de-escalation may or may not occur.

Procedure Risks

Risks of procedure include the same risks outlined by the health system for special procedure of cardiac catheterization but also include and are not limited to pain, infection, bleeding complications related to venous/arterial access, bleeding complications related to coronary engagement and wire cannulation, bleeding complications related to myocardial perforation including but not limited to pericardial effusion, coronary dissection, medium/large artery dissection, thromboembolism with/without stroke, possible need for emergent , severe disability, death, brady arrhythmias, ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia, right or left bundle branch block, 1st/2nd/3rd degree heart block, need for implantation of permanent pacemaker or defibrillator, ventricular septal rupture or defect formation, myocardial infarction of inadvertent site, renal failure.

Physician/Staffing Requirements

This procedure must be performed with a team approach led by an interventional cardiologist with expertise in hypertrophic cardiomyopathy with thorough knowledge of catheterization anatomy and coronary interventional techniques, as well as echocardiographic and (even MRI) imaging of the left ventricular and mitral apparatus anatomy. In addition to the cardiologist performing the procedure, additional assistance will be needed from a sonographer/echocardiography technologist. All cases will be performed by an interventional cardiologist. Surgical backup will be necessary, and a cardiothoracic surgeon must be immediately available in the event a surgical intervention is needed. The procedure will be carried out in the cardiac catheterization lab (as of 9/9/2018 only in labs 2 or 6). A cardiovascular technician proficient in wire management and temporary pacemaker management will be necessary as well a dedicated nurse for intravenous moderate conscious sedation and administration of life sustaining medications.

Criteria for Competency (Harold JG, et al. ACCF/AHA/SCAI Clinical Competence Statement. JACC 2013;62:357-96.)

Using the ACGME core competencies to define the issues, it is the recommendation of this writing committee that the following be considered:

Patient Care: The operator should have a thorough knowledge of the impact HOCM physiology plays in the patient’s symptom complex. Many of the symptoms attributed to HOCM overlap with other disease states, particularly if there is concurrent lung disease, coronary disease, anemia, etc., so optimal patient care requires the operator to differentiate symptoms related to HOCM from these other issues. Medical therapy should be appropriate and considered to have been a failure before the procedure is attempted. At least 1 dedicated surgeon with a working knowledge of myectomy and valve repair should be part of the overall program, and there should be regular case reviews. For complex cases, surgical consultation should be sought and the multidisciplinary team should agree that the interventional procedure is warranted. Nursing staff should be trained to recognize complications, both early and late, following the procedure.

Medical Knowledge and Procedural Volume: To gain the appropriate skill set for the performance of alcohol ablation requires the knowledge base related to the disease process (as described above) and the technical skills to safely perform the procedure. Medical knowledge regarding the procedure can be gained at courses at major meetings, participation in clinical trials or by working with colleagues at one’s own institution or at another facility.

To gain the particular skill of alcohol ablation for HOCM patients, the committee suggests that initially each operator perform the first 5 studies in a proctored situation assisting a skilled operator. These procedures could be done at the operator’s own facility or at the skilled operator’s facility. The ACCF/AHA HOCM guideline suggests that an experienced operator should not be defined until one has performed >20 procedures or the procedures have all been performed at a facility that has a cumulative volume of 50 procedures. If the procedures are performed at a facility with a cumulative experience of <50 cases, it is recommended that the catheterization laboratory quality assurance committee (or one appointed by the institution) be responsible for reviewing all of the first 20 cases performed. For maintenance of skills, it is recommended that each individual principal operator perform at least 10 procedures per year. This latter number has also been suggested in a report from the SCAI training program directors (164) as being the minimal number for certification of cardiovascular trainees within the structural heart disease program who desire alcohol ablation skills as part of their interventional training.

The minimal number of procedures, however, does not correlate with either operator skill or patient outcomes. The committee feels strongly that alcohol ablation for HOCM should be performed only with a multidisciplinary team, and that volume is just 1 of many factors that should be considered in assessing operator competency. After each operator has developed the needed skillset in a proctored environment, then, given the rarity of the procedure, 5 alcohol ablations for HOCM per year should be considered a reasonable volume to maintain that skillset. The bottom line remains that the onus is on the local credentialing process and the quality assurance committee to ensure an operator is qualified and his/her procedural outcomes are of the highest possible quality.

Practice-based Learning: The facility should provide a regular forum for the presentation of individual cases and provide the operators with feedback on the techniques and results obtained. These reviews should stress the use of evidence-based therapy and discuss best practices. As the field develops, these regular conferences should stress ways to improve the procedure and both institutional and individual outcomes. Literature reviews should be incorporated and verification confirmed that the practices being used conform to the established guidelines.

Interpersonal and Communication Skill: At the recommended periodic review sessions, any communication or conflicts regarding the appropriateness of the procedures or the technical issues should be directly discussed. Patient satisfaction should be addressed and criticisms acted upon. Feedback from staff and nursing should also be provided to ensure optimal patient care is being performed and that staff members are receiving the appropriate training.

Professionalism: Any criticism of the handling of the patient’s care at any stage should be addressed. This includes ensuring the patient and his family understand the procedure, are treated respectfully and honestly, the consent process is clear, the referring physician is kept well informed, and all of the team members are acknowledged for their contributions.

Systems-based Practice: The facility should have a formal commitment to the structural heart disease program and be supportive of establishing and maintaining the highest quality. Since care of the patient requires careful follow- up, it is important that the practitioners in the entire health system be aware of the potential complications from the procedure, and that a system is in place that allows for potential issues to be addressed should an untoward event occur after the procedure. As many patients will receive the bulk of their care locally and not at the referral center, a systems-wide educational effort should be made to inform the health care professionals of the indications and contraindications of the procedure and the expected outcomes. A clear mechanism should be in place that allows ready access to a member of the procedural team should questions arise.

Staff Competency

Many of the core competencies that apply to the operator are transferrable to staff involved as well. There should be a dedicated staff that has an interest in the procedure. It is particularly important that the cardiac catheterization team and the echocardiographic team work together, and they are considered a vital part of the procedural effort. The staff should be trained to anticipate all aspects of the procedure. Not only should initial training be formalized, but also continuing education should be considered a key element in the program design and maintenance.

Selected References

Bach GR, Singh GD, Southard JA. Alcohol Septal Ablation for Obstructive Hypertrophic Cardiomyopathy. In: Lasala JM, Rogers JG, eds. Interventional Procedures for Adult Structural Heart Disease. Philadelphia, PA: Elsevier Saunders; 2014.

Gersh B, et al. 2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: Executive Summary. JACC. 2011;58:2703-38.

Harold JG, et al. ACCF/AHA/SCAI Clinical Competence Statement. JACC 2013;62:357-96.

Lau E, Tuczu EM. Septal Ablation in Obstructive Hypertrophic Cardiomyopathy. In: Carroll JD, Webb JG, Eds. Structural Heart Disease Interventions. Philadelphia, PA; Lippincott Williams & Wilkins; 2012.