Saturday, September 29

NOTES—

Debate: Surgery Will Always be the Right Option Steven Bolling, MD

Debate: The Future is PCI Cindy Grines, MD

Debate: Surgery Will Always be the Right Option—Rebuttal Steven Bolling, MD

Debate: The Future is PCI—Rebuttal Cindy Grines, MD

9/17/2012

OPTIMAL MANAGEMENT OF CAROTID ARTERY DISEASE: Carotid endarterectomy vs. stenting

Jean Starr, MD, FACS, RPVI Associate Professor of Clinical Surgery Division of Vascular Diseases and Surgery Director of Endovascular Services

Objectives

ƒ Stay awake ƒ General stroke stats ƒ Stay awake ƒ Ischemic causes ƒ Stay awak e ƒ Workup ƒ Stay wake ƒ Treatment options

Fun vascular facts

ƒ Brain is 2% of total body weight ƒ Brain consumes 25% of inspired oxygen and 15% of total cardiac output ƒ Brain has more significance in women ƒ OK…I made that up ƒ Circle of Willis incomplete in 50% in autopsy studies ƒ Cerebral blood flow is under tight autoregulation to maintain perfusion pressure

1 9/17/2012

Striking Stroke Statistics ƒ Incidence ƒ Every 45 seconds someone in the U.S. has a stroke. ƒ Each year 700,000 people experience a stroke. 500,000 are first attacks and 200,000 are recurrent attacks. ƒ Each year about 40,000 more women than men have a stroke. ƒ African-Americans have almost twice the risk of first-ever stroke compared to whites.

Heart Disease and Stroke Statistics – 2004 Update, American Heart Association, 2004, pgs 13-15.

Striking Stroke Statistics ƒ Mortality ƒ Stroke accounts for more than 1 of every 15 deaths in the U.S. (150,000 annually) ƒ Stroke ranks no.3 among all causes of death behind diseases of heart and cancer. ƒ On average, every three minutes someone dies of a stroke. ƒ Because women live longer than men, 61% of deaths from stroke in 2001 were females.

Heart Disease and Stroke Statistics – 2004 Update, American Heart Association, 2004, pgs 13-15.

Striking Stroke Statistics ƒ Aftermath ƒ Stroke is the leading cause of serious, long-term disability in the U.S. ƒ In 1999, more than 1,100,000 Americans reported difficulty with functional limitations resulting from strokes. ƒ Cost ƒ In 2004 the estimated direct and indirect cost of stroke is $53.6 billion. ƒ The mean lifetime cost of ischemic stroke in the U.S. is $140,000.

Heart Disease and Stroke Statistics – 2004 Update, American Heart Association, 2004, pgs 13-15.

2 9/17/2012

Carotid Epidemiology – 2005 (US)1

2.46 million with >50% carotid stenosis2

10% 90% 3 Symptomatic Asymptomatic4

74,000 172,000 266,000 1,510,000 Undiagnosed Diagnosed/yr Diagnosed/yr Undiagnosed

Need to get 438,000 diagnosed/yr Need to get patients patients diagnosed diagnosed

1. Numbers reflect epidemiology of United States only. 2. Primary Prevention of Ischemic Stroke, Circulation, 2001;103:1632001;103:163--182.182. 3. Endarterectomy for Asymptomatic Carotid Artery Stenosis, JAMA, 1995. Vol273, No. 18. P.1421-P.1421-1428.1428. 4. New Insights on Stroke Prevention in Patients without Symptoms. London, Ontario. June 7, 2000.

Prevalence of Stroke

Prevalance of Stroke by Age and Sex 12.0 11.5 12 NHANES: 1999-2002 10

tion 8 Men a 666.6 Women 636.3 6

4 3.1 3.0

% of Popul of % 2.1 2 1.1 0.8 1.2 0.4 0.34 0 20-34 35-44 45-54 55-64 65-74 75+ Ages

Heart Disease and Stroke Statistics –2006 Update, American Heart Association, 2006, pg 88. 8

Ischemia may be caused by:

ƒ Embolic occlusion - caused by thrombus, platelet aggregates, and atheromatous debris ƒ May be related to intraplaque hemorrhage, ulceration of plaque with exposure of underlying debris and deposition of thrombus ƒ Arterial thrombosis (()less common) ƒ Originates from critical stenosis and propogates proximally and distally to the next major collateral (external prox and ophthalmic dist…will not continue into MCA unless ophthalmic flow is poor) ƒ Reduction in total cerebral blood flow ƒ May present with nonlateralizing cerebral ischemic attacks (ataxia, bilateral symptoms, homonymous hemianopsia, drop attacks)

3 9/17/2012

Diagnostic evaluation

ƒ Physical examination ƒ BP in both arms; orthostatics ƒ Cardiac rate and rhythm ƒ Murmurs assoc. with valvular disease or septal defects ƒ Pulses in cervical, upper and lower extremity ƒ Pulsatile masses and thrills ƒ Cervical/supraclavicular bruits; 40% of pts. with stenosis have bruit; 20% of pt. with a bruit will have a significant stenosis ƒ General vascular exam

Carotid duplex

ƒ Initial study of choice (non-invasive, painless, readily available) ƒ High resistive signal in ECA and low resistance in ICA ƒ Degree of stenosis and character of the atheroma (color flow and B- mode imaging) ƒ Dense calcium may obscure the results ƒ Limited ability to predict ararchch and intracranial disease ƒ Many perform CEA based on duplex imaging alone ƒ Utility for post-procedural follow up

CT Angiography

ƒ May be more precise than MRA; gives information on inflow ƒ Calcium may obscure the results ƒ Utilizes radiation and contrast ƒ Motion artifacts ƒ Images dependent on post-processing

4 9/17/2012

MRA

ƒ Physiologic evaluation of blood flow (indirectly evaluates vascular anatomy) ƒ Limited with complex, turbulent, minimal flow (such as at carotid bulb), ulcerations, tandem lesions, orificial lesions ƒ May overestimate degree of stenosis ƒ Non-invasive, can evaluate cerebral anatomy, avoids iodinated contrast, less operator variability than with duplex imaging, techniques can vary between centers, CLAUSTROPHOBIA ƒ Nephrogenic systemic fibrosis

Magnetic Resonance Angiography

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Angiography

ƒ ?Gold standard ƒ Invasive (although risks are low: 1.2% in ACAS) ƒ Involves contrast and radiation ƒ Diagnose and treat during the same setting ƒ BttBetter vessel ldli delinea tion

5 9/17/2012

Ulceration

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ANGIOGRAPHY

DSA CTA MRA

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Treatment history

ƒ 1875 – Gowers linked stroke to carotid artery disease ƒ 1937 – carotid artery occlusion could be diagnosed by angiography ƒ 1953 – first unsuccessful attempt at endarterectomy of totally occluded artery ƒ 1954 – first successful carotid reconstruction (resection and anatomosis by Eastcott, Pickering, and Robb) ƒ 1951 – Carrera – resection and anastomosis to ECA; not reported until 1955 ƒ 1953 - DeBakey and Cooley – CEA but not published until 1975 and 1956

6 9/17/2012

Medical treatment

ƒ Antiplatelet therapy ƒ ASA, ticlopidine, dipyridamole/ASA, clopidigrel ƒ Anticoagulant therapy ƒ No data that it is beneficial for stroke prevention except in thromboembolic stroke due to afib ƒ Potential use in crescendo TIA ƒ No randomized studies utilizing best medical management with these drugs and statins

Surgical treatment

ƒ Carotid endarterectomy ƒ General vs regional or local anesthesia ƒ Weigh patient anxiety and potential for longer operation vs. ability to assess neurologic function and decreased anesthetic risks ƒ Positioning: slight neck hyperextension, turned to opposite side, reverse Trendelenberg ƒ Maintaining cerebral blood flow (“To shunt or not to shunt”)

Surgical treatment

ƒ Carotid endarterectomy (cont.) ƒ Vagus nerve may spiral anteriorly ƒ Common facial vein marks the bifurcation ƒ Lidocaine standing by for carotid body and sinus ƒ Avoid manipulation of carotid bifurcation ƒ Mobilize distal ICA beyond disease ƒ Identify CN XII; potentially divide posterior belly of the digastric

7 9/17/2012

Carotid Endarterectomy

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Surgical treatment

ƒ Complications ƒ Hematoma – 0.7-1.5% incidence ƒ Infection – 0.09% ƒ Post-op hyper- or hypotension – neurons in the bulb adventitia, transmitted by nerve of Hering (CN IX) ƒ Peripheral nerve palsies: 7% RLN, 6% hypoglossal, 2% MM, 2% SLN, greater auricular , glossopharyngeal… 33% were asymp (CCF study). Most recover in 3 mos. ƒ TIA/CVA – 3, 5, and 7% ƒ Asymptomatic thrombosis – 2-18% ƒ Intracranial hemorrhage – several days post-op, devastating ƒ Post-op seizure – excruciating unilateral headache ƒ Cardiac events

Endovascular management

ƒ Carotid stenting ƒ Stenotic artery is opened and plaque “wallpapered” to vessel wall ƒ FDA approved for surgical high and standard risk patients (but not necessarily reimbursed by CMS) ƒ Several systems available ƒ Distal protection required for reimbursement ƒ High operator learning curve; requires advanced endovascular skills ƒ Can be done with local anesthesia

8 9/17/2012

High Risk Criteria

ƒ Anatomic criteria ƒ Previous neck dissection or radiation ƒ High or low lesion ƒ Recurrent carotid stenosis after CEA ƒ Contralateral carotid occlusion ƒ Medical criteria ƒ Unstable angina ƒ Recent MI ƒ Class III/IV heart failure ƒ Severe lung disease ƒ Need for CABG ƒ Age > 80

Carotid Artery Stenting

ƒ Advantages ƒ Treatment option for patients contraindicated for CEA ƒ Avoids the risk of cranial nerve damage ƒ Does not require general anesthesia ƒ Disadvantages ƒ Currently there are fewer experienced clinicians ƒ Not all patients are suitable for carotid stenting ƒ Severe aortic arch and supra-aortic vessel tortuosity ƒ Thrombus ƒ Very long severe lesions ƒ String sign ƒ Heavy circumferential calcification

Arch Types

9 9/17/2012

Carotid Stenting Overview

ƒ FDA approved 2004 ƒ Alternative treatment for high risk patients ƒ Uses 0.014 wire and distal embolic protection device ƒ Early clinical investigations had poor outcomes ƒ Initial approval based mostly on industry– sponsored trials and compared to historic surgical trials ƒ Randomized comparisons recently completed (CREST) ƒ Requires antiplatelet therapy

Overview of Stent Procedure Steps

ƒ Percutaneous femoral arterial access ƒ Arch and selective carotid angiography if not previously performed ƒ Guide catheter/sheath placement in CCA ƒ Neurologic assessment each step of the way (“Squeeze the duck”) ƒ Embolic protection device positioned beyond carotid stenosisPre-dilatation using an appropriately -sized balloon catheter (coronary balloon if needed) ƒ Stent delivery and deployment ƒ Post-dilatation ƒ Removal of embolic protection device ƒ Completion intracerebral imaging

Carotid Artery Stenting

Tapered

Straight

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10 9/17/2012

CAROTID STENTING

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CREST Results

ƒ Carotid Revascularization Endarterectomy vs. Stenting Trial ƒ Funded by National Institute of Neurologic Disorders and Stroke (NINDS), part of NIH ƒ 2,502 participants, NIH sponsored, 117 centers, 9 years ƒ 2.3% MI in surgical group vs. 1.1% in stent group ƒ 4.1% stroke in stent group vs. 2.3% in surgical group ƒ Composite endpoint for safety and efficacy similar (7.1 vs. 6.6% stroke/death/MI)

STANDARDS MET

ƒ The rates of death and stroke meet the AHA guideline of < 6.0% for symptomatic and 3.0% for asymptomatic CAS patients (5.9% and 2.3%, respectively).

11 9/17/2012

Current Status of CAS Approval

ƒ Currently FDA approved for: ƒ >50% symptomatic and high risk ƒ >80% asymptomatic and high risk (but only in PMA registry) ƒ >50% symptomatic and standard risk (but no CMS reimbursement))( (for Acculink Carotid Stent Sy stem only) ƒ >60% asymptomatic and standard risk (no CMS reimbursement) (for Acculink Carotid Stent System only)

What the heck?

ƒ CAS ƒ CEA ƒ Invasive ƒ Invasive ƒ Higher risk of CVA ƒ Higher risk of MI ƒ Risk from contrast ƒ Higher risk of CN ƒ Greater learning injury curve, less operators ƒ Potential anesthetic ƒ Higher risk of risks recurrence ƒ Perceived as less ƒ ?Higher risk in elderly desirable by the public

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How I handle it…

ƒ First, don’t change the indication to intervene ƒ If high risk, offer CAS (if asymp, enroll in PMS) ƒ If standard risk, discuss CAS and CEA; if Medicare, not going to be reimbursed; if private insurance, consider pre-certification if CAS is chosen

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SUMMARY

ƒ Patients with vascular disease (esp. carotid) increasing with better recognition ƒ Number of specialists remaining stable ƒ Improvement in endovascular techniques ƒ Increasing number and types of patients that can be treated with less invasive means ƒ Individualize to each patient ƒ Next frontier: preventing vascular disease; combined training paradigms?

Questions?

ƒ Stay tuned for the panel… ƒ Thank-you for being awake!

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The PMA analysis of the CREST study demonstrates: ƒ CAS is non-inferior to CEA for: ƒ the primary endpoint ƒ death, stroke or MI at 30 days ƒ The primary endpoint rates were similar for CAS and CEA for symptomatic or octogenarian status ƒ Very low event rates for both CAS and CEA, lower than historical rates and within the AHA guidelines for 30-day event rates. ƒ CAS shows similar durability to CEA by freedom from the primary endpoint, mortality, ipsilateral stroke, and TLR to 4 years ƒ A lower primary endpoint rate was observed in CAS patients treated with the Accunet® EPS as compared to CAS without an EPD ƒ The PMA Per Protocol and NIH Intent-to-Treat analyses are consistent and reveal similar outcomes.

14 9/17/2012

Diseases of the Ascending Aorta

Michael S Firstenberg, MD FACC Assistant Professor of Surgery Division of Cardiac Surgery Ohio State’s Heart and Vascular Center

No relevant conflicts of interest or disclosures.

Diseases of the Ascending Aorta

1 9/17/2012

ƒ Simple Approach to Complex Problem ƒ Two completely different problems ƒ Different indications for Aortic operation Pathology ƒ Aneurysms can dissection ƒ Dissections can Aneurysms Dissections become aneurysm

But, not always so easy..

ƒ Aneurysm: ƒ “Localized” dilatation of an artery ƒ Typically >50% of normal diameter ƒ Often involving all walls of an artery (vs pseudoaneurysms) ƒ Classified by: ƒ Shape: Fusiform vs saccular ƒ Size ƒ Location ƒ Structure: True vs false ƒ Etiology ƒ Aortic dissection: ƒ Persistent false channel of outer media and adventitia gradually enlarges ƒ Chronic traumatic aortic transection: ƒ False aneurysm contained only by aortic adventitia ƒ Annulo-aortic ectasia: ƒ Aneurysmal dilation of sinuses of Valsalva

ƒ Inflammatory ƒ Associated Arteritis ƒ SLE ƒ Takayasu’s ƒ Giant Cell ƒ Degenerative ƒ Dissecting ƒ Nonspecific (I.e. atherosclerotic) ƒ Associated with Pregnancy ƒ Fibrodysplasia ƒ Graft ƒ Connective Tissue Diseases ƒ Marfan’s ƒ Congenital ƒ Ehlers-Danlos ƒ Idiopathic ƒ Mechanical ƒ Tuberous sclerosis ƒ Poststenotic ƒ Turner’s syndrome ƒ Traumatic ƒ Infection ƒ Anastomotic ƒ Bacterial ƒ Prosthetic ƒ Syphilitic ƒ False aneurysm ƒ Fungal

2 9/17/2012

ƒ 13th leading cause of mortality in the United States

ƒ 5.9 cases per 100,000

ƒ Mean age at the time of diagnosis ranges from 59 to 69 years

ƒ Men are typically younger age and a 2:1 to 4:1 predominance

ƒ Risk factors: ƒ Smoking, Hypertension, Atherosclerosis, ƒ Genetic disorders (Marfan and Ehlers- Danlos syndromes) ƒ Inherited metabolic disorders – undefined role. ƒ Syphilis (historical)

ƒ Bicuspid and unicuspid aortic valves

Bostroem, 1887

Classification System

ƒ Ascending aorta 45% ƒ Aortic Arch 10% ƒ Descending 55% ƒ Thoraco-abd 10%

Aortic Aneurysm: Influence of Size and Why We Fix Yearly Risk of Complications

Davies RR, Goldstein LJ, Coady MA, et al: Yearly rupture or dissection rates for thoracic aortic aneurysms: Simple prediction based on size. Ann Thorac Surg 2002; 73(1):17-27. 9

3 9/17/2012

Aortic Aneurysms and Risk of Dissection

Indications for Surgery

•Marfan’s Patients f Complication f nt Increase in i o •CittSConcomitant Surgery •Stratified for BSA Percent Po Percent Probability Probability Aortic Size (cm) Hinge point at 6.0cm (p<0.006)

Coady MA, et al: Surgical intervention criteria for thoracic aortic aneurysms: A study of growth rates and complications. Ann Thorac Surg 1999; 67(6):1922-1926.

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Aortic Aneurysm: Presentation

ƒ Most are asymptomatic ƒ Incidental findings on CXR/CT scan or echo for “murmur” or aortic valve ƒ 25% and 75% of patients present with chest pain that results in the diagnosis of an aneurysm ƒ The pain may be acute in onset siggygnifying impendin g rupture, or a chronic gnawing pain from compression of the overlying sternum. ƒ Hoarseness: Stretch injury of the left recurrent laryngeal nerve ƒ SVC Syndrome ƒ Pain implies sudden extension or rupture of aneurysm ƒ Ascending aorta - neck, jaw ƒ Descending aorta - back, inter-scapular ƒ Thoraco-abdominal aorta - low back

ƒ Imaging Studies ƒ Chest X-Ray ƒ Echocardiography ƒ Ventricular Function ƒ Associated Aortic Valve Disease ƒ Cardiac Catheterization ƒ Associated CAD

ƒ CT Scanningg( (Gold Standard) ƒ Provides rapid and precise evaluation of the ascending aorta ƒ Detects calcification, identifies dissections and thrombus. ƒ 3-D Reconstruction useful in determining the proximal and distal extent of aortic disease - aid in operative planning.

4 9/17/2012

Indications for Repair: Symptoms

ƒ Emergent operation is indicated in the setting of acute ascending aortic dissection or rupture.

ƒ Ascending aortic aneurysms rupture into the pericardial space and result in death from acute cardiac tamponade. ƒ May compromise coronary or cerebral circulation. ƒ Operative mortality is significant in this setting, ƒ BtdthiBut death is cert tiithain in the case o f rupt ure and pro bblithbable in the case o f acu tdite dissec tiifttion if not surgi ica lllly addressed.

ƒ Symptomatic aortic insufficiency or stenosis may be the primary indication for operation. ƒ 4 cm required subsequent operation for aortic replacement. ƒ 27% incidence of aortic dissection following aortic valve replacement in patients with diameters greater than 5 cm. ƒ Recommended that aortic diameters of 4 to 5 cm be dealt with at the time of aortic valve surgery.

Aneurysms: Surgical Technique

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Surgical Technique: Options

15

5 9/17/2012

Surgical Technique: Elephant Trunk

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Independent predictors of mortality

ƒ Risk factor p-value (range) ƒ ƒ Emergent operation .0001–.0017 ƒ NYHA .0001–.015 ƒ Age .01–.045 ƒ CPB time <.001–.018 ƒ Dissection <.001–.04 ƒ Concomitant CABG .001–.0014 ƒ Previous cardiac <.001–.0068 Surgery ƒ Arch replacement <.001 ƒ Reoperation for bleed .0009–.032

NYHA = New York Heart Association classification; CPB = cardiopulmonary bypass; CABG = coronary artery bypass grafting. Only risk factors found to be predictive on multivariate analysis are reported. Some of the reported risk factors were not significant in some series.

Late Survival ƒ 81% to 95% at 1 year,

ƒ 73% to 92% at 5 years,

ƒ 60% to 73% at 8 to 10 years,

ƒ 48% to 67% at 12 to 14 years. Early Mortality ƒ Predictors of late mortality: (Bleeding, neuro, MI) ƒ Elevated NYHA ƒ Requirement for arch reconstruction, •Ascending aorta 4-10% ƒ Marfan syndrome ƒ Extent of distal disease. •Arch 5-50% •Descending 5-15% •Thoraco-abd up to 50% ƒ The most common cause of late death is cardiac, but distal aortic disease accounted for 32% of late deaths in one series

6 9/17/2012

ƒ A true emergency ƒ Why we fix aneurysms

Michael DeBakey Jon Ritter King George II Jonathan Larson

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Aortic Dissection – NOT AN ANEURYSM

Prompt diagnosis is important

Most common surgical emergency of the aorta Incidence uncertain Up to 1/3 diagnosed post-mortem Over 2000 cases / year in U.S.

Intramural Hematoma

•Intimal Tear – primary event •Dissection of hematoma within media Penetrating Ulcer •Intramural hemorrhage due to rupture of vasa vasorum in a defective media •Intimal tear - secondary event •Pulsatile force creates a plane of dissection

Macura KJ, Corl FM, Fishman EK, Bleumke DA. Pathogenesis in Acute Aortic Syndromes: Aortic dissection, intramural hematoma, and penetrating ahterosclerotic aortic ulcer. Am J Roentgenol 2003;181(2):309-16.

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Natural History ƒ 1934 Shennan: 300 cases reviewed ƒ Multiple recent studies - validating ƒ 40% ascending dissections died suddenly ƒ Within first 24 hours ƒ 50-70% within first 48 hours ƒ 80-94% within first week ƒ 100 % mortality at 5 weeks ƒ ~1% per hour risk of death ƒ Causes: ƒ Acute aortic insufficiency ƒ Tamponade ƒ Coronary dissection ƒ Free rupture ƒ Malperfusion syndromes

Anagnostopoulos CE, Prabhakar MJ, Kittle CF. Aortic dissections and dissecting aneurysms. Am J Cardiol 1972;30(3):263-73.

Male gender Age greater than 50 yo Hypertension Known aneurysm Family history Connective tissue disorders (Marfan, Ehler-Danlos) Others including: ƒ Coarctation of the aorta ƒ Bicuspid or unicuspid aortic valve ƒ Trauma ƒ Pregnancy ƒ Temporal arteritis ƒ Weight lifting ƒ Cocaine use

Imaging ƒ Chest X ray ƒ Widened Mediastinum ƒ Pleural effusion ƒ CT scan: 88-100% accuracy History and Physical ƒ Beware of “PE” protocols • Index of suspicion ƒ Motion artifacts • History of aneurysm ƒ Transthoracic Echo • Family history ƒ Suggestive, but limited windows ƒ Acute onset pain ƒ Pain (~90%) ƒ Transesophageal Echo ƒ Ripping & Tearing ƒ Confirmatory test, often in OR ƒ Worst pain in life ƒ Site of tear, assess aortic valve ƒ HTN / Syncope ƒ MRI – 90-100 accurate ƒ Stroke / Paraplegia ƒ Limited in acute situations ƒ Hypotension

8 9/17/2012

“Gold Standard” Helical CT: Aneurysm Protocol ƒ Sensitivity / specificity >95% ƒ Rapid ƒ Better delineation of: ƒ Branches and intimal tear ƒ Involvement of the Tear ascending aorta ƒ Size of Aorta and presence of AI ƒ Extent of the false lumen ƒ Pericardial effusion ƒ Watch for motion artifacts!

Aortic Dissection Management: Classification - Simple As Possible

Stanford AAB DeBakey I II III

15% 25%

IIIa 60%

IIIb

Surgical Medical 26

Aortic Dissection Management: International Registry Data

A/medical (n=81) lity (%) lity a

B/surgery (n=35) ALL PATIENTS (n=464) A/surgery (n=208)

B/medical (n=140) Cumulative Mort

Days Following Presentation

Hagan PG, et al. The International Registry of Acute Aortic Dissection (IRAD): New Insights Into an Old Disease. JAMA 2000;283:897-903. 27

9 9/17/2012

Surgical therapy ƒ Must have confirmatory study: CT/TEE/MRI ƒ Prevent extension ƒ Prevent coronary Medical therapy malperfusion •Prevent extension ƒ Manage acute aortic •Control blood pressure insufficiency •Beta-blockade ƒ Excise the intimal tear •Reduce dP/dT ƒ Restore distal perfusion •Relieve pain ƒ Excise diseased aorta •Transfer to tertiary care center •Immediate cardiothoracic ƒ Technically – very surgical consultation similar to aneurysm management.

Early (hospital) death Ascending aorta 5-10% (up to 30%) Arch 10-25% (up to 50%) Descending 10% (up to 25-60%) Bleeding, multi-organ failure, stroke, CAD/CHF

ƒ 10 year survival 46%

ƒ 1/3 late death related to residual old false channel or re-dissection

ƒ Aneurysm of false channel ƒ 50% Uncontrolled hypertension ƒ 10-20% Controlled blood pressure ƒ Re-dissection 10% (Marfan higher)

Aortic Dissection: The OSU Experience

Intra-op Variable Patients (n=117) Operation N CANNULATION Performed Femoral 42 (36%) AORTA Axillary 60 (51%) Replacement 115 (98.3%) Aorta 15 (13%) Repair 2 (1.7%) Hemopericardium 39 (33.3%) VALVE SITE OF TEAT Any 42 (35 .9%) Proximal aorta 99 (84.6%) Bentall 15 (12.8%) (AVR+coronary) Arch 16 (13.7) Repair 27 (23.1%) Retrograde 2 (1.7%) Arch (yes) 23 (19.7%) X-clamp time 83.4 +/- 49.6 min CPB time 160.8 +/- 55.7 min Circ arrest time 26.4 +/- 15.0 min

Kilic A, Firstenberg MS, Sirak JH, Sai-Sudhakar CB, Crestanello J, Higgins RSD. Contemporary outcomes following operative repair of acute type A aortic dissection in the elderly: a single institution experience. 59th Annual Meeting – Southern Thoracic Surgery Association, Naples, Florida (to be given – November 10, 2012). 30

10 9/17/2012

Aortic Dissection: The OSU Experience

OUTCOMES: Renal Failure: 13.7% Stroke 16.2%

Survival: TdihTo discharge 86. 3% 30 day 85.5% 1 year 79.8% 5 years 53.3%

Ave LOC 15.7+/- 11.6

Kilic A, Firstenberg MS, Sirak JH, Sai-Sudhakar CB, Crestanello J, Higgins RSD. Contemporary outcomes following operative repair of acute type A aortic dissection in the elderly: a single institution experience. 59th Annual Meeting – Southern Thoracic Surgery Association, Naples, Florida (to be given – November 10, 2012).

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The Ohio State University - Aortic Center A Multidisciplinary Acute Aortic Treatment Center

ƒ Access ƒ Thoracic Radiology (CT/MRI) ƒ Outreach ƒ Cardiovascular medicine service ƒ Transfer Center / Med-Flight ƒ Management of long term BP control, ƒ 24 hour immediate phone access prevention ƒ Medical genetics

ƒ Facilities ƒ Aortic clinic ƒ Cardiac/Vascular On-Call ƒ Research programs ƒ Open and endovascular suite ƒ Clinical outcomes, database mgmt, capability (hybrid suite) basic science / genetics / molecular ƒ Cardiovascular anesthesia ƒ CSF drainage, blood conservation ƒ Multidisciplinary clinic / conference protocols, neuromonitoring / education ƒ Dedicated perfusionists ƒ Distal aortic perfusion, differing cannulation strategies, cerebral protective adjuncts ƒ Nursing: ƒ Operative, ICU, Floor ƒ Intensivists

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Diseases of the Ascending Aorta: Conclusions Aortic aneurysms are common causes of significant morbidity and mortality. Aneurysms ARE NOT Dissections But they can dissect – and – Dissections can become aneurysms Education and awareness are keys to early diagnosis Medical Management – “Pre-dissection” Better screening for high risk individuals Genetic, tissue, family risk factors, Prevention / blood pressure control Imaging surveillance Timely surgical intervention

Dissections: Prompt referral and management is critical Medical stabilization – BP control Evaluation for emergent surgery Surgical techniques continue to evolve Outcomes are good – but can always be better Thank You! Multi-disciplinary Teamwork is Cornerstone of Success

11 NOTES—

9/17/2012

NON-INVASIVE WORKUP OF CLAUDICATION

Jean Starr, MD, FACS, RPVI Associate Professor of Clinical Surgery Division of Vascular Diseases and Surgery Director of Endovascular Services

OVERVIEW

ƒ Classic case scenario ƒ Clinical implications of claudication ƒ Office testing ƒ Other non-invasive testing choices ƒ MtManagement

CASE SCENARIO

ƒ 55 yr old with 7 year history of bilateral calf fatigue after ambulating 1 block, relieved with rest ƒ Progressively worse over time with shorter distance to onset; foot numbness occasionally wakhitihtkes him at night ƒ 40 pack year history of smoking, quit 10 years ago ƒ Family history of MI; recently retired

1 9/17/2012

CLINICAL IMPLICATIONS

ƒ Over 3-5 yrs, 20% risk of severe clinical deterioration, necessitating intervention and 5% risk of major limb amputation ƒ 15-30% of those undergoing surgical bypass are claudicants in a tertiary referral center ƒ High prevalence of associated CAD; 2-6.5% risk of post-op MI after LE bypass

CLINICAL IMPLICATIONS

ƒ Candidates for intervention (surgical or interventional): ƒ Significantly disabled by claudication (unable to perform occupation, unable to carry out ADL’s) ƒ Lifestyle significantly limited (could be retirement age)

MANAGEMENT OPTIONS

ƒ Smoking cessation ƒ Risk factor modification ƒ Lifestyle modification ƒ Exercise program ƒ Pharmaceutical management ƒ Non-invasive workup ƒ Invasive workup ƒ Interventional/surgical therapy

2 9/17/2012

GOALS OF WORKUP

ƒ Identify PAD as the sole cause or possibility of other contributing factors (pseudo-claudication, musculoskeletal problems) ƒ Identify and manage/treat other co-morbidities ƒ Identify anatomic pattern of disease in order to devise a treatment plan

NON-INVASIVE WORKUP (OF CLAUDICATION) ƒ Physical exam ƒ Blood pressure ƒ Bruits ƒ CV exam ƒ Aneurysm evaluation ƒ Skin examination ƒ Motor/sensory exam ƒ Pulse examination at all levels ƒ Ankle-brachial index (ABI) ƒ Laboratory testing

FUNCTIONAL STATUS TESTS

ƒ Hemodynamic assessment (ABI, waveform analysis) ƒ Treadmill testing ƒ Six-minute walk test ƒ Questionnaire assessment (functional status and quality of life) ƒ When treadmill testing not feasible ƒ Should be appropriately validated

3 9/17/2012

ABI

ƒ Highest value of DP or PT (bilateral) over brachial BP; uses hand-held doppler; an office test ƒ Medial calcification >1.2 ƒ Normal >.9 ƒ Mild .75-.9 ƒ Moderate .5-.75 ƒ Severe <.5 ƒ Poor wound healing <.25

NON-INVASIVE VASCULAR LABORATORY ƒ First step usually ABI combined with segmental pressures and waveforms ƒ Identify presence of PAD and localize segment involved ƒ Cannot discern occlusion or patency ƒ Can co mb ine with pu lse vo l um e r ecor din gs, w av ef orm analysis, and toe pressures to improve quantification of arterial occlusive disease ƒ Can be useful as a baseline to gauge success of any interventions

ABI, SEGMENTAL WAVEFORMS, PRESSURES

12

4 9/17/2012

NON-INVASIVE VASCULAR LABORATORY ƒ Exercise testing ƒ Crucial for patients with palpable pulses or normal ABI but with convincing symptoms ƒ Numerous regimens ƒ Resting ABI; 3.5 km/hr on treadmill at 12% incline until onset of symptoms, then take ABI again; >20% decrease for >3 min after walking cessation is positive ƒ Use consistent method

EXERCISE TESTING

14

DISEASE LOCALIZATION

ƒ Hemodynamic information is sufficient for screening, making a treatment plan, and monitoring results of any intervention ƒ When necessary to define anatomic location of hemodynamically significant lesions, imaging thitechniques are necessary (ldl(color duplex imag ing, MRA, CTA, DSA) ƒ No need for these tests unless intervention is planned and warranted

5 9/17/2012

COLOR DUPLEX IMAGING

ƒ Yields both anatomic and hemodynamic information without use of contrast ƒ Can have similar accuracy to conventional CTA ƒ Cossman, et al: sens=99%, spec=87% for >50% stenosis, higher spec for occlusions ƒ Less a ble to iden tify dis ta l tibia l ar tery targe t for revasc (Ascher, et al) ƒ Other studies needed in the presence of extensive ulcers, extensive calcifications, severe edema, and poor runoff

COLOR DUPLEX IMAGING

17

COMPUTED TOMOGRAPHIC ANGIOGRAPHY ƒ 64-slice detectors a great improvement (able to visualize tibials, obtained quickly, 3-dimensional reconstructions, able to rotate vessels 360 degrees) ƒ Overall sens=92%, spec 93%; slightly higher abthkbove the knee ƒ Limitations: use of contrast, significant arterial wall calcification obscures image, metallic artifact, use of radiation

6 9/17/2012

CTA

19

MAGNETIC RESONANCE IMAGING ƒ Gadolinium-enhanced images can visualize entire arterial tree ƒ Kreitner, et al: 38% of MRA studies revealed a patent pedal vessel not seen on angiography ƒ Exaggeration of degree of stenosis not uncommon; need to use multiple datasets (“not all MRA’s are created equal”) ƒ Limitations: metallic implants, lying flat, claustrophobia, worsening of renal function, nephrogenic systemic fibrosis

MRA

21

7 9/17/2012

CONVENTIONAL CONTRAST ANGIOGRAPHY ƒ Typically the gold standard ƒ Most commonly used for planning bypass and percutaneous interventions ƒ Definitely not non-invasive

IMAGING MODALITY SELECTION

ƒ First, decide if the timing is right…”How will this test change how I treat this patient?” ƒ Consider: risks of renal failure, implants, patient comfort, radiation usage ƒ Visser, et al: if treatment limited to angioplasty, then MRA more cost-effective; if surgery anticipated, DSA superior ƒ Accuracy best with contrast-enhanced MRA when evaluating the entire arterial tree ƒ Multiple modalities are unnecessary

SUMMARY

ƒ Non-invasive workup of claudication: ƒ Clinical implications ƒ Goals of workup ƒ Evaluation of functional status ƒ Non-invasive vascular lab ƒ CTA ƒ MRA

8 9/20/2012

A Patient With Syncope of Unknown Etiology

A Challenging EP Case

Charles J Love, MD FACC FAHA FHRS CCDS Professor of Medicine Director, Cardiac Rhythm Device Service The Ohio State University Heart and Vascular Center

Patient Profile

ƒ 37 year old white male ƒ Normal state of health until 2010 ƒ Developed seizures ƒ Witnessed by spouse ƒ Patient would become abruptly unconscious ƒ Clonic/Tonic movements ƒ No lounge biting ƒ No loss of continence ƒ Would last 30-60 seconds ƒ Rapidly regained consciousness ƒ No post seizure confusion ƒ Occur very sporadically

2

Initial evaluation

ƒ Seen by neurologist ƒ CT scan of head negative ƒ MRI scan of head negative ƒ Baseline EEG negative ƒ Treated with a series of anti-epileptic drugs, most recently on Tegretol ƒ No significant effect on seizures

3

1 9/20/2012

Extended Evaluation

ƒ Seen at a major tertiary care medical center for further evaluation (not Ohio State) ƒ Complete re-evaluation of head negative ƒ 24 hour EEG monitoring while hospitalized, also negative

4

Continued Evaluation

ƒ Patient continued with these episodes ƒ Several serious injuries occurred including hitting his head, and burns to his hands and arms when he collapsed into his grill ƒ Resting ECG was normal ƒ Echocardiogram was unremarkable ƒ Nuclear Stress Study was normal

5

ƒ 24 Hour Holter ƒ Normal sinus rhythm ƒ Normal heart rate ranges ƒ No significant arrhythmias

6

2 9/20/2012

ƒ 30 day event monitor ƒ Syncope the morning he was going to have it placed ƒ No syncope during the 30 days he wore the monitor

7

November 2011

ƒ Head Up Tilt ƒ After 22 minutes BP dropped to 50 and HR dropped to 27 ƒ Clinical syndrome was not reproduced

ƒ PtitPatient st art tded on Flor ine f 010.1mg a day ƒ Subsequently started on midodrine 5mg tid

8

Clinical Result

ƒ Symptoms continued ƒ Repeat head up tilt study negative

Referred to Ohio State for further evaluation of refractory vasovagal syncope

9

3 9/20/2012

Additional History

ƒ Spells can happen at any time ƒ Standing ƒ Sitting ƒ SLEEPING!

This is NOT vasovagal syncope

10

ƒ Echocardiogram ƒ EF 65% ƒ Normal valves ƒ No evidence of HOCM

11

Next Step?

ƒ Discussed options with the patient and spouse ƒ Holter Monitor ƒ 30 Day Event Monitor ƒ Invasive Electrophysiologic Study ƒ Implantable Loop Memory Recorder

Chose the latter

12

4 9/20/2012

Result

ƒ 5 weeks post ILR implant he had a typical spell ƒ Transmission of the stored recording showed…

13

But First

ƒ This is a very powerful diagnostic tool ƒ A positive result for a brady or tachy arrhythmia can lead to a direct therapeutic intervention ƒ Pacemaker ƒ ICD ƒ Medical Therapy ƒ Ablation ƒ A normal heart rhythm rules out an arrhythmia as the cause of the spells ƒ Could still be due to hypotension, but in this case, unlikely as they also occur when he is supine

14

Rhythm retrieval from the ILR…

15

5 9/20/2012

Therapy Applied

ƒ Dual chamber pacemaker implanted ƒ No further episodes of “seizures”

16

Conclusion

ƒ Don’t‘ pound a square peg into a round hole ƒ When a diagnosis does not seem to fit, don’t force it ƒ In this case, the atypical presentation was believed to be neurologic due to the clonic/tonic activity ƒ No blood to the brain can cause this to happen ƒ Recognize that there are powerful diagnostic tools available that can assist us in correlating heart rhythm (or lack of it) to clinical symptoms

17

6 9/17/2012

Anticoagulation Options for Stroke Prevention: Focus on New Oral Agents

Vincent Brinkman, MD Assistant Professor of Clinical Medicine Director, Inpatient Cardiovascular Consult Services Ohio State’s Heart and Vascular Center

Anticoagulation Options for Stroke Prevention in Atrial Fibrillation

ƒ Objectives: ƒ Review the current options for stroke prevention in atrial fibrillation ƒ Summarize the major studies for the newer oral anticoagulants ƒ Discuss the current controversies with the various agents

2

Warfarin

ƒ Known, effective agent ƒ 60% risk reduction compared to placebo ƒ Around 50% risk reduction compared to aspirin Events

Adapted from Connolly SJ, et al, JACC 1991; 18:349 3

1 9/17/2012

Warfarin ƒ 2012 Meta-analysis concluded overall risk of stroke was 1.66% on warfarin ƒ Absolute rate of major bleeding is 2.2 events per 100 patient-years (versus 1.3 with aspirin)

Agarwal et al., Arch Intern Med., 2012; 172(8):623 4

Time in Therapeutic Range (TTR) ƒ Best results occur when TTR is > 70% ƒ Most studies show TTR of 55-65%

Major Hemorrhage Embolic event

Wan et al., Circulation: Cardiovascular Quality and Outcomes. 2008(1):84-91 5

Warfarin

ƒ Why do we need newer agents? ƒ Warfarin is underutilized ƒ One study reports 55% of eligible patients receive Warfarin ƒ 28% discontinue warfarin by one year ƒ Risk of bleeding ƒ Major bleeding may be as high as 20% for patients with CHADS2 scores ≥4 ƒ Difficulty in dosing ƒ Drug and food interaction, therapeutic window, lab monitoring

Granger and Armaganizan, Circulation. 2012;125:159 6

2 9/17/2012

New Oral Agents

ƒ Dabigatran ƒ Rivaroxaban ƒ Apixaban

DeCaterina et al., JACC. 2012: 59(16):1413 7

New Oral Agents

Dabigatran Rivaroxaban Apixaban

Mechanism FIIa Inhibitor FXa Inhibitor FXa Inhibitor

Half Life 12-17 hours 5-13 hours 8-15 hours

Renal Elimination 85% 66% 27% Time to Maximum 0.5-2 hours 1-4 hours 1-4 hours effect Drug Interaction P-gp CYP3A4 CYP3A4

8

Dabigatran

ƒ RE-LY Trial ƒ 18,000 patients with non-valvular atrial fibrillation over 2 years ƒ Primary outcome – stroke or embolization ƒ Mean age 71 years with mean CHADS2 score 2.1 ƒ TTR 64% ƒ 150mg and 110mg dose (twice daily)

9

3 9/17/2012

RE-LY Trial

10

RE-LY Trial

ƒ GI bleeding was increased with 150mg dose ƒ Non-life threatening or life-threatening ƒ 1.5% versus 1.02% ƒ 1.1% with 110mg dose ƒ Dyspepsia was significant ƒ 11% with Dabigatran compared to 6% with warfarin

11

Rivaroxaban

ƒ ROCKET-AF Trial ƒ 14,000 patients ƒ Mean age 73years with mean CHADS2 of 3.47 ƒ Mean TTR was 55% ƒ 20mg once daily ƒ Non-ifinfer ior to war fari n in itinten tion to treat ƒ Superior to warfarin in “per-protocol as-treated”

12

4 9/17/2012

Rocket-AF Trial

“Clinically relevant” bleeding ~14%

13

Apixaban

ƒ ARISTOTLE ƒ 18,000 patients for 2 years ƒ Mean age 70 years with mean CHADS2 of 2.1 ƒ 5mg twice daily ƒ AVERROES Study ƒ Abixaban versus Aspirin ƒ Stopped early as Abixaban was significantly more effective ƒ Bleeding rates similar

14

Aristotle Trial

15

5 9/17/2012

Primary Endpoints

Granger and Armaganijan, Circulation 2012:125:159 DeCaterina et al., JACC. 2012: 59(16):1413 Bleeding Events 16

Summary of New Oral Drugs Compared to Warfarin

ƒ All drugs were shown to be non-inferior for the primary outcome of embolic events and stroke ƒ Dabigatran and Apixaban were superior with intent-to-treat analysis ƒ All three drugs have less intracranial bleeding ƒ Overall, equivalent risk of major bleeding ƒ Only Apixaban showed mortality benefit

17

Problems with Newer Agents

ƒ Valvular atrial fibrillation ƒ Renal Failure ƒ Cannot use if CrCl < 15 mL/min ƒ Dabigatran: 75mg BID if CrCl between 15-30 ƒ Rivaroxaban & Apixaban: Limited Data ƒ Half Life ƒ Not ideal for the non-compliant

18

6 9/17/2012

Drug Interactions

ƒ Dabigatran ƒ P-glycoprotein ƒ Do not use with Dronaderone ƒ Verapamil will increase concentrations ƒ Rifampicin, Phenytoin may reduce concentrations ƒ Rivaroxaban and Apixaban ƒ CYP3A4 and P-gp ƒ Not recommended with azoles or HIV protease inhibitors (potent inhibitors) ƒ Use with caution in “inducers”

19

Reversal of Agents

ƒ No known effective reversal agents ƒ Not reflected in overall outcomes ƒ Dabigatran ƒ Hemodialysis (35% bound to plasma) ƒ Activated Charcoal ƒ Rivaroxaban and Apixaban ƒ Hemodialysis not effective ƒ Prothrombin Complex Concentrate

20

Problems With Newer Agents

ƒ Many adverse events related to prescribing error ƒ Switching from coumadin ƒ Off label use

21

7 9/17/2012

Dabigatran and Post-Marketing Bleeding

ƒ FDA Safety Report in 2011 ƒ Post-marketing data ƒ Recognized bleeding risk with all anticoagulants ƒ Ongoing registry for adverse events ƒ Abstracts on “Real World Use” ƒ 113 patients 6 months before and after switching to Dabigatran ƒ 70%TTR in coumadin group ƒ Discontinuation or side effects in 11% versus 1% of warfarin group

Wurster et al., Research abstracts. Am J Hematol 2012; 87:S146-S200 22

Dabigatran and Bleeding in Elderly

Intracranial Bleeding Warfarin 110mg Dabigatran 150mg Dabigatran

Extracranial Major Bleeding

Eikelboom J W et al. Circulation 2011;123:2363-2372 23

Dabigatran and Risk of Myocardial Infarction

ƒ 2012 Meta-analysis ƒ Increased risk of MI with Dabigatran ƒ Absolute Difference 0.27%

Uchino et al., Arch Int Med 2012; 172(5):397 24

8 9/17/2012

Dabigatran and Risk of Myocardial Infarction ƒ Myocardial Ischemic Events in the RE-LY Trial ƒ Concluded Non-significant increase in MI’s

Hohnloser et al., Circulation. 2012; 125:669-676 25

When should we use these agents?

26

Patients already on Coumadin

Wallentin et al., Lancet 2010; 376:975 27

9 9/17/2012

Patients already on Coumadin

Time to Primary Outcome

28

Patients already on Coumadin

Time to Primary Outcome

* No significant difference

29

Patients already on Coumadin

Time to Major Bleeding

30

10 9/17/2012

Patients already on Coumadin

Time to Major Bleeding

* No significant difference

31

When to use…Patient Considerations

ƒ Warfarin ƒ Newer Agents ƒ Valvular Disease ƒ Poor INR control ƒ Renal Failure ƒ Patient preference ƒ Others: ƒ New onset atrial fibrillation ƒ Elderly ƒ ? First line agent ƒ GI bleeding risk ƒ Compliance issues ƒ Excellent TTR

32

33

11 NOTES—

9/20/2012

Atrial Fibrillation: Rate vs Rhythm Control

Charles J Love, MD FACC FAHA FHRS CCDS Professor of Medicine Director, Cardiac Rhythm Device Service The Ohio State University Heart and Vascular Center

Atrial fibrillation accounts for 1/3 of all patient 6% discharges PSVT with arrhythmia as 6% principal diagnosis. PVCs 18% Unspecified 4% Atrial Flutter

9% 34% SSS Atrial Fibrillation

8% Conduction Disease 10% VT 3% SCD

2% VF Data source: Baily D. J Am Coll Cardiol. 1992;19(3):41A.

Total Hospitalization Days Based on Presenting Arrhythmia

900 AF 800 Atrial Flutter Cardiac arrest 700 Conduction disease 600 Junctional

500 Prem atur e beats Sick sinus syndrome 400 VF 300 VT Unspecified 200

100

0 Presenting Arrhythmia

Camm AJ. Am J Cardiol. 1996;78(8A):3-11.

1 9/20/2012

Atrial Fibrillation Demographics by Age

U.S. population Population with AF x 1000 x 1000

30,000 Population with 500 atrial fibrillation U.S. population 400 20,000 300

200 10,000

100

0 0 <5 5- 10- 15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65- 70- 75- 80- 85- 90- >95 9 14 19 24 29 34 39 44 49 54 59 64 69 74 79 84 89 94 Age, yr

Adapted from Feinberg WM. Arch Intern Med. 1995;155:469-473.

Atrial Fibrillation: Causes

ƒ Cardiac ƒ Non-cardiac ƒ “Lone” atrial fibrillation

Atrial Fibrillation: Cardiac Causes

ƒ Hypertensive heart disease ƒ Ischemic heart disease ƒ Valvular heart disease ƒ Rheumatic: mitral stenosis ƒ Non-rheumatic: aortic stenosis, mitral regggurgitation ƒ Pericarditis ƒ Cardiac tumors: atrial myxoma ƒ Sick sinus syndrome ƒ Cardiomyopathy ƒ Hypertrophic ƒ Idiopathic dilated (? cause vs. effect) ƒ Post-coronary bypass surgery

2 9/20/2012

Atrial Fibrillation: Non-Cardiac Causes

ƒ Pulmonary

ƒ COPD

ƒ Pneumonia

ƒ Pulmonary embolism ƒ Metabolic

ƒ Thyroid disease: hyperthyroidism

ƒ Electrolyte disorder ƒ Toxic: alcohol (‘holiday heart’ syndrome) ƒ Other drugs (legal or otherwise)

Atrial Fibrillation: Clinical Problems

ƒ Embolism and stroke (presumably due to LA clot) ƒ Acute hospitalization with onset of symptoms ƒ Anticoagulation, especially in older patients (> 75 yr.) ƒ Congestive heart failure ƒ Loss of AV synchrony ƒ Loss of atrial “kick” ƒ Rate-related cardiomyopathy due to rapid ventricular response ƒ Rate-related atrial myopathy and dilatation ƒ Chronic symptoms and reduced sense of well-being

Therapeutic Approaches to Atrial Fibrillation

ƒ Anticoagulation ƒ Rhythm Control ƒ Antiarrhythmic suppression ƒ Curative procedures ƒ Surgery (maze) ƒ Catheter ablation ƒ Control of ventricular response (Rate Control) ƒ Pharmacologic ƒ Catheter modification/ablation of AV node

3 9/20/2012

Atrial Length of time Fibrillation in AF prior to cardioversion Duration of atrial 100 < 3 Months 3 - 12 Months fibrillation may > 12 Months predict likelihood of 80 remaining in normal sinus rhythm after cardioversion 60 ythm (%) h

40 *

20

Patients in in sinus Patients r 0 *P = <0.02 Initial One month Six months post-CV post-CV

Dittrich HC. Am J Cardiol. 1989;63:193-197.

Control of Ventricular Rate in Atrial Fibrillation by Drug Therapy

ƒ Digoxin ƒ Calcium channel blockers Diltiazem, Verapamil ƒ Beta blockers ƒ Carvedilol ƒ Metoprolol succinate ƒ Esmolol ƒ Others

Antiarrhythmic Drugs to Suppress Atrial Fibrillation

ƒ Class I agents

ƒ IA: quinidine, procainamide, disopyramide

ƒ IC: flecainide, propafenone ƒ Class III agents

ƒ amiodarone, sotalol, dofetilide, dronedarone

4 9/20/2012

100 Stage I Use of Serial Stage II Antiarrhythmics Stage III 80 to Maintain NSR After Cardioversion

60 free patients free

40 % Event-

20 Stage I 127 56 47 43 43 43 43 40 40 Stage II 53 29 23 16 13 13 10 6 6 Stage III 34 20 12 11 6 3 3 1 1

0 0510 15 20 25 Months follow-up Crijns HJ. Am J Cardiol. 1991;68:335-341.

Medication for Rate Control in Atrial Fibrillation

Oral Immediate maintenance Agent Action IV dose therapy Avoid use in Digoxin Cardiac 0.5 mg + 0.125-0.5 mg/day; WPW, HCM glycoside 0.25 mg in 4-6 h + renal 0.25 mg in 4-6 h

Diltiazem Calcium 20 mg (or 25-35 120-360 mg/day; WPW, constipation, channel mggg)/kg) over 2 min hepatic ppperipheral edema , blocker + 2nd bolus CHF allowed after 20 min + 5, 10, 15 mg/h infusion

Verapamil Calcium 5-10 mg every 120-240 mg/day; Same as diltiazem, channel 30 min or 5 mg/h hepatic risks with CHF blocker possibly greater

Adapted from Blackshear JL. Mayo Clin Proc. 1996;71:150-160.

Medication for Rate Control in Atrial Fibrillation

Oral Immediate maintenance Agent Action IV dose therapy Avoid use in Propranolol ß-blocker 0.5-1.0 mg every 40-320 mg/day; Bronchospastic 5 min up to 5 mg hepatic lung disease, total CHF

Metaprolol ß-blocker 5mgevery5min5 mg every 5 min 50-200 mg/day; Same as up to 15 mg total hepatic propranolol

Esmolol ß-blocker 0.5 mg/kg/min None Same as load over 1 min propranolol + 0.05-0.3 mg/ kg/min

Adapted from Blackshear JL. Mayo Clin Proc. 1996;71:150-160.

5 9/20/2012

Medication for Rate Control in Atrial Fibrillation

Drug Oral Dose Useful in Avoid in Class IA Quinidine gluconate 324-648 mg Q 8-12 hr Chronic renal failure CHF, liver failure Procainamide 0.5-1.5 g Q 12 hr* Men, short-term therapy Renal failure, CHF, joint disease Disopyramide 200-400 mg Q 12 hr Women Older men at risk for urinary retention, CHF, glaucoma, renal failure

Class IC Flecainide 75-150 mg Q 12 hr Failure of Class IA drugs CHF, CAD Propafenone 150-300 mg Q 8 hr Failure of Class IA drugs CHF

Class III Sotalol 80-240 mg Q 12 hr Failure of IA or IC drug Where beta blockade is May be used with mild- contraindicated moderate LV dysfunction Amiodarone 1200 mg QD for 5 days Severe LV dysfunction, Young patients, followed by 400 mg QD for failure of other drugs, pulmonary disease 1 month, then 200-400 mg QD CHF, renal failure Many alternative dosing regimens

* For newer preparation. Adapted from Gilligan DM. Am J Med. 1996;101:413-421.

Recommendations for Management of Atrial Fibrillation > 48 Hours Atrial Fibrillation > 48 Hours

Control ventricular rate Start antithrombotic therapy (heparin and/or warfarin or aspirin) Duration < 1 year Duration > 1 year or Warfarin therapy 3-4 weeks

Cardioversion or pharmacologic conversion

Antiarrhythmic therapy No antiarrhythmic therapy if if Stable hemodynamics, Unstable hemodynamics infrequent recurrences, or or frequent recurrences first episode Chronic antithrombotic Continue warfarin 1-2 months therapy Monitor for recurrences Assure control of Adapted from Golzari H. Ann Intern Med. 1996;125:311-323. ventricular rate

Antiarrhythmic Therapy for Atrial Fibrillation

ƒ Disadvantages

ƒ Advantages ƒ High recurrence rate

ƒ High efficacy for some ƒ High long-term cost patients, at least initially ƒ NtiNoncurative (< 50% of all patients) ƒ Adverse effects ƒ Low initial cost ƒ Potential ƒ Noninvasive proarrhythmia

18

6 9/20/2012

Rate Control for Atrial Fibrillation

ƒ Some “idiopathic” cardiomyopathies are due to atrial fibrillation with rapid ventricular response. When rate control is achieved, LV function often improves dramatically.

ƒ In some patients, pharmacologic therapy is ineffective for rate control, and catheter ablation and permanent pacing are indicated.

Case Study

60 52 Improved EF of 48 36-year-old male who presented with 40 AF (HR 140 bpm) 1 week prior to 30 29 initial echo EF (%) 20

0 Initial 4 days 2 months 8 months Heart rate AF 75* SR 80 SR 80 SR 60 (bpm) Primary Rx: DC cardioversion * Heart rate 140 one week earlier Other Rx: digoxin and quinidine

Grogan M. Am J Cardiol. 1992;69:1570-1573.

Case Study

60 60 Improved EF in 60 80-year-old female 40 with chronic AF 40 but with improved ) 30 % rate control EF ( 20

0 Initial 1 month 4 months 8 months Heart rate AF 120 AF 70 AF 76 AF 70 (bpm) Primary Rx: digoxin and propranolol Grogan M. Am J Cardiol. 1992;69:1570-1573.

7 9/20/2012

Case Study 61 Markedly improved EF in 55-year-old female 60 with both rate control 52 & NSR, with reversion to AF (HR 140 bpm) and subsequent 40 decrease in EF (%)

EF 20 20 20

0 Initial 3 months 51 months 56 months Heart rate AF 150 AF 75 AF 140 SR 80 (bpm) Primary Rx: amiodarone

Grogan M. Am J Cardiol. 1992;69:1570-1573. Other Rx: digoxin and lisinopril

Catheter Ablation of AV Nodal Conduction and Permanent Pacemaker Implantation

ƒ Treatment for patients with atrial fibrillation with a rapid ventricular response

Intracardiac Electrograms: During RF Ablation

24

8 9/20/2012

16 15 14 Subjective Benefits of 13 Catheter Ablation of AV 12 Nodal Conduction and 11 Permanent Pacemaker 10 Implantation 9 8 nutes

Mi 7 Treadmill exercise 6 performance before and

5 after procedure. 4 All patients were in rate- adaptive pacing mode for 3 follow-up. 2 1

0 Pre Post Kay GN. Am J Cardiol. 1988;62:741-744.

Subjective Benefits of Catheter Ablation of AV Node and Permanent Pacemaker Implantation

1.0 110

100 .90

90 .80

80 .70 70 MHIQ .60 PGWB 60

.50 50

.40 40

0 30 Pre Post Pre Post McMaster Health Index Questionnaire physical Psychological General Well-Being Index scores dimension scores before and after procedure. before and after procedure. High score = High score = better functional capacity. greater perception of health and well-being. Kay GN. Am J Cardiol. 1988;62:741-744.

Objective Benefits of Catheter Ablation of AV Nodal Conduction and Permanent Pacemaker Implantation

70 55

mean 50 mean 60 54 + 7 34 + 5 45

50 40 mean mean D (mm) F (%) 43 + 8 40 + 5 35 LVE 40 LVES

p < 0.001 30 p < 0.003 30 25

20 20 Before After Before After

A Left ventricular ejection B Left ventricular end systolic fraction (%) diameter (mm)

Rodriguez LM. Am J Cardiol. 1993;72:1137-1141.

9 9/20/2012

Atrial Fibrillation Curative Procedures: Surgical Maze

Kawaguchi AT. J Am Coll Cardiol. 1996;28:985-990.

Efficacy of 100 Surgical Maze Maze Procedure for 90 Atrial Fibrillation 80

70 60

50 trial fibrillation (%) fibrillation trial

a 40 30

20 Control 10

Freedom from 0 01 2 3 Post-op years

Kawaguchi AT. J Am Coll Cardiol. 1996;28:985-990.

AFFIRM ƒ Atrial Fibrillation Follow-up Investigation of Rhythm Management ƒ Hypothesis: Effect on mortality of antiarrhythmic therapy to maintain sinus rhythm vs. ventricular rate control alone, in the presence of anticoagulation ƒ Primary endpoint: Total mortality ƒ Secondary endpoint: Disabling CVA Cost of therapy Quality of life

NHLBI AFFIRM Investigators. Am J Cardiol. 1997;79:1198-1202.

10 9/20/2012

AFFIRM Inclusion Criteria

ƒ Age > 65 yrs

ƒ Age < 65 yrs + 1 or more risk factors

ƒ 1 episode of AF , duration > 6 hours, within 6 months

NHLBI AFFIRM Investigators. Am J Cardiol. 1997;79:1198-1202.

AFFIRM Study Protocol

Atrial Fibrillation

Screening

Qualifying atrial fibrillation

NliNo exclusions

Unsuccessful Cardioversion Exclude cardioversion permitted

Consent

Baseline data

Randomize

NHLBI AFFIRM Investigators. Am J Cardiol. 1997;79:1198-1202. 32

AFFIRM Study Protocol

Randomize

Heart rate control STEP I Maintain sinus rhythm anticoagulation anticoagulation

Antithrombotic therapy per guidelines Antithrombotic therapy per guidelines Follow-up Cardioversion prn > 2 pharmacologic trials Follow-up > 2 pharmacologic trials

STEP I failure STEP I failure or intolerance or intolerance

Protocol-specified innovative STEP II Protocol-specified innovative therapy therapy for heart rate control, for maintenance of sinus rhythm, or continue step I or continue step I pharmacologic pharmacologic trials trials and prn cardioversion

Antithrombotic therapy per guidelines Antithrombotic therapy per guidelines Follow-up Cardioversion prn Follow-up

NHLBI AFFIRM Investigators. Am J Cardiol. 1997;79:1198-1202. 33

11 9/20/2012

AFFIRM Mortality Data

34

AFFIRM Results:

35

AFFIRM Results:

36

12 9/20/2012

AF Triggers in the Pulmonary Veins

‹ 94% of atrial triggers arise from pulmonary veins ‹ Ablation of these foci may reduce episodes of paroxysmal A Fib Haissaguerre M, NEJM, 1998; 339: 659-666

37

Pulmonary Vein Ablation ƒ Milestones ƒ Studies confirm ectopic foci within pulmonary vein can cause PAF ƒ Mapping, determining site of origin and ablating these ectopic foci is a challenging task

Clinical Problems in AF

ƒ Frequent hospitalizations ƒ Wide range of symptoms ƒ High mortality ƒ Increased risk of stroke ƒ 5 times more common than in the general population ƒ May also have TIA or peripheral embolus ƒ May have asymptomatic strokes

13 9/20/2012

AF Management Today’s Solutions?

Drugs Holter Cardioversion

Anticoagulation

Change Drugs

Ablation

Consider Surgery

Device See a different MD

40

Management of Atrial Tachyarrhythmias Therapy goals may include: ƒ Control of the heart rate (symptom-reduction, rate-control) ƒ Restoration and maintenance of normal sinus rhythm (intervention and termination, rhythm-control) ƒ Reduction in thrombo-embolic complications (risk reduction for stroke) ƒ Control of symptoms (Quality of Life)

Management of Atrial Tachyarrhythmias Terminology ƒ AF Burden “Total time spent in an atrial tachyarrhythmia” Summation of durations of individual episodes

ƒ AF Burden Percentage “Percentage of time patients atrial rhythm is in an atrial tachyarrhythmia versus normal sinus rhythm”

14 9/20/2012

AT Management Success

Drugs Chemical Electrical Cardioversion Cardioversion

20 30 40 50 60 70 80 90 100%

% Success Flutter Linear Ablation Ablation Focal AT Ablation

PV Quadrant/ Total Isolation

43

About Hybrid Therapy

Combinations of device-based and other therapies that work adjunctively to provide optimal medical care. Continuous Monitoring to assess Control -Control Control -Control Reduced Risk of Stroke RateRate- Rhythm Rhythm-

Why Hybrid Therapy?

ƒ Given the heterogeneous nature of AF, no single solution has been proven effective ƒ Implantable devices provide complementary tools and therapies as part of an overall management strategy ƒ Monitoring facilitates therapy titration ƒ Intervention features provide proactive and responsiilithtddive pacing algorithms to address potentially proarrhythmic events ƒ Early termination restores sinus rhythm, and may reduce symptoms and the risk of thromboembolic complications

15 9/20/2012

Therapy Goals for Co-arrhythmia Patients

Primary Indication (bradycardia, VT/VF) ƒ Improve hemodynamic performance ƒ Protect against sudden cardiac death, if at risk Secondary Goal (atrial tachyarrhythmias) ƒ Rate-control ƒ Rhythm-control ƒ Reduce risk of stroke

16 9/17/2012

Treatment of Atrial Fibrillation Drugs vs. Ablation

Steven J. Kalbfleisch, M.D., FACC, FHRS Professor of Medicine Medical Director, Electrophysiology Laboratory Ohio State’s Heart and Vascular Center

SPEAKER DISCLOSURE

ƒ Affiliation / Financial support as follows: ƒ Research funding from St Jude Medical, Medtronic, Boston Scientific, Biosense Webster and Biotronik ƒ Advisory Boards for St Jude Medical and Biosense Webster

Atrial Fibrillation AF dominates the arrhythmia market

Arrhythmia related QOL Hospitalizations

2X increased mortality with AF Bialy, et al. JACC 1992

1 9/17/2012

Atrial Fibrillation: Financial Costs

European Data Estimated cost burden 15.7 billion / yr in the European Union French Data Cost distribution = Hospitalizations (52%), Drugs (23%), Consultations ((),9%), Further testing g(), (8%), loss of work ( (),6%), paramedical procedures (2%) Avg. Annual cost per patient approx. $3600 US Data 35% of arrhythmia hospitalizations are for AF Average hospital stay = 5 days Mean cost of hospitalization = $18,800

AHA / ACC / ESC Guidelines, JACC 2006. Heuzey et al, Am Heart J 2004.

AHA/HRS 2011 Guidelines Update Treatment of Atrial Fibrillation At present ablation is listed as a second line strategy

“In some patients, especially young individuals with very symptomatic AF, ablation may be preferred over years of drug therapy.” *

Wann LS. J Am Coll Cardiol. 2011 Jan 11;57(2):223-42.2011. * Knight B. HRS Practical Rate and Rhythm Management of Atrial Fibrillation. Updated January 2010. http://www.hrsonline.org/Policy/ClinicalGuidelines/upload/2010_rate-rhythm_guide1.pdf

AARx vs RFA What are the issues

ƒ Efficacy ƒ % with durable NSR ƒ QOL ƒ Mortality benefit ƒ Safety ƒ Side effects of AARX vs procedural complications ƒ Increased Mortality ƒ Cost ƒ Decreased health care utilization ƒ Decreased hospitalizations

2 9/17/2012

AF Efficacy: Maintaining NSR > 6 Months

70

60

50

% 40

30 NSR,

20

10

0 No Quin Diso Prop Flec Sot Dof Azim Amio drug

AFFIRM: Rate vs Rhythm control

Overall Mortality

30 4060 patients Rate 25 Rhythm p=0.07 20

15

10 Mortality, % Mortality, 5

0 01 2 3 4 5 Time (years)

The AFFIRM Investigators. NEJM 2002 The AFFIRM Investigators. Circ 2004

Drug-Induced Proarrhythmia

Life-threatening arrhythmia related to use of antiarrhythmic medications: 1-1.8% / yr

Mortality Benefit Has Never Been Demonstrated for Any Antiarrhythmic Drug for Any Arrhythmia for Any Patient Population

3 9/17/2012

Comparison of AARx vs RFA in Patients With PAF: A Randomized Controlled Trial

Patients randomize to RFA vs. AARx after Drug failure

RFA n=106, Mean # ablations = 1.1/pt 66% QOL vs. Improved in RFA group AARx n=61 Unchanged in AARx group 16%

Major Adverse Events: Ablation 4.9% vs. AARx 8.8% Conclusion Among patients with paroxysmal AF who had not responded to at least 1 antiarrhythmic drug, the use of catheter ablation compared with ADT resulted in a longer time to treatment failure during the 9-month follow-up period. JAMA 2010

RFA

Wazni et al JAMA 2005

Four Randomized Trials of RFA vs AA Drugs for AF Arranged according to Duration of AF 100 – Ablation 90 –

80 – Drug

70 –

60 – Freedom from 50 – Recurrent 40 – AF 30 – (%) 20 –

10 –

0 – RAAFT A4 APAF CACAF (n = 70) (n = 112) (n = 198) (n = 137)

Paroxysmal Persistent

Callans. Circulation. 2008

4 9/17/2012

Cost Comparison of Ablation Versus Antiarrhythmic Drugs as First-Line Therapy for Atrial Fibrillation: An Economic Evaluation of the RAAFT Pilot Study

$18,000 Ablation Antiarrhythmic drug $16,000 $15,303 $12,823 $14,000 $14,392 $10,465 $12,000 $10,000 $8000 $6000 $6,053 $4000 $2000 $2,556 2005 Canadian Dollars $0 2mths 1yr 2yr Ablation cost neutral after 2 years Khaykin et al, JCE 2009

1,171 consecutive AF patients; 589 RFA vs. 582 AARx

Observed = Expected Mortality Observed > Expected Mortality

Observed vs Expected (age / gender matched) Mortality

Pappone et al, JACC 2003

Conclusion: Ablation vs AARx of Atrial Fibrillaiton

Ablation AARx Efficacy (%NSR) + QOL + Adverse even ts---- Cost + Mortality ? --

5 9/17/2012

Atrial Fibrillation: Ablation vs Drug Rx.

Ablation Drug Rx. 80% success 50% success PV stenosis Proarrhythmia AE fistula End Organ Toxicity TIA/CVA ? Increased Mortality Pick Your Poison Torsades

AE fistula

PV stenosis

The AF Patient Population – Industry estimates

Failed Rx 6% of candidates Ablation Candidate receive an ablation Asymptomatic 30% 40%

Rx Effective • Patients are looking for symptom relief 30% • Ablation procedure volumes are still small (US: 68,000 in 2010)*

• Catheter ablation is underutilized for indicated patients

*Canaccord Adams, SMH Capital and Medtronic internal estimates.

A-Fib vs. EP Labs

6 9/17/2012

Current State of Catheter-Based RFA Who is a good candidate? Symptomatic / Frequent Paroxysmal / Short term persistent AF Limited Heart Dz EF > 35% LA < 5.5cm No Mitral Stenosis No LA thrombus or Hx of CVA Medically Refractory / Intolerant Younger Patients - ? First line Tx

7 NOTES—

9/17/2012

Advancements in the Surgical Approach to Treat Atrial Fibrillation

Michael S Firstenberg, MD FACC Assistant Professor of Surgery Division of Cardiac Surgery Ohio State’s Heart and Vascular Center

No relevant conflicts of interest or disclosures.

Atrial Fibrillation: The Burden of the Problem ƒ 2.5 millions adults in the U.S. ƒ 80% > 65 years/old ƒ Incidence to double in 40 years ƒ 2x increased in stroke rate (vs NSR) ƒ 3x more likely to have CHF ƒ PlPrevalence ƒ 0.1% for <55 ƒ 9.0% for >80

ƒ Medicare Costs: ƒ $15.7 billion/year in new diagnosis/treatment ƒ $8 billion/year in stroke management

3

1 9/17/2012

Atrial Fibrillation: Classification System

Recurrent A.F.

Duration Duration > 7 days <7 days Paroxysmal Persistent Or requires cardioversion

Longstanding Duration > 1 year

Permanent No intent to restrore NSR

Atrial Fibrillation Origins: Muscle Bundle Transitions & Epicardial Autonomics ƒ Increased automaticity in PVs ƒ Shortened refractory period in LA

5

Origins of Atrial Fibrillation: Heterogeneous Left Atrial Conduction ƒ Stretch/degeneration → fibrosis → anisotropy ƒ Auto-triggering of adjacent, semi-autonomous circuits

2 9/17/2012

Atrial Fibrillation: Treatment Options ƒ Debate: Rate vs Rhythm Control ƒ Coumadin ƒ Reduce stroke risk to 2% year ƒ Major bleeding ~2% year ƒ Reduce lifetime relative risk of stroke by 60% ƒ Medications ƒ Beta-blockers ƒ Anti-arrhythmics ƒ Percutaneous Endocardial Catheter Ablations ƒ AVNode ablation with pacemakers ƒ Surgical Options

7

Principles of Modern Atrial Fibrillation Therapy

ƒ Compartmentalization ƒ Isolation of known arrhythmogenic areas ƒ Pulmonary antra ƒ Posterior LA ƒ SVC, distal coronary sinus ƒ Peri-mitral macro re-entry interruption ƒ Denervation ƒ Mapping/ablation of autonomics ƒ Complete dissection of LA dome/ligament of Marshall ƒ Debulking ƒ “Corridorization” and reduction of contiguous substrate

Atrial Fibrillation: Indications for Surgery

ƒ Concomitant elective cardiac surgery ƒ Symptomatic “atrial fibrillation” ƒ Asymptomatic “atrial fibrillation” with low additional risk for procedure ƒ Recommended with patients with persistent or permanent Afib. ƒ Prefer surgical management vs medical/catheter ƒ Recurrent embolic complications ƒ Failed at least 1 catheter attempt ƒ Contraindications for catheter (i.e. mural thrombus) ƒ Can not tolerate anticoagulation ƒ i.e. intra-cranial bleed

9

3 9/17/2012

Cox-Maze III: Cut and Sew Left Atrial Lesions Left Side Pulmonary Veins Mitral Valve LAA

Right Side Pulmonary Veins

10

Cox-Maze Surgical Results

78-97% freedom from atrial fibrillation ? Durable ? Reproducible ? Technically very complex

But – proof of principle and let way to less invasive options.

11

Basis of Epicardial Ablation: Five-Box Thoracoscopic Maze Lesion Set

12

4 9/17/2012

Thoracoscopic Right Sided Lesions

Aorta RCA

RA SVC IVC

RSPV Bipolar RF Probe RIPV

Images adopted from Edgerton JR, “Total Thoracscopic Ablation of Atrial Fibrillation Using the Dallas Lesion Set, Partial Autonomic Denervation, and Left Atrial Appendectomy” in Operative Techniques in Thoracic and Cardiovascular Surgery, 2009 13

Thoracoscopic Left Atrial Dome Lesions

L-SPV Dome Left Atrium Aorta R-SPV SVC

R-PA

RF Probe

14

Thoracoscopic Left Sided Lesions

LAA

Phrenic

Lung L-IPV L-SPV L-PA

15

5 9/17/2012

Critical Steps:

Ligation of Left Atrial Confirmation of Appendage Transmurality

16

FAST Study: Ablation vs Surgery

Boersma LVA, et al. Atrial Fibrillation Catheter Ablation Versus Surgical Ablation Treatment (FAST): A 2-Center Randomized Clinical Trial. Circulation 2012;125:230-30

150 pts 21 Refused eligible (Registry)

129 10 Catheter 11 Surgery randomized

63/66 61/63 Catheter Surgery

17

FAST: Procedure Adverse Events

Adverse Event Catheter Surgery P Effusion/Tamponade 1 1 TIA/Stroke 1 1 Pneumothorax 6 Hemothorax 1 Rib fracture 1 Sternotomy for bleeding 1 Pneumonia 1 Pacemaker 2 Death 0 0 TOTAL 2 (3.2%) 14 (23.0%) 0.001

Boersma LVA, et al. Atrial Fibrillation Catheter Ablation Versus Surgical Ablation Treatment (FAST): A 2-Center Randomized Clinical Trial. Circulation 2012;125:230-30

18

6 9/17/2012

FAST: Follow-up Adverse Events

Adverse Event Catheter Surgery P Stroke 1 0 TIA 1 0 Pneumonia 2 2 Hydrothorax 0 2 CHF from afib 2 0 Subarachnoid Bleed/Death 1 0 Pericarditis 1 Fever, unknown 1 Ileus 1 1 TOTAL 8 (12.6%) 7 (11.5%) 1.0

Boersma LVA, et al. Atrial Fibrillation Catheter Ablation Versus Surgical Ablation Treatment (FAST): A 2-Center Randomized Clinical Trial. Circulation 2012;125:230-30

19

FAST Study: Overall Conclusions

Boersma L V et al. Circulation 2012;125:23-30

20

FAST Study: Freedom from Atrial Fibrillation

Freedom Catheter Surgery P-value from AFib (n=63) (n=61) Overall, 12 23 (36.5%) 40 (65.6%) 0.0022 month Overall, 12 27 (()42.9%) 48 (()78.7%) 0.0001 month w meds Overall, 6 28 (44%) 41 (67.2%) 0.0178 month Prior failed 14/38 30/44 0.0089 catheter (36.8%) (68.2%)

Boersma L V et al. Circulation 2012;125:23-30

21

7 9/17/2012

Minimally Invasive Surgery: Bipolar RF Registry Database Kasirajan et al. Minimally Invasive Surgery Using Bipolar Radiofrequency Energy Is Effective Treatment for Refractory Atrial Fibrillation. Annals Thoracic Surgery. 2012;93:1456-61. ƒ 118 patients – 4 center in US ƒ 06/2006 – 02/2011 ƒ 92% anti-arrhythmic medications ƒ 78% coumadin ƒ 30% previous catheter ablation

ƒ 80 (68%) Paroxysmal ƒ 35 (30%) Persistent ƒ 3 (2%) Long-standing, persistent ƒ Mean left atrial size: 4.4 cm

22

Minimally Invasive Surgery: Bipolar RF Registry Database ƒ Surgical Procedure: ƒ 69 (58%) Bilateral mini-thoracotomy ƒ 49 (42%) Totally thoracoscopy ƒ 112 (95%) ligation of left atrial appendage ƒ Surgical Complications: ƒ No deaths ƒ Intubation >24 hrs 5 (4%) ƒ Acute lung injury 5 (5%) ƒ Pulmonary embolus 1 (1%) ƒ Pacemaker 3 (3%) ƒ Phrenic nerve 1 (1%) ƒ Length of stay: 5 days

Kasirajan et al. Annals Thoracic Surgery. 2012;93:1456-61. 23

Minimally Invasive Surgery: Bipolar RF Registry Database

100 90 80 70 50 40

out AF>30 out AF>30 sec 30 h 20 10 Months

% Wit 0 0 5 10 15 20 25 Number 118 113 107 102 102 0 At Risk

Kasirajan et al. Annals Thoracic Surgery. 2012;93:1456-61. 24

8 9/17/2012

Quality of Life Results:

All patients referred for symptomatic refractory atrial fibrillation

Time Point Variable Index 6 months (n=86) Mean +/- SD 1.0 +/- 4.2 Range 0 – 30 12 months (n=78) Mean +/- SD 0.4 +/- 3.1 Range 0 - 27 Almost all patients had significant improvements in their overall quality of life – in addition to being free of afib.

The unhealthy summary index is calculated by taking the number of mental days not good + number of physical days not good with a maximum of 30 days.

Kasirajan et al. Annals Thoracic Surgery. 2012;93:1456-61. 25

Atrial Fibrillation: Appendage Management ƒ 60-90% of stroke originate in the LAA ƒ “most lethal human attachment” ƒ Ligation/closure at time of mitral valve surgery (even without afib procedure) reduces embolic risks. ƒ Typically “closure” is indicated (controversial) ƒ Clipping/Over-sewing/Stapling – do they work?

From Surgical Approaches for Atrial Fibrillation, Saltman/Gillinov. Cardio Clinics 26

The Ohio State Experience: Five-Box TTM Patient Characteristics

ƒ 229 Patients ƒ 220 longstanding persistent ƒ 6 persistent ƒ 3 paroxysmal

ƒ MAFdti57(Mean AF duration 5.7 yrs (range 050.5-20 yrs ) ƒ Mean LA diameter 5.2 (range 3.6-7.0!) cm

ƒ 228/229 with 1 week of continuous automatic event monitoring at 3, 6, 13, 24 months with LifeWatch ACT III Platinum

ƒ Failure defined as any sustained arrhythmia > 30s beyond three months postop

9 9/17/2012

The Ohio State Experience: Five-Box TTM Patient Outcomes ƒ In-Hospital ƒ Average LOS 3.9 days – no intra-operative deaths ƒ 2 unplanned conversions to open procedure ƒ Rhythm ƒ Typical 4 wk course class III AAD (all stopped by 8 wk) ƒ Failure defined by any tachyarrhythmia > 30 sec beyond 3 mos ƒ 191/202 (94.6%) normal sinus rhythm @ 3 mos ƒ 1 “failure” NSR no AAD at 6 and 13 mos ƒ 2 “failures” with A-flutter at 3 mos, but mapped and treated for cavotricuspid flutter, now NSR ƒ 164/173 (94.8%) NSR/no AAD @ 6mos; ƒ 109/114 (95.6%) NSR/no AAD @ 13 mos ƒ 34/37 (92%) NSR/no AAD @ 24 mos. ƒ Warfarin stopped after cleared by 3-month monitoring session

Unanswered Controversies:

ƒ Ideal lesion set ƒ Surgical approach ƒ Surgical vs Hybrid ƒ Particularly in concomitant/high-risk patients ƒ PVI vs 5-box (bi-atrial) approach ƒ Right sided lesions ƒ Ideal energy source and applications tools ƒ Transmural ƒ Intra-operative validation ƒ Standardize follow-up and protocol ƒ Many patients early still have arrythmias ƒ Results can take months to ‘mature’ ƒ Difficult to manage atrial flutter ƒ Anti-coagulation and anti-arrhythmics 29

Keys to Success vs Barriers to Implementation?

Sinus Rhythm: On or Off Protocol On-Proto

>90% Off-Proto Success Percent

Medical

Months Post-OP

•Close follow-up – Team Approach •Aggressive management of arrhythmias •Compliance with medications •Patience!

Ad, Henry, Hunt: The implementation of a comprehensive clinical protocol improves long-term success after surgical treatment of atrial fibrillation. JTCVS 2010. 30

10 9/17/2012

Conclusions: ƒ Atrial fibrillation with/without associated cardiac valve disease is a common problems ƒ Substantial morbidity and mortality ƒ Significant cost to health care system ƒ Surgical treatment of atrial fibrillation is indicated as a lone procedure or with concomitant cardiac surgery. ƒ SbfdflithiiSurgery can be performed safely with a mini-iiinvasive thoracoscopic approach. ƒ Transmural interruption of aberrant pathways can eliminate atrial arrythmias and the need for anti- arrhythmic medications and anticoagulation. ƒ Good quality of life and long-term freedom from atrial fibrillation can be accomplished with a Team approach and attention to details.

31

Surgery for Atrial Fibrillation

Thank you……

Active Surgical Trials

33

11 9/17/2012

Protocol

34

12 9/20/2012

Approach to the Patient with Wide Complex Tachycardia

Charles J Love, MD FACC FAHA FHRS CCDS Professor of Medicine Director, Cardiac Rhythm Device Service The Ohio State University Heart and Vascular Center

Differential Dx of Wide Complex Tachycardias

ƒ Ventricular Tachycardia ƒ SVT with Aberration ƒ SVT with pre-existing bundle branch block ƒ SVT with acute MI - QRS distortion ƒ SVT with metabolic or drug effect ƒ WPW ƒ Ventricular pacing or endless loop tachycardia ƒ Also known as pacemaker induced tachycardia or PMT

History is the First Clue!

ƒ Patient age ƒ History of myocardial infarction ƒ Family history of arrhythmias ƒ Age of onset ƒ Type of arrhythmia if known

1 9/20/2012

Physical Exam and Basic Studies

ƒ Evidence of structural heart disease ƒ Dyskinetic apex ƒ Enlarged heart ƒ 12 Lead Electrocardiogram ƒ Evidence of delta waves, BBB or prior infarct ƒ Best if available at baseline and during tachycardia ƒ Echocardiogram ƒ Evidence of scar, LVH, LVE

Normal Sequence of Conduction

3 1

2

V1 V6

Normal

R´ R

R

RBBB

T↓ q S S

LBBB

2 9/20/2012

Normal vs BBB conduction Patterns

V1 V6

Normal conduction

Typical RBBB pattern

Typical LBBB pattern

Atrio-Ventricular Re-Entry WPW

„Accessory pathway that conducts from atrium to ventricle (and usually from V to A too) „Simultaneous conduction creates fusion beat with a delta wave

delta wave

9

3 9/20/2012

Atrio-Ventricular Re-Entry WPW

„ May proceed up or down the accessory

pathway orthodromic ‹Up = orthodromic

) narrow complex ) common

10

11

Atrio-Ventricular Re-Entry WPW

„ May proceed up or down the accessory pathway antidromic ‹Down = antidromic

) wide complex ) not common

12

4 9/20/2012

13

14

Criteria Favoring Ventricular Tachycardia

Brugada Criteria: Absence of precordial RS complex RS > 100ms QRS Morphology: Right Bundle Lead V1 – monophasic, biphasic, atypical triphasic (R’ > R) Lead V6 – R : S < 1 (not helpful with left axis deviation) Left Bundle Lead V1 – R > 30 ms, RS > 60 ms NthiNotching on S wave Lead V6 – Q wave QRS Axis: Extreme left axis deviation (-90 to + 180 degrees) Right axis deviation during a left bundle morphology tachycardia QRS Duration: > 140 ms with a right bundle morphology tachycardia > 160 ms with a left bundle morphology tachycardia Precordial Concordance: Positive concordance stronger predictor than negative concordance AV relationship: AV dissociation, VA block, capture or fusion beats Clinical Criteria: Structural heart disease (prior MI).

5 9/20/2012

Examples

65 yo M with CAD referred for atrial flutter Rx Describe the ECG

RB morphology, QRS > 140 ms, Normal Axis, R:S < 1 This is VT!

6 9/20/2012

Describe the ECG. Morphology V1 / V6 QRS Duration Axis

19

Atypical RB Morphology (R > R’) QRS > 140 ms LAD (R:S < 1 V6 criteria not useful)

20

Describe the ECG. Morphology V1 / V6 QRS Duration Axis

7 9/20/2012

LB morphology, QRS = 120 ms, R < 30 ms, RS = 50 ms V1 Notching!!!

What ECG criteria favor VT for this WCT?

Brugada Criteria: RS = 160 ms V1 QRS = 280 ms, LB morphology + Right Axis Deviation

8 9/20/2012

65 yo M, s/p BiV ICD admitted with palpitations. Patient was referred for EPS / RFA of SVT

Not!!! SVT Brugada Criteria: R-S V5 > 100ms

SVT or VT? You make the call

9 9/20/2012

RB Morphology, Monophasic V1 Extreme Left Axis Deviation

Rhythm and QRS Regularity

65 yo with a Hx of CAD Transferred for treatment of PSVT

10 9/20/2012

I

II

V1

A A A A HRA

19 yo M brought to ER by squad after syncope while running BP = 80 / 50

ECG after DCCV

11 9/20/2012

Conclusion

ƒ Diagnosis of wide complex tachycardia can be complex! ƒ Use history and diagnostic data to help increase your chances of making the correct diagnosis ƒ Whenever possible, compare baseline and arrhythmic ECGs ƒ When needed, consult your friendly, local EP

12 9/17/2012

Newer Treatment Approaches for VT

Steven J. Kalbfleisch, M.D., FACC, FHRS Professor of Medicine Medical Director, Electrophysiology Laboratory Ohio State’s Heart and Vascular Center

SPEAKER DISCLOSURE

ƒ Affiliation / Financial support as follows: ƒ Research funding from St Jude Medical, Medtronic, Boston Scientific, Biosense Webster and Biotronik ƒ Advisory Boards for St Jude Medical and Biosense Webster

Whats New in the Treatment of VT?

ƒ Device Therapy NO ƒ Antiarrhythmic Therapy NO ƒ More Aggressive Ablation Therapy YES ƒ PVC related myopathy ƒ LVOT / Aortic Cusp VTs ƒ Epicardial VTs

1 9/17/2012

Relation Between Efficacy of Radiofrequency Catheter Ablation and Site of Origin of Idiopathic VT

18 patients, 20 VTs 10 RVOT

RFA Success RVOT 100% Other 50% Hugh Calkins et al, Am J Cardiol 1993

Relationship of Anatomy to VT Location

RVOT vs LVOT

Suleiman et al, Heart Rhythm, 2008 Ouyanf, F et al. JACC, 2002

51 year old M. with a Hx of “Benign” PVCs NIDCM (EF = 20%). Meds = ACEI, Coreg, Aldactone Holter: PVCs = 25K/24hr, 25% of QRS complexes Referred for ICD Implant

2 9/17/2012

Ao Cusp VT Site – Relation to LM

EGM timing

I

II 3D Map “GPS of the Heart” V1

HRA

Abl p Early Site Abl d Non L RV R

RF application

I

II

V1

HRA

Abl p

Abl d

RF on 3 months F/U: EF = 45%

Benign PVCs?

RFA of Frequent, idiopathic PVCs: 60 pts with PVCs referred for RFA. RFA Successful in 48 (80%) 22/60 with decreased EF Mean PVC Burden: 37% with reduced EF vs 11% with normal EF LVEF normalized in 18 / 22 (82%) with baseline LV dysfunction Conclusions: LV dysfunction in the setting of frequent PVCs may be reversible with catheter ablation. Bogun et al, Heart Rhythm 2007

Predictors of developing a myopathy PVC burden (> 20%), Duration (> 3 yrs), Gender (M)

Yokokawa et al, Heart Rhythm 2012

3 9/17/2012

Idiopathic PVC / VT – Therapy

Indications for Ablation Symptomatic Medically Refractory / Intolerant PVC Related Myopathy ? Very frequent asymptomatic PVCs

Epicardial vs Endocardial Anatomy

Epicardial vs Endocardial Anatomy Pericardial Anatomy

RV LV

RF Lesion

11

Courtesty of A d’Avila

12

4 9/17/2012

Potential problems with an epicardial approach

ƒAccess! ƒCoronary artery occlusion ƒPhrenic nerve damage ƒPericardial inflammation

Transthoracic Sub-Xyphoid Pericardial Puncture Approach

Tuohy needle

Sternum PA

LV RV

Xyphoid Liver

Sousa et al, JCE- 1996 Needle

57 yo with ARVD ICD shocks x 20, Prior RFA attempt (10 hours)

5 9/17/2012

Pericardial Puncture – The tricky part

RV Epicardial Mapping

AP Fluro Image AP Fluro Image RV

RCA Tag 2cm

3D electro-anatomical Image

VT termination with RFA @ Tricuspid Annulus

VT Termination

Tricuspid Annulus

600ms

RCA

6 9/17/2012

“One of the first duties of the physician is to educate the masses not to take medicine.”

Sir William Osler (1849-1919)

7 NOTES—

9/20/2012

ECG and Clinical Findings of Brugada and Long QT Syndromes

Charles J Love, MD FACC FAHA FHRS CCDS Professor of Medicine Director, Cardiac Rhythm Device Service The Ohio State University Heart and Vascular Center

Risk Factors for SCD in Young People ƒ Structural congenital heart disease ƒ Before and after corrective surgery ƒ Congenital anomalies of coronaries ƒ Myocarditis ƒ Hypertrophic and other cardiomyopaties ƒ Wolff-Parkinson-White Syndrome ƒ Long QT Syndrome ƒ Brugada Syndrome

LQTS: Historical Aspects

ƒ 1957: 1st LQTS family reported ƒ 1963-4: Romano-Ward Syndrome ƒ 1958-70: 25 LQTS cases reported ƒ 1971: 1st LQTS Rx ƒ Left stellate ganglionectomy ƒ 1979: LQTS Registry started ƒ 1991-2001: 6 LQTS genes identified

1 9/20/2012

LQTS: Characteristics

ƒ Genetic disorder: Multiple Versions! ƒ 1:5,000 to 1:10,000 ƒ ECG Evidence: ƒ QTc prolonged ƒ >440ms in males ƒ >450ms in females ƒ Hallmark arrhythmia: Torsade de pointes ƒ Primary presenting symptom: Syncope ƒ SCD in children and young males

LQTS: Identification of Risk

ƒ Most common presenting symptom: ƒ Unexplained Syncope ƒ Syncope on exertion in pediatric patients should be considered malignant until proven otherwise ƒ History and ECG ƒ OtdfftfOnset and offset of syncopal lid episode ƒ Siblings/family members with syncope or SCD ƒ Family history of “seizures” or congenital deafness ƒ Prolonged QTc on ECG

Causes of Arrhythmic Syncope

ƒ Very rapid VT or TdP with hypotension ƒ Atrial fibrillation or flutter with very rapid ventricular response as in WPW ƒ AV Block ƒ Sinus Arrest

2 9/20/2012

Holter ECG Recording in LQTS Patient with Syncope (1 of 2)

Holter ECG Recording in LQTS Patient with Syncope (2 of 2)

LQTS: Clinical Features

ƒ Symptoms ♥ECG Signs ƒ Syncope ƒ Seizures ♥ Prolonged QTc ƒ SddSudden Dea th ♥ Torsade de Pointes ƒ Palpitations ƒ Chest Pain

3 9/20/2012

Long QT Syndrome in a 16-year-old girl QT=520 ms; Atrial Tachycardia with 2:1 AV conduction

LQTS ECG Patterns

Additional LQTS ECG Patterns

4 9/20/2012

What Should You do with the ECG?

ƒ Don’t rely on computer evaluation of ECG ƒ Obtain an independent review of the ECG ƒ Have an experienced cardiologist measure the QTc interval ƒ If the ECG, clinical presentation or family history is suspicious for LQTS, refer the patient for cardiac evaluation

QTc Interval and Risk

Long QT Syndrome Subtypes

Variant Gene Chromosome Function

LQT1 KCNQ1 11p15.5 IKs alpha subunit

LQT2 KCNH2 7q35-35 IKr alpha subunit

LQT3 SCN5A 3p21-23 INa alpha subunit LQT4 ANK2 4q25-2 Targeting protein

LQT5 KCNE1 21p22.1-22-2 IKs beta subunit

LQT6 KCNE2 21p22.1-22-2 IKr beta subunit

LQT7 KCNJ2 17p23.1-24.2 IK1

LQT8 CACNA1 12p13.3 ICa alpha subunit C

JLN1 KCNQ1 11p15.5 IKs alpha subunit

JLN2 KCNE1 21p22.1-22-2 IKr beta subunit

5 9/20/2012

Triggering Events for Syncope and SCD in LQTS

ƒ Exercise (LQT-1), especially swimming ƒ Emotions or emotional stress (LQT-2) ƒ Events occurring during sleep or at rest, with or without arousal (LQT 2/3)

LQTS: Phenotype-Genotype Considerations ƒ 6 Genotypes ƒ 200 different mutations ƒ Clinical differences among LQT1, LQT2 and LQT3 genotypes ƒ Clinical variabilityyg among members of a famil y with the same gene mutation suggests presence of modifier genes

T-wave Morphology in LQTS by Genotype

6 9/20/2012

Probability of a Cardiac Event by Genotype

Therapies Available and Current Management

Drugs in Long QT

ƒ Certain drugs may provoke arrhythmias ƒ Anti-arrhythmics: Sotalol, procainamide, quinidine, amiodarone etc ƒ Antihistamines: Astemizole, terfenadine, etc ƒ Antimicrobials and antifungals: Thiomethoprim sulfa, erythromycin, ketoconazole, etc ƒ Psychotropics: haloperidol, risperidone, thioridazine, tricyclics, et al ƒ Other: epinepherine, diuretics, cisapride, bepridil, ketanserin, etc ƒ Avoid nonessential OTC medications ƒ More info at www.qtdrugs.org

7 9/20/2012

Current Treatments

ƒ Beta Blockers ƒ Pacemakers ƒ TdP is often bradycardia or pause dependent ƒ Implantable Defibrillators ƒ Left stellate ganglionectomy ƒ Occasionally used in infants and patients refractory to other forms of therapy

Management by Genotype

ƒ LQT1 and LQT2 benefit the most from Beta- blocker therapy ƒ Benefit less clear in LQT3 ƒ ICDs indicated ƒ If the patient presents as SCD survivor or aborted cardiac arrest ƒ If Beta-blockers are not effective in preventing cardiac events ƒ Strong family history of SCD

Limitations of B-Blockers in LQTS

ƒ SCD can occur despite Rx with Beta blockers ƒ Long-term compliance with daily therapy is problematic ƒ Usual side effects of beta-blockers

8 9/20/2012

ICD Experience in LQTS

ƒ An ICD is indicated for all patients with documented VT, VF or aborted cardiac arrest ƒ Aborts SCD in patients with prior cardiac events ƒ Provides a back-up for patients on B-Blocker therapy who continue to be symptomatic ƒ 88 patients, no deaths in 2.5 year follow up of group (.1 to 9 years)

Pacing Experience in LQTS

ƒ Reduces frequency of syncope in patients with bradycardia triggered events ƒ Most useful when combined with Beta blocker therapy ƒ Does not prevent cardiac arrest in long term therapy ƒ Appears most useful in patients with LQT3 and bradycardia

LQTS Conclusions

ƒ Unexplained syncope with exertion in children and young adults should be considered serious until proven otherwise ƒ ECGs should be obtained on the patient and read by a cardiologist or pediatric cardiologist if patient is a child ƒ ECGs s hou ld be o bta ine d on a ll imme dia te fam ily members ƒ Referral to a cardiac specialist if suspicious for LQTS. ƒ Patients need to avoid meds which increase QT and lead to arrhythmias ƒ Those at risk can avoid target situations and meds and take preventative measures: meds and cardiac defibrillator placements

9 9/20/2012

Brugada Syndrome

Definition: Brugada Syndrome ƒ Definitive diagnosis ƒ Type 1 ST-segment elevation (Brugada EKG) ƒ Observed in more than one right precordial lead in the presence or absence of sodium channel - blocking agent ƒ In conjunction with one or more of the following ƒ documented VT Arrest ƒ a family history of SCD (<45 years old) ƒ coved-type EKGs in family members ƒ inducibility of VT with programmed electrical stimulation (PES) ƒ syncope or nocturnal agonal respiration

Background and Significance:

ƒ Affects young, otherwise healthy individuals ƒ Presentation is unpredictable

Makes this condition extremelyyp important because of its devastating consequences to their families and society

10 9/20/2012

Background and Significance:

ƒ Brugada Syndrome is be due to multiple genetic disorders with a common phenotypic pattern ƒ Controversies still exist in regards to structural heart disease

Historical Overview:

ƒ The first patient suspected to be affected with Brugada’s syndrome was a 3y/o child in 1986 ƒ The first report by Pedro and Josep Brugada in 1992 described 8 patients with typical EKG changes and sudden cardiac death ƒ Review of the literature showed previous reports with patients with similar characteristics ƒ Nadamanee in 1996 reported patients with similar characteristics from Southeast Asia

Typical Electrocardiographic Characteristics: Type 1

♥Right bundle branch block pattern V1 to V3 ♥J-point elevation of more than 0.2 mV in leads V1 to V3 ♥ST segment elevation > 0.2 mV in leads V1 to V3 with inverted T-wave ♥First degree atrio-ventricular block ♥Typical widening of the S wave is absent in lateral leads ♥Waxing and Waning pattern of the EKG ♥Other non-specific (LAD)

33

11 9/20/2012

Typical ECG pattern patient showing the RBBB and ST-segment elevation in V1 through V3: Type 1

34

Three types of ST segments elevation generally observed in patients with the Brugada syndrome

PACE 2006; 29:1130–1159

Nademanee: Circulation, Volume 96(8).October 21, 1997.pp 2595-2600. 36

12 9/20/2012

Epidemiology:

ƒ 10:1 male to female ratio

ƒ Higher incidence in Asians ƒ Mean age of first arrhythmic event peaks in the fourth decade of life ƒ Range of age of affected individuals 2 days to 84 years-old

Epidemiology:

♥The prevalence of the Brugada syndrome is estimated at 1–5 per 10,000 inhabitants worldwide ♥The frequency is lower in western countries and hig her (≥5 per 10, 000) in Sout heast As ia ♥In Thailand, Brugada is the second greatest cause of death in young males (1:2500)

38

Clinical Manifestation:

♥Asymptomatic ♥Syncope or near-syncope ♥Agonal nocturnal respiration ♥Sudden unexpected cardiac death

39

13 9/20/2012

Differential Diagnosis:

ƒ Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) ƒ Long QT ƒ Ischemia ƒ Cardiac tumors

Other Clinical Situations that Modulates the the ST-Segment in Patients with Brugada Syndrome

ƒ Fever ƒ Tri or tetracyclic antidepressants ƒ Alcohol ƒ First generation ƒ Cocaine antihis tam ines ƒ Hyperkalemia ƒ Hypothermia ƒ Hypokalemia ƒ Sticky rice ƒ Glucose + Insulin ƒ Hypercalcemia

41

Genetics:

ƒ Mutation related to Na+ channel SCN5A has being described by Chen et. al. (nature 1988, 392:293-296) ƒ The mutations described are located in a different place than the LQTS or ARVC. ƒ The mutations produce two functional changes in the cardiac cell. ƒ Acceleration of the recovery of the Na+ channel (missense mutation) ƒ Non-functional Na+ channels (insertion and deletion mutation)

14 9/20/2012

Risk Stratification:

ƒ Type 1 EKG and SCD at presentation =ICD ƒ Type 1 EKG and syncope at presentation =ICD ƒ Type 1 EKG and Famil y Hx of SCD =ICD

Who needs Risk Stratification???

Treatment:

ƒICD ƒ ? Quinidine

ƒ Ito Blockers

Rationale for Treatment:

J. Brugada et. al. Circulation 1998;97: 457-60

15 9/20/2012

Twelve-lead electrocardiogram (ECG) tracings in an asymptomatic 26-year-old man with the Brugada syndrome.

PACE 2006; 29:1130–1159

Brugada Conclusions:

ƒ RBBB-ST-segment elevation and SCD is a “pure” channelopathy ƒ Brugada, in addition to WPW, LQTS and ARVC is EKG marker for SCD ƒ RBBB-STE syndrome is the most frequent cause of SCD in young patients with structurally normal heart ƒ It is the leading cause of death in young affected individuals in Southeast Asia

Conclusions:

ƒ There is an autosomal dominance mode of inheritance and a clear genetic heterogeneity ƒ Risk stratification of the asyypmptomatic patient is problematic ƒ ICD at the present time is the only proven treatment

16 9/20/2012

Who Should or Should Not Get an ICD?

Steven J. Kalbfleisch, M.D., FACC, FHRS Professor of Medicine Medical Director, Electrophysiology Laboratory Ohio State’s Heart and Vascular Center

SPEAKER DISCLOSURE

ƒ Affiliation / Financial support as follows: ƒ Research funding from St Jude Medical, Medtronic, Boston Scientific, Biosense Webster and Biotronik ƒ Advisory Boards for St Jude Medical and Biosense Webster

The First Thing to Understand Primary vs Secondary Prevention ƒ Secondary Prevention ƒ Something bad has already happened ƒ Aborted SCD ƒ Sustained VT, Syncope with structural heart dz ƒ NtdNot due to an ob bivious revers ible cause (drug, MI) ƒ Primary Prevention ƒ Nothing really bad has happened ƒ Felt to be high risk ƒ Decreased EF, CHF, NSVT, Hereditary dz

1 9/20/2012

Major ICD Trials

*

* *

No CHF Class

Class II / III

* = secondary prevention trial 4

ICD / CRT History in a Nutshell

ƒ 1985 FDA approval of 1st AID ƒ Medically refractory VT / VF ƒ 1991 1st Medicare National Coverage Determination (NCD) ƒ SCD not due to reversible causes ƒ 1993 FDA approval of Non-thoracotomy lead ƒ 1999 2nd Medicare NCD ƒ Sustained VT induced or spontaneous ƒ High risk LQT / HCM ƒ 2001 FDA approval of CRT system ƒ CHF III / IV, DCM, QRS > 120ms ƒ 2003 3rd Medicare NCD (primary prevention) ƒ CAD, EF < 35%, VT @ EPS or ƒ CAD, EF < 30%, QRS > 120ms ƒ MI > 40 days, revasc. > 3 months ƒ 2005 4th Medicare NCD (primary prevention) ƒ EF < 35%, class II / III CHF, CAD or NICM

The Quagmire of ICD /CRT Implant Indications Who should be implanted?

ƒ Study Inclusion / Exclusion Criteria ƒ FDA approval ƒ ACC / AHA / HRS / CHF Guidelines ƒ Medicare - National Coverage Determination (NCD) ƒ Local Insurance Coverage (LCD) ƒ Department of Justice (DOJ) – The final arbitrator

2 9/20/2012

Why the question?

Other results; In hospital death > for non-evidence based ICDs Reasons for non-evidence based ICDs MI < 40 days (37%), New CHF Dx < 3months (62%) Class IV CHF (12%), CABG < 3 months (3%) Al-Kahtib et al, JAMA 2011 7

The real reason for the question?

8

CMS (Medicare) NCD for ICDs “Some of The Rigid Fine Print”

Indications and Limitations of Coverage B. Covered Indications Documented episode of cardiac arrest due to ventricular fibrillation (VF), not due to a transient or reversible cause (effective July 1, 1991). Documented sustained ventricular tachyarrhythmia (VT), either spontaneous or induced by an electrophysiology (EP) study, not associated with an acute myocardial infarction (MI) and not due to a transient or reversible cause (effective July 1, 1999). Documented familial or inherited conditions with a high risk of life-threatening VT, such as long QT syndrome or hypertrophic cardiomyopathy (effective July 1, 1999). Additional indications effective for services performed on or after October 1, 2003: Coronary artery disease with a documented prior MI, a measured left ventricular ejection fraction (LVEF) < 0.35, and inducible, sustained VT or VF at EP study. (The MI must have occurred more than 40 days prior to defibrillator insertion. The EP test must be performed more than 4 weeks after the qualifying MI.) Documented prior MI and a measured LVEF < 0.30 and a QRS duration of >120 milliseconds (the QRS restriction does not apply to services performed on or after January 27, 2005) . Patients must not have: New York Heart Association (NYHC) classification IV; Cardiogenic shock or symptomatic hypotension while in a stable baseline rhythm; Had a coronary artery bypass graft (CABG) or percutaneous transluminal coronary angioplasty (PTCA) within past 3 months; Had an enzyme positive MI within past month (Effective for services on or after January 27, 2005, patients must not have an acute MI in the past 40 days); Clinical symptoms or findings that would make them a candidate for coronary revascularization; or Any disease, other than cardiac disease (e.g., cancer, uremia, liver failure), associated with a likelihood of survival less than 1 year. Patients with ischemic dilated cardiomyopathy (IDCM), documented prior MI, NYHA Class II and III heart failure, and measured LVEF < 35%; Patients with non-ischemic dilated cardiomyopathy (NIDCM) >9 months, NYHA Class II and III heart failure, and measured LVEF < 35%; Patients who meet all current Centers for Medicare & Medicaid Services (CMS) coverage requirements for a cardiac resynchronization therapy (CRT) device and have NYHA Class IV heart failure; All indications must meet the following criteria: Patients must not have irreversible brain damage from preexisting cerebral disease; Indications 3 - 8 (primary prevention of sudden cardiac death) must also meet the following criteria: Patients must be able to give informed consent; Patients must not have: Had a CABG or PTCA within the past 3 months; Had an acute MI within the past 40 days; Clinical symptoms or findings that would make them a candidate for coronary revascularization; Any disease, other than cardiac disease (e.g., cancer, uremia, liver failure), associated with a likelihood of survival less than 1 year; Ejection fractions must be measured by angiography, radionuclide scanning, or echocardiography; For purposes of this coverage decision, CMS will determine whether specific registries or clinical trials meet these criteria. Providers must be able to justify the medical necessity of devices other than single lead devices. This justification should be available in the patient's medical record.

3 9/20/2012

SCD-HeFT: Preventing SCD in Heart Failure The Most Important Primary Prevention Study

Inclusion: EF < 35%, CAD or NICM, Class II/III CHF SCD-HeFT Size: 2521 patients in North America 23% Reduction in the risk of allall--causecause mortality and New Zealand when using an ICD vs Med Rx alone Endpoint: All-cause mortality (p = 0.007) Published: NEJM 2005

ICD therapy saved NYHA Class II/III patients’ lives from tachyarrhythmias – but a major cause of mortality remained: heart failure

•Note: Absolute Reduction in Mortality was 7.2% over 5 years •Arrhythmic death decreased by 60%

NYHA Classification A Subjective (changing) Measurement Class Patient Symptoms • No limitation of physical activity AI Mild • No undue fatigue, palpitation or dyspnea

• Slight limitation of physical activity II Mild • Comfortable at rest B • Less than ordinary activity results in fatigue, palpitation, or dyspnea • Marked limitation of physical activity IIIC Moderate • Comfortable at rest • Less than ordinary activity results in fatigue, palpitation, or D dyspnea IV • Unable to carry out any physical activity without discomfort Severe • Symptoms of cardiac insufficiency at rest • Physical activity causes increased discomfort

11

COMPANION – CRT Trial OPT vs CRT and CRT-D

Inclusion: CHF III/IV, EF < 35%, QRS > 120ms COMPANION 20% Size: 1520 U.S. patients Reduction in the risk of allall--causecause mortality Endpoint: All-cause mortality or first or first hospitalization with CRTCRT--DD (p = hospitalization 0.011) Published: NEJM 2004

CRT-Ds save lives in NYHA Class III/IV HF patients

• 70% of HF patients are in NYHA Class I/II.

4 9/20/2012

Early CRT Intervention (Class I/II) Reduces Death and Heart Failure Events Expanded Criteria: 1. EF ≤ 30% 2. LBBB with QRS ≥ 130 ms 3. NYHA Class I ischemic or Class II nonischemic heart failure

13

What questions have to be asked prior to ICD or CRT device ƒ Has the patient had an event? (cardiac arrest, sustained VT, syncope) ƒ EF measurement? ƒ Does the patient have CAD or NICM? ƒ Class of CHF? Duration of CHF sxs? ƒ Date of last documented (coded) MI? ƒ Date of PTCA / CABG? ƒ Are they the rare high risk patient (HCM, ARVD, sarcoid, giant cell, LQT, Brugada’s) ƒ For CRT: QRS duration, type of BBB? ƒ Other disease limiting life expectancy < 1 yr

ICD Indications – Black / White

ƒ OK to Implant ƒ Secondary Prevention (aborted SCD, Sustained VT, syncope in high risk group) ƒ EF < 30% / CAD / Prior MI ƒ EF < 35% / CHF (class II / III), ƒ CHF (class IV) if implanting with CRT ƒ Not OK to Implant (for Primary Prevention) ƒ MI < 40 days ƒ Revascularization < 3 months ƒ Life expectancy < 1 yr ƒ Class IV CHF or Class I Non-ischemic

5 9/20/2012

CRT-D Indications – Black / White ƒ OK to Implant ƒ EF < 35%, CHF (class III, IV), QRS > 120ms ƒ EF < 30%, CAD (class I), Non-ischemic (class II), QRS LBBB and > 130ms ƒ Not OK to implant ƒ Not on good (optimal) medical therapy ƒ New onset CHF < 3 months

Some of the 50 Shades of Gray

ƒ EF 35 to 40% ƒ CHF class ƒ Duration of CHF (3 vs 6 vs 9 months) ƒ (Non-reversible myopath y, S xs vs EF) ƒ Troponin-itis (real MI or not?) ƒ “Ugly” NSVT and new decreased EF ƒ Needs a PCMK post MI / CABG / PTCA ƒ EF < 35% ƒ EF < 35% pre PTCA and now post PTCA

Even Simpler Who should be referred for possible ICD? ƒAnyone with an EF < 35% ƒ Patients with aborted SCD or VT / syncope with structural heart dz ƒ High risk hereditary or infiltrative dz ƒ Let the electrophysiologist figure out who and what to implant ƒ Reasons they may delay the implant ƒ < 40 days from the time of MI ƒ < 90 days from PCI/CABG ƒ New onset CHF < 3 months

6 9/20/2012

The Good Old Days?

19

7 NOTES—

9/20/2012

Devices in Every Day Life: What to Tell Patients About Electronic Devices

Charles J Love, MD FACC FAHA FHRS CCDS Professor of Medicine Director, Cardiac Rhythm Device Service The Ohio State University Heart and Vascular Center

We live in a world bathed in EMI

Device/Patient Response to EMI Will Depend On…

ƒ Intensity of the field(s) ƒ Signal spectrum / frequency ƒ Distance from EMI source and position of the patien t rel a tive to th e source vect or ƒ Duration of exposure to the EMI ƒ Non-programmable device characteristics ƒ Lead configuration / polarity

1 9/20/2012

Device/Patient Response to EMI Will Depend On…

ƒ Programmed parameters ƒ Sensitivity ƒ Mode (operating, noise reversion) ƒ Committed versus non-committed (ICDs) ƒ Patient characteristics ƒ Pacemaker dependency ƒ Response to asynchronous pacing ƒ Response to rapid pacing rates

Device Response To EMI

ƒ NOTHING or… ƒ Pacing Inhibition ƒ Tracking of atrial sensed signal ƒ Rate Response Sensor Activation ƒ Noise Reversion Mode ƒ Tachycardia Detection ƒ Therapy Delivery ƒ Induction of arrhythmia ƒ Over Estimation of Non-Sustained or Short V-V events ƒ Power On Reset (POR)

Power On Reset

6

2 9/20/2012

Magnetic Resonance Imaging

ƒ Static magnetic field ƒ Reed switch closure ƒ Generator displacement ƒ Radiofrequency field ƒ Alterations of pacing rate (inhibition or triggering) ƒ SiSpurious thtachyarrh hthidttiythmia detection ƒ Heating ƒ Electrical reset ƒ Time-varying magnetic gradient field ƒ Induction voltage (resulting in pacing) ƒ Heating ƒ Reed switch closure

MRI Conditional Pacemakers

ƒ “MRI Conditional” device available for pacing ƒ Must be used with MRI Safe leads ƒ Patient cannot have any abandoned leads ƒ Must be programmed pre and post MRI ƒ A protocol to manage these patients should be in place to assure all pre-conditions are met, and that programming is done before and after the MRI Scan is complete

MRI-What about “Non-MRI Safe” devices?

ƒ What is your experience? ƒ We have done about 12 patients (head scan only) ƒ No issues other than pacing at magnet rate in some pacemakers where the feature cannot be disabled ƒ Recent data from Johns Hopkins and other institutions strongly supports the safety of this, but regulatory agencies may not agree and payers may not pay

3 9/20/2012

ECG Monitoring During MRI Scanning

10

Cell Phones

ƒ In excess of 1 Billion cell phones in use

Cell Phone Use

ƒ The operational frequency of certain systems may interfere with operation of CIEDs. ƒ Generally, this does not happen often with current devices ƒ Rule #1: Keep the cell phone at least 10cm from the CIED and this will virtually eliminate all issues ƒ Don’t put it in your shirt pocket!

4 9/20/2012

Electronic Article Surveillance

ƒ More and more common ƒ Significance of interaction depends on the type of unit being used ƒ No way for patients to know what type used ƒ Rule #2 ƒ “Walk, Don’t Linger” ƒ Do not lean on these or stand next to them ƒ Same rule for metal detectors

Left Ventricular Assist Devices

ƒ Special interaction issue with St Jude ICDs ƒ HeartMate-II operates on same frequency as some St. Jude ICDs (8KHz) ƒ Creates great difficulty in communicating with the ICD ƒ Best solution is to use a different manufacturer ICD ƒ Shielding can be used to overcome issue in some cases (iron pan)

Radiation: Therapeutic/Diagnostic

ƒ Rare issues with EMI ƒ Have seen inhibition, tracking ƒ Have also seen piezo sensor activation ƒ Major issue is damage to the CMOS circuitry by therapeutic ionizing radiation ƒ Each manufacturer states different limits ƒ Device should NOT be in the direct beam ƒ Scatter can still cause problems ƒ Malfunction type also unpredictable

5 9/20/2012

Household Current leak

ƒ Most tools are OK ƒ Poor electrical grounds can be dangerous!

Radiation: Therapeutic/Diagnostic ƒ Therapeutic radiation should never be directed directly to the device ƒ In some cases it may be necessary to move the device to another location ƒ Leaving leads behind may prevent use of MRI in the future ƒ Consider extraction ƒ Consider using lead extenders and moving pacemaker/ICD while reusing same device in a different location

Electronic Neurological Stimulation; TENS, DBS, SCS

„ Transcutaneous Electrical Nerve Stimulation (TENS) ‹ Needs to be tested applied to site and at the stimulation pattern and power to be used „ Deep Brain Stimulation (DBS) ‹ Not reported to be a problem „ Spinal Cord Stimulator (SCS) ‹ Should be tested ) Use Bipolar SCS and pacemaker sensing

6 9/20/2012

Cardioversion/Defibrillation

ƒ Can cause transient inhibition ƒ Can cause permanent damage ƒ Inductive Coupling ƒ Current parallel to one conductor induces a current in another conductor ƒ Usually prevented by the Zener Diode ƒ Repeated shocks can degrade the diode and allow damage to the device

Work and Industrial Environment ƒ High voltage power lines ƒ Transformers ƒ Electric arc welders ƒ Up to 200 Amp OK ƒ Electric motors ƒ Electric induction furnaces ƒ Degaussing coils

Personal Electronic Devices

ƒ iPod ƒ MP3 player ƒ Remote control ƒ Stereo Speakers ƒ Special case for Guidant/BSX ICDs ƒ May cause tachycardia detection to be programmed to off

7 9/20/2012

Electrocautery

ƒ Very common cause of concern ƒ In many operations, especially below the diaphragm, it is not an issue ƒ Most common with unipolar applications

Management in the OR

ƒ Disable tachyarrhythmia therapies ƒ Deactivate rate responsive features ƒ Consider asynchronous mode ƒ Asynchronous pacing is not available in many ICDs, so consider ƒ Decrease the maximum sensitivity ƒ Program the noise reversion mode to asynchronous (if available) ƒ Pre-apply external transthoracic pacing system

Management in the OR

ƒ Consider temporary transvenous pacing ƒ Monitor heart rate with pulse or oximeter ƒ ECG is obscured by artifact ƒ Position the ground pad to keep the current pathway as far away as possible and perpendicular from the pulse generator-to- electrode pathway ƒ Use true electrocautery or bipolar electrocoagulation whenever possible

8 9/20/2012

Management in the OR

ƒ Limit ESU current use to short bursts ƒ Use the lowest effective power output ƒ Do not use cautery near device ƒ Magnet may be used to force asynchronous pacing or suspend tachycardia detection (pacer/ICD) ƒ Be aware of potential device deactivation in Guidant/ Boston Scientific devices

RF Catheter Ablation

ƒ Very common procedure on patients with implanted devices ƒ AVNRT, VT and AVJ ablation ƒ Tachycardia detections should be programmed off ƒ Same issues apply as with use of electrosurgical devices ƒ That is what an RF ablation system is!

Conclusion

ƒ We are surrounded by EMI ƒ Patients with devices are bombarded by RF, electrical and magnet fields directly and indirectly ƒ Real world issues are minimal but not insignificant ƒ Proper patient education, and when needed, preparation can avoid most all problems

9 NOTES—

9/17/2012

Evaluation and Treatment of Syncope with Structural Heart Disease but EF > 35%

Steven J. Kalbfleisch, M.D., FACC, FHRS Professor of Medicine Medical Director, Electrophysiology Laboratory Ohio State’s Heart and Vascular Center

SPEAKER DISCLOSURE

ƒ Affiliation / Financial support as follows: ƒ Research funding from St Jude Medical, Medtronic, Boston Scientific, Biosense Webster and Biotronik ƒ Advisory Boards for St Jude Medical and Biosense Webster

Real Syncope = Abrupt LOC due to global cerebral hypoperfusion associated with loss of postural tone and followed by spontaneous recovery

For some the difference between syncope and sudden death is a few seconds

3

1 9/17/2012

Syncope / Structural disease and EF > 35%

ƒ Why the question? ƒ Because everyone knows in patients with an EF < 35% that syncope may be a malignant symptom. ƒ The reverse is not true. If your EF is > 35% syncope is not always benign. ƒ Syncope is common – affects 10% of the population at some point and accounts for 3% to 6% of ER visits / admissions.

Age Distribution / Incidence of Syncope

Bimodal age distribution of first syncopal event

Who gets structural Heart Dz

Increase in % with syncope over time

What is Structural Heart disease?

ƒ CAD / Prior MI ƒ Non-ischemic Myopathy ƒ Conduction disease – BBB ƒ Infiltrative disease – Sarcoid ƒ Hereditary disease – Hypertrophic cardiomyopathy, Arrhythmogenic RV dysplasia ƒ Obstructive Cardiac lesions – Valve disease (AS), atrial myxoma, Pulmonary HTN

2 9/17/2012

Age and Cause of Syncope

Conclusions: For all age groups reflex syncope is most common OH and Cardiovascular causes increase with age

ESC / HRS Syncope Guidelines, EHJ 2009 7

73 y/o woman - recurrent defecation syncope Event Monitor results

• Reflex (neurally(neurally--mediated)mediated) • Neurocardiogenic syncope • Situational • Cough syncope • Swallow syncope • Micturation syncope • Defecation syncope • Syncope associated with pain • Carotid sinus hypersensitivity

8

Prognosis and Cause Syncope

Cause 1 Yr. Mortality Examples

Cardiovascular 19% - 33% VT, AVB, AS

Unexplained 5%

Reflex < 2% VDS, CSH, Cough

1980’s Data

9

3 9/17/2012

Risk Stratification by Hx

Event Hx: High risk: Prodrome / Residua Abrupt onset / injury Activity / Posture During exercise Related Injury Structural heart dz Advanced age PMHx: FilhfdddhFamily hx of sudden death Prior Episodes Cardiac disease Low risk: Medications Typical VDS prodrome / residua Multiple episodes FHx: Young age / no heart dz Sudden Death Orthostatic trigger Hereditary Heart Dz

10

Cardiac Indications for admission ESC / HRS Syncope Guidelines, EHJ 2009

•Syncope during exertion •Palpitations preceding syncope History •CHF, Prior MI •Fhx of SCD •NSVT •IVCD (bifascicular block), QRS > 120ms ECG •Sinus Bradycardia (<40bpm), Pauses (> 3sec) Telemetry •AV block (> 2nd degree) •WPW, prolonged QT, Brugada Pattern •Inverted T waves V1-V3 •ECHO: EF < 40% Echo •Myxoma, AS, HCM, Effusion

11

Specialized Testing

Vasodepressor

Dysautonomia

Pots VT Psychogenic SVT

Sinus Node

AV conduction Tilt Test EP study

12

4 9/17/2012

Combined Use of EP and Tilt Table Testing for Syncope

Unexplained Syncope (86pts.)

+EPS 34% -EPS 66%

Tachyarrhythmia Bradyarrhythmia +HUT -HUT 21 VT, 5 SVT 1 SSS, 2 AVB 60% 40%

(EPS most sensitive for VT / SVT)

70% of pts were dx’d with combined use of EP and Tilt Testing

Sra et al, 1993

13

Mechanism of Syncope in Patients with Heart Disease and a Negative EP study

ƒ 35 patients with prior MI or CM and negative EPS ƒ Loop monitor implanted in all patients ƒ Recurrent syncope in 6 pts (mean of 6 mths) ƒ 3 had bradyarrhythmias, 3 non-arrhythmic ƒ 1 other with sustained VT ƒ No patients died or suffered injury ƒ Conclusion: a negative EPS predicts a favorable mid-term prognosis

Menozzi, Circ, 2002 14

Long Term ECG monitoring

Holter External Event Implantable Loop Monitor Monitor Monitor

24 to 48 hr 30 Days 3 years Useless? Useful? Most Useful

15

5 9/17/2012

Utility of ILR in patients with syncope of unknown cause ILR Yield Pooled Data in 506 pts ILR diagnostic in 176 (35%) 56% with Bradyarrhythmias 11% Tachycardia 33% no arrhythmia

Brignole et al, Europace 2009 16

Treatment – Cause Specific

ƒ VDS – Salt and Fluid loading ƒ Trigger avoidance ƒ Counterpressure maneuvers ƒ Midodrine, Florinef, SSRIs ƒ OH – Discontinue offending agents ƒ StStkiMiddiSupport Stockings, Midodrine ƒ VT – ICD ƒ AARx / Ablation ƒ SVT – Ablation ƒ SSS / AVB – PCMK ƒ Reflex mediated asystole – PCMK ƒ SSRIs, Midodrine

PCMK Therapy in Patients with Neurally Mediated Syncope and Documented Asystole

511 patients > 40 yo with ILR / Syncope

89 patients with asystole > 3 sec + syncope or > 6 sec

77 patients with PCMK implanted

38 PCMK on 39 PCMK off

Recurrent syncope Recurrent syncope 8 19

Pacing is effective in treating neurally mediated asystole Brignole, Circ, 2012 18

6 9/17/2012

The End

19

7 NOTES—

9/18/2012

Screening Athletes: When to Worry –When Not to Worry

Robert A. Vogel, MD Clinical Professor of Medicine University of Colorado

Disclosure: Consultant –NFL

SCD in Notable Athletes Anomalous HCM HCM Coronary CAD

Tom Herion (23y) Reggie Lewis (27y) Pete Maravich (40y) Jim Fixx (52y)

1:100K INCIDENCE WITH AGE 1:100

Maron B et al, Circ 2007;115:1643 Non‐Traumatic, Non‐Drug Causes of SCD in 1435 Young Competitive American Athletes Normal Heart Other Congenital HD Ion Channel Dz Aortic Rupture Sarcoidosis HCM Dilated CM Aortic Stenosis 44% CAD Tunneled LAD LVH ‐ MVP ?HCM ARVC Coronary Anomalies Myocarditis

1 9/18/2012

AHA/ACC Recommendations for Screening of Competitive Athletes • Personal History • Family History – Chest pain – Premature sudden cardiac – Syncope or near death (<50) syncope – Disability from HD (<50) – Unexplained excess – HCM, long QT, Marfan’s. etc dyspnea • Physical Exam – Hx of heart murmur – Heart murmur – Systolic hypertension – ↓ Femoral pulse – Marfan’s stigmata – Seated blood pressure

Circ 2007;115:1643

Corrado D et al, Europ Heart J 2010;31:243 Revised ECG Criteria in Athletes

Common and training‐ Uncommon and training‐unrelated related ECG changes ECG changes • Sinus bradycardia • T‐wave inversion • First‐degree AV block • ST‐segment depression • Incomplete RBBB • Pathological Q‐waves • ↑ST segment (ERS) • Left atrial enlargement • Isolated QRS voltage for • L anterior or posterior hemiblock LVH • Ventricular pre‐excitation • RBBB or LBBB • Long or short QT* • Brugada‐like early repolarization * QTc >470♂, >480♀ or <300 msec

Choo JK et al, Am J Cardiol 2002;90:198 Frequency of ECG Abnormalities in 1,282 NFL Players by Race

20% 18% Black 16% White 14% 12% All players: 10% 55% abnormal 8% ECGs 6% 4% 2% 0% STTWA ERS LVH RVH Q wave

2 9/18/2012

“Normal” Repolarization Changes

23 year old asymptomatic professional soccer player found to have abnormal ECG during routine pre-season screening

Fudge J et al, Am Med Soc Sports Med 4/12 Sensitivity and Specificity for SCD Disorder in 1339 Young Athletes (6/1339)

3 9/18/2012

Grenier MA et al, ASE Abstract 7/12 Abbreviated Echo (10 min –15 view) Exams in Young Athlete Screening • N = 85, ages 14‐18 • 10 (12%) abnormal echos • No false positives • 4 LV abnormalities (3 LVH, 1 noncompaction) • 4 dilated Ao roots • 1 ASD, 1 PDA • 2 athletes DQ’ed (LVH, noncompaction)

CMR: Variable patterns of HCM

Maron MS et al, JACC 2009;54:220

Pellicia A et al, NEJM 1991;324:295, Tucker A et al, JAMA 2009;301:2111, Bove A (personal comm.) Distribution of LV Wall Thickness in Athletes

946 Italian Olympic Athletes 103 NFL Players 180 NBA Players 30%

10%

20%

17%

5% 10%

1.6%

0% 0% <7 8 9 10 11 12 13 14 15 16 7 8 9 10 11 12 13 14 15 16 17

Borderline Abnormal Borderline Abnormal

4 9/18/2012

SCD Risk Criteria in HCM Major criteria • Minor criteria • Prior arrest • Resting gradient >30 • Sustained VT • Stress‐induced • Fm hx HCM death ihischemi a • Unexplained syncope • High‐risk genotype • Exertional ↓BP • Abnormal resting • LVH >30 mm (echo) ECG • LGE on MRI

Goldberger et al, JACC 2008;52:1179

Pedoe DT, Marathon Medicine, Royal Society Medical Press, 2000:5, Kim JH N EJM 2012;366:130 Which activity has a higher mortality risk per hour?

Absolute mortality: 1:100K per event

Redelmaier DA, et al, BMJ 2007;335:1275; Noakes TD, Med Sci Sports Exerc 1987;19:187 Sudden Cardiac Death in Marathon Runners

14

12 Mean age: 44 years Best time: 3:28 (2:33 – 4:28) 10 CAD: 75% (+ HCM in 6%)

8 Prior symptoms: 71%

6

4

2

0 2468101214161820222426 Mile of occurrence

5 9/18/2012

Waller BF, Roberts WC, AJC 1980;45:1292 ECG Findings Prior to SCD in Seasoned Runners (55 km/wk) 30% 25%

al 20%

m All had 3V CAD 15% 10% Abnor

% 5% 0% Resting ECG Exercise ECG

Event‐free Survival in Marathon Runners: CAC Score LGE on CMR

Mohlenkamp, S. et al. Eur Heart J 2008 29:1903‐1910; doi:10.1093/eurheartj/ehn163 Breuckmann et al. Radiology 251 (1) 2009.

Kloner RA et al, Am J Cardiol 2009;103:1647 CV Death Rates in Los Angeles for the 2 Week Period after the 1980 and 1984 Super Bowls

P = 0.0056 aths/100K e D

CV

Daily

6 9/18/2012

Evaluation of Heart Disease: The Value of the Stethoscope

Blase Carebello, MD

63 Y/O MAN

• CLASSIC ANGINA

• ECHO: LITTLE AV MOVEMENT

• MEAN GRADIENT 18 mm Hg

• AVA: 1.4cm2

CATH

• CLEAN CORONARIES

• CLASSIC ANGINA

1 9/18/2012

EXAM

• HARSH LATE PEAKING SEM

• DELAYED REDUCED CAROTIDS

• SOFT SINGLE SECOND SOUND

BAYES THEOREM

2 9/18/2012

• SENSITIVITY = TP/TP+ FN

• SPECIFICITY = TN/ TN + FP

• ACCURACY POS = TP/TP + FP

• ACCURACY NEG = TN/TN+FN

EXAM

• HARSH LATE PEAKING SEM

• DELAYED REDUCED CAROTIDS

• SOFT SINGLE SECOND SOUND

ASSUME

• 90 % OF PATIENTS WITH THAT EXAM HAVE AT LEAST MODERATE AS

• ECHO IS 90 % SSSENSITIVE AND 90 % SPECIFIC

3 9/18/2012

1000 PATIENTS WITH THAT EXAM

• 900 HAVE MOD‐SEVERE AS ; 100 DO NOT

• ECHO SENS: 810/810+90

• ECHO SPEC 90/ 90 +10

• ACCNEG 90/ 90+90

57 Y/O MAN

• TYPICAL ANGINA

• BP: 110/80, P: 84

• DELAYED CAROTID UPSTROKES

• 2/6 LATE PEAKING SEM

ECHO

• POST WALL th: 13mm

• JET Vmax 4.2 m/sec

• AVA: 0.6 cm2

4 9/18/2012

CALLED TO THE CATH LAB

• CO: 5.5 l/min

• GRAD: 22 mm Hg

5 9/18/2012

Dx OF VHD

• STARTS IN THE OFFICE

• GOES TO PHYSIOLOGICAL IMAGING

• INVASIVE HEMODYNAMICS IF NEEDED

6 9/20/2012

Aortic Stenosis Natural History, Prognosis & Diagnosis

Patrick T. O’Gara, MD Brigham and Women’s Hospital Harvard Medical School

No Disclosures

Aortic Stenosis

Pathogenesis of Calcific AS

Bosse Y et al. J Am Coll Cardiol 2008;51:1327-1336

1 9/20/2012

Disease Progression in Aortic Stenosis

Otto C. N Engl J Med 2008;359:1395-1398

Aortic Sclerosis Focal Thickening/Calcification & Velocity < 2.5 m/sec

5 YR NL Ao Scler AS P EVENT (N=3919) (N=1610) (N=92) (trend)

DEATH 14.9% 21.9% 41.3% <0.001

CV DEATH 6.1% 10.1% 19.6% <0.001

MI 6.0% 8.6% 11.3% <0.001

Otto CM et al. CV Health Study. N Engl J Med 1999; 341:142.

SEAS Aortic Valve Events

50

40 Placebo

30 ts, % ts, HR 0.97, p=0.73 Simva + Eze 20 Patien 10

0 012345

Years in Study

Rossebǿ A et a. N Engl J Med 2008; 359:1343-56.

2 9/20/2012

Aortic Stenosis

Obstruction

After load HthHypertrophy Cor flow

Diastolic O2 dysfunction mismatch

CP1006390-22

Natural History of Aortic Stenosis

Onset severe symptoms Angina 100 Syncope Failure 80 Latent period,period (increasing obstruction, 60 increasing obstruction, myocardialhypertrophy overload) 0246 Avg survival (yr) 40 YfttYrs after onset Average death 20 age ( ) 0 0 4050607080 Age (yr) Ross J Jr. and Braunwald E: Circ 38(Suppl 5):61, 1968

Left Ventricular Hypertrophy in Aortic Stenosis

Adaptive Maladaptive - Normalizes Wall Stress - Impairs CBF - Preserves Ejection Performance - Leads to Diastolic Dysfunction - Risk Factor for Mortality

• Genetic Determinants • Role of Systemic Hypertension • Variable Regression Following AVR

3 9/20/2012

Myocardial Fibrosis in Symptomatic Severe AS

Weidemann F et al. Circulation 2009;120:577-584

Incidence and Patterns of LGE

Rudolph A et al. J Am Coll Cardiol 2009;53:284-291

Severe Symptomatic AS Survival

Schwarz F et al. Circulation 1982;66:1105–10

4 9/20/2012

Survival of Patients With Unoperated AS

Bach D S et al. J Am Coll Cardiol 2007;50:2018-2019

Contemporary Surgical Outcomes What Are the Benchmarks? Demographics Outcomes • 2004-2008 • 30 day mortality 0% • n=190 • Re-op bleeding 4.7% • Age 68 (21% >80) • AF 23. 2% • Min Inv AVR 61% • Permanent stroke 0% • NYHA III/IV 34% • Prolonged vent 5.3% • STS 3.6% • ALOS 5.0 days • Tissue valve 99% • 1 yr. survival 97%

Malaisrie SC et al. Ann Thorac Surg 2010; 89: 751-757.

Considerations in the Asymptomatic Patient

RiskValve Benefit Surgery

Operative mortality ↓ LVH, Fibrosis, LV dysfunction Prosthesis complications Heart failure Anticoagulation Arrhythmia, sudden death Age, gender, co-morbidities, life style

5 9/20/2012

Event-Free Survival

100 Vmax < 3.0

Predictors 80 Vmax 3.0-4.0 • V max 60 • Δ V max 40 • NYHA Class Vmax > 4.0 20

0 0 6 12 18 24 30 36 42 48 54 60 Months

Otto CM et al. Circulation 1997; 95: 2262-70.

Event-Free Survival

Rosenhek R et al. Circulation 2010;121:151-156

Event-Free Survival Valve Calcification

100 N= 126 V max 5.0 m/s 80 No or mild Ca++ 1 SCD, 8 TOTAL

60 Survival

Predictors Mod or severe Ca++ • Calcium 40 • Δ V max 20 Event-free Event-free

0 012345 Years

Rosenhek R et al. NEJM 2000; 343: 611-7

6 9/20/2012

Exercise Testing Asymptomatic AS

100

80 NEG urvival 60 S

40 POS 20 Event-free Event-free 0 0 6 12 18 24 30 36 42 48 54 60 Months Amato MCM et al. Heart 2001; 86:381.

Role of BNP Bergler-Klein J et al. Circulation 2004;109:2302

1 Nt-BNP < 80

0.8 urvival S 0.6

0.4 Nt-BNP > 80

0.2 P< 0.001 Symptom-free Symptom-free 0 0 50 100 150 200 250 300 350 Days

Risk Score in Asymptomatic AS Score=[peak velocity (m/s)x2]+(log BNP x1.5)+1.5 (if female)

Monin J-L et al. Circulation 2009;120:69-75

7 9/20/2012

Asymptomatic AS Risk Score

Score = [Vmax x2] + (Ln BNP x1.5) +1.5 (if female)

Monin JL et al. Circulation 2009;120:69-75

Longitudinal LV Mechanics in Asymptomatic Severe Aortic Stenosis

Dal-Bianco J P et al. J Am Coll Cardiol 2008;52:1279-1292

Diastolic Function and Survival in Unoperated Severe Aortic Stenosis

Biner S et al. J Am Coll Cardiol Img 2010;3:899-907

8 9/20/2012

Severe AS with Low EF Look at the Valve !

Dobutamine Stress Echo (DSE)

↑ CO ↑ CO ↔ CO ↑ Gradient ↑ Gradient ↔ Gradient ↑ AVA > 1.0 cm2 AVA < 1.0 cm2 AVA < 1.0 cm2

? AVR, TAVI ?

Severe AS with Low EF European Multi-Center Study Risks: High EuroSCORE Multi-vessel CAD MPG < 20 mm Hg No CR

N=217, AVA < 1.0 cm2, MPG < 30, EF < 0.35 Peri-op mort 16%

Levy F et al. J Am Coll Cardiol 2008;51:1466-1472

Patient With a Typical Pattern of Low-Gradient Aortic Stenosis with Normal EF

Herrmann S et al. J Am Coll Cardiol 2011;58:402-412

9 9/20/2012

Paradoxical Low Flow Aortic Stenosis

Pibarot P et al. J Am Coll Cardiol Img 2009;2:400-403

AS with Low Gradient / Normal EF Survival

Hachicha Z et al. Circulation 2007;115:2856-2864

Overall Survival Versus Zva

Hachicha Z et al. J Am Coll Cardiol 2009;54:1003-1011

Copyright ©2009 American College of Cardiology Foundation. Restrictions may apply.

10 9/20/2012

TTE Appearance of AS Types

Apical 5 Chamber View

Aortic Stenosis Doppler Gradient 200

150 heter) (mm Hg) (mm heter) t 100

50 n=100 R=0.92 SEE=15

Mean gradient (ca 0 005050 100 150 200 Use mean gradient Mean gradient (Doppler) (mm Hg)

11 9/20/2012

52 year old male: Class II dyspnea

LVOT diam 2.0cm AV TVI 98 cm LVOT TVI 25 cm

Area 1 x TVI1 = Area 2 x TVI2 ..785 ( )2 x = AVA x AVA = 78.8 / 98 = 0.8cm2

Aortic Valve Area CT vs. TTE

Feuchtner G M et al. J Am Coll Cardiol 2006;47:1410-1417

12 9/18/2012

When to Operate in Severe Aortic Stenosis: Only After St?Symptoms? Blase Carabello, MD

WHAT TO DO WITH THIS 71 Y/O MAN? ASYMPTOMATIC ; HEALTHY;

• JET VEL 4.3 m/sec

60 mm Hg GRADIENT; AVA 0.8 cm2

EF 0.65

LVH TH 1.7 cm

HEAVY VALVE CALCIFICATION

WE KNOW

• THAT IF HE IS TRULY ASYMPTOMATIC HE IS FAIRLY SAFE

1 9/18/2012

Latent Period 100100

8080 Increasing obstruction, Symptoms myocardial overload 6060 (percent)

ival 4040 v Sur 2020 Average Age Death

00 40 50 60 70 80 Age (years)

PAP =CO X PR Ao BP= CO X SVR valve

R3 RV R1 LV R2

2 9/18/2012

PELLIKKA et al

• 622 ASYMPTOMATIC Pts

• 4.5 m/s JET

ROSENHEK et al

• 116 ASYMPTOMATIC Pts WITH SEVERE AS

• 1 SUDDEN DEATH IN 6 YEARS

3 9/18/2012

RISK OF SD IN ASYMPTOMATIC AS Pts

• 0.5 % /YEAR

SCD IN ASYMPTOMATIC Pts

11 IN PELLIKKA’S STUDY

ANOTHER 26 IN THE LITERATURE WHO PROGRESSED RAPIDLY FROM ASYMPTOMATIC TO SCD

IF WE OPERATE

4 9/18/2012

STS RISK SCORE

0.7 % MORTALITY 7% MORBIDITY

ROCK AND A HARD PLACE

• LOW RISK TO WAIT FOR Sxs

• LOW RISK AVR

CURRENT STRATEGY

5 9/18/2012

• FIND A HIGH RISK GROUP WHERE THE RISK OF WAITING EXCEEDS AVR

OTTO et al CIRC ‘97

ROSENHEK et al

6 9/18/2012

ROSENHEK et al

WHAT ABOUT LVH

• 2b INDICATION FOR AVR IN 1998

• DISAPPEARED IN 2006

LVH

• IT’S GOOD; IT NORMALIZES STRESS σ= PxR/2Th

• IT’S BAD: INCREASSSES MORTALITY IN VIRTUALLY EVERY DISEASE WHERE IT IS PRESENT

7 9/18/2012

DUNCAN et al ATS 2008

• PROPENSITY MATCHED 964 PATIENTS WITH AND WITHOUT CONCENTRIC GEOMETRY UNERGOING AVR

DUNCAN et al ATS 2008

• AVR MORTALITY • CONC GEO NO CONC GEO • 38/964 (3.9%) 18/964 (1.9%)

• MORBIDITY • 33/964 (3.4%) 17/964 (1.8%)

BERGLER‐KLEIN

BNP<550 BNP>550 • TRUE MED 4/4 3/5 • TRUE AVR 8/8 6/12

• PSEUD MED 17/19 7/12 • PSEUD AVR 4/5 2/4

8 9/18/2012

IS THE Pt TRULY ASYMPTOMATIC?

DAS et al

WHAT TO DO WITH THIS 71 Y/O MAN? ASYMPTOMATIC AS;

• JET VEL 4.3 m/sec

60 mm Hg GRADIENT; AVA 008.8 cm2 EF 0.65;

9 9/18/2012

EX TEST

• QUIT 3 MINUTES INTO BRUCE STAGE 1

• NO INCREASE IN BP

• WHAT IF TAVI WERE A DURABLE LOW RISK OPTION?

CONCLUSION

• SYMPTOMATIC AS REMAINS ONE OF THE MOST LETHAL DISEASES IN ALL OF MEDICINE

• WE CAN IDENTIFY HIGH RISK ASYMPTOMATIC Pts THAT MAY BENEFIT FROM AVR • + ETT, HIGH GRADIENT, HEAVY Ca++, LVH

10 Choosing the Right Valve and the Right Procedure for Aortic Stenosis Steven Bolling, MD

9/18/2012

Echocardiographic Assessment of Mitral Regurgitation

Vincent Brinkman, MD Assistant Professor of Clinical Medicine Director, Inpatient Cardiovascular Consult Services Ohio State’s Heart and Vascular Center

Echocardiographic Assessment of Mitral Regurgitation

ƒ Objectives

ƒ Review the potential etiologies of mitral regggurgitation ƒ Review the standard echocardiographic assessment of mitral regurgitation and guidelines ƒ Discuss the role of quantification of mitral regurgitation

2

Echo Exam of Mitral Regurgitation

ƒ Quantify the regurgitation ƒ Identify the etiology ƒ Assess the effect on the LV ƒ Identify secondary issues (i.e. pulmonary hypertension ) ƒ Evaluate feasibility of repair

3

1 9/18/2012

Etiology

ƒ 2D ECHO and transesophageal ECHO ƒ 3D ECHO ƒ Jet Direction and Color Doppler

4

Mitral Valve

ƒ Mitral Apparatus ƒ Leaflets ƒ Annulus ƒ Chordae Tendineae ƒ Papillary muscles

Image adapted from Patrick J. Lynch 5

Etiology

Leaflets •Myxomatous (most common) •Rheumatic Disease •Endocarditis •Congenital •HOCM (SAM)

6

2 9/18/2012

Etiology

Annulus •Annular Dilatation •Mitral Annular Calcification

7

Etiology

Chordae •Choral Rupture •Rheumatic fibrosis •Radiation

8

Etiology

Papillary Muscles •Ischemic •Infiltrative (amyloid, sarcoid) •Congenital

9

3 9/18/2012

Etiology – Not so simple

ƒ Rheumatic ƒ Leaflets, chordae ƒ Ischemic MR ƒ Annulus, papillary ƒ Radiation ƒ Leaflets, chordae

10

3D Imaging of the Mitral Valve

ƒ Normal Valve

11

3D Imaging of the Mitral Valve

ƒ Flail Leaflet

12

4 9/18/2012

3D Imaging of the Mitral Valve

ƒ Flail Leaflet

13

3D Imaging of the Mitral Valve

ƒ Prosthetic valve leak

14

Repair versus Replacement

ƒ Repair (Better outcome) ƒ Mitral valve prolapse ƒ Annular dilatation ƒ Some rheumatic cases ƒ Replacement ƒ Severe endocarditis ƒ Severe calcification ƒ Chordal disruption

15

5 9/18/2012

Hemodynamic Effects and Outcomes

ƒ In patients before valve surgery, outcomes are worse with decreasing LVEF and increasing LV end-systolic dimensions

M Enriquez-Srano, et al., Circulation 1994; 90:830 16

Hemodynamic Effects - Indications for surgery

ƒ Evaluate chamber size ƒ LVEF Class I 1. MV surgery is recommended for the ƒ Regional Wall Motion symptomatic patient with acute severe MR. 2. MV Surgery is beneficial for patients with chronic severe MR and NYHA functional call II, III, or IV symptoms in the absence of severe LV dys func tion. (llBlevel B) 3. MV surgery is beneficial for asymptomatic patients with chronic severe MR and mild to moderate LV dysfunction, ejection fraction 0.30 to 0.60, and/or end-systolic dimension greater than or equal to 40mm. (level B) 4. MV repair is recommended over MV replacement in the majority of patients with severe chronic MR who require surgery, and patients should be referred to experienced surgical centers. (level C)

17

Hemodynamic Effects - Indications for surgery

Class IIa ƒ Evaluate rhythm 1. MV repair is reasonable in experienced surgical centers for asymptomatic patients ƒ Atrial Dimensions with preserved LV function in whom the likelihood of successful repair without residual ƒ Estimate right MR is greater than 90%. 2. MV surgery is reasonable for asymptomatic ventricular pressures patients with chronic severe MR, preserved LV function, and new onset of atrial fibrillation. 3. MV surgery is reasonable for asymptomatic patients with chronic severe MR, preserved LV function, and pulmonary hypertension. (pulmonary artery systolic pressure greater than 50 mm Hg at rest or greater than 60 mm Hg with exercise). 4. MV surgery is reasonable for patients with a primary abnormality of the mitral apparatus and NYHA functional class III–IV symptoms and severe LV dysfunction (ejection fraction less than 0.30 and/or end-systolic dimension greater than 55 mm) in whom MV repair is highly likely.

18

6 9/18/2012

Grading Severity

ASE Valve Guidelines,, JASE 2003; 16:777 19

Grading Severity – Jet Appearance

Mild Severe Small, central jet < 4cm2 or <20% Large jet, >10cm2 or >40% of LA or LA Area Area Exceptions: Eccentric / Swirling

20

Doppler ECHO

Mild Severe ƒ Mitral Inflow is A wave ƒ Mitral inflow is E wave dominant dominant (> 1.2 m/s)

A E E

A

21

7 9/18/2012

Doppler ECHO

Mild Severe ƒ Mitral Inflow is A wave ƒ Mitral inflow is E wave dominant dominant (> 1.2 m/s) ƒ Pulmonary Vein Flow ƒ Pulmonary Vein Flow systolic dominance has systolic reversal

Normal Blunting Reversal

22

Doppler ECHO

Mild Severe ƒ Mitral Inflow is A wave ƒ Mitral inflow is E wave dominant dominant (> 1.2 m/s) ƒ Pulmonary Vein Flow ƒ Pulmonary Vein Flow systolic dominance has systolic reversal ƒ Incomplete CW ƒ Dense CW Doppler Doppler sometimes with early peaking

23

Vena Contracta

ƒ Mild <0.3cm and Severe > 0.7cm ƒ Parasternal long axis view ƒ Works for central and eccentric jets ƒ 3D vena contracta might be better

24

8 9/18/2012

Specific Findings

ƒ Severe Mitral Regurgitation ƒ Vena Contracta > 0.7cm with large or eccentric jet ƒ Large area of flow convergence (0.9cm at Nyquist limit or 40cm/s) ƒ Flail Leaflet ƒ Systolic reversal of Pulmonay veins ƒ Mild Mitral Regurgitation ƒ A wave dominant mitral inflow is not severe MR ƒ Vena Contracta < 0.3cm ƒ Small jet ( < 4cm2 or < 20% of LA area)

ASE Valve Guidelines,, JASE 2003; 16:777 25

Quantifying Mitral Regurgitation

Severe ? Mild

26

Quantification of Severity

ƒ Regurgitatant Volume = A - B

B

A

27

9 9/18/2012

Quantification of Mitral Regurgitation

ƒ Regurgitatant Volume

SVMR = SVannulus−SVLVOT

ƒ Regurgitant Fraction SV RF = MR SVMR + SVLVOT

ASE Valve Guidelines,, JASE 2003; 16:777 28

Quantification of Mitral Regurgitation

Mild Moderate Severe

Regurgitant Volume (mL) <30 30-44 45-59 >60

Regurgitant Fraction (%) <30 30-39 40-49 >50

ASE Valve Guidelines,, JASE 2003; 16:777 29

PISA

ƒ Flow Convergence

30

10 9/18/2012

PISA

31

PISA

2πr 2 ×V ROA = a Vmr

32

Quantification of Mitral Regurgitation

ƒ ROA = Volume / VTIMR

ƒ Volume = ROA x VTIMR

Mild Moderate Severe

Regurgitant Volume (mL) <30 30-44 45-59 >60

Regurgitant Fraction (%) <30 30-39 40-49 >50

2 ROA(cm ) <0.20 0.20-0.29 0.30-0.39 >0.40

ASE Valve Guidelines,, JASE 2003; 16:777 33

11 9/18/2012

ROA and Outcomes

ƒ 456 patient with asymptomatic mitral regurgitation

Enriquez-Sarano, NEJM 2005; 352(9): 875 34

Quantification of Mitral Regurgitation

ƒ Difficulty of measurements ƒ Time consuming ƒ Small measurements mean large errors

35

Quantifying Mitral Regurgitation

ƒ 18 academic cardiologists, 16 patients ƒ Judged interobserver agreement

Biner et al., JACC: Cardiovascular Imaging, 2010; 3(3): 237 36

12 9/18/2012

Integrated approach to MR grading

ƒ Look at all of the data and put in clinical context ƒ LV function and etiology ƒ Quantification if needed ƒ Secondary effects ƒ Left atrial size ƒ Mitral inflow ƒ Pulmonary hypertension

37

Integrated approach to MR grading

MR Color Flow imaging •Central Jet Appears to be mild •No PISA seen •Jet Area < 4.0 cm2 Vena Contracta or <20% LA area <0.3cm •CWD not intense >0. 7cm

Jet Direction

Central Eccentric

Severe PISA Pulse Doppler Mild MR RV and ROA RV and ROA MR

From Otto, Textbook of Clinical Echocardiography. Elsevier Inc.2004 38

13 NOTES—

9/18/2012

Timing of Mitral Valve Surgery in Asyypmptomatic Patient

Blase Carabello, MD

52 Y/O WOMAN

• RUN 3 MILES/DAY

• BP 110/70

• 3/6 HOLOSYSTOLIC MURMUR

ECHO

• EDD 60 mm

• ESD 38 mm

• EF 0.65

• BILEAFLET PROLAPSE

1 9/18/2012

• SEVERE MR

• ERO 0.42 cm2

ONE STRATEGY FOR MR IS WATCHFUL WAITING

WAITING FOR WHAT?

• SYMPTOMS

• LV DYSFUNCTION

• PULM HTN

2 9/18/2012

TRIBOUILLOY etal, CIRC 99:400,1999

ENRIQUEZ‐SARANO etal CIRC, 90:830, 1994

3 9/18/2012

ROSENHEK et al

KANG et al

• 447 Pts, SEVERE ASYMPTOMATIC MR

• 161 GOT EARLY SURGERY 286, WATCHFUL WAITING

4 9/18/2012

HOW TO RESOLVE WATCHFUL WAITING vs EARLY SURGERY

• NEITHER IS AN RCT

• ZERO MORTALITY SURGICAL GROUP

• 6 CHF PATIENTS IN THE CONV’NTL GROUP REFUSED Sx

• ESD 45 vs 40

ROSENHEK et al

WATCHFUL WAITING

• A SOUND STRATEGY

• BUT WATCH OUT

5 9/18/2012

MITRAL REPAIR

25

20

15 MENM % MENM+M 10 WOMENM WOMENM+M 5

0 50 60 70 80 90

AGE

SURGERY 2a (2b)

• NO Sxs; NL LV FUNCTION (EF >.60, • ESD < 40mm) WHEN REPAIR LIKELY (95%)

SARANO et al

6 9/18/2012

GILLINOV et al

FOR SEVERE ORGANIC MR WITH A REPARABLE VALVE

JUST DO IT!!

BOLLING ATS 2010, 90:1904

• AVERAGE PER SURGEON : 41% (0‐100)

• MEDIAN # OF TOTAL MITRAL Ops PER SURGEON: 5 (1‐165)

7 NOTES—

Functional MR : Choosing the Right Surgical Procedure

Steven F Bolling Professor of Cardiac Surgery University of Michigan

FMR : Ventricular Problem!!

Badhwar, Bolling , chapter in: Advances in Heart Failure, 2004

Optimal Medical Therapy of FMR

1.0 : survival is not optimal!

0.8

0.6 ival v

sur 0.4 MR grade No. None 9,405 Mild 2,062 0.2 Moderate 210 Severe 171 0.0 012345 Years Hickey et al: Circulation 78:178:1--51,51, 1988

1 FMR…Not just a “late marker” !

FMR – worsened odds ratio of death Rossi A et al. Heart 2011;97:1675-1680 ©2011 by BMJ Publishing Group Ltd and British Cardiovascular Society

Mitral Repair for FMR in CHF Bolling JTCVS 1995 200 pts Chen Circ 1998 81 pts Bishay Eur JCTS 2000 44 pts Calafiore Ann TS 2000 49 pts BfflBuffolo ABCAr Br Car d 2000 80 p ts Bitran J Card Surg 2001 21 pts Dreyfus JHLT 2000 45 pts Suma JTCVS 2001 44 pts ACORN JTCVS 2006 193 pts 30 day mortality 1 -5- 5 %

“Undersized” Mitral Repair Feasible Low mortality Relief of MR Better Quality of life

2 Mitral Repair and CHF : benefit ?

Why - No mortality benefit ?

FMR : residual / recurrent MR

Progression of 3 or 4+ MR post-undersized annuloplasty (585)

McGee, Gillinov et al, JTCVS, 2004;128:916-24

MVR and CHF Even a good operation, when done badly… will not help a sick patient ! …recurrent FMR is still bad

3 Flexible and/or partial bands don’t provide a durable solution for FMR

Magne et al. Cardiology 2009;112:244-2009;112:244-259259

IMR-FMR ring designs Disproportionate AP dimension reduction

Bothe W, Swanson J, et al., JTCVS 2010

MV repair – 30 day mort 1.6%

Freedom from >1+ MR = 90% !! JTCVS 2006

4 Braun J, et al., Leiden Ann Thorac Surg 2008;85:430 –437

FMR : Ventricular Problem!!

LVEDD < 65 mm ! Braun J, et al., Leiden Ann Thorac Surg 2008;85:430 –437

Randomized FMR trial – JTCVS Fatouch 2009

5 FMR -survival

FMR – exercise MR

Randomized CABG + MVr for mod IMR

Mitral regurg volume -69% - 69% vs 14%

LV end systolic volumes -24% - 24% vs 10%

LV sphericity-18% - 18% vs + 1.7 %

Peak oxygen capacity + 3.0 vs 1.0

Brain natriuretic peptide - 76% vs 59% All p < 0.01 !

Mitral Valve Annuloplastyin Addition to Coronary Artery Bypass Grafting in Moderate Functional Ischemic Mitral Regurgitation Reverses Left Ventricular Remodelling and Restores Left Ventricular Geometry: Chan et al , CIRC March 2012

6 Catheter-Based Mitral Valve Repair MitraClip® System – COAPT Trial

MR Reduction to 1+ Baseline to 12 Months, Surgery achieves lower degree of residual “acceptable” MR

p<0.0001

100 100 1+-2+ 2+ 1+ 2+ 0+ 80 36.1%80

60 60 1+ tients 3+ 1+-2+ 3+ a

40 40 75.6 % 2+ Percent P Percent

20 20 1+-2+ 4+ 3+ 4+ 2+ 3+ 0 4+ 0 Baseline 12 Months Baseline 12 Months (n=124) (n=124) (n=67) (n=67) Device Surgery

p-value compares the distribution of MR grade in device with the distribution of MR grade in control at 12 months (Fishers’ Exact test)

Septal-Lateral Annular Dimension Baseline vs 12 Months, 3.9 – 3.8 !!

End Systole End Diastole 6

5 p=0.0163 p=0.6716 3.9 4 3.8 cm)

( 333.3 333.3 3

2 Dimension

1

0 Baseline 12 Months Baseline 12 Month n=111 n=111 p-value compares baseline to 12 month measurements within device Septal-Lateral Annular Dimension not collected in Control group due to the presence of annuloplasty ring or replacement valve

7 Re‐Inventing a Failed Surgical technique ? The Importance of Annuloplasty

Annuloplasty

NlltNo annuloplasty

• 260 pts • Overall freedom reop 90% (68% without ring)

Alfieri O, et al. JTCVS 2001;122:674-81

Mitraclip Functional MR Results “high risk” EF - 55 %

8% mort @ 30 d 25% mort @ 1 yr

DMR / FMR No controls Not random Left 2-4+ MR !

50 pts > 3+ MR CRT failed --2121 Age 70; euroSCORE 34; LVEDD 70mm; LVEDV 252 ml; LVEF 19%

Franzen et al Eur J Heart Fail 2011; 13:569-76

8 Mitral Clip in FMR – 17 % mortality !

Franzen O et al. Eur J Heart Fail 2011;13:569-576

Optimal treatment for FMR

GOOD SURGERY ! Careful patient selection Beware the big LV and the bad RV!

Repair - use complete rigid ring Replacement - selective RCT !

Optimal treatment of FMR Find MR ! Fix MR! OMT, CRT, Surgery, Clip

9 NOTES—

NOTES—

Valvular Heart Disease Cases Thomas Ryan, MD

NOTES—