Sudden Cardiac Death in Heart Failure: What Do We Need to Know in 2018 ?

Sudden Cardiac Death in Heart Failure: What do we need to know in 2018 ?

Juan M. Aranda, Jr. MD FACC Professor of Medicine Director of Heart Failure and Cardiac Transplantation University of Florida

Disclosures

Consultant for Zoll LifeVest.

1 Sudden Cardiac Death Statistics

• One of the most common causes of death in developed countries:

Incidence Survival (cases/year)

Worldwide 3,000,000 1 <1% U.S. 450,000 2 5% W. Europe 400,000 3 <5%

• High recurrence rate

1 Myerberg RJ, Catellanos A. Cardiac Arrest and Sudden Cardiac Death. In: Braunwald E, ed. Heart Disease: A Textbook of Cardiovascular Medicine . 5 th Ed. New York: WB Saunders. 1997: 742-779. 2 Circulation. 2001; 104: 2158-2163. 3 Vreede-Swagemakers JJ et al. J Am Coll Cardiol 1997; 30: 1500-1505.

Leading cause of Death in the US

Septicemia SCA is a leading cause of Nephritis death in the U.S., second to Alzheimer’s Disease all cancers combined . Influenza/Pneumonia

Diabetes

Accidents/Injuries

Chronic Lower Respiratory Diseases

Cerebrovascular Disease Other Cardiac Causes Sudden Cardiac Arrest (SCA) All Cancers

0% 5% 10% 15% 20% 25%

National Vital Statistics Report. 2001;49;11. MMWR. 2002;51:123-126.

2 Disease States Associated with SCD

1) Atherosclerotic CAD 2) Dilated Cardiomyophay: 10% of SCD cases in adults. 3) Hypertrophic Cardiomyopathy: 2/1,000 young adults. 48% of SCD in athletes ≤ 35yo. 4) Valvular Heart Disease 5) Congenital Heart Disease: Four conditions associated with increased post-op risk of SCD (Tetrology of Fallot, transposition of the great vessels, Aortic Stenosis, pulmonary vascular obstruction). 6) Wolff-Parkinson-White Syndrome: Risk of SCD 1/1000 Mechanism: Afib with 1:1 conduction down accessory pathway leading to VF. 7) Arrhythmogenic Right Ventricular dysplasia. 8) Congenital long QT syndromes/Brugada/CPVT

Background for the current role of ICDs in cardiac patient management

• Sudden cardiac death (SCD) accounts for ≈400,000 American deaths/year (0.1% in the general population). Single most common cause of death in the USA. • Roughly two-thirds of Sudden Cardiac Arrest (SCA) deaths occur out-of-hospital. • The survival rate in the U.S. for out-of-hospital cardiac arrest: 9.5%. • Survivors who ultimately leave the hospital without significant neurologic deficit: 3% • In-hospital SCA survival rate: 23.9%

3 © The vast majority of the 400,000 SCA deaths are due to VT or VF.

© Sustained MMVT associated with myocardial scar/old MI is the most common clinical VT. – Mechanism: scar related reentry. – Multiple triggers: neuroendocrine, drugs, electrolyte imbalances, sympathetic/parasympathetic tone.

4 SCA Relation to LVEF

8 7.5% EF is an 7 Important Risk 6 Stratifier 5.1% 5 4 3 2.8%

% SCA Victims % SCA 2 1.4 % 1 0 0-30% 31-40% 41-50% >50% LVEF

Gorgels PMA. European Heart Journal . 2003;24:1204-1209.

Prophylactic Implantable Cardioverter-Defibrillator Therapy in Patients With Left Ventricular Systolic Dysfunction: A Pooled Analysis of 10 Primary Prevention Trials

Death from all causes in all available primary prevention trials.

Nanthakumar K, et al. J Am Col Cardiol 2004;44:2166-2172.

5 Clinical Course of MI and Heart Failure

Circulation 2012, 125:1928-1952 5

Sudden Death in Heart Failure

6 Key Randomized Post-MI Antiarrhythmic Drug Trials for Prevention of SCD

Post-MI trials have shown limited clinical utility for antiarrhythmic drug therapy for either primary or secondary prevention of arrhythmic death in patients with baseline moderate to severe LV dysfunction post-MI EF < 40%.

CAST 1 Flecainide/encained/moricizine Harm CAST 2 Moricizine Harm SWORD d-Sotalol Harm Julian d,l-Solalol Neutral EMIAT Amiodarone Neutral CAMIAT Amiodarone (no EF criteria) Neutral DIAMOND MI Dofetilide Neutral ALIVE Azimilide Neutral b-blockers Propranolol,metoprolol, others. Benefit

Guidelines for Waiting Period for ICD LV Dysfunction Primary Prevention

2017 ACCF/AHA/HRS 2015 ESC Guidelines Post MI EF <35% Greater 40 days EF <35% 6-12 weeks Class I level of evidence A Class I Level of evidence C Post CAD revascularization Greater 3 months Greater 3 months Nonischemic Greater 3-6 months Greater 3 months cardiomyopathy CMS 9 months EF <35% Class II-III Survival >1 year

7 Medical Therapy Optimization Required Prior To Managing Long-Term Arrhythmic Risk

‹ Medical optimization and stabilization can take 3 months or more. ° Beta blocker doses effective in HF are generally achieved in 8 to 12 weeks and do not impart any mortality benefit until at least 3 months

Merit-HF 1 COPERNICUS 2 CIBIS-II 3 100 100 Placebo 15 90 Carvedilol Bisoprolol

80 80 10

70 Survival % % Survival % 5 Metoprolol Placebo Placebo CR/XL 60 60

0 3 6 9 12 15 18 0 3 6 9 12 15 18 21 0 200 400 600 800 Cardiovascular Mortality (%) Mortality Cardiovascular Months Months Days

1 Merit-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF) Lancet 1999;353:2001-7. 2 Packer M, et al. Effect of Carvedilol on survival in severe chronic heart failure. NEJM 2001;344:1651-8. 3 CIBIS-II Investigators. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II). Lancet 1999;353:9-13.

Understanding the Risk LV Systolic Dysfunction and SCD Risk ‹ SCD accounted for ~50% (35-64%) of total mortality ° EF was the single most important risk factor for SCD

8 Medical Therapy Optimization Required HF Patient Improvement

‹ Time course of LVEF improvement A HF patient’s cardiac with β-blocker use 3 function can improve from the benefits of optimized medical therapy ° IMAC-2 study showed a mean LVEF increase of 17% in newly diagnosed cardiomyopathy patients 1 ° REFINE Study average relative improvement in EF was 18% at 8-10 weeks 2

1 McNamara D et al.. Clinical and Demographic Predictors of Outcomes in Recent Onset Dilated Cardiomyopathy. JACC 2011 ;58:1112-8. 2 Exner D et al. Noninvasive Risk Assessment Early After a Myocardial Infarction. JACC 2007;50:2275-84. Hall S, et al. Time Course of Improvement in Left Ventricular Function, Mass and Geometry in Patients with 3 Congestive Heart Failure Treated With Beta-Adrenergic Blockade. JACC 1995;25:1154-61

Medical Therapy Optimization Opportunity for SCD Risk Protection

‹ Rates of medication usage in patients discharged from Patients at Target Dose (%) from hospital with HF have OPTIMIZE-HF (n=48,612) 2 improved but continue to not meet guidelines 100% ° Prescription rates are 70%, 60% 90% and 35% for ACE inhibitors, β- 80% blockers and aldosterone 70% 1 antagonists, respectively. 60% 50% ‹ When medications used in HF are 40% prescribed, they do not achieve doses shown to improve 30% mortality 2 20% ° The percentage of patients that achieve 10% optimal doses of heart failure medications is low. 0% Carvedilol > 50 mg Metoprolol XL > 200 mg

1 Adams K., et al., Characteristics and outcomes of patients hospitalized for heart failure in the United States: rationale, design, and preliminary observations from the first 100,000 cases in the ADHERE registry. American Heart Journal. 2005;149:209–16. 2 Fonarow, G. et al. Dosing of beta-blocker therapy before, during, and after hospitalization for heart failure (OPTIMIZE-HF) American Journal of Cardiology 2008;102:1524–9.

9 Preventing SCD with Medications

Al-Khatib SM, et al. Heart Rhythm 2017, epub ahead of print.

10 Non – Evidence-Based ICD Implants (n=21,145)

• MI within 40 days before ICD implantation (23%)

• CABG surgery within 3 months before ICD implantation (3%)

• NYHA class IV symptoms (12%)

• Newly diagnosed heart failure at the time of ICD implantation (62%)

Early AICD Implant in Heart Failure

CAD/MI NONISCHEMIC CARDIOMYOPATHY

DINAMIT 2004 (N=674) MI (6 to 40 days), EF <35%, HR >80 bpm, No NSVT, 72 Ant MI, 2/3 revascularization, 32-month f/u, No difference in total mortality

IRIS (Immediate Risk Stratification Improves Survival) 2009 N=898 MI (5 to 31 days), EF <40%, HR >90bpm or NSVT 30-month f/u No difference in mortality

11 DINAMIT

Estimates of the cumulative risk of death from arrhythmia (A) and nonarrhythmic (B) causes.

Hohnloser SH, et al. N Engl J Med 2004;351:2481-2488.

IRIS

Cumulative Risk of Sudden Cardiac Death Cumulative Risk of Nonsudden Cardiac Death

Steinbeck G, et al. New Engl J Med 2009;361:1427-1436.

12 Valiant Trial High Early Risk for SCD

Post-MI patients with heart failure are at 4-6 times greater risk of SCA in the first 30 days post-MI 1

‹83% of SCA occurred after hospital discharge.

‹74% of those resuscitated in the first 30 days were alive at 1 year

1 Adabag AS, et al. Sudden Death After Myocardial Infarction. JAMA 2008; 300: 2022-2029.

13 Predictors of Sudden Death: VALIANT

1. Higher baseline heart rate (HR 1.2 per 10 bpm)

2. Impaired baseline creatinine clearance (HR 0.82 per 10 ml/min)

3. EF < 30%

4. QRS duration

Piccini, et al. European Heart J 2010;31:211-222.

Wealth of Evidence Supports Post-PCI Risk

The CADILLAC Cleveland Clinic CathPCI-NCDR 3 (n=343,466) Trial 1 (n=2082) Registry 2 32% STEMI

11% (60% SCD) 13% 12% w/o STEMI 90 day mortality day 90

Post-PCI, AMI EF ≤35% EF <30%, Post-PCI, Patient Post-PCI, AMI Age >65 yo

LVEF, Age Mortality Renal insufficiency LVEF, Age Predictors Multi-vessel LVEF, Age Renal insufficiency Killip Class II/III Diabetes Mellitus, Multi-vessel Anemia Female gender TIMI flow

1 Halkin, A et al. Prediction of Mortality After Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction: CADILLAC Risk Score. JACC 2005;45:1397-1405. 2 Zishiri ET, et al. Early Risk of Mortality after Coronary Artery Revascularization in Patients with Left Ventricular Dysfunction and Potential Role of the Wearable Cardioverter Defibrillator. Circulation: Arrhythmia and Electrophysiology; 2013;6: 117-128 3 Weintraub et al. Prediction of Long-Term Mortality After Percutaneous Coronary Intervention in Older Adults: Results From the National Cardiovascular Data Registry. Circulation 2012;125:1501-1510.

14 Early AICD Implant in Heart Failure

CAD/MI NONISCHEMIC CARDIOMYOPATHY

DINAMIT 2004 (N=674) The Cardiomyopathy Trial ( CAT ) MI (6 to 40 days), EF <35%, 2002 (N=104) HR >80 bpm, No NSVT, HF <9 months, 72 Ant MT, 2/3 revascularization, No difference in all-cause 32-month f/u, mortality, Trial stopped at one No difference in total mortality year, No NSVT

IRIS (Immediate Risk Stratification Improves Survival) 2009 N=898 MI (5 to 31 days), EF <40%, HR >90bpm or NSVT 30-month f/u No difference in mortality

Early AICD Implant in Heart Failure

CAD/MI NONISCHEMIC CARDIOMYOPATHY

IRIS (Immediate Risk DEFINITE (n=458) Stratification Improves Survival) HF duration 2.8 years 2009 N=898 EF 28 %, NSVT or >10 pvc’s per MI (5 to 31 days), EF <40%, hour on holter HR >90bpm or NSVT Non significant reduction death 30-month f/u from any cause p=0.08 No difference in mortality

15 Death from Arrhythmia Among Patients who Received Standard Therapy and Patients who Received an ICD

Kadish A, et al. N Engl J Med 2004;350:2151-2158.

Death From Any Cause by Duration of HF, (Inclusion Criteria: NSVT on telemetry or greater than 10 PVC’s/Hr on holter monitoring

Kadish A, et al. J Am Coll Cardiol 2006;47:2477-2482.

16 Gulati A, et al. JAMA 2013; 309:896-908.

17 6.2 Nonischemic Cardiomyopathy

Al-Khatib SM, et al. Circulation 2017; epub ahead of print.

Predictors of Sudden Death New onset Cardiomyopathy Post MI

1. Higher baseline heart rate

2. Impaired baseline creatinine clearance

3. EF< 30 percent

4. QRS duration

5. Elevated BUN

18 Risk Stratification for Primary Implantation of a Cardioverter-Defibrillator in Patients with Ischemic Left Ventricular Dysfunction

Goldenberg I, et al. J Am Coll Cardiol 2008;51:288-296.

High Risk Features for Sudden Death in New Onset Nonischemic Cardiomyopathy

• Greater than 10 PVC/hr on Holter • Confirmed sarcoid heart disease, giant cell myocarditis, noncompaction cardiomyopathy • LBBB, greater QRS duration • ( increased LVEDD, ) • Myocardial fibrosis

19 Clinical Course of MI and Heart Failure

Circulation 2012, 125:1928-1952 5

LifeVest System

Self-Gelling ECG Electrodes Defibrillation • Dry & non- Electrodes adhesive • 4 electrodes providing 2 Response channels of Buttons monitoring Monitor • 150 joules biphasic • Stores ECG, daily use, etc.

20 Alarm Sequence

1. Arrhythmia detected, activating vibration alert (continues throughout sequence). 2. Siren alerts begin (continues throughout sequence). 3. Siren alerts get louder. 4. Patient audible prompt: “Electrical shock possible. ” 5. Gel release. 6. Bystander audible prompt: "Do not touch patient.” 7. Treatment shock.

21 WEARIT-II Registry {MADIT-RIT -3 app shock per 100 pt years}

Kutyifa V, et al. Circulation 2015 [epub ahead of print 8/27/15].

WEARIT-II: Arrhythmia Events

Kutyifa et al. Circulation. 2015;132:1613-1619.

22 LifeVest by the Numbers

¢ 98% first shock success rate ¢ 92% shocked event survival (conscious ER arrival or stayed at home) ¢ Average duration of use is 2 to 3 months ¢ Median daily use is 94% (22.6 hours/day)

WEARIT-II Registry End of Use EF Improvement and ICD Implantation Rates by Disease Etiology

Kutyifa V, et al. Circulation 2015 [epub ahead of print 8/27/15].

23 WEARIT-II Registry Rate of First Arrhythmic Events in WCD Patients by Disease Etiology

P=0.02

Kutyifa V, et al. Circulation 2015 [epub ahead of print 8/27/15].

Wearable Cardioverter-Defibrillator

Al-Khatib SM, et al. Heart Rhythm 2017, epub ahead of print.

24 Secondary and Primary Prevention of SCD in Patients With NICM

1 2 3

Al-Khatib SM, et al. Circulation 2017; epub ahead of print.

New Onset Cardiomyopathy Risk Stratification for SCD beyond an ejection fraction <35%

High baseline HR Impaired baseline crea QRS duration Nonsustained VT BNP

Post MI <40 days CAD revascularization <3 months

Nonischemic Helpful cardiomyopathy Unhelpful <3 months EP Testing PVC frequency >10 PVC/hr Sarcoid, myocarditis noncompact HRV QRS duration BRS ↑ LVEDD HRT Myocardial fibrosis

25 Case Study: Non-Ischemic Cardiomyopathy (UF 1/20/16)

‹ 38 y/o year old with new onset HF (D/C Toprol 150mg, ACE and lifevest) ‹ 1. Location of Event: The patient was on an ocean cruise NYHA class 2 , in Honduras 2 months out from initial hospitalization . ‹ 2. Patient’s Neurological Status: The patient was sleeping. He had a great day ‹ 3. Event Witness and Interactions: Patient’s wife sees husband begin to gasp. . ‹ 4. shock with subsequent shock the following day. Does not tell crusie ship

Case Study: Non-Ischemic Cardiomyopathy VT/VF Event 3/23 7:44am

26 All-cause mortality by VT/VF event on the WCD

Kutyifa V, et al. One-Year Follow-Up of the Prospective Registry of Patients Using the Wearable Defibrillator (WEARIT-II Registry), presented as Late-Breaking Clinical Trial at CARDIOSTIM/EUROPACE 2016, June 10, 2016.

Trends Features Overview

90 45 84 bpm 30

0 1 2 3

• Avg daily • Total steps • Overall body • Clinicians can select heart rate per day position (movement, up to 12 questions upright, reclined, lying) • Avg heart rate • Steps in 5 for patients to in 5 min min • Body angle while answer on a daily or increments for increments reclined or lying weekly basis each day for each day • Body position while reclined or lying (prone, supine, left, right)

27 Case Study: Non-Ischemic Cardiomyopathy

Clinical Course of Heart Failure

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