Heart failure and sudden cardiac death

Heart Failure and Sudden Cardiac Death

Raja Selvaraj, JIPMER

What is sudden cardiac death?

Sudden Cardiac Death

Unexpected deaths from cardiovascular causes
Preceded by a witnessed collapse
Occur within 1 hour of an acute change in clinical condition
Or < 24 hours after the person was known to be in usual state of health

SCD - Cause

ICM
- Ventricular fibrillation
- Asystole / PEA (usually late after VF)
- Recurrent MI (40 to 50%, early post MI)
- Mechanical causes (very early post MI)
NICM
- Severe bradycardia / Asystole
- Ventricular arrhythmias

SCD is a mode of death. Causes vary Cause of death varies depending on duration after MI (non-arrhythmic more early, arrhythmic more late) and pathology - VF more in ICM, less in NICM

Why is it a problem in patients with heart failure?

Survival in patients with heart failure

Lane RE, Cowie MR, Chow AWC. Prediction and prevention of sudden cardiac death in heart failure. Heart 2005;91:674-680.

More than 50% of patients with chf are dead at 4 years

SCD in heart failure

CHF increases risk of SCD by 6-9 times
Primarly in HFrEF
About 3% per year now (20% per year previously)

SCD HeFT

Bardy et a. Amiodarone or an Implantable Cardioverter–Defibrillator for Congestive Heart Failure. N Engl J Med 2005;352:225-37.

Mortality more in ischemics than non. About 40% in placebo grp at 5 yrs

Mode of death and severity of symptoms

Sudden death as proportion of all deaths is higher for patients with less severe heart failure

What can be done to identify and reduce risk

Identification of high risk patients

LVEF is the one consistent marker
Others - varying results across studies
- NSVT
- TWA
- HRV
- HRT
- EP study
- MRI

Non-pharmacologic

Exercise
Revascularization

Drugs

Beta blockers

Consistently improves survival in patients with heart failure
Around 50% reduction in SCD
Best studied - Carvedilol, Bisoprolol and Metoprolol

Chatterjee Saurav et al. Benefits of β blockers in patients with heart failure and reduced ejection fraction: network meta-analysis BMJ 2013; 346 :f55

Consistent effect across trials No specific effect favoring one drug over another

ACEI - SOLVD trial

SOLVD investigators. Effect of Enalapril on Survival in Patients with Reduced Left Ventricular Ejection Fractions and Congestive Heart Failure. N Engl J Med 1991; 325:293-302

ACEI

Reduce total mortality
Reduce arrhythmic mortality ?

Naccarella F et al. Do ACE inhibitors or angiotensin II antagonists reduce total mortality and arrhythmic mortality? A critical review of controlled clinical trials. Curr Opin Cardiol. 2002 Jan;17(1):6-18

ARB as compared to ACEI

No difference in mortality with ARB as compared to ACEI (1)

Pitt et al. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial–the Losartan Heart Failure Survival Study ELITE II. Lancet. 2000 May 6;355(9215):1582-7.

ELITE showed less mortality with losartan over captopril in elderly, but was secondary endpoint ELITE II showed no difference

Aldosterone antagonist

Spironolactone - 30% reduction in mortality (1)
Eplerenone - 15% reduction in overall mortality and 21% reduction in SCD (2)
Especially important in early mortality reduction after MI when ICD has no benefit

Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized aldactone evaluation study investigators. N Engl J Med1999;341:709–17
Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med2003;348:1309–21.

Statins

Lower rate of arrhythmias - MADIT II post hoc analysis (1)
No SCD reduction in prospective trials (2,3)

Vyas AK et al. MADIT-II Research Group. Reduction in ventricular tachyarrhythmias with statins in the multicenter automatic defibrillator implantation trial (MADIT)-II. J Am Coll Cardiol 2006;47:769–73
Kjekshus et al, CORONA Group. Rosuvastatin in older patients with systolic heart failure. N Engl J Med 2007;357:2248–61
GISSI-HF Investigators. Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet 2008;372:1231–9

Optimal medical management - Huge impact

Review of multiple studies shows steady decline in sudden death incidence with time. As death rates come down, studies need a larger population to show benefit. GISSI and CORONA studied Rosuvastatin

Li Shen et al. Declining Risk of Sudden Death in Heart Failure. N Engl J Med 2017; 377:41-51

Implantable devices

Implantable Cardioverter Defibrillator (ICD)

ICDs are effective in identification of VF and immediate defibrillation shock

ICD - 20 to 30% reduction in deaths

Bardy et a. Amiodarone or an Implantable Cardioverter–Defibrillator for Congestive Heart Failure. N Engl J Med 2005;352:225-37.

CRT

Reduction of all cause mortality compared to optimal medical treatment (24%)

(COMPANION) - Bristow MR, Saxon LA, Boehmer J, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med2004;350:2140–50

Role of Sacubitril-Valsartan

PARADIGM-HF

Neprlisyn inhibitor with ARB
About 4200 patients in each group
27 months follow up
Significant reduction in composite endpoint (death + hospitalization for heart failure
NNT 32 to prevent one cardiovascular death

prev evaluation of neprilysin inhibitor with ACEI severe angioedema

McMurray et al. Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure. N Engl J Med 2014; 371:993-1004

Mode of death in PARADIGM-HF

Cardiovascular deaths
- Sudden - 44.8%
- Heart failure related - 26.5%
Less cardiovascular deaths with ARNI
Benefit seen in both sudden and heart failure deaths
Reduction in sudden death even in patients with ICD

Desai et al. Effect of the angiotensin-receptor-neprilysin inhibitor LCZ696 compared with enalapril on mode of death in heart failure patients. European Heart Journal, Volume 36, Issue 30, 7 August 2015, Pages 1990–1997

Equal effect in reducing hospitalization, non-sudden and sudden deaths

ARNI and survival in CHF patients

Remarkable in setting of drug therapy already being taken

Summary

All patients with heart failure should receive
- Beta blockers
- ACEI
- Aldosterone antagonists
Patients at high risk of SCD should receive
- ICD
Patients with wide QRS may require
- CRT

Should ARNI replace ACEI

Existing evidence is compelling
Guidelines suggests replacing ACEI (US) or using when patients still symptomatic (EUR)
Single trial, no long term follow up
When changing
- High dose ACEI tolerated?
- 36 hour washout
- Cost benefit ratio

Dilemma is should it replace ACEI Some concerns about increased Alzheimers in long term More hypotension Need 36 hour washout of ACEI to avoid angioedema

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Heart Failure and Sudden Cardiac Death Raja Selvaraj, JIPMER