Primary Prevention of SCD in Heart Failure : Should we look beyond LV EF ?

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Raja Selvaraj MD DNB FCE (Toronto)
Cardiac Electrophysiologist
Professor of Cardiology
JIPMER

Introduction

Heart failure is not a homogenous entity

  • Ischemic cardiomyopathy (old MI)
  • Non ischemic cardiomyopathy (Idiopathic DCMP)
  • Others
    • Hypertrophic cardiomyopathy
    • Sarcoidosis
    • Arrhythmogenic RV Cardiomyopathy
    • HFPEF

Concepts in Risk stratification

  • To identify patients who will benefit from ICD implantation
  • SCD risk is continuous
  • Competing risk (risk of non sudden death)
  • Find patients with high risk of SCD and low competing risk

Ischemic cardiomyopathy (old MI with LV dysfunction)

Current guidelines - class I indication

  • LVEF 40% or less, NSVT, inducible sustained VT
  • LVEF 35% or less, 40 d post MI, 90 d post revasc, NYHA class II or III, despite GDMT
  • LVEF 30% or less, 40 d post MI, 90 d post revasc, NYHA class I, despite GDMT

Al-Khatib SM et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation. 2018 Sep 25;138(13):e272-e391. doi: 10.1161/CIR.0000000000000549.

MUSTT

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Buxton et al. Electrophysiologic Testing to Identify Patients with Coronary Artery Disease Who Are at Risk for Sudden Death. N Engl J Med 2000; 342:1937-1945

SCD-HeFT - Ischemic

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Bardy GH et al. Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) Investigators. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med. 2005 Jan 20;352(3):225-37. doi: 10.1056/NEJMoa043399.

MADIT II

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Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med. 2002; 346: 877–88

Summary

  • EF strong and best predictor. Base for everything else
  • However primarily EF based indication has low sensitivity (NNT - MADIT II 18, SCD-HeFT 13)
  • NYHA class, NSVT, Inducible VT
  • All others not stood test of time

Prospective study - Previous MI with EF < 40%

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Selvaraj RJ et al. Sudden death and its predictors in myocardial infarction survivors in an Indian population. Indian Pacing Electrophysiol J. 2021 Mar-Apr;21(2):82-87. doi: 10.1016/j.ipej.2020.12.002. Epub 2020 Dec 19. PMID: 33352202; PMCID: PMC7952752.

Non Ischemic Cardiomyopathy (Idiopathic DCMP)

Current guidelines

  • Class I - LVEF 35% or less, class II or III despite GDMT for at least 3 months

Evidence in NICM

  • DEFINITE - Reduces SCD, trend towards reduction in overall mortality
  • SCD-HeFT - 27% to 21% mortality at 5 years in NICM group
  • DANISH - > 1000 patients, CRT in 58% of the patients, less SCD, no change in mortality

SCD-HeFT - Non-Ischemic

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Bardy GH et al. Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) Investigators. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med. 2005 Jan 20;352(3):225-37. doi: 10.1056/NEJMoa043399.

Danish trial

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Køber L et al. DANISH Investigators. Defibrillator Implantation in Patients with Nonischemic Systolic Heart Failure. N Engl J Med. 2016 Sep 29;375(13):1221-30. doi: 10.1056/NEJMoa1608029. Epub 2016 Aug 27. PMID: 27571011.

NICM - A different kettle of fish

  • Heterogenous population, overall lower risk of sudden death
  • Risk of sudden death has reduced with time
  • Benefit definitely lesser compared to ICMP (is there a benefit at all ?)
  • CRT eligible vs CRT ineligible

Multiparametric assessment

  • History - Family history of SCD, unexplained syncope
  • ECG - fQRS, anterolateral T inversion, Tp-Te
  • Holter - PVCs, NSVT
  • Echo - LVEF, RV function, Global longitudinal strain

Cardiac MRI

  • LGE seen in about 30-45%
  • These patients at higher risk of arrhythmias
  • Distribution and extent of LGE may carry prognostic information
  • Interstitial fibrosis - may not show LGE, but associated with arrhythmias

Meta analysis

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Andrea Di Marco et al. Late Gadolinium Enhancement and the Risk for Ventricular Arrhythmias or Sudden Death in Dilated Cardiomyopathy: Systematic Review and Meta-Analysis. JACC: Heart Failure Volume 5, Issue 1, January 2017, Pages 28-38

Genetic testing

  • Specific mutations associated with higher risk
  • Risk may be high despite absence of significant LV dysfunction
  • LMNA mutations, truncating FLNC variants

Lamin A/C mutations

  • LVEF < 45%
  • Male sex
  • NSVT

Van Rijsingen et al. Risk Factors for Malignant Ventricular Arrhythmias in Lamin A/C Mutation Carriers: A European Cohort Study. Journal of the American College of Cardiology Volume 59, Issue 5, 31 January 2012, Pages 493-500

Lamin A/C mutations

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LV reverse remodeling

  • Occurs in 40%, associated with better prognosis
  • Those unlikely to remodel may be chosen for early ICD implant
  • Larger ventricle, longer QRS duration, intolerance to beta blockers may be predictors

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Stolfo et al. Arrhythmic Risk Stratification in Patients With Idiopathic Dilated Cardiomyopathy. AJC 2018;121:1601-1609

An integrated approach

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Cannata et al. Arrhythmic risk stratification in non-ischaemic dilated cardiomyopathy beyond ejection fraction. Heart 2020;0:1–9. 10.1136/heartjnl-2019-315942

Special populations

Listed for transplant

  • Not eligible by standard guidelines
  • However, they become eligible if they are listed for transplant
  • Improves survival
  • Wearable defibrillator is an option

Heart failure with preserved ejection fraction (HFpEF)

  • Lower risk of SCD compared to HFrEF
  • Still comprises nearly a quarter of all deaths
  • No consistent risk factors identified

Others

  • ECG / AI
  • Biomarkers
  • Genetic studies

Summary

  • SCD is a definite issue in patients with heart failure
  • ICD is an effective treatment but carries significant cost considerations and morbidity
  • Need understanding SCD risks and competing risks to utlise ICD efficiently
  • EF still remains the basis for risk assessment
  • Additional parameters may help improve risk stratification, area of ongoing study
  • In general ICDs for ICMP, CRT for NICMP
  • Don't forget optimal medical management