Sudden Cardiac Death - In search of an electrical signature

Raja Selvaraj

Introduction

Sudden cardiac death

SCD - what is it and why is it important

  • Unexpected, natural death from cardiac causes (< 24 h)
  • Significant contributor to all deaths in the West
  • About 10% of all deaths in the community

Rao BH, Sastry BK, Chugh SS, Kalavakolanu S, et al. Contribution of sudden cardiac death to total mortality in India - a population based study. Int J Cardiol. 2012; 154:163-7

SCD - Mechanism

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Causes

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Myocardial infarction

Myocardial infarction (Heart attack)

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Invisible problem - 100 patients after MI

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At one year - Angina -> PCI

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Angina -> CABG

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Worsen -> Death

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Follow up - Medically managed

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Sudden death

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AICD - the revolution

The history

Drugs for prevention of sudden death

CAST

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EMIAT

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Michel Mirowski

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History of development

  • Young Polish Cardiologist
  • Trained in France
  • Joined Professor Harry Heller in Israel in 1963

Professor Harry Heller

  • Recurrent ventricular arrhythmias
  • DC cardioversion
  • Dies suddenly (1966)

Idea for ICD

  • Early defibrillation can be life saving
  • Implanted device that can defibrillate ?
  • Scepticism
  • Moved to USA

Evolution

Early results - 1969

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First report - 1970s

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Technical improvements

  • Miniaturization
  • Refinements in shock waveform
  • Smaller, transvenous electrodes
  • Implantation today a simple procedure

Evolution

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ICD today

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Trials, patient groups

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Anthony Van Loo

Subcutaneous ICD

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The End ?

Or, is it just the beginning?

Identifying patients at high risk

Lifesavers, but carry risks too

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EF and sudden death

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Solomon et al. Circulation 2005;112:3738-3744

Why not sufficient?

  • Cost of device implantation
  • Only 15-20% of patients with CAD will have sudden death
  • LV ejection fraction is a marker of risk
  • But only one component of a probably multifactorial risk profile
  • NNT about 15 over 3 years with EF alone
  • Many deaths in patients with EF > 30%

ECG

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ECG signature

  • Electrocardiogram is a representation of the electrical activity of the heart
  • Encodes the rhythm, depolarization, repolarization
  • Should carry information regarding risk of sudden death

Premature Ventricular beats

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  • Beats that originate in the ventricles

More abnormal beats - worse the outcome

Heart rate variability (HRV)

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HRV - Outcomes

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Kleiger RE, Miller JP, Bigger JT Jr, Moss AJ. Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol. 1987 Feb 1;59(4):256-62.

Signal averaged ECG (SAECG)

  • 200 to 300 beats averaged and amplified
  • High pass filter
  • Low amplitude, high frequency signal in last part of filtered QRS

SAECG

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SAECG

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SAECG

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  • High negative predictive value

Kuchar DL, Thorburn CW, Sammel NL. Late potentials detected after myocardial infarction: natural history and prognostic significance. Circulation. 1986 Dec;74(6):1280-9

QT dispersion

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T wave alternans

  • Change in morphology of T waves on alternate beats
  • Heralds onset of dangerous arrhythmias

TWA - Macroscopic

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Microscopic T wave alternans

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Chauhan VS, Selvaraj RJ. Utility of microvolt T-wave alternans to predict sudden cardiac death in patients with cardiomyopathy. Curr Opin Cardiol. 2007 Jan;22(1):25-32

Microvolt T wave alternans

  • Can be detected in some patients
  • Elevated heart rates (exercise / pacing)
  • Associated with risk of sudden death

Genesis of alternans

  • Alternans of cellular action potential duration and calcium levels
  • Alternans can be detected locally in heart muscle
  • Heterogeneity of alternans in the heart at different regions

Selvaraj RJ, Picton P, Nanthakumar K, Mak S, Chauhan VS. Endocardial and epicardial repolarization alternans in human cardiomyopathy: evidence for spatiotemporal heterogeneity and correlation with body surface T-wave alternans. J Am Coll Cardiol. 2007 Jan 23;49(3):338-46

Calcium and pressure alternans

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Selvaraj RJ, Suszko A, Subramanian A, Mak S, Wainstein R, Chauhan VS. Microscopic systolic pressure alternans in human cardiomyopathy: noninvasive evaluation of a novel risk marker and correlation with microvolt T-wave alternans. Heart Rhythm. 2011 Feb;8(2):236-43.

APD restitution

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Dynamic instability

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Restitution slopes

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Selvaraj RJ, Picton P, Nanthakumar K, Chauhan VS. Steeper restitution slopes across right ventricular endocardium in patients with cardiomyopathy at high risk of ventricular arrhythmias. Am J Physiol Heart Circ Physiol. 2007 Mar;292(3):H1262-8

TWA in clinical practice

  • Commercial systems
  • Promising initial results
  • Not consistent across studies

Better measurement methods? - Noise / other methods

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  1. Selvaraj RJ, Chauhan VS. Effect of noise on T-wave alternans measurement in ambulatory ECGs using modified moving average versus spectral method. Pacing Clin Electrophysiol. 2009 May;32(5):632-41
  2. Ghoraani B, Krishnan S, Selvaraj RJ, Chauhan VS. Adaptive time-frequency matrix features for T wave alternans analysis. Conf Proc IEEE Eng Med Biol Soc.2009;2009:39-42
  3. Ghoraani B, Krishnan S, Selvaraj RJ, Chauhan VS. T wave alternans evaluation using adaptive time-frequency signal analysis and non-negative matrix factorization. Med Eng Phys. 2011 Jul;33(6):700-11.

Body surface mapping

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Selvaraj RJ, Suszko AM, Subramanian A, Sivananthan D, Hill A, Nanthakumar K, Chauhan VS. Body surface projection of action potential duration alternans: a combined clinical-modeling study with implications for improving T-wave alternans detection. Heart Rhythm. 2009 Aug;6(8):1211-9.

Heart Rate Turbulence (HRT)

  • Changes in beat-to-beat intervals following premature beats
  • Marker of autonomic function

HRT

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HRT

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Georg Schmidt, Marek Malik, Petra Barthel, Raphael Schneider, Kurt Ulm, Linda Rolnitzky, A John Camm, J Thomas Bigger, Albert Schömig, Heart-rate turbulence after ventricular premature beats as a predictor of mortality after acute myocardial infarction, In The Lancet, Volume 353, Issue 9162, 1999, Pages 1390-1396

HRT good

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HRT bad

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QRS fractionation

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QRS fractionation - Meta analysis

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Rosengarten JA, Scott PA, Morgan JM. Fragmented QRS for the prediction of sudden cardiac death: a meta-analysis. Europace. 2015 Jun;17(6):969-77.

ECG markers of risk - What is the current status?

  • Many markers studied
  • Measures of autonomic function
    • Heart rate variability
    • Heart rate turbulence
  • Measures of abnormal depolarization
    • Fractionated QRS
    • Signal averaged ECG - Late potentials
  • Measures of abnormal repolarization
    • QT dispersion
    • T wave alternans

How are we placed to study these?

  • Magnitude of problem in India
  • Most patients dont get ICDs - Surrogate vs true outcomes
  • Datasets / Modeling tools

Study in JIPMER

  • 58 patients
  • LV dysfunction post MI (LVEF < 40%)
  • Multiple parameters measured at baseline
  • Followed up for 2 years

Outcomes

  • Mean age 46.8 yrs
  • 7/58 died suddenly
  • PVCs, HRV, TWA, HRT were not predictive
  • EF was strongest predictor

The future

  • New markers ?
  • Better measurement methods
  • Combine markers

Thank you