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

Prominent recent example in India - Dr. Abdul Kalam Collapsed while delivering a lecture

SCD - Mechanism

Causes

Myocardial infarction

Myocardial infarction (Heart attack)

Death of heart muscle due to blockage of blood supply
Residual dead tissue (scar)
Reduced pump function
Prone to arrhythmias

Invisible problem - 100 patients after MI

At one year - Angina -> PCI

Angina -> CABG

Worsen -> Death

Follow up - Medically managed

Sudden death

AICD - the revolution

The history

Drugs for prevention of sudden death

CAST

EMIAT

Michel Mirowski

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

First report - 1970s

Technical improvements

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

Evolution

ICD today

Trials, patient groups

Anthony Van Loo

Subcutaneous ICD

The End ?

Or, is it just the beginning?

Identifying patients at high risk

Lifesavers, but carry risks too

EF and sudden death

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

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

Beats that originate in the ventricles

More abnormal beats - worse the outcome

Heart rate variability (HRV)

HRV - Outcomes

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.

808 MI survivors SD of normal RR in 24 hour Holter Mortality - Outcome

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

SAECG

SAECG

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

T wave alternans

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

TWA - Macroscopic

Microscopic T wave alternans

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

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

Dynamic instability

Restitution slopes

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

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
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
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

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

HRT

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

HRT bad

QRS fractionation

QRS fractionation - Meta analysis

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

Abstract Sudden cardiac death is an unexpected natural death from cardiac causes, usually due to a rapid heart rhythm. This is the cause of about 10% of all deaths in the community. Most of these occur in patients who have had a heart attack before. Implantation of a defibrillator can save these lives, but the challenge has been to identify those at risk. Since sudden death is a disorder of the heart's electrical rhythm, there has been a search for an electrical signature for sudden death. This has been a ripe area for collaboration between engineers with interest in signal processing and physicians. This talk will cover the different signatures that have been investigated and their current status in identifying patients at risk.

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Sudden Cardiac Death - In search of an electrical signatureRaja Selvaraj