SCD in Ischemic Cardiomyopathy: Markers beyond EF

Raja Selvaraj
Professor of Cardiology
JIPMER

The problem

Olmsted County, Minnesota

2997 patients with MI
Mean follow up of 4.7 years
0-30 days - 1.2% sudden death
after 30 days - 1.2% per year

Adabag AS, Therneau TM, Gersh BJ, Weston SA, Roger VL. Sudden Death After Myocardial Infarction. JAMA. 2008;300(17):2022–2029. https://doi.org/10.1001/jama.2008.553

ICD benefit depends on rate of sudden death

Clinically relevant risk threshold for predicting sudden cardiac death Jussi Hernesniemi, Roni Ahola, Mikko Uimonen. medRxiv 2026.03.18.26348515; doi: https://doi.org/10.64898/2026.03.18.26348515

Risk of sudden death and NNT

Clinically relevant risk threshold for predicting sudden cardiac death Jussi Hernesniemi, Roni Ahola, Mikko Uimonen. medRxiv 2026.03.18.26348515; doi: https://doi.org/10.64898/2026.03.18.26348515

Early post MI phase

Higher competing risk
No reduction in overall mortality (1, 2)

G. Steinbeck, D. Andresen, K. Seidl, et al. Defibrillator implantation early after myocardial infarction. N Engl J Med, 361 (15) (2009), pp. 1427-1436, 10.1056/NEJMoa0901889

S.H. Hohnloser, K.H. Kuck, P. Dorian, et al. Prophylactic use of an implantable cardioverter–defibrillator after acute myocardial infarction. N Engl J Med, 351 (24) (2004), pp. 2481-2488, 10.1056/NEJMoa041489

EF and sudden death

Solomon SD et al. Valsartan in Acute Myocardial Infarction Trial (VALIANT) Investigators. Sudden death in patients with myocardial infarction and left ventricular dysfunction, heart failure, or both. N Engl J Med. 2005 Jun 23;352(25):2581-8. doi: 10.1056/NEJMoa043938.

Markers other than EF

Electrical markers
Imaging (MRI)
Biomarkers
Multiparameter risk scores

Non EF risk markers

Refine risk in EF < 35
Identify high risk with EF > 35

Electrical markers of risk (1990-2010)

Heart rate variability

Heart rate turbulence

T wave alternans

TWA - Methods

Chauhan, Vijay S; Selvaraj, Raja J. Utility of microvolt T-wave alternans to predict sudden cardiac death in patients with cardiomyopathy. Current Opinion in Cardiology 22(1):p 25-32, January 2007. | DOI: 10.1097/HCO.0b013e328011aa49

ABCD trial

Costantini, O, Hohnloser, S, Kirk, M. et al. The ABCD (Alternans Before Cardioverter Defibrillator) Trial: Strategies Using T-Wave Alternans to Improve Efficiency of Sudden Cardiac Death Prevention. JACC. 2009 Feb, 53 (6) 471–479. https://doi.org/10.1016/j.jacc.2008.08.077

MASTER trial

Chow, T, Kereiakes, D, Onufer, J. et al. Does Microvolt T-Wave Alternans Testing Predict Ventricular Tachyarrhythmias in Patients With Ischemic Cardiomyopathy and Prophylactic Defibrillators?: The MASTER (Microvolt T Wave Alternans Testing for Risk Stratification of Post-Myocardial Infarction Patients) Trial. JACC. 2008 Nov, 52 (20) 1607–1615. https://doi.org/10.1016/j.jacc.2008.08.018

NSVT on Holter

Programmed ventricular stimulation

Requires invasive study
Variability in protocol
Low sensitivity

Sudden death after prior MI - Assessment of various electrical parameters

58 patients with prior MI and EF < 40
ECG (QRS width), Echo (LVEF), Holter (NSVT), EP study (HRT, TWA)
2 year follow up
SCD in 7 patients (12%)
LVEF < 30 (HR 5.6) and NSVT (HR 5.7)

Sudden death and its predictors in myocardial infarction survivors in an Indian population. Raja J. Selvaraj et al. Indian Pacing and Electrophysiology Journal 2021;21:82-87

LVEF strongest predictor

MRI

Scar in NICMP vs ICMP

EF is poor surrogate for scar in NICMP
Quality of scar more important in ICMP

Peri-infarct zone (Gray zone)

Yan AT et al. Characterization of the peri-infarct zone by contrast-enhanced cardiac magnetic resonance imaging is a powerful predictor of post-myocardial infarction mortality. Circulation. 2006 Jul 4;114(1):32-9. doi: 10.1161/CIRCULATIONAHA.106.613414.

Biomarkers

Biomarkers - hsTNT and sST2

Lepojärvi ES, Huikuri HV et al. Biomarkers as predictors of sudden cardiac death in coronary artery disease patients with preserved left ventricular function (ARTEMIS study). PLoS One. 2018 Sep 18;13(9):e0203363. doi: 10.1371/journal.pone.0203363.

Protein based biomarkers

Zhang M et al. Novel Protein-Based Biomarkers of Out-of-hospital Sudden Cardiac Death After Myocardial Infarction. Circ Arrhythm Electrophysiol. 2025 Apr;18(4):e013217. doi: 10.1161/CIRCEP.124.013217.

Patients newly diagnosed with AMI who underwent coronary angiography and were discharged alive were included. In the discovery cohort (105 SCD cases and 105 survivors), mass spectrometry discovered 44 differential proteins associated with SCD, unveiling early circulating features characterized by inflammatory response and complement activation in out-of-hospital SCD cases. Targeted proteomics identified the optimal SCD-warning 3-protein combination, including coronin-1A, haptoglobin, and CFD (complement factor D), to assess out-of-hospital SCD risk. An ELISA-based SCD-warning 3-protein combination model significantly outperformed left ventricular ejection fraction alone (C statistic: 0.752 versus 0.548; P<0.001) and improved their performanc Finally, an SCD-W3P including CORO1A (P31146), CFD (P00746), and HP (P00738) was identified as the optimal protein classifier to identify out-of-hospital SCD risk e

Multi parameter risk scores

Seattle Proportional Risk Model

Levy WC et al. The Seattle Heart Failure Model: prediction of survival in heart failure. Circulation. 2006 Mar 21;113(11):1424-33. doi: 10.1161/CIRCULATIONAHA.105.584102.

https://depts.washington.edu/sprm/app.php

Combination of SHFM and SPRM

Among 98,846 patients with HF (87,914 with ICDs and 10,932 without ICDs), the SHFM was strongly associated with all-cause mortality (p < 0.0001). The ICD−SPRM interaction was significant (p < 0.0001), such that SPRM quintile 5 patients had approximately twice the reduction in mortality with the ICD versus SPRM quintile 1 patients (adjusted hazard ratios [HR]: 0.602; 95% confidence interval [CI]: 0.537 to 0.675 vs. 0.793; 95% CI: 0.736 to 0.855, respectively). Among patients with SHFM-predicted annual mortality ≤5.7%, those with a SPRM-predicted risk of sudden death below the median had no reduction in mortality with the ICD (adjusted ICD HR: 0.921; 95% CI: 0.787 to 1.08; p = 0.31), whereas those with SPRM above the median derived the greatest benefit (adjusted HR: 0.599; 95% CI: 0.530 to 0.677; p < 0.0001).

cut-offs SHFM 5.7% SPRM 44.3%

Of note, the SPRM*ICD interaction term favored the ICD more strongly when the cohort was limited to patients with ischemic cardiomyopathy

MADIT ICD benefit score

Goldenberg I, … MADIT-II Investigators. Risk stratification for primary implantation of a cardioverter-defibrillator in patients with ischemic left ventricular dysfunction. J Am Coll Cardiol. 2008 Jan 22;51(3):288-96. doi: 10.1016/j.jacc.2007.08.058.