Combined Analysis of Cardiac Repolarization Entropy and Magnetic Resonance Imaging Enhances Risk Stratification of Patients Receiving a Primary-Prevention ICD.

Published: 03/24/2026

Authors: Gokhale TA, Dey S, Limpitikul WB, Gautam N, Al'Aref SJ, Cross B, Saba S, Estes NAM, Vaughan BL, Jones SR, Tomaselli GF, Wu KC, DeMazumder D

Abstract

Accurate selection of patients who will benefit from a primary-prevention implantable cardioverter-defibrillator (ICD) remains a challenge. Cardiac magnetic resonance imaging (CMR) of myocardial tissue heterogeneity and EntropyX, a nonlinear electrocardiographic (ECG) measure of cardiac repolarization dynamics, predict ventricular tachyarrhythmias (VTs) and sudden cardiac arrest.

Because CMR and EntropyX are fundamentally distinct structural and electrical measures, we hypothesized that they add major independent prognostic value to conventional clinical predictors of sudden cardiac arrest.

In 230 consecutive patients with a left ventricular ejection fraction ≤35% in sinus rhythm, baseline exposures before primary prevention ICD implantation included demographics, history, medications, laboratory results, conventional ECG indices of heart rate and QT variability, CMR myocardial tissue characterization, and EntropyX. The primary endpoint was ICD shock for VT, and secondary endpoints included all-cause events, including mortality.

Over 6.1 ± 3.3 years of follow-up, 62 patients (27%) received appropriate ICD shocks. In multivariable analyses, EntropyX and CMR gray zone mass yielded adjusted hazard ratios (per SD change) of 1.8 (95% CI: 1.4-2.3) and 1.5 (95% CI: 1.2-1.8), respectively, and improved Harrell's C-statistic from 0.59 to 0.73 in a model composed of conventional clinical predictors, left ventricular end-systolic volume (LVESV) and prescribed diuretics. EntropyX was the strongest predictor in years 1-3, whereas CMR and LVESV were stronger in years >3. Moreover, EntropyX independently predicted the secondary endpoints.

EntropyX and CMR gray zone mass complement each other and conventional risk factors, improving risk stratification for appropriate ICD shock and mortality, and together may enhance the selection of primary prevention ICD recipients. (Prospective Observational Study of the ICD in Sudden Cardiac Death Prevention (PROSe-ICD; NCT00733590).

PMID: 41823943