Late-Gadolinium Enhancement Interface Area and Electrophysiological Simulations Predict Arrhythmic Events in Patients With Nonischemic Dilated Cardiomyopathy

Abstract

Objectives: This study sought to investigate whether shape-based late gadolinium enhancement (LGE) metrics and simulations of re-entrant electrical activity are associated with arrhythmic events in patients with nonischemic dilated cardiomyopathy (NIDCM).

Background: The presence of LGE predicts life-threatening ventricular arrhythmias in NIDCM; however, risk stratification remains imprecise. LGE shape and simulations of electrical activity may be able to provide additional prognostic information.

Methods: Cardiac magnetic resonance (CMR)-LGE shape metrics were computed for a cohort of 156 patients with NIDCM and visible LGE and tested retrospectively for an association with an arrhythmic composite endpoint of sudden cardiac death and ventricular tachycardia. Computational models were created from images and used in conjunction with simulated stimulation protocols to assess the potential for re-entry induction in each patient's scar morphology. A mechanistic analysis of the simulations was carried out to explain the associations.

Results: During a median follow-up of 1,611 (interquartile range: 881 to 2,341) days, 16 patients (10.3%) met the primary endpoint. In an inverse probability weighted Cox regression, the LGE-myocardial interface area (hazard ratio [HR]: 1.75; 95% confidence interval [CI]: 1.24 to 2.47; p = 0.001), number of simulated re-entries (HR: 1.40; 95% CI: 1.23 to 1.59; p < 0.01) and LGE volume (HR: 1.44; 95% CI: 1.07 to 1.94; p = 0.02) were associated with arrhythmic events. Computational modeling revealed repolarization heterogeneity and rate-dependent block of electrical wavefronts at the LGE-myocardial interface as putative arrhythmogenic mechanisms directly related to the LGE interface area.

Conclusions: The area of interface between scar and surviving myocardium, as well as simulated re-entrant activity, are associated with an elevated risk of major arrhythmic events in patients with NIDCM and LGE and represent novel risk predictors.

Keywords: arrhythmic risk; computational modeling; dilated cardiomyopathy; fibrosis; late gadolinium enhancement.