Clinical Implications of Transmural Late Gadolinium Enhancement in Genotype-Positive Arrhythmogenic and Dilated Cardiomyopathy.

Abstract

Midmyocardial and subepicardial late gadolinium enhancement (LGE) are typical in inherited arrhythmogenic cardiomyopathy (ACM) and dilated cardiomyopathy (DCM). Transmural LGE, usually considered ischemic and excluded from ACM criteria, may also occur, but its clinical relevance is unclear. The objective of this study was to assess the prevalence, genetic associations, and prognostic significance of transmural LGE in patients with genotype-positive, nonischemic ACM/DCM. We retrospectively analyzed 1,379 genotype-positive patients with ACM/DCM, identifying 711 with cardiac magnetic resonance imaging and no significant coronary artery disease. Patients were stratified by LGE pattern (transmural, nontransmural, or absent). Major ventricular arrhythmic (MVA) and advanced heart failure (AHF) events were evaluated using Kaplan-Meier and age-adjusted Cox regression analyses. Transmural LGE was present in 5% (33/711) of patients and was enriched in LMNA and DSP variant carriers. Compared with nontransmural or absent LGE, transmural LGE was associated with higher rates of thromboembolic events, atrial fibrillation, and implantable cardioverter-defibrillator implantation (all P ≤ 0.003). It also conferred increased rates of MVA events (45% vs 27% vs 14%) and AHF therapies (18% vs 12% vs 6%) (P < 0.05). In age-adjusted models, transmural LGE independently predicted the composite endpoint of MVA/AHF compared with nontransmural LGE (HR: 1.9; P = 0.03) and no LGE (HR: 2.9; P = 0.0005). Transmural LGE identifies a small but high-risk subset of genotype-positive ACM/DCM, particularly among patients with LMNA and DSP variants, with significantly increased arrhythmic and heart failure risk.