European task force reclassification of dilated and non-dilated cardiomyopathies identifies a high arrhythmic-risk overlap phenotype.

BACKGROUND

The classification of left ventricular cardiomyopathies is challenging due to evolving definitions and overlapping phenotypes. The European Task Force Criteria, by incorporating structural, functional, arrhythmic, and genetic parameters, refine the diagnostic criteria for arrhythmogenic cardiomyopathy. This study aimed to characterize the genotype-phenotype features of patients with arrhythmogenic left ventricular/biventricular cardiomyopathy (ALVC/ABVC), dilated cardiomyopathy (DCM), and their potential overlap.

METHODS

We retrospectively evaluated 306 patients with DCM or non-dilated left ventricular cardiomyopathy (NDLVC). Following European Task Force criteria, patients were reclassified as: isolated DCM, isolated ALVC/ABVC and a DCM-ALVC/ABVC overlapping phenotype. NDLVC not fulfilling the criteria, and isolated arrhythmogenic right ventricular cardiomyopathy were excluded. The study endpoint was a composite of cardiac death, sustained ventricular tachycardia, or ventricular fibrillation.

RESULTS

Overall, 66, 79 and 76 patients were categorized as DCM, ALVC/ABVC, DCM-ALVC/ABVC, respectively. Genetic likely-pathogenic/pathogenic variants were more frequent in ALVC/ABVC than in DCM and DCM-ALVC/ABVC (50.6 % vs 28.8 % and 27.6 %, p = 0.004). DCM-ALVC/ABVC patients presented extensive LGE, higher NT-proBNP, and the highest arrhythmic burden (all p < 0.05). Moreover, they had significantly lower event-free survival (log-rank p = 0.002). In Cox analysis, LVEF (HR: 0.96, 95 % CI 0.94-0.99, p = 0.002) and LGE extent (HR: 1.04, 95 % CI 1.00-1.07, p = 0.016) independently predicted the endpoint.

CONCLUSIONS

The European Task Force Criteria enabled the identification of an overlapping phenotype associated with increased arrhythmic risk, supporting the clinical utility of multiparametric diagnostic approaches to improve risk stratification and guide therapeutic decisions in patients with cardiomyopathies.