The clinical impact of genetic testing in comprehensive cardiomyopathies

Cardiomyopathies and idiopathic ventricular fibrillation have traditionally been studied as distinct entities; however, emerging evidence suggests that arrhythmias may represent an early manifestation of cardiomyopathy. The clinical utility of genetic testing in these conditions requires comprehensive evaluation.

We retrospectively analyzed 51 consecutive patients with idiopathic cardiomyopathies and/or idiopathic ventricular fibrillation who were admitted between 2020 and 2024. Genetic testing was performed using either whole-exome sequencing or targeted gene panels. Clinical characteristics, myocardial biopsy findings, and outcomes-including arrhythmia recurrence following catheter ablation-were assessed in relation to the presence of pathogenic or likely pathogenic (P/LP) genetic variants.

P/LP variants were identified in 24 % of patients. Those harboring P/LP variants had a higher prevalence of family history (58 % vs. 21 %, p = 0.012). No significant difference in myocardial interstitial fibrosis was observed between P/LP carriers and non-carriers. Patients with P/LP variants exhibited significantly earlier clinical manifestations, including diagnosis, heart failure onset, and arrhythmic events (all p < 0.05). However, P/LP variant status did not significantly affect recurrence rates after catheter ablation for atrial or ventricular tachyarrhythmias. All P/LP variant carriers were diagnosed before age 60 years.

P/LP genetic variants are associated with earlier disease onset; however, they do not appear to influence the severity of myocardial fibrosis or the recurrence of arrhythmias following catheter ablation. Genetic testing is recommended for younger patients presenting with cardiomyopathy, although further investigation is warranted to clarify its impact on therapeutic responses.