Genetics in Probands With Idiopathic Ventricular Fibrillation A Multicenter Study

BACKGROUND Different genes have been associated with idiopathic ventricular fibrillation (IVF); however, there are no studies correlating genotype with phenotype. OBJECTIVES The aim of this study was to define the genetic background of probands with IVF using large gene panel analysis and to correlate genetics with long-term clinical outcomes. METHODS All consecutive probands with a diagnosis of IVF were included in a multicenter retrospective study. All patients had: 1) IVF diagnosis throughout the follow-up; and 2) genetic analysis with a broad gene panel. All genetic variants were classified as pathogenic/likely pathogenic (Pthorn), variants of unknown significance (VUS) or no variants (NO-V), following current guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. The primary endpoint was occurrence of ventricular arrhythmias (VA). RESULTS Forty-five consecutive patients were included. A variant was found in 12 patients, 3 Pthorn and 9 VUS carriers. After a mean follow-up time of 105.0 months, there were no deaths and 16 patients (35.6%) experienced a VA. NO-V patients had higher VA free survival during the follow-up, compared with both VUS (72.7% vs 55.6%, log-rank P < 0.001) and Pthorn (72.7% vs 0%, log-rank P = 0.013). At Cox analysis, Pthorn or VUS carrier status was a predictor of VA occurrence. CONCLUSIONS In probands with IVF, undergoing genetic analysis with a broad panel, the diagnostic yield for Pthorn is 6.7%. Pthorn or VUS carrier status is a predictor of VA occurrence. (c) 2023 by the American College of Cardiology Foundation.

Automated summary

This study aims to define the genetic background of individuals with idiopathic ventricular fibrillation (IVF) using large gene panel analysis and correlate genetics with long-term clinical outcomes. It was found that Pthorn or VUS carrier status is a predictor of ventricular arrhythmia occurrence.