Genetics in Probands With Idiopathic Ventricular Fibrillation: A Multicenter Study

Different genes have been associated with idiopathic ventricular fibrillation (IVF); however, there are no studies correlating genotype with phenotype. 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. 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 (P+), 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). Forty-five consecutive patients were included. A variant was found in 12 patients, 3 P+ 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 P+ (72.7% vs 0%, log-rank P = 0.013). At Cox analysis, P+ or VUS carrier status was a predictor of VA occurrence. In probands with IVF, undergoing genetic analysis with a broad panel, the diagnostic yield for P+ is 6.7%. P+ or VUS carrier status is a predictor of VA occurrence.