Genetics in Probands With Idiopathic Ventricular Fibrillation: A Multicenter Study

Luigi Pannone, Anaïs Gauthey, Giulio Conte, Randy Osei, Daniela Campanale, Enrico Baldi, Paola Berne, Alessandro Vicentini, Pasquale Vergara, Antonio Sorgente, Christine Rootwelt-Norberg, Domenico Giovanni Della Rocca, Cinzia Monaco, Antonio Bisignani, Vincenzo Miraglia, Marcello Spolverini, Gaetano Paparella, Ingrid Overeinder, Gezim Bala, Alexandre AlmoradErwin Ströker, Thomy de Ravel, Argelia Medeiros-Domingo, Juan Sieira, Kristina H Haugaa, Pedro Brugada, Mark La Meir, Angelo Auricchio, Gian-Battista Chierchia, Sonia Van Dooren, Carlo de Asmundis

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


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 (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).

RESULTS: 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.

CONCLUSIONS: 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.

Original languageEnglish
Pages (from-to)1296-1306
Number of pages11
JournalJACC. Clinical electrophysiology
Issue number8
Early online date2023
Publication statusPublished - Aug 2023


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