Identification of concealed cardiomyopathy using next-generation sequencing-based genetic testing in Korean patients initially diagnosed with idiopathic ventricular fibrillation

Abstract

Aims: Idiopathic ventricular fibrillation (IVF) is a disease in which the cause of ventricular fibrillation cannot be identified despite comprehensive clinical evaluation. This study aimed to investigate the clinical yield and implications of genetic testing for IVF.

Methods and results: This study was based on the multi-centre inherited arrhythmia syndrome registry in South Korea from 2014 to 2017. Next-generation sequencing-based genetic testing was performed that included 174 genes previously linked to cardiovascular disease. A total of 96 patients were clinically diagnosed with IVF. The mean age of the onset was 41.2 ± 12.7 years, and 79 patients were males (82.3%). Of these, 74 underwent genetic testing and four (5.4%) of the IVF probands had pathogenic or likely pathogenic variants (each having one of MYBPC3, MYH7, DSP, and TNNI3). All pathogenic or likely pathogenic variants were located in genes with definite evidence of a cardiomyopathy phenotype, either hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy.

Conclusion: Next-generation sequencing-based genetic testing identified pathogenic or likely pathogenic variants in 5.4% of patients initially diagnosed with IVF, suggesting that genetic testing with definite evidence genes of cardiomyopathy may enable molecular diagnosis in a minority of patients with IVF. Further clinical evaluation and follow-up of patients with IVF with positive genotypes are needed to unveil concealed phenotypes, such as the pre-clinical phase of cardiomyopathy.

Keywords: Cardiomyopathy; Channelopathy; Genetic testing; High-throughput nucleotide sequencing; Idiopathic ventricular fibrillation.