Clinical and Genetic Features of Korean Inherited Arrhythmia Probands

Area of Science:

• Cardiovascular Genetics
• Clinical Electrophysiology
• Genomic Medicine

Background:

• Inherited arrhythmias (IA) are a significant cause of sudden cardiac death, particularly in Asian populations.
• Limited understanding exists regarding the genetic basis of IA in Asian individuals.
• This study focuses on a Korean cohort to address this knowledge gap.

Purpose of the Study:

• To investigate the clinical characteristics of inherited arrhythmia probands in a Korean cohort.
• To analyze the genetic underpinnings and diagnostic yield of genetic testing in these patients.
• To compare genetic findings across different inherited arrhythmia types.

Main Methods:

• A multicenter cohort study involving the Korean Inherited Arrhythmia Registry (2014-2017).
• Genetic testing utilized a next-generation sequencing panel covering 174 cardiovascular disease genes.
• Analysis included clinical data and genetic variant detection in 265 IA probands.

Main Results:

• Idiopathic ventricular fibrillation (IVF) and Brugada Syndrome (BrS) were the most common diagnoses.
• Genetic variants were identified in 31.9% of tested probands, with a 6.4% pathogenic/likely pathogenic variant yield.
• IVF probands exhibited the highest positive genotype yield (54.0%), significantly lower left ventricular ejection fraction in genotype-positive cases.

Conclusions:

• Significant clinical and genetic yield differences exist among Brugada Syndrome (BrS), Long QT Syndrome (LQTS), and Idiopathic Ventricular Fibrillation (IVF).
• Genetic testing showed limited utility for BrS and LQTS in this cohort.
• For IVF, multi-gene panel testing may facilitate molecular diagnosis of concealed genotypes, potentially impacting future management.