Impact of rs1805127 and rs55742440 Variants on Atrial Remodeling in Hypertrophic Cardiomyopathy Patients with Atrial Fibrillation: A Romanian Cohort Study

Abstract

Abstract Background Atrial fibrillation (AFib), the most prevalent cardiac arrhythmia globally, is characterized by a complex genetic component. In hypertrophic cardiomyopathy, the most commonly encountered genetic cardiac disease, atrial fibrillation is frequently reported in about 20 to 25%, its appearance being associated with poor long-term prognosis. The purpose of this study was to investigate the association between variation in genes related to cardiac ion handling and AFib in a cohort of Romanian patients with hypertrophic cardiomyopathy (HCM). Methods Forty-five unrelated probands with HCM were genotyped by targeted next generation sequencing (NGS) for 24 genes associated with cardiac ion channels and ion homeostasis. Subsequently, the study cohort was divided into two groups based on the presence or absence of AFib detected during ECG monitoring. Results We identified two polymorphisms (rs1805127, c.112A > G located in KCNE1 and rs55742440, c.629T > C located in SCN1B) linked to AFib susceptibility. In AFib group, rs1805127 was associated with increased indexed left atrial (LA) maximal volume (LAVmax = 58.42 ± 21 ml/m2 vs LAVmax = 32.54 ± 6.47 ml/m2, p < 0.001) and impaired LA strain reservoir (LASr = 13.3 ± 7.5% vs LASr = 24.4 ± 6.8%, p < 0.05) compared to those without respective variant. The rs55742440 allele was less frequent in patients with AFib (12 out of 25, 48%) compared to those without arrhythmia (15 out of 20, 75%, p = 0.05). Also, AFib + c.629T > C carriers had significantly lower LAVmax compared to those genotype-negative. Conclusion Among patients with HCM and AFib, rs1805127 variant was accompanied by pronounced LA remodeling, whereas rs55742440’s presence was related to a milder LA enlargement.