Causal Effect of Atrial Fibrillation on Heart Failure Risk in East Asian Ancestry: A Bidirectional Mendelian Randomization Study Using Genome-wide Association Data

BACKGROUND: Atrial fibrillation (AF) and heart failure (HF) are prevalent cardiovascular conditions in East Asia, with a complex interrelationship. The directionality of the causal impact of AF on HF risk remains uncertain. This study employs Mendelian randomization (MR) to investigate the potential causal effect of AF on HF. METHODS: Utilizing summary data from genome-wide association studies (GWAS) within the Medical Research Council Integrative Epidemiology Unit open GWAS database, we analyzed 8180 AF cases and 28 612 controls, alongside 9413 HF cases and 203 040 controls, all of East Asian descent. We conducted MR analysis using the inverse variance weighted (IVW) method, complemented by various sensitivity analyses, including bidirectional MR to assess causality in the reverse direction. RESULTS: Genetically predicted AF was found to be causally associated with an increased risk of HF in East Asian populations (odds ratio = 1.14, 95% CI: 1.10-1.19, P <.001) as per the IVW method. These findings were consistent across multiple MR methods. Sensitivity analyses revealed no significant heterogeneity or pleiotropy. Notably, bidirectional MR analysis showed no causal effect of HF on the risk of developing AF. CONCLUSIONS: The MR analysis supports a unidirectional causal relationship between AF and increased HF risk in East Asian individuals. The absence of a reverse causal effect reinforces the importance of maintaining sinus rhythm to mitigate HF risk. Further research is warranted to corroborate these findings and to explore their clinical implications in depth.