Atrial Cardiomyopathy and Longitudinal Outcomes in the UK Biobank
Background: Atrial cardiopathy often precedes atrial fibrillation (AF) and has emerged as an independent risk factor for cardiovascular outcomes. Previous studies assessing atrial function in relation to clinical outcomes have been small, and the importance of right-sided function is largely unknown.
Methods: In 51,693 UK Biobank participants with no previous history of AF, we assessed left and right atrial volumes and ejection fraction from cardiac magnetic resonance imaging (CMR) using deep learning segmentation. We evaluated associations with new-onset AF, ischemic stroke, heart failure, and dementia and conducted a genome-wide association study of each atrial measure. Potential causal associations with downstream outcomes were evaluated using Mendelian randomization.
Results: During a median follow-up time of 4.0 (IQR 2.9-5.4) years, 964 (1.9%) developed AF, 266 (0.5%) developed ischemic stroke, 365 (0.7%) developed heart failure, and 72 (0.1%) developed dementia. After adjustment for clinical risk factors, left and right atrial measures were independently associated with risk of new-onset AF, ischemic stroke, and heart failure, with stronger associations in women. Left atrial minimal volume was also associated with increased risk of dementia. We identified 51 genetic loci associated with left and right atrial measures (p <5Ã 10-8), including 27 novel trait-locus associations, many of which do not overlap with established AF loci. Genetic correlations showed that both chambers had similar correlations with AF but varying correlations with blood pressure, body mass index, and type II diabetes. In Mendelian randomization analyses, left atrial measures had direct causal effects on AF, ischemic stroke, and cardioembolic stroke, though stroke associations were no longer significant after accounting for AF variants.
Conclusion: In this largest assessment of atrial structure and function to date, both left and right atrial cardiopathy were associated with clinical outcomes attributed to AF. We identified several novel genetic loci for left and right atrial traits and observed unique genetic correlations between left and right atrial traits and cardiovascular phenotypes, providing insight into chamber-specific remodeling. Several of these measures are likely to be causal determinants of cardiovascular complications previously attributed to AF, which may be mediated by intercurrent AF. These findings highlight atrial cardiopathy’s potential as a screening tool to identify individuals at high risk for cardiovascular complications.