Sex differences in human atrial electrophysiology: the dark side of the moon? Will engineered heart tissue help to bring light into the darkness?

Abstract

Sex-related differences in cardiac electrophysiology are well established in the ventricle and have reached textbook level. In contrast, our understanding of sex effects in the human atrium remains limited, despite clear clinical observations such as the lower incidence of atrial fibrillation (AF) in women. In this review, we summarize sex differences and discuss potential reasons for the imbalance in knowledge, including the lack of ECG markers for atrial repolarization, the minimal contribution of I Ks in atrial tissue, and possible sex differences in inward rectifier currents. We also address the role of aging and hormonal changes, the complexity of studying the perimenopausal transition, and the current limitations of available models. Finally, we highlight the potential of engineered heart tissues to detect genetically encoded differences and to dissect genomic versus non-genomic hormone effects.

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