Asatryan Babken, Yee Lauren, Ben-Haim Yael, Dobner Stephan, Servatius Helge, Roten Laurent, Tanner Hildegard, Crotti Lia, Skinner Jonathan R, Remme Carol Ann, Chevalier Philippe, Medeiros-Domingo Argelia, Behr Elijah R, Reichlin Tobias, Odening Katja E, Krahn Andrew D
Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Switzerland (B.A., S.D., H.S., L.R., H.T., T.R., K.E.O.).
Heart Rhythm Services, Division of Cardiology, Department of Medicine, University of British Columbia, Vancouver, Canada (L.Y., A.D.K.).
Circulation. 2021 Feb 16;143(7):739-752. doi: 10.1161/CIRCULATIONAHA.120.048250. Epub 2021 Feb 15.
Sex-related differences in prevalence, clinical presentation, and outcome of cardiac channelopathies are increasingly recognized, despite their autosomal transmission and hence equal genetic predisposition among sexes. In congenital long-QT syndrome, adult women carry a greater risk for Torsades de pointes and sudden cardiac death than do men. In contrast, Brugada syndrome is observed predominantly in adult men, with a considerably higher risk of arrhythmic sudden cardiac death in adult men than in women. In both conditions, the risk for arrhythmias varies with age. Sex-associated differences appear less evident in other cardiac channelopathies, likely a reflection of their rare(r) occurrence and our limited knowledge. In several cardiac channelopathies, sex-specific predictors of outcome have been identified. Together with genetic and environmental factors, sex hormones contribute to the sex-related disparities in cardiac channelopathies through modulation of the expression and function of cardiac ion channels. Despite these insights, essential knowledge gaps exist in the mechanistic understanding of these differences, warranting further investigation. Precise application of the available knowledge may improve the individualized care of patients with cardiac channelopathies. Promoting the reporting of sex-related phenotype and outcome parameters in clinical and experimental studies and advancing research on cardiac channelopathy animal models should translate into improved patient outcomes. This review provides a critical digest of the current evidence for sex-related differences in cardiac channelopathies and emphasizes their clinical implications and remaining gaps requiring further research.
尽管心脏离子通道病呈常染色体显性遗传，因此男女具有相同的遗传易感性，但人们越来越认识到其在患病率、临床表现和预后方面存在性别差异。在先天性长QT综合征中，成年女性发生尖端扭转型室速和心源性猝死的风险高于男性。相比之下，Brugada综合征主要见于成年男性，成年男性发生心律失常性心源性猝死的风险显著高于女性。在这两种情况下，心律失常的风险均随年龄变化。在其他心脏离子通道病中，性别相关差异似乎不那么明显，这可能反映出它们发病率较低以及我们对此了解有限。在几种心脏离子通道病中，已经确定了与性别相关的预后预测因素。除了遗传和环境因素外，性激素通过调节心脏离子通道的表达和功能，导致心脏离子通道病出现性别相关差异。尽管有这些认识，但在对这些差异的机制理解方面仍存在重要的知识空白，需要进一步研究。准确应用现有知识可能会改善心脏离子通道病患者的个体化治疗。在临床和实验研究中促进对性别相关表型和预后参数的报告，并推进心脏离子通道病动物模型的研究，有望改善患者的预后。本综述对目前关于心脏离子通道病性别相关差异的证据进行了批判性总结，并强调了其临床意义以及仍需进一步研究的空白。
