TY - JOUR
T1 - Sex-Related Differences in Cardiac Channelopathies: Implications for Clinical Practice
AU - Asatryan, Babken
AU - Yee, Lauren
AU - Ben-Haim, Yael
AU - Dobner, Stephan
AU - Servatius, Helge
AU - Roten, Laurent
AU - Tanner, Hildegard
AU - Crotti, Lia
AU - Skinner, Jonathan R.
AU - Remme, Carol Ann
AU - Chevalier, Philippe
AU - Medeiros-Domingo, Argelia
AU - Behr, Elijah R.
AU - Reichlin, Tobias
AU - Odening, Katja E.
AU - Krahn, Andrew D.
N1 - Publisher Copyright: © 2021 Lippincott Williams and Wilkins. All rights reserved.
PY - 2021/2/16
Y1 - 2021/2/16
N2 - 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.
AB - 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.
KW - Brugada syndrome
KW - arrhythmias, cardiac
KW - death, sudden, cardiac
KW - gender identity
KW - genetics
KW - long QT syndrome
KW - sex
UR - http://www.scopus.com/inward/record.url?scp=85101441637&partnerID=8YFLogxK
U2 - https://doi.org/10.1161/CIRCULATIONAHA.120.048250
DO - https://doi.org/10.1161/CIRCULATIONAHA.120.048250
M3 - Article
C2 - 33587657
SN - 0009-7322
VL - 143
SP - 739
EP - 752
JO - Circulation
JF - Circulation
IS - 7
ER -