Sex-differences in inherited heart conditions

Cardiogenetics encompasses a diverse group of heart conditions unified by their inherited nature. Sex-differences in cardiogenetics are understood to varying degrees; while a mechanism underlying sex-differences in Long-QT Syndrome (LQTS) is well-established, disease prevalence and severity by sex is inconsistent across different Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) cohorts. This thesis explores sex-differences in cardiogenetics by posing three hypotheses: (1) high precordial leads increase the detection of ARVC with sex-specific implications, (2) sex-stratification of a diagnostic treadmill testing algorithm will aid in the diagnosis of LQTS, and (3) the menstrual cycle affects the QT-interval in LQTS. The first study showed clear differences in high leads of ARVC and healthy controls, with no Type 1 or 2 Brugada pattern or sex-differences. The second study suggested that the 3-step algorithm is a valid and simple screening method for detecting LQTS, while a sex-specific approach offers additional insight for LQTS1/2 and should be used in the interpretation of exercise testing. The preliminary result of the third study suggests the menstrual cycle has a clear differential effect in controls, but not in LQTS patients, which will be clarified using a larger sample size. Ultimately, it is evident that sex-differences in cardiogenetic conditions remains a complicated and multifaceted area.Medicine, Faculty ofExperimental Medicine, Division ofGraduat