Sex differences in disease progression and arrhythmic risk in patients with arrhythmogenic cardiomyopathy

Abstract

Aims We aimed to assess sex-specific phenotypes and disease progression, and their relation to exercise, in arrhythmogenic cardiomyopathy (AC) patients. Methods and results In this longitudinal cohort study, we included consecutive patients with AC from a referral centre. We performed echocardiography at baseline and repeatedly during follow-up. Patients’ exercise dose at inclusion was expressed as metabolic equivalents of task (MET)-h/week. Ventricular arrhythmia (VA) was defined as aborted cardiac arrest, sustained ventricular tachycardia, or appropriate therapy by implantable cardioverter-defibrillator. We included 190 AC patients (45% female, 51% probands, age 41 ± 17 years). Ventricular arrhythmia had occurred at inclusion or occurred during follow-up in 85 patients (33% of females vs. 55% of males, P = 0.002). Exercise doses were higher in males compared with females [25 (interquartile range, IQR 14–51) vs. 12 (IQR 7–22) MET-h/week, P < 0.001]. Male sex was a marker of proband status [odds ratio (OR) 2.6, 95% confidence interval (CI) 1.4–5.0, P = 0.003] and a marker of VA (OR 2.6, 95% CI 1.4–5.0, P = 0.003), but not when adjusted for exercise dose and age (adjusted OR 1.8, 95% CI 0.9–3.6, P = 0.12 and 1.5, 95% CI 0.7–3.1, P = 0.30, by 5 MET-h/week increments). In all, 167 (88%) patients had ≥2 echocardiographic examinations during 6.9 (IQR 4.7–9.8) years of follow-up. We observed no sex differences in deterioration of right or left ventricular dimensions and functions. Conclusion Male AC patients were more often probands and had higher prevalence of VA than female patients, but not when adjusting for exercise dose. Importantly, disease progression was similar between male and female patients.

Sex‐Related Differences in Genetic Cardiomyopathies

“… 67 , 68 In particular, men more frequently have abnormal ECGs and late potentials, worse biventricular cardiac function with a higher risk for ventricular arrhythmias compared with women. 68 , 69 To explain this phenomenon, a role of sex hormones has been postulated. In an induced pluripotent stem cell–derived arrhythmogenic cardiomyopathy cardiomyocyte model, elevated testosterone levels worsened, whereas normal estradiol levels decreased cardiomyocyte apoptosis and lipogenesis.…”

“… 72 Although in a limited sample, when adjusted for exercise, odds of proband status and ventricular arrhythmias did not differ between sexes, and, after introduction of exercise restrictions, disease progression did not differ between sexes. 69 …”

Clinical characteristics of various arrhythmogenic cardiomyopathy phenotypes in the pediatric population: a systematic review and meta-analysis

“…Количество мальчиков по результатам нашего систематического обзора было в 1,66 раз больше, чем девочек (1,7:1), что соответствует литературным данным [18]. Следует подчеркнуть, что мужской пол у пациентов с АКМП ассоциирован с более высоким риском ВСС и худшим прогнозом [18,30]. Однако в нашем систематическом обзоре мы не смогли оце- [31].…”

“…Также нарастание клинической симптоматики в виде появления/ учащения жалоб на сердцебиение, синкопальные состояния, признаки сердечной недостаточности (СН) и др. свидетельствуют о прогрессировании заболевания и повышении риска ВСС [12,18,19]. Следует отметить и высокую озабоченность стратификацией риска ВСС, а также показаниями к имплантации имплантируемого кардиовертера-дефибриллятора (ИКД) с целью ее первичной профилактики у детей.…”

Male sex hormone and reduced plakoglobin jointly impair atrial conduction and cardiac sodium currents

“…ARVC has recently been reported to show more adverse outcomes in men (19) related to sex hormone levels (20). Emerging evidence suggests increased incidence of atrial arrhythmias in cardiomyopathies (21).…”