Sex Differences in Right Ventricular Dysfunction: Insights From the Bench to Bedside

Figure 1. Comparison of the etiologies of right ventricular dysfunction in pulmonary hypertension and arrhythmogenic right ventricular cardiomyopathy/dysplasia. CTEPH, chronic thromboembolic pulmonary hypertension; PH, pulmonary hypertension; RV, right ventricular; WHO, World Health Organization.

Figure 2. Effects of Sex Hormones on Right Ventricular Function in Pulmonary Hypertension. Estrogen improves RV function in PH via modulation of apoptosis, enhancement of mitochondrial function, and reduction in inflammation and oxidative stress. Testosterone increases RV mass, hypertrophy, and fibrosis, which results in decreased RV function. Higher DHEA levels in women are associated with lower RV ejection fraction and greater RV mass. Survival curve adapted from Rafikova et al. (2015). Images for MCP-1 and IL-6 adapted from Lubkowski et al. (1997) and Somers et al. (1997), respectively. Bcl-2/bax, B-cell lymphoma 2/bcl-2-associated X; DHEA, dehydroepiandrosterone; Glut1, glucose transporter 1; GSH, glutathione; IL-6, interleukin-6; MCP-1, monocyte chemoattractant protein-1; ROS, reactive oxygen species; RV, right ventricle/ventricular; RVEF, right ventricular ejection fraction.

Figure 3. Effects of Sex Hormones in Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia. Testosterone is associated with increased risk of severe ventricular arrhythmias, cardiomyocyte apoptosis, and lipid accumulation in ARVC/D. Conversely, estrogen decreases cardiomyoyte apoptosis and cardiomyocyte lipogenesis. Testosterone and estrogen's divergent effects on apoptosis and lipotoxicity provide a potential molecular understanding for the clinical observation that female ARVC/D patients have improved RV function and survival compared to males. Event-free survival curve adapted from Lin et al. (2017). RV, right ventricle/ventricular.