IJCS | Volume 32, Nº4, July/August 2019

415 Colombo et al. Sudden cardiac death in female athletes Int J Cardiovasc Sci. 2019;32(4):414-417 Review Article present a slower development of the pathological features of the disease, which can explain the “lower prevalence” of HCM in females, despite the Mendelian inheritance particularly in the youngers. 7 This is a relevant finding, considering that HCM has a prevalence of 1:500 individuals and it is reported as a major cause of SCD in young athletes. It has been known for decades that prolonged QT interval is more common in women than men. 8 Some data have demonstrated that this difference is due to shortening of the QT interval that occurs between puberty and the age of 55 years in men, whereas there is a QT prolongation in women during the reproductive years, suggesting that estrogen affects the regulation of cardiac repolarization. 9 In addition, experimental data have shown that estrogen downregulates the activity and expression of Kv4.3 channels, whichmay have some influence in the clinical presentation of channelopathies, although the prevalence of these conditions is low in the general population. 10 Interestingly, prolonged QT dispersion, which has been suggested as a predictive parameter of SCD and life-threatening arrhythmias in athletes, was described as shorter in female athletes than in male athletes, despite the longer QT interval. 11,12 Previous studies have demonstrated that QT dispersion is greater in post-menopausal women than in pre- menopausal women, showing that it is influenced by sex hormone secretion, and this may play a role in the prevalence of SCD in female athletes. 13 Physiological cardiac adaptation in female athletes Cardiac remodelling seems to occur in a different way in female athletes. The pioneer study 14 on a large cohort of elite female athletes, all Caucasians, reported that females rarely exhibit significant myocardial hypertrophy. In this cohort, left ventricular wall thickness (LVWT) had an average of 8 mm and none of the athletes showed a LVWT > 12 mm, measured by echocardiography. 14 Data including Afro-descendant female athletes are few, but probably ethnicity also influences the women's heart. Current literature shows that 3% of female athletes may have a LVWT > 11 mm, but none > 13 mm. 15 These findings suggest that the overlapping of measurements of female athletes’ heart with HCM is unlike, since they do not reach values compatible with the so-called "grey's zone" for the "athlete's heart". On the other hand, electrocardiogram (ECG) in female athletes must be carefully analysed to avoidmisinterpretation. Some ECG findings described asmore common in cardiomyopathies, such as anterior T wave inversion (V1-3) and a flat ST segment, were reported to be more frequent in female athletes but they did not fulfil diagnostic criteria for ARVC after further investigations. As a matter of fact, this ECG pattern has been considered as non-specific in low-risk populations such as women. 16,17 The effects of cardiac adaptation to exercise on left ventricular (LV) geometry have been studied recently. A large study with healthy elite athletes (41% female) described different LV geometry according to sex and sports discipline anddemonstrated limit values for LVWT in Caucasian female athletes similar to previous data. 18 Interestingly, LV cavity dimension, indexed for body surface area, was higher in women, demonstrating that eccentric hypertrophy was more common in endurance female athletes, whereas concentric hypertrophy/ remodelling was more common in male athletes. Thus, one may infer that cardiac remodelling could be related to women’s “cardiac protection” for SCD. Where is the key? A recent review reported some mechanisms of cardiac remodelling and highlighted that hormones and genes may play a role in this process. 19 Some studies have shown the presence of androgenic and estrogenic receptors in myocytes and the hormonal effects on myocardial response. Whereas testosterone stimulates myocardial hypertrophy, estrogens inhibit the proliferation of cardiac fibroblasts. 20 This depends on hormone levels and their bindings to cardiac receptors, which is modulated by genetic expression. The angiotensin-converting enzyme activity, which is related to blood pressure levels and myocardial hypertrophy, is also influenced by testosterone and estrogen. 21 Some data have shown the association between LV hypertrophy degree in endurance athletes and renin-angiotensin systemencoding genes, suggesting that sex hormones affect the expression of these genetic polymorphisms. 22 In addition, a higher level of nitric oxide (NO), which promotes peripheral vasodilation and afterload reduction, is associated with stimulation of strogen release. 23 Consequently, women have a lower systolic blood pressure peak during exercise what is advocated to contribute to less LV hypertrophy. Experimental studies have also shown that some enzymes involved in energy substrate (fatty acids, glucose) availability are related to prevention of cardiac