Improving translational research in sex-specific effects of comorbidities and risk factors in ischaemic heart disease and cardioprotection: position paper and recommendations of the ESC Working Group on Cellular Biology of the Heart.

Ischaemic heart disease (IHD) is a complex disorder and a leading cause of death and morbidity in both men and women. Sex, however, affects several aspects of IHD, including pathophysiology, incidence, clinical presentation, diagnosis as well as treatment and outcome. Several diseases or risk factors frequently associated with IHD can modify cellular signalling cascades, thus affecting ischaemia/reperfusion injury as well as responses to cardioprotective interventions. Importantly, the prevalence and impact of risk factors and several comorbidities differ between males and females, and their effects on IHD development and prognosis might differ according to sex. The cellular and molecular mechanisms underlying these differences are still poorly understood, and their identification might have important translational implications in the prediction or prevention of risk of IHD in men and women. Despite this, most experimental studies on IHD are still undertaken in animal models in the absence of risk factors and comorbidities, and assessment of potential sex-specific differences are largely missing. This ESC WG Position Paper will discuss: (i) the importance of sex as a biological variable in cardiovascular research, (ii) major biological mechanisms underlying sex-related differences relevant to IHD risk factors and comorbidities, (iii) prospects and pitfalls of preclinical models to investigate these associations, and finally (iv) will provide recommendations to guide future research. Although gender differences also affect IHD risk in the clinical setting, they will not be discussed in detail here.

Impact and Determinants of High-Sensitivity Cardiac Troponin-T Concentration in Patients With COVID-19 Admitted to Critical Care.

Cardiac Troponin (hs-TnT) elevation has been reported in unselected patients hospitalized with COVID-19 however the mechanism and relationship with mortality remain unclear. Consecutive patients admitted to a high-volume intensive care unit (ICU) in London with severe COVID-19 pneumonitis were included if hs-TnT concentration at admission was known. Kaplan-Meier survival analysis performed, with cohorts classified a priori by multiples of the upper limit of normal (ULN). 277 patients were admitted during a 7-week period in 2020; 176 were included (90% received invasive ventilation). hs-TnT at admission was 16.5 (9.0 to 49.3) ng/L, 56% had concentrations >ULN. 56 patients (31.8%) died during the index admission. Admission hs-TnT level was lower in survivors (12.0 (8.0-27.8) vs 28.5 (14.0 to 81.0) ng/L, p = 0.001). Univariate predictors of mortality were age, APACHE-II Score and admission hs-TnT (HR 1.73, p = 0.007). By multivariate regression, only age (HR 1.33, CI: 1.16.to 1.51, p < 0.01) and admission hs-TnT (HR 1.94, CI: 1.22 to 3.10, p = 0.006) remained predictive. Survival was significantly lower when admission hs-TnT was >ULN (log-rank p-value<0.001). Peak hs-TnT was higher in those who died but was not predictive of death after adjustment for other factors. In conclusion, in critically ill patients with COVID-19 pneumonitis, the hs-TnT level at admission is a powerful independent predictor of the likelihood of surviving to discharge from ICU. In most cases, hs-TnT elevation does not represent major myocardial injury but acts as a sensitive integrated biomarker of global stress. Whether stratification based on admission Troponin level could be used to guide prognostication and management warrants further evaluation.