Background Emerging evidence from China suggests that coronavirus disease 2019 (COVID-19) is deadlier for infected men than women with a 2.8% fatality rate being reported in Chinese men versus 1.7% in women. Further, sex-disaggregated data for COVID-19 in several European countries show a similar number of cases between the sexes, but more severe outcomes in aged men. Case fatality is highest in men with pre-existing cardiovascular conditions. The mechanisms accounting for the reduced case fatality rate in women are currently unclear but may offer potential to develop novel risk stratification tools and therapeutic options for women and men. Content The present review summarizes latest clinical and epidemiological evidence for gender and sex differences in COVID-19 from Europe and China. We discuss potential sex-specific mechanisms modulating the course of disease, such as hormone-regulated expression of genes encoding for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) entry receptors angiotensin converting enzyme (ACE) 2 receptor and TMPRSS2 as well as sex hormone-driven innate and adaptive immune responses and immunoaging. Finally, we elucidate the impact of gender-specific lifestyle, health behavior, psychological stress, and socioeconomic conditions on COVID-19 and discuss sex specific aspects of antiviral therapies. Conclusion The sex and gender disparities observed in COVID-19 vulnerability emphasize the need to better understand the impact of sex and gender on incidence and case fatality of the disease and to tailor treatment according to sex and gender. The ongoing and planned prophylactic and therapeutic treatment studies must include prospective sex- and gender-sensitive analyses.

Although health disparities in women presenting with acute coronary syndrome (ACS) have received growing attention in recent years, clinical outcomes from ACS are still worse for women than for men. Women continue to experience higher patient and system delays and receive less aggressive invasive treatment and pharmacotherapies. Gender- and sex-specific variables that contribute to ACS vulnerability remain largely unknown. Notwithstanding the sex differences in baseline coronary anatomy and function, women and men are treated the same based on guidelines that were established from experimental and clinical trial data over-representing the male population. Importantly, younger women have a particularly unfavourable prognosis and a plethora of unanswered questions remains in this younger population. The present review summarizes contemporary evidence for gender and sex differences in vascular biology, clinical presentation, and outcomes of ACS. We further discuss potential mechanisms and non-traditional risk conditions modulating the course of disease in women and men, such as unrecognized psychosocial factors, sex-specific vascular and neural stress responses, and the potential impact of epigenetic modifications.

The ability to obtain quantitative values of flow and myocardial flow reserve (MFR) has been perceived as an important advantage of PET over conventional nuclear myocardial perfusion imaging (MPI). We evaluated the added diagnostic value of MFR over MPI alone as assessed with 13 N-ammonia and PET/CT to predict angiographic coronary artery disease (CAD). Methods: Seventy-three patients underwent 1-d adenosine stress-rest 13 N-ammonia PET/CT MPI, and MFR was calculated. The added value of MFR as an adjunct to MPI for predicting CAD (luminal narrowing $ 50%) was evaluated using invasive coronary angiography as a standard of reference. Results: Per patient, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MPI for detecting significant CAD were 79%, 80%, 91%, 59%, and 79%, respectively. Adding a cutoff of less than 2.0 for global MFR to MPI findings improved the values to 96% (P , 0.005), 80%, 93%, 89% (P , 0.005), and 92% (P , 0.005), respectively. Conclusion: The quantification of MFR in 13 N-ammonia PET/CT MPI provides a substantial added diagnostic value for detection of CAD. Particularly in patients with normal MPI results, quantification of MFR helps to unmask clinically significant CAD.Key Words: myocardial flow reserve; 13 N-ammonia; positron emission tomography; diagnostic value; myocardial perfusion imaging Nucl Med 2012; 53:1230 53: -1234 53: DOI: 10.2967 The PET technique confers advantages over SPECT related to improved image resolution and intrinsic attenuation correction (1). In addition, in myocardial perfusion imaging (MPI) PET offers quantitative assessment of myocardial blood flow (MBF) at rest and pharmacologic stress allowing calculation of myocardial flow reserve (MFR) (2). The latter is an index to evaluate blood circulation from the epicardial coronary arteries down to the microcirculation (3), which therefore provides functional information far beyond the epicardial section of the coronary vascular tree. Relative MPI such as SPECT (or PET without quantitative measurement) relies on induction of flow heterogeneities by hyperemic stress, which may sometimes underestimate the extent of coronary artery disease (CAD), as only the most severely underperfused territory may be evidenced (4). By contrast, absolute flow and MFR may reveal the true extent of CAD even at an early stage of subclinical atherosclerotic CAD. This possibility is supported by recent results documenting an added prognostic value for MFR over PET MPI alone with either 13 N-ammonia (5) or 82 Rb (6,7). Interestingly, MFR remained predictive throughout a 10-y follow-up period (5). Although many studies have revealed a reversed correlation of increasing coronary artery lesion narrowing with decreasing hyperemic flow and MFR in the respective myocardial territory (8-10), its diagnostic added value over MPI PET has not been assessed systematically. JWe evaluated the hypothesis that patients with decreased MFR (,2.0) would have a higher probability of CAD and that, thus, MFR would co...

INTRODUCTION: Left ventricular non-compaction cardiomyopathy (LVNC) is a rare cardiomyopathy, originally described as an isolated disease without other structural cardiac abnormalities. The aim of this study was to explore the prevalence of LVNC among adults with different types of congenital heart disease. METHODS: From our databases we identified adults with congenital heart disease who fulfilled diagnostic criteria for LVNC. We report frequencies of associated congenital cardiac defects and the prevalence of LVNC among patients with different congenital heart defects. RESULTS: From a total of 202 patients with LVNC, 24 patients (12%; mean age 32±11years, 19 males) had additional congenital cardiac defects. Associated defects were left ventricular outflow tract abnormalities in 11 patients (46%), including 7 uni-or bicuspid aortic valves; two aortic coarctations; one diffuse aortic hypoplasia and one subaortic stenosis, Ebstein anomaly in 6 patients (25%), tetralogy of Fallot in two (8%), and double outlet right ventricle in one patient (4%). In our cohort, the prevalence of LVNC was highest among patients with Ebstein anomaly (6/40, 15%), followed by aortic coarctation (2/60, 3%), tetralogy of Fallot (3/129, 2%) and uni-or bicuspid aortic valves (7/963, 1%). CONCLUSION: In adults, various forms of congenital heart disease are associated with LVNC, particularly stenotic lesions of the left ventricular outflow tract, Ebstein anomaly, and tetralogy of Fallot. In the future, studying these patients in more depth may provide a better understanding of the interplay between genetic and hemodynamic factors that lead to the phenotype of LVNC.

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Current evidence suggests that severity and mortality of COVID-19 is higher in men than in women, whereas women might be at increased risk of COVID-19 reinfection and development of long COVID. Differences between sexes have been observed in other infectious diseases and in the response to vaccines. Sex-specific expression patterns of proteins mediating virus binding and entry, and divergent reactions of the immune and endocrine system, in particular the hypothalamic-pituitary-adrenal axis, in response to acute stress might explain the higher severity of COVID-19 in men. In this Personal View, we discuss how sex hormones, comorbidities, and the sex chromosome complement influence these mechanisms in the context of COVID-19. Due to its role in the severity and progression of SARS-CoV-2 infections, we argue that sexual dimorphism has potential implications for disease treatment, public health measures, and follow-up of patients predisposed to the development of long COVID. We suggest that sex differences could be considered in future pandemic surveillance and treatment of patients with COVID-19 to help to achieve better disease stratification and improved outcomes.

BackgroundAs coronary computed tomography angiography (CCTA) has emerged as a non-invasive alternative for evaluation of coronary anatomy with a lower referral threshold than invasive coronary angiography (ICA), the prevalence of coronary anomalies in CCTA may more closely reflect the true prevalence in the general population. Morphological features of coronary anomalies can be evaluated more precisely by CCTA than by ICA, which might lead to a higher identification of congenital coronary anomalies in CCTA compared to ICA.To evaluate the incidence, clinical and morphological features of the anatomy of patients with coronary anomalies detected either by coronary computed tomography angiography (CCTA) with prospective ECG-triggering or invasive coronary angiography (ICA).MethodsConsecutive patients underwent 64-slice CCTA (n = 1′759) with prospective ECG-triggering or ICA (n = 9′782) and coronary anatomy was evaluated for identification of coronary anomalies to predefined criteria (origin, course and termination) according to international recommendations.ResultsThe prevalence of coronary anomalies was 7.9% (n = 138) in CCTA and 2.1% in ICA (n = 203; p < 0.01). The most commonly coronary anomaly detected by CCTA was myocardial bridging 42.8% (n = 59) vs. 21.2% (n = 43); p < 0.01, while with ICA an absent left main trunk was the most observed anomaly 36.0% (n = 73; p < 0.01). In 9.4% (n = 13) of identified coronary anomalies in CCTA 9.4% were potentially serious coronary anaomalies, defined as a course of the coronary artery between aorta and pulmonary artery were identified.ConclusionThe prevalence of coronary anomalies is substantially higher with CCTA than ICA even after exclusion of patients with myocardial bridging which is more frequently found with CCTA. This suggests that the true prevalence of coronary anomalies in the general population may have been underestimated based on ICA.