Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal agent of the current pandemic of coronavirus disease 2019 (COVID-19). SARS-CoV-2 is a positive-sense single-stranded RNA betacoronavirus sharing genetic similarities with the severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and the Middle East respiratory syndrome-related coronavirus (MERS-CoV).¹ SARS-CoV-2 enters the cells mainly through angiotensin-converting enzyme 2 (ACE2), and triggers an intense inflammatory host response, sometimes leading to a life-threatening acute respiratory distress syndrome (ARDS).¹ Several randomized controlled trials (RCTs) are investigating the safety and efficacy of various antiviral and immunosuppressive agents. Still, many of these drugs have serious adverse effects, and may not be readily available in some healthcare settings, such as in low-income countries.

Aim: To investigate the impact of epicardial adipose tissue (EAT) thickness on cardiopulmonary performance in patients with type 2 diabetes (T2D) and normal heart function. Materials and methods: We analysed EAT thickness in subjects with T2D and normal biventricular systo‐diastolic functions undergoing a maximal cardiopulmonary exercise test combined with stress echocardiography, speckle tracking and pulmonary function assessment, as well as serum N‐terminal pro B‐type natriuretic peptide (NT‐proBNP). Results: In the 72 subjects enrolled, those with EAT thickness above the median (> 5 mm) showed higher body fat mass, smaller indexed left ventricular dimensions and marginally reduced diastolic function variables at rest. Higher EAT thickness was associated with lower peak oxygen uptake (VO _2peak 17.1 ± 3.6 vs. 21.0 ± 5.7 ml/min/kg, P = .001), reduced systolic reserve (ΔS′ 4.6 ± 1.6 vs. 5.8 ± 2.5 m/s, P = .02) and higher natriuretic peptides (NT‐proBNP 64 [29‐165] vs. 31 [26‐139] pg/ml, P = .04), as well as chronotropic insufficiency and impaired heart rate recovery. Ventilatory variables and peripheral oxygen extraction were not different between groups. EAT was independently associated with VO _2peak and linearly and negatively correlated with peak heart rate, heart rate recovery, workload, VO ₂ at the anaerobic threshold and at peak, and cardiac power output, and was directly correlated with natriuretic peptides. Conclusion: Higher EAT thickness in T2D is associated with worse cardiopulmonary performance and multiple traits of subclinical cardiac systolic dysfunction.

Aims: The relationship between resistance artery remodelling and endothelial function remains unknown. In this study, we assessed (i) the capacity of endothelial function and nitric oxide (NO) availability to provide more information on the severity of resistance artery remodelling than common cardiovascular risk factors in subjects at low or high cardiovascular risk; and (ii) differences between patterns of resistance artery remodelling associated with deficit of NO availability and with exposure to cardiovascular risk factors. Methods and results: All analyses were conducted on the microvascular data set of the Italian Society for Arterial Hypertension (SIIA) that includes 356 patients with measures of small resistance arteries remodelling acquired with pressure or wire myography. Information on endothelial function and NO availability were also available in 116 patients. The European Heart Score (HS) was used to define the total cardiovascular risk of each patient. Endothelial function was inversely related with the severity of the resistance artery remodelling, and this association remained significant after adjustment for the HS. By contrast, the HS lost its significant association with the media-to-lumen (M/L) ratio and the media cross-sectional area after adjustment for endothelial function. The strength of these associations was similar in subjects at high and low cardiovascular risk. The addition of endothelial function and NO availability to the HS significantly improved the identification of subjects at more and less severe resistance artery remodelling. A severe deficit of NO availability was associated with hypertrophic remodelling, while a higher HS was more clearly associated with eutrophic remodelling. Conclusion: Resistance artery endothelial function and NO availability might represent important factors involved in resistance artery remodelling, independently from cardiovascular risk factor exposure.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome resulting from the interaction between cardiac diseases, comorbidities and ageing. HFpEF is characterised by the activation of neurohormonal axes, namely of the renin-angiotensin-aldosterone system and the sympathetic nervous system, although to a lesser extent compared with heart failure with reduced ejection fraction. This provides a rationale for neurohormonal modulation as a therapeutic approach for HFpEF. Nonetheless, randomised clinical trials have failed to demonstrate a prognostic benefit from neurohormonal modulation therapies in HFpEF, with the sole exception of patients with left ventricular ejection fraction in the lower range of normality, for whom the American guidelines suggest that such therapies may be considered. In this review, the pathophysiological rationale for neurohormonal modulation in HFpEF is summarised and the clinical evidence on pharmacological and nonpharmacological approaches backing current recommendations discussed.