Background: Recent studies have increasingly shown that sodium‐glucose cotransporter 2 (SGLT2) inhibitors may have beneficial cardiovascular and metabolic effects in patients without diabetes mellitus. Hence, we conducted a systematic review and meta‐analysis to determine the effect of SGLT2 inhibitors on cardiovascular and metabolic outcomes in patients without diabetes mellitus. Methods and Results: Four electronic databases (PubMed, Embase, Cochrane, and SCOPUS) were searched on August 30, 2020 for articles published from January 1, 2000 to August 30, 2020, for studies that examined the effect of SGLT2 inhibitors on cardiovascular and metabolic outcomes in patients without diabetes mellitus. A random‐effects pairwise meta‐analysis model was used to summarize the studies. A total of 8 randomized‐controlled trials were included with a combined cohort of 5233 patients. In patients without diabetes mellitus, those with heart failure treated with SGLT2 inhibitors had a 20% relative risk reduction in cardiovascular deaths and heart failure hospitalizations, compared with those who were not treated (risk ratio, 0.78; P <0.001). We additionally found that treatment with SGLT2 inhibitors improved multiple metabolic indices. Patients on SGLT2 inhibitors had a reduction in body weight of −1.21 kg ( P <0.001), body mass index of −0.47 kg/m ² ( P <0.001), systolic blood pressure of −1.90 mm Hg ( P =0.04), and fasting plasma glucose of −0.38 mmol/L ( P =0.05), compared with those without. There were no between‐group differences in NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) levels, waist circumference, diastolic blood pressure, glycated hemoglobin, low‐density lipoprotein cholesterol levels, and estimated glomerular filtration rates. Across our combined cohort of 5233 patients, hypoglycemia was reported in 22 patients. Conclusions: SGLT2 inhibitors improve cardiovascular outcomes in patients without diabetes mellitus with heart failure. In patients without diabetes mellitus, SGLT2 inhibitors showed positive metabolic outcomes in weight and blood pressure control.

Cognitive impairment (CI) is common in heart failure (HF). Patients with HF demonstrate reduced global cognition as well as deficits in multiple cognitive domains compared to controls. Degree of CI may be related to HF severity. HF has also been associated with an increased risk of dementia. Anatomical brain changes have been observed in patients with HF, including grey matter atrophy and increased white matter lesions. Patients with HF and CI have poorer functional independence and self-care, more frequent rehospitalisations as well as increased mortality. Pathophysiological pathways linking HF and CI have been proposed, including cerebral hypoperfusion and impaired cerebrovascular autoregulation, systemic inflammation, proteotoxicity and thromboembolic disease. However, these mechanisms are poorly understood. We conducted a search on MEDLINE, Embase and Scopus for original research exploring the connection between HF and CI. We then reviewed the relevant literature and discuss the associations between HF and CI, the patterns of brain injury in HF and their potential mechanisms, as well as the recognition and management of CI in patients with HF.

Background: Infections following cardiac implantable electronic device (CIED) implantation can require surgical device removal and often results in significant cost, morbidity, and potentially mortality. We aimed to systemically review the literature and identify risk factors associated with mortality following CIED infection. Methods: Electronic searches (up to June 2021) were performed on PubMed and Scopus. Twelve studies (10 retrospective, 2 prospective cohort studies) were included for analysis. Meta-analysis was conducted with the restricted maximum likelihood method, with mortality as the outcome. The overall mortality was 13.7% (438/1398) following CIED infection. Results: On meta-analysis, the male sex (OR 0.77, 95%CI 0.57–1.01, I² = 2.2%) appeared to have lower odds for mortality, while diabetes mellitus appeared to be associated with higher mortality (OR 1.47, 95%CI 0.67–3.26, I² = 81.4%), although these trends did not reach statistical significance. Staphylococcus aureus as the causative organism (OR 2.71, 95%CI 1.76–4.19, I² = 0.0%), presence of heart failure (OR 1.92, 95%CI 1.42–4.19, I² = 0.0%) and embolic phenomena (OR 4.00, 95%CI 1.67–9.56, I² = 69.8%) were associated with higher mortality. Surgical removal of CIED was associated with lower mortality compared with conservative management with antibiotics alone (OR 0.22, 95%CI 0.09–0.50, I² = 62.8%). Conclusion: We identified important risk factors associated with mortality in CIED infections, including Staphyloccocus aureus as the causative organism, and the presence of complications, such as heart failure and embolic phenomena. Surgery, where possible, was associated with better outcomes.

Wee CF, et al. J Cardiovasc Imaging. 2022 Jul;30(3):153-168. https://doi.org/10.4250/jcvi.2021.0159

Endothelial progenitor cells (EPCs) are bone-marrow derived cells that are critical in the maintenance of endothelial wall integrity and protection of ischemic myocardium through the formation of new blood vessels (vasculogenesis) or proliferation of pre-existing vasculature (angiogenesis). Diabetes mellitus (DM) and the metabolic syndrome are commonly associated with ischemic heart disease through its pathological effects on the endothelium and consequent endothelial dysfunction. Thymosin-β4 (Tβ4) which expressed in the embryonic heart is critical in epicardial and coronary artery formation. In this study, we explored the effects of Tβ4 treatment on diabetic EPCs in vitro and intramyocardial injection of Tβ4-treated and non-Tβ4 treated EPCs following acute myocardial infarction (MI) of diabetic rats in vivo. It was found that 10 ng/mL Tβ4 increased migration, tubule formation, and angiogenic factor secretion of diabetic EPCs in vitro. In vivo, although implantation of Tβ4 treated diabetic EPCs significantly increased capillary density and attracted more c-Kit positive progenitor cells into the infarcted hearts as compared with implantation of non-Tβ4 treated diabetic EPCs, the significantly improved left ventricular ejection fraction was only found in the rats which received non-Tβ4 treated EPCs. The data suggests that a low dose Tβ4 increases diabetic EPC migration, tubule formation, and angiogenic factor secretion. However, it did not improve the effects of EPCs on left ventricular pump function in diabetic rats with MI.