Search

Abstract Aims Changes in peak exercise oxygen uptake (VO2) and cardiac output (CO) 6 months after successful percutaneous edge‐to‐edge mitral valve repair (pMVR) in severe primary (PMR) and functional mitral regurgitation (FMR) patients are unknown. The aim of the study was to assess the efficacy of pMVR at rest by echocardiography, VO2 and CO (inert gas rebreathing) measurement and during cardiopulmonary exercise test with CO measurement. Methods and results We evaluated 145 and 115 patients at rest and 98 and 66 during exercise before and after pMVR, respectively. After successful pMVR, significant reductions in MR and NYHA class were observed in FMR and PMR patients. Cardiac ultrasound showed reverse remodelling (left ventricular end‐diastolic volume from 158 ± 63 mL to 147 ± 64, P

Background CD34+ stem/progenitor cells are involved in vascular homeostasis and in neovascularization of ischemic tissues. The number of circulating CD34+ stem cells is a predictive biomarker of adverse cardiovascular outcomes in diabetic patients. Here, we provide evidence that hyperglycemia can be “memorized” by the stem cells through epigenetic changes that contribute to onset and maintenance of their dysfunction in diabetes mellitus. Methods and Results Cord‐blood–derived CD34+ stem cells exposed to high glucose displayed increased reactive oxygen species production, overexpression of p66shc gene, and downregulation of antioxidant genes catalase and manganese superoxide dismutase when compared with normoglycemic cells. This altered oxidative state was associated with impaired migration ability toward stromal‐cell–derived factor 1 alpha and reduced protein and mRNA expression of the C‐X‐C chemokine receptor type 4 (CXCR4) receptor. The methylation analysis by bisulfite Sanger sequencing of the CXCR4 promoter revealed a significant increase in DNA methylation density in high‐glucose CD34+ stem cells that negatively correlated with mRNA expression (Pearson r=−0.76; P=0.004). Consistently, we found, by chromatin immunoprecipitation assay, a more transcriptionally inactive chromatin conformation and reduced RNA polymerase II engagement on the CXCR4 promoter. Notably, alteration of CXCR4 DNA methylation, as well as transcriptional and functional defects, persisted in high‐glucose CD34+ stem cells despite recovery in normoglycemic conditions. Importantly, such an epigenetic modification was thoroughly confirmed in bone marrow CD34+ stem cells isolated from sternal biopsies of diabetic patients undergoing coronary bypass surgery. Conclusions CD34+ stem cells “memorize” the hyperglycemic environment in the form of epigenetic modifications that collude to alter CXCR4 receptor expression and migration.

BackgroundLiterature studies suggested a lower prevalence of coronary artery disease (CAD) in bicuspid aortic valve (BAV) than in tricuspid aortic valve (TAV) patients. However, this finding has been challenged. We performed a meta‐analysis to assess whether aortic valve morphology has a different association with CAD, concomitant coronary artery bypass grafting (CABG), and postoperative mortality. Methods and ResultsDetailed search was conducted according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta‐Analyses) guideline to identify all patients with BAV or TAV and presence of CAD, concomitant myocardial surgical revascularization, and the postoperative mortality. Thirty‐one studies on 3017 BAV and 4586 TAV patients undergoing aortic valve surgery were included. BAV patients showed a lower prevalence of CAD (odds ratio [OR]: 0.33; 95% CI: 0.17, 0.65), concomitant CABG (OR, 0.45; 95% CI: 0.35, 0.59), and postoperative mortality (OR, 0.62; 95% CI: 0.40, 0.97) than TAV. However, BAV subjects were significantly younger than TAV (mean difference: −7.29; 95% CI: −11.17, −3.41) were more frequently males (OR, 1.61; 95% CI: 1.33, 1.94) and exhibited a lower prevalence of hypertension (OR, 0.58; 95% CI: 0.39, 0.87) and diabetes (OR, 0.71; 95% CI: 0.54, 0.93). Interestingly, a metaregression analysis showed that younger age and lower prevalence of diabetes were associated with lower prevalence of CAD (Z value: −3.03; P=0.002 and Z value: −3.10; P=0.002, respectively) and CABG (Z value: −2.69; P=0.007 and Z value: −3.36; P=0.001, respectively) documented in BAV patients. ConclusionsAnalysis of raw data suggested an association of aortic valve morphology with prevalence of CAD, concomitant CABG, and postoperative mortality. Interestingly, the differences in age and diabetes have a profound impact on prevalence of CAD between BAV and TAV. In conclusion, our meta‐analysis suggests that the presence of CAD is independent of aortic valve morphology.