Extracellular Vesicles From Epicardial Fat Facilitate Atrial Fibrillation.

BACKGROUND: The role of epicardial fat (eFat)-derived extracellular vesicles (EVs) in the pathogenesis of atrial fibrillation (AF) has never been studied. We tested the hypothesis that eFat-EVs transmit proinflammatory, profibrotic, and proarrhythmic molecules that induce atrial myopathy and fibrillation. METHODS: We collected eFat specimens from patients with (n=32) and without AF (n=30) during elective heart surgery. eFat samples were grown as organ cultures, and the culture medium was collected every 2 days. We then isolated and purified eFat-EVs from the culture medium, and analyzed the EV number, size, morphology, specific markers, encapsulated cytokines, proteome, and microRNAs. Next, we evaluated the biological effects of unpurified and purified EVs on atrial mesenchymal stromal cells and endothelial cells in vitro. To establish a causal association between eFat-EVs and vulnerability to AF, we modeled AF in vitro using induced pluripotent stem cell-derived cardiomyocytes. RESULTS: Microscopic examination revealed excessive inflammation, fibrosis, and apoptosis in fresh and cultured eFat tissues. Cultured explants from patients with AF secreted more EVs and harbored greater amounts of proinflammatory and profibrotic cytokines, and profibrotic microRNA, as well, than those without AF. The proteomic analysis confirmed the distinctive profile of purified eFat-EVs from patients with AF. In vitro, purified and unpurified eFat-EVs from patients with AF had a greater effect on proliferation and migration of human mesenchymal stromal cells and endothelial cells, compared with eFat-EVs from patients without AF. Last, whereas eFat-EVs from patients with and without AF shortened the action potential duration of induced pluripotent stem cell-derived cardiomyocytes, only eFat-EVs from patients with AF induced sustained reentry (rotor) in induced pluripotent stem cell-derived cardiomyocytes. CONCLUSIONS: We show, for the first time, a distinctive proinflammatory, profibrotic, and proarrhythmic signature of eFat-EVs from patients with AF. Our findings uncover another pathway by which eFat promotes the development of atrial myopathy and fibrillation.

Type 2 diabetes mellitus increases the mortality risk after acute coronary syndrome treated with coronary artery bypass surgery.

BACKGROUND: Type 2 diabetes mellitus (DM) is a risk factor for cardiovascular diseases and is common among patients undergoing coronary artery bypass grafting (CABG) surgery. The main objective of our study was to investigate the impact of DM type 2, and its treatment subgroups, on short- and long-term mortality in patients with acute coronary syndrome (ACS) who undergo CABG. METHODS: The study included 1307 patients enrolled from the biennial Acute Coronary Syndrome Israeli Survey between 2000 and 2016, who were hospitalized for ACS and underwent CABG. Of them, 527 (40%) patients were with and 780 (60%) were without DM. RESULTS: Compared with the non-diabetic group, the diabetic group of patients comprised more women and had more comorbidities such as hypertension, dyslipidemia, renal impairment, peripheral vascular disease and prior ischemic heart disease. Overall 30-day mortality rate was similar between DM and non-DM patients (4.2% vs. 4%, p = 0.976). Ten-year mortality rate was higher in DM compared with non-diabetic patients (26.6% vs. 17.7%, log-rank p < 0.001), and higher in the subgroup of insulin-treated patients compared to non-insulin treated patients (31.5% vs. 25.6%, log-rank p = 0.019). Multivariable analysis showed that DM increased the mortality hazard by 1.61-fold, and insulin treatment among the diabetic patients increased the mortality hazard by 1.57-fold. CONCLUSIONS: While type 2 DM did not influence the in-hospital mortality hazard, we showed that the presence of DM among patients with ACS referred to CABG, is a powerful risk factor for long-term mortality, especially when insulin was included in the diabetic treatment strategy.

Outcomes of isolated surgical aortic valve replacement in the era of transcatheter aortic valve implantation.

BACKGROUND AND AIMS: Until early into the 21st century, the only therapeutic option for aortic valve (AV) stenosis was surgical aortic valve replacement (AVR), but this changed with the introduction of transcatheter aortic valve implantation (TAVI). Our objective was to present the results of surgical AVR performed in low-risk patients in the era of TAVI, in a large tertiary medical center. METHODS: Data from low surgical risk patients (defined as Euroscore < 5) greater than 60 years of age, who underwent isolated AVR surgery between 2004 and 2018, were obtained from our departmental database. Of the 313 study patients, 110 (35%) underwent isolated AVR before 2010 (early period) and 203 patients (65%) underwent the same procedure from 2010 onward (late period). RESULTS: Mean age was 67 ± 5 years and 182 (58%) were male. Fifty-six patients (18%) had a unicuspid or bicuspid AV. Patient characteristics were similar between the early and late periods. There was no in-hospital or 30-day mortality throughout the entire cohort, with one case (0.3%) of postoperative stroke. Permanent pacemaker implantation was required in 2.2% (N = 7). Patients in the early period required significantly more re-exploration due to bleeding/tamponade (8.2% vs 1.5%; P = .008). Long-term mortality (1, 3, and 5 years) was higher in the early compared with the late period (2.7% vs 1%, 7.3% vs 3%, and 15.5% vs 3.4%, respectively; log-rank P = .005). CONCLUSIONS: Surgical AVR provides excellent short- and long-term results with low morbidity and mortality in low surgical risk patients. While patient characteristics did not change dramatically over the years, the long-term results were encouraging.

Coronary Artery Bypass Grafting Following Acute Coronary Syndrome: Impact of Gender.

The impact of gender on clinical outcomes after coronary artery bypass grafting (CABG) has generated conflicting results. We investigated the impact of gender, on 30 day mortality, complications and late survival in patients with acute coronary syndrome (ACS) undergoing CABG. The study included 1308 patients enrolled from the biennial Acute Coronary Syndrome Israeli Survey between 2000 and 2016, who were hospitalized for ACS and underwent CABG. Of them, 1045 (80%) were men and 263 (20%) women. While women were older and had more hypertension and hyperlipidemia, they demonstrated less diabetes mellitus, previous ischemic heart disease, smoking, and fewer implicated coronary arteries. Women presented with more atypical symptoms as compared to men (26.3% vs 19.4%, p = 0.017). Overall multivariable-adjusted 30 day mortality was higher in women than in men (OR 2.47 95% CI 1.19-5.1, p = 0.015). Among patients with ST-elevation myocardial infarction (STEMI) or non-STEMI, women had a higher 10 year mortality rate than men (42.5% vs 19.2%, log-rank p < 0.001 and 31.5% vs 20.7%, log-rank, p = 0.012). However, in patients with unstable angina pectoris on admission, these differences were not seen (16.9% vs 13.4%, log-rank p = 0.540). Multivariable analysis demonstrated that female gender was a significant predictor for 10 year mortality (HR 1.39, 95% CI 1.02-1.9, p = 0.038). In a real-life setting, women constitute an independent predictor for short- and long-term mortality following ACS treated by CABG surgery. The reasons for a higher mortality in women should be further investigated as well as specific and/or more intensive therapies after CABG in this high-risk group of patients.