This is the first systematic review and meta-analysis demonstrating the positive dose-dependent association between TMAO plasma levels and increased cardiovascular risk and mortality.

Our data suggest that cardiac remodeling associated with HCM determines a significant release of miRNAs into the bloodstream: the circulating levels of both cardiac- and non-cardiac-specific miRNAs are significantly increased in the plasma of HCM patients. However, correlation with left ventricular hypertrophy parameters holds true for only a few miRNAs (i.e., miR-199a-5p, -27a, and -29a), whereas only miR-29a is significantly associated with both hypertrophy and fibrosis, identifying it as a potential biomarker for myocardial remodeling assessment in HCM.

Objective To assess the risks and benefits of P2Y 12 inhibitor monotherapy compared with dual antiplatelet therapy (DAPT) and whether these associations are modified by patients’ characteristics. Design Individual patient level meta-analysis of randomised controlled trials. Data sources Searches were conducted in Ovid Medline, Embase, and three websites ( www.tctmd.com , www.escardio.org , www.acc.org/cardiosourceplus ) from inception to 16 July 2020. The primary authors provided individual participant data. Eligibility criteria Randomised controlled trials comparing effects of oral P2Y 12 monotherapy and DAPT on centrally adjudicated endpoints after coronary revascularisation in patients without an indication for oral anticoagulation. Main outcome measures The primary outcome was a composite of all cause death, myocardial infarction, and stroke, tested for non-inferiority against a margin of 1.15 for the hazard ratio. The key safety endpoint was Bleeding Academic Research Consortium (BARC) type 3 or type 5 bleeding. Results The meta-analysis included data from six trials, including 24 096 patients. The primary outcome occurred in 283 (2.95%) patients with P2Y 12 inhibitor monotherapy and 315 (3.27%) with DAPT in the per protocol population (hazard ratio 0.93, 95% confidence interval 0.79 to 1.09; P=0.005 for non-inferiority; P=0.38 for superiority; τ 2 =0.00) and in 303 (2.94%) with P2Y 12 inhibitor monotherapy and 338 (3.36%) with DAPT in the intention to treat population (0.90, 0.77 to 1.05; P=0.18 for superiority; τ 2 =0.00). The treatment effect was consistent across all subgroups, except for sex (P for interaction=0.02), suggesting that P2Y 12 inhibitor monotherapy lowers the risk of the primary ischaemic endpoint in women (hazard ratio 0.64, 0.46 to 0.89) but not in men (1.00, 0.83 to 1.19). The risk of bleeding was lower with P2Y 12 inhibitor monotherapy than with DAPT (97 (0.89%) v 197 (1.83%); hazard ratio 0.49, 0.39 to 0.63; P<0.001; τ 2 =0.03), which was consistent across subgroups, except for type of P2Y 12 inhibitor (P for interaction=0.02), suggesting greater benefit when a newer P2Y 12 inhibitor rather than clopidogrel was part of the DAPT regimen. Conclusions P2Y 12 inhibitor monotherapy was associated with a similar risk of death, myocardial infarction, or stroke, with evidence that this association may be modified by sex, and a lower bleeding risk compared with DAPT. Registration PROSPERO CRD42020176853.

No abstract

Diabetes mellitus is an established risk factor of atherosclerosis 1 and restenosis after percutaneous coronary interventions (PCI).2 New-generation drug-eluting stents (DES) provide improved safety and efficacy when compared with balloon angioplasty, bare-metal stents, and early-generation DES, 3 including patients with diabetes mellitus. 4 In addition, advances in medical therapy including high-dose statins seem to mitigate the markedly accelerated progression of native atherosclerosis in diabetic patients. 5 Intriguingly, although diabetes mellitus has historically been considered a powerful Background-Diabetes mellitus and angiographic coronary artery disease complexity are intertwined and unfavorably affect prognosis after percutaneous coronary interventions, but their relative impact on long-term outcomes after percutaneous coronary intervention with drug-eluting stents remains controversial. This study determined drug-eluting stents outcomes in relation to diabetic status and coronary artery disease complexity as assessed by the Synergy Between PCI With Taxus and Cardiac Surgery (SYNTAX) score. Methods and Results-In a patient-level pooled analysis from 4 all-comers trials, 6081 patients were stratified according to diabetic status and according to the median SYNTAX score ≤11 or >11. The primary end point was major adverse cardiac events, a composite of cardiac death, myocardial infarction, and clinically indicated target lesion revascularization within 2 years. Diabetes mellitus was present in 1310 patients (22%), and new-generation drug-eluting stents were used in 4554 patients (75%). Major adverse cardiac events occurred in 173 diabetics (14.5%) and 436 nondiabetic patients (9.9%; P<0.001). In adjusted Cox regression analyses, SYNTAX score and diabetes mellitus were both associated with the primary end point (P<0.001 and P=0.028, respectively; P for interaction, 0.07). In multivariable analyses, diabetic versus nondiabetic patients had higher risks of major adverse cardiac events (hazard ratio, 1.25; 95% confidence interval, 1.03-1.53; P=0.026) and target lesion revascularization (hazard ratio, 1.54; 95% confidence interval, 1.18-2.01; P=0.002) but similar risks of cardiac death (hazard ratio, 1.41; 95% confidence interval, 0.96-2.07; P=0.08) and myocardial infarction (hazard ratio, 0.89; 95% confidence interval, 0.64-1.22; P=0.45), without significant interaction with SYNTAX score ≤11 or >11 for any of the end points. Conclusions-In this population treated with predominantly new-generation drug-eluting stents, diabetic patients were at increased risk for repeat target-lesion revascularization consistently across the spectrum of disease complexity. The SYNTAX score was an independent predictor of 2-year outcomes but did not modify the respective effect of diabetes mellitus. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00297661, NCT00389220, NCT00617084, and NCT01443104. The complexity of coronary artery disease (CAD) strongly affects outcomes after PCI. The Sy...

Among selected patients with native pure AR deemed at high risk for SAVR, TAVR is technically feasible and associated with an acceptable risk of early mortality.

No abstract

BackgroundUncoupling protein 3 (ucp3) is a member of the mitochondrial anion carrier superfamily of proteins uncoupling mitochondrial respiration. In this study, we investigated the effects of ucp3 genetic deletion on mitochondrial function and cell survival under low oxygen conditions in vitro and in vivo.Methods and ResultsTo test the effects of ucp3 deletion in vitro, murine embryonic fibroblasts and adult cardiomyocytes were isolated from wild‐type (WT, n=67) and ucp3 knockout mice (ucp3−/−, n=70). To test the effects of ucp3 genetic deletion in vivo, myocardial infarction (MI) was induced by permanent coronary artery ligation in WT and ucp3−/− mice. Compared with WT, ucp3−/− murine embryonic fibroblasts and cardiomyocytes exhibited mitochondrial dysfunction and increased mitochondrial reactive oxygen species generation and apoptotic cell death under hypoxic conditions in vitro (terminal deoxynucleotidyl transferase‐dUTP nick end labeling–positive nuclei: WT hypoxia, 70.3±1.2%; ucp3−/− hypoxia, 85.3±0.9%; P<0.05). After MI, despite similar areas at risk in the 2 groups, ucp3−/− hearts demonstrated a significantly larger infarct size compared with WT (infarct area/area at risk: WT, 48.2±3.7%; ucp3−/−, 65.0±2.9%; P<0.05). Eight weeks after MI, cardiac function was significantly decreased in ucp3−/− mice compared with WT (fractional shortening: WT MI, 42.7±3.1%; ucp3−/− MI, 24.4±2.9; P<0.05), and this was associated with heightened apoptotic cell death (terminal deoxynucleotidyl transferase‐dUTP nick end labeling–positive nuclei: WT MI, 0.7±0.04%; ucp3−/− MI, 1.1±0.09%, P<0.05).ConclusionsOur data indicate that ucp3 levels regulate reactive oxygen species levels and cell survival during hypoxia, modulating infarct size in the ischemic heart.