Background-In animal models, brief periods of ischemia performed just at the time of reperfusion can reduce infarct size, a phenomenon called postconditioning. In this prospective, randomized, controlled, multicenter study, we investigated whether postconditioning may protect the human heart during coronary angioplasty for acute myocardial infarction. Methods and Results-Thirty patients, submitted to coronary angioplasty for ongoing acute myocardial infarction, contributed to the study. Patients were randomly assigned to either a control or a postconditioning group. After reperfusion by direct stenting, control subjects underwent no further intervention, whereas postconditioning was performed within 1 minute of reflow by 4 episodes of 1-minute inflation and 1-minute deflation of the angioplasty balloon. Infarct size was assessed by measuring total creatine kinase release over 72 hours. Area at risk and collateral blood flow were estimated on left ventricular and coronary angiograms. No adverse events occurred in the postconditioning group. Determinants of infarct size, including ischemia time, size of the area at risk, and collateral flow, were comparable between the 2 groups. Area under the curve of creatine kinase release was significantly reduced in the postconditioning compared with the control group, averaging 208 984Ϯ26 576 compared with 326 095Ϯ48 779 (arbitrary units) in control subjects, ie, a 36% reduction in infarct size. Blush grade, a marker of myocardial reperfusion, was significantly increased in postconditioned compared with control subjects: 2.44Ϯ0.17 versus 1.95Ϯ0.27, respectively (PϽ0.05). Conclusions-This

Among patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.).

BACKGROUNDExperimental and clinical evidence suggests that cyclosporine may attenuate reperfusion injury and reduce myocardial infarct size. We aimed to test whether cyclosporine would improve clinical outcomes and prevent adverse left ventricular remodeling. METHODSIn a multicenter, double-blind, randomized trial, we assigned 970 patients with an acute anterior ST-segment elevation myocardial infarction (STEMI) who were undergoing percutaneous coronary intervention (PCI) within 12 hours after symptom onset and who had complete occlusion of the culprit coronary artery to receive a bolus injection of cyclosporine (administered intravenously at a dose of 2.5 mg per kilogram of body weight) or matching placebo before coronary recanalization. The primary outcome was a composite of death from any cause, worsening of heart failure during the initial hospitalization, rehospitalization for heart failure, or adverse left ventricular remodeling at 1 year. Adverse left ventricular remodeling was defined as an increase of 15% or more in the left ventricular end-diastolic volume. RESULTSA total of 395 patients in the cyclosporine group and 396 in the placebo group received the assigned study drug and had data that could be evaluated for the primary outcome at 1 year. The rate of the primary outcome was 59.0% in the cyclosporine group and 58.1% in the control group (odds ratio, 1.04; 95% confidence interval, 0.78 to 1.39; P = 0.77). Cyclosporine did not reduce the incidence of the separate clinical components of the primary outcome or other events, including recurrent infarction, unstable angina, and stroke. No significant difference in the safety profile was observed between the two treatment groups. CONCLUSIONSIn patients with anterior STEMI who had been referred for primary PCI, intravenous cyclosporine did not result in better clinical outcomes than those with placebo and did not prevent adverse left ventricular remodeling at 1 year. ( n engl j med 373;11 nejm.org September 10, 2015 1022T h e ne w e ngl a nd jou r na l o f m e dicine O ver the past three decades, major progress has been made in the treatment of patients with ST-segment elevation myocardial infarction (STEMI).1 Nevertheless, the rates of death, heart failure, and recurrent ischemic events occurring in the first year after infarction remain unacceptably elevated in this highrisk population. Although many advances have been made in the development of methods to reopen the culprit coronary artery and prevent reocclusion, there is currently no specific treatment that targets myocardial reperfusion injury, which is a paradoxical form of myocardial damage that occurs as a result of the restoration of vessel patency.2 Growing evidence from experimental studies and small-size proof-of-concept clinical trials shows that reperfusion injury contributes greatly to the final infarct size.3-5 Preclinical studies indicate that the opening of the mitochondrial permeability transition pore (PTP) in the inner mitochondrial membrane plays a major role in reperfusion injury. ...

No abstract

No abstract

Diabetes has emerged as a major threat to worldwide health. The exact mechanisms underlying the disease are unknown; however, there is growing evidence that the excess generation of reactive oxygen species (ROS) associated with hyperglycemia, causes oxidative stress in a variety of tissues. In this context, various natural compounds with pleiotropic actions like α-lipoic acid (LA) are of interest, especially in metabolic diseases such as diabetes. LA, either as a dietary supplement or a therapeutic agent, modulates redox potential because of its ability to match the redox status between different subcellular compartments as well as extracellularly. Both the oxidized (disulfide) and reduced (di-thiol: dihydro-lipoic acid, DHLA) forms of LA show antioxidant properties. LA exerts antioxidant effects in biological systems through ROS quenching but also via an action on transition metal chelation. Dietary supplementation with LA has been successfully employed in a variety of in vivo models of disease associated with an imbalance of redox status: diabetes and cardiovascular diseases. The complex and intimate association between increased oxidative stress and increased inflammation in related disorders such as diabetes, makes it difficult to establish the temporal sequence of the relationship.

Background The COVID-19 pandemic has had a profound effect on general health care. We aimed to evaluate the effect of a nationwide lockdown in France on admissions to hospital for acute myocardial infarction, by patient characteristics and regional prevalence of the pandemic. Methods In this registry study, we collected data from 21 centres participating in the ongoing French Cohort of Myocardial Infarction Evaluation (FRENCHIE) registry, which collects data from all patients admitted for ST segment elevation myocardial infarction (STEMI) or non-ST segment elevation myocardial infarction (NSTEMI) within 48 h of symptom onset. We analysed weekly hospital admissions over 8 weeks: the 4 weeks preceding the institution of the lockdown and the 4 weeks following lockdown. The primary outcome was the change in the number of hospital admissions for all types of acute myocardial infarction, NSTEMI, and STEMI between the 4 weeks before lockdown and the 4 weeks after lockdown. Comparisons between categorical variables were made using χ² tests or Fisher's exact tests. Comparisons of continuous variables were made using Student's t tests or Mann-Whitney tests. Poisson regression was used to determine the significance of change in hospital admissions over the two periods, after verifying the absence of overdispersion. Age category, region, and type of acute myocardial infarction (STEMI or NSTEMI) were used as covariables. The FRENCHIE cohort is registered with ClinicalTrials.gov, NCT04050956. Findings Between Feb 17 and April 12, 2020, 1167 patients were consecutively admitted within 48 h of acute myocardial infarction (583 with STEMI, 584 with NSTEMI) and were included in the study. Admissions for acute myocardial infarction decreased between the periods before and after lockdown was instituted, from 686 before to 481 after lockdown (30% decrease; incidence rate ratio 0⋅69 [95% CI 0⋅51-0⋅70]). Admissions for STEMI decreased from 331 to 252 (24%; 0⋅72 [0⋅62-0⋅85]), and admissions for NSTEMI decreased from 355 to 229 (35%; 0⋅64 [0⋅55-0⋅76]) following institution of the lockdown, with similar trends according to sex, risk factors, and regional prevalence of hospital admissions for COVID-19. Interpretation A marked decrease in hospital admissions was observed following the lockdown, irrespective of patient characteristics and regional prevalence of COVID-19. Health authorities should be aware of these findings, in order to adapt their message if the COVID-19 pandemic persists or recurs, or in case of future major epidemics. Funding Recherche Hospitalo-Universitaire en Santé iVasc.

The aim of this study was to evaluate the value of microvascular obstruction (MO) and infarct size as a percentage of left ventricular mass (IS%LV), as measured by contrast-enhanced cardiac magnetic resonance, in predicting major cardiovascular adverse events (MACE) at 2 years in patients with ST-segment elevation myocardial infarction reperfused by primary percutaneous coronary intervention. Individual data from 1,025 patients were entered into the pooled analysis. MO was associated with the occurrence of MACE, defined as a composite of cardiac death, congestive heart failure, and myocardial re-infarction (adjusted hazard ratio: 3.74; 95% confidence interval: 2.21 to 6.34). IS%LV ≥25% was not associated with MACE (adjusted hazard ratio: 0.90; 95% confidence interval: 0.59 to 1.37). The authors conclude that MO is an independent predictor of MACE and cardiac death, whereas IS%LV is not independently associated with MACE.