BACKGROUNDExperimental and clinical evidence supports the role of inflammation in atherosclerosis and its complications. Colchicine is an orally administered, potent antiinflammatory medication that is indicated for the treatment of gout and pericarditis. METHODSWe performed a randomized, double-blind trial involving patients recruited within 30 days after a myocardial infarction. The patients were randomly assigned to receive either low-dose colchicine (0.5 mg once daily) or placebo. The primary efficacy end point was a composite of death from cardiovascular causes, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina leading to coronary revascularization. The components of the primary end point and safety were also assessed. RESULTSA total of 4745 patients were enrolled; 2366 patients were assigned to the colchicine group, and 2379 to the placebo group. Patients were followed for a median of 22.6 months. The primary end point occurred in 5.5% of the patients in the colchicine group, as compared with 7.1% of those in the placebo group (hazard ratio, 0.77; 95% confidence interval [CI], 0.61 to 0.96; P = 0.02). The hazard ratios were 0.84 (95% CI, 0.46 to 1.52) for death from cardiovascular causes, 0.83 (95% CI, 0.25 to 2.73) for resuscitated cardiac arrest, 0.91 (95% CI, 0.68 to 1.21) for myocardial infarction, 0.26 (95% CI, 0.10 to 0.70) for stroke, and 0.50 (95% CI, 0.31 to 0.81) for urgent hospitalization for angina leading to coronary revascularization. Diarrhea was reported in 9.7% of the patients in the colchicine group and in 8.9% of those in the placebo group (P = 0.35). Pneumonia was reported as a serious adverse event in 0.9% of the patients in the colchicine group and in 0.4% of those in the placebo group (P = 0.03). CONCLUSIONSAmong patients with a recent myocardial infarction, colchicine at a dose of 0.5 mg daily led to a significantly lower risk of ischemic cardiovascular events than placebo. (Funded by the Government of Quebec and others; COLCOT ClinicalTrials.gov number, NCT02551094.

Background-Recent clinical studies suggest that endurance sports may promote cardiac arrhythmias. The aim of this study was to use an animal model to evaluate whether sustained intensive exercise training induces potentially adverse myocardial remodeling and thus creates a potential substrate for arrhythmias. Methods and Results-Male Wistar rats were conditioned to run vigorously for 4, 8, and 16 weeks; time-matched sedentary rats served as controls. Serial echocardiograms and in vivo electrophysiological studies at 16 weeks were obtained in both groups. After euthanasia, ventricular collagen deposition was quantified by histological and biochemical studies, and messenger RNA and protein expression of transforming growth factor-␤1, fibronectin-1, matrix metalloproteinase-2, tissue inhibitor of metalloproteinase-1, procollagen-I, and procollagen-III was evaluated in all 4 cardiac chambers. At 16 weeks, exercise rats developed eccentric hypertrophy and diastolic dysfunction, together with atrial dilation. In addition, collagen deposition in the right ventricle and messenger RNA and protein expression of fibrosis markers in both atria and right ventricle were significantly greater in exercise than in sedentary rats at 16 weeks. Ventricular tachycardia could be induced in 5 of 12 exercise rats (42%) and only 1 of 16 sedentary rats (6%; Pϭ0.05). The fibrotic changes caused by 16 weeks of intensive exercise were reversed after an 8-week exercise cessation. Conclusions-In this animal model, we documented cardiac fibrosis after long-term intensive exercise training, togetherwith changes in ventricular function and increased arrhythmia inducibility. If our findings are confirmed in humans, the results would support the notion that long-term vigorous endurance exercise training may in some cases promote adverse remodeling and produce a substrate for cardiac arrhythmias. (Circulation. 2011;123:13-22.)Key Words: arrhythmia Ⅲ exercise Ⅲ fibrosis R egular physical activity confers benefits that are widely recognized such as improved cardiovascular risk profiles and prevention of coronary heart disease and diabetes mellitus. 1,2 Regular exercise also directly and positively affects cardiac physiology (eg, increased myocardial oxygen supply and enhanced myocardial contractility), both in the general population 3 and in patients with cardiovascular disease. 4 Editorial see p 5 Clinical Perspective on p 22Long-term exercise induces hemodynamic changes and alters the loading conditions of the heart, with specific effects depending on the type of sport and intensity, that are most evident among athletes. 5 Cardiac adaptations in highly trained subjects include increased left ventricular (LV) and right ventricular (RV) diameters, enlarged left atrial (LA) dimensions, and increased cardiac mass and LV wall thickness. 5,6 These changes, together with a preserved ejection fraction, have classically characterized the physiology of the "athlete's heart." 5 Despite the evident benefits of an active lifestyle, 1-4 numerous observation...

This review article focuses on the morphological and functional alterations that characterize patients with myocardial bridges (MB) as well as the currently available diagnostic and treatment strategies. Because of incomplete understanding of the pathophysiology of MB, their clinical significance has been the subject of debate for the last quarter century. Investigational tools now available in the cardiac catheterization laboratory have helped clarify why symptoms and signs of ischemia can occur in such patients, especially when the only angiographic finding appears to be systolic compression or milking effect of a coronary vessel. Quantitative coronary angiography and intravascular ultrasound (IVUS) clearly demonstrate that the phasic systolic vessel compression visualized on the angiogram is coupled with a persistent diastolic diameter reduction. Intracoronary Doppler reveals increased flow velocities, retrograde systolic flow, and reduced coronary flow reserve. The clinical diagnosis can be established by significant percent lumen diameter and area narrowing, increased flow velocity, and by characteristic patterns such as the "half moon" phenomenon on IVUS and the early diastolic "finger tip" phenomenon on intracoronary Doppler. Successful medical, interventional, or surgical therapy leads not only to marked improvement or normalization of these alterations but also relief of angina and ischemia.

Background Evidence suggests a role for excessive inflammation in COVID-19 complications. Colchicine is an oral anti-inflammatory medication beneficial in gout, pericarditis, and coronary disease. We aimed to investigate the effect of colchicine on the composite of COVID-19-related death or hospital admission.Methods The present study is a phase 3, randomised, double-blind, adaptive, placebo-controlled, multicentre trial. The study was done in Brazil, Canada, Greece, South Africa, Spain, and the USA, and was led by the Montreal Heart Institute. Patients with COVID-19 diagnosed by PCR testing or clinical criteria who were not being treated in hospital were eligible if they were at least 40 years old and had at least one high-risk characteristic. The randomisation list was computer-generated by an unmasked biostatistician, and masked randomisation was centralised and done electronically through an automated interactive web-response system. The allocation sequence was unstratified and used a 1:1 ratio with a blocking schema and block sizes of six. Patients were randomly assigned to receive orally administered colchicine (0•5 mg twice per day for 3 days and then once per day for 27 days thereafter) or matching placebo. The primary efficacy endpoint was the composite of death or hospital admission for COVID-19. Vital status at the end of the study was available for 97•9% of patients. The analyses were done according to the intention-to-treat principle. The COLCORONA trial is registered with ClinicalTrials.gov (NCT04322682) and is now closed to new participants. FindingsTrial enrolment began in March 23, 2020, and was completed in Dec 22, 2020. A total of 4488 patients (53•9% women; median age 54•0 years, IQR 47•0-61•0) were enrolled and 2235 patients were randomly assigned to colchicine and 2253 to placebo. The primary endpoint occurred in 104 (4•7%) of 2235 patients in the colchicine group and 131 (5•8%) of 2253 patients in the placebo group (odds ratio [OR] 0•79, 95•1% CI 0•61-1•03; p=0•081). Among the 4159 patients with PCR-confirmed COVID-19, the primary endpoint occurred in 96 (4•6%) of 2075 patients in the colchicine group and 126 (6•0%) of 2084 patients in the placebo group (OR 0•75, 0•57-0•99; p=0•042). Serious adverse events were reported in 108 (4•9%) of 2195 patients in the colchicine group and 139 (6•3%) of 2217 patients in the placebo group (p=0•051); pneumonia occurred in 63 (2•9%) of 2195 patients in the colchicine group and 92 (4•1%) of 2217 patients in the placebo group (p=0•021). Diarrhoea was reported in 300 (13•7%) of 2195 patients in the colchicine group and 161 (7•3%) of 2217 patients in the placebo group (p<0•0001).Interpretation In community-treated patients including those without a mandatory diagnostic test, the effect of colchicine on COVID-19-related clinical events was not statistically significant. Among patients with PCR-confirmed COVID-19, colchicine led to a lower rate of the composite of death or hospital admission than placebo. Given the absence of orally administered therapies to pr...

BACKGROUND Optimal management of patients with stable chest pain relies on the prognostic information provided by noninvasive cardiovascular testing, but there are limited data from randomized trials comparing anatomic with functional testing. METHODS In the PROMISE trial (Prospective Multicenter Imaging Study for Evaluation of Chest Pain), patients with stable chest pain and intermediate pretest probability for obstructive coronary artery disease (CAD) were randomly assigned to functional testing (exercise electrocardiography, nuclear stress, or stress echocardiography) or coronary computed tomography angiography (CTA). Site-based diagnostic test reports were classified as normal or mildly, moderately, or severely abnormal. The primary end point was death, myocardial infarction, or unstable angina hospitalizations over a median follow-up of 26.1 months. RESULTS Both the prevalence of normal test results and incidence rate of events in these patients were significantly lower among 4500 patients randomly assigned to CTA in comparison with 4602 patients randomly assigned to functional testing (33.4% versus 78.0%, and 0.9% versus 2.1%, respectively; both P<0.001). In CTA, 54.0% of events (n=74/137) occurred in patients with nonobstructive CAD (1%–69% stenosis). Prevalence of obstructive CAD and myocardial ischemia was low (11.9% versus 12.7%, respectively), with both findings having similar prognostic value (hazard ratio, 3.74; 95% confidence interval [CI], 2.60–5.39; and 3.47; 95% CI, 2.42–4.99). When test findings were stratified as mildly, moderately, or severely abnormal, hazard ratios for events in comparison with normal tests increased proportionally for CTA (2.94; 7.67–10.13; all P<0.001) but not for corresponding functional testing categories (0.94 [P=0.87], 2.65 [P=0.001], 3.88 [P<0.001]). The discriminatory ability of CTA in predicting events was significantly better than functional testing (c-index, 0.72; 95% CI, 0.68–0.76 versus 0.64; 95% CI, 0.59–0.69; P=0.04). If 2714 patients with at least an intermediate Framingham Risk Score (>10%) who had a normal functional test were reclassified as being mildly abnormal, the discriminatory capacity improved to 0.69 (95% CI, 0.64–0.74). CONCLUSIONS Coronary CTA, by identifying patients at risk because of nonobstructive CAD, provides better prognostic information than functional testing in contemporary patients who have stable chest pain with a low burden of obstructive CAD, myocardial ischemia, and events. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01174550.

Residual cardiovascular risk persists despite statins, yet outcome studies of lipid‐targeted therapies beyond low‐density lipoprotein cholesterol (LDL‐C) have not demonstrated added benefit. Triglyceride elevation is an independent risk factor for cardiovascular events. High‐dose eicosapentaenoic acid (EPA) reduces triglyceride‐rich lipoproteins without raising LDL‐C. Omega‐3s have postulated pleiotropic cardioprotective benefits beyond triglyceride‐lowering. To date, no large, multinational, randomized clinical trial has proved that lowering triglycerides on top of statin therapy improves cardiovascular outcomes. The Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE‐IT; NCT01492361) is a phase 3b randomized, double‐blinded, placebo‐controlled trial of icosapent ethyl, a highly purified ethyl ester of EPA, vs placebo. The main objective is to evaluate whether treatment with icosapent ethyl reduces ischemic events in statin‐treated patients with high triglycerides at elevated cardiovascular risk. REDUCE‐IT enrolled men or women age ≥45 years with established cardiovascular disease or age ≥50 years with diabetes mellitus and 1 additional risk factor. Randomization required fasting triglycerides ≥150 mg/dL and <500 mg/dL and LDL‐C >40 mg/dL and ≤100 mg/dL with stable statin (± ezetimibe) ≥4 weeks prior to qualifying measurements. The primary endpoint is a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina. The key secondary endpoint is the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Several secondary, tertiary, and exploratory endpoints will be assessed. Approximately 8000 patients have been randomized at approximately 470 centers worldwide. Follow‐up will continue in this event‐driven trial until approximately 1612 adjudicated primary‐efficacy endpoint events have occurred.

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