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.