Colchicine is safe and efficacious in the prevention of the PPS and its related complications and may halve the risk of developing the syndrome following cardiac surgery. ClinicalTrials.gov number, NCT00128427.

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MD; for the COPPS InvestigatorsBackground-Inflammation and pericarditis may be contributing factors for postoperative atrial fibrillation (POAF), and both are potentially affected by antiinflammatory drugs and colchicine, which has been shown to be safe and efficacious for the prevention of pericarditis and the postpericardiotomy syndrome (PPS). The aim of the Colchicine for the Prevention of the Post-Pericardiotomy Syndrome (COPPS) POAF substudy was to test the efficacy and safety of colchicine for the prevention of POAF after cardiac surgery. Methods and Results-The COPPS POAF substudy included 336 patients (mean age, 65.7Ϯ12.3 years; 69% male) of the COPPS trial, a multicenter, double-blind, randomized trial. Substudy patients were in sinus rhythm before starting the intervention (placebo/colchicine 1.0 mg twice daily starting on postoperative day 3 followed by a maintenance dose of 0.5 mg twice daily for 1 month in patients Ն70 kg, halved doses for patients Ͻ70 kg or intolerant to the highest dose). The substudy primary end point was the incidence of POAF on intervention at 1 month. Despite well-balanced baseline characteristics, patients on colchicine had a reduced incidence of POAF (12.0% versus 22.0%, respectively; Pϭ0.021; relative risk reduction, 45%; number needed to treat, 11) with a shorter in-hospital stay (9.4Ϯ3.7 versus 10.3Ϯ4.3 days; Pϭ0.040) and rehabilitation stay (12.1Ϯ6.1 versus 13.9Ϯ6.5 days; Pϭ0.009). Side effects were similar in the study groups. Key Words: atrial fibrillation Ⅲ cardiac surgery Ⅲ colchicine Ⅲ postpericardiotomy syndrome Ⅲ prevention P ostoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery; it is reported in 10% to 65% of cases, depending on the surgery type (coronary artery bypass graft surgery, valve surgery, or combined coronary artery bypass graft/valve surgery), patient features, definition of arrhythmia, and surveillance. 1 Nowadays, POAF is becoming more common because of the increasing number of cardiac surgery operations and the aging of the population. This complication increases patient morbidity, length of hospital stay, and management costs. 2 Conclusion-Colchicine Editorial see p 2281 Clinical Perspective on p 2295Prevention of POAF is an important management goal supported by American and European guidelines. 3-5 Many different agents have been studied to fit this goal and may be grouped into 2 main categories: agents with antiarrhythmic properties and agents with antiinflammatory activity such as corticosteroids, statins, and free radical scavengers. 6 The development of POAF is likely multifactorial. Pericardial inflammation, autonomic imbalance during the postoperative time, excessive production of catecholamines, and fluid shift may all contribute. 7,8 Inflammation, inhomogeneity of atrial conduction, and the incidence of POAF are significantly decreased by corticosteroids. 9 Thus, antiinflammatory therapy may be beneficial for the prevention of POAF. In the Colchicine for the Prevention of the Postpericardiotomy ...

Increased oxidative stress has been implicated in the pathogenesis of a number of cardiovascular diseases. Recent findings suggest that myeloperoxidase (MPO) may play a key role in the initiation and maintenance of chronic heart failure (CHF) by contributing to the depletion of the intracellular reservoir of nitric oxide (NO). NO consumption through MPO activity may lead to protein chlorination or nitration, leading to tissue damage. Primary cultures of human endocardial endothelial cells (EEC) obtained at heart transplantation of patients with CHF and human umbilical vein endothelial cells (HUVEC) were subjected to oxidative stress by incubation with hydrogen peroxide at non lethal (60 microM) dose for different exposure times (3 and 6 h). Treated and control cells were tested by immunohistochemistry and RT-PCR for MPO and 3-chlorotyrosine expression. Both endothelial cell types expressed myeloperoxidase following oxidative stress, with higher levels in EEC. Moreover, 3-chlorotyrosine accumulation in treated cells alone indicated the presence of MPO-derived hypochlorous acid. Immunohistochemistry on sections from post-infarcted heart confirmed in vivo the endothelial positivity to MPO, 3-chlorotyrosine and, to a minor extent, nitrotyrosine. Immunohistochemical observations were confirmed by detection of MPO mRNA in both stimulated EEC and HUVEC cells. This study demonstrates for the first time that EEC can express MPO after oxidative stress, both in vitro and in vivo, followed by accumulation of 3-chlorotyrosine, an end product of oxidative stress. Deregulation of endothelial functions may contribute to the development of a number of cardiovascular diseases, including CHF. The results also highlight the notion that endothelium is not only a target but also a key player in oxidative-driven cardiovascular stress.

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