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This article provides information and a commentary on key trials relevant to the pathophysiology, prevention, and treatment of heart failure (HF) presented at the annual American College of Cardiology meeting held in New Orleans in 2011. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. The STICH trial failed to show a benefit of revascularization on all-cause mortality in patients with HF and coronary artery disease; however, cardiovascular deaths were reduced compared with medical therapy alone. Results from the NorthStar study suggest that patients with clinically stable systolic HF, who are on optimal medical therapy, including those with elevated amino-terminal B-type natriuretic peptide levels, may not benefit from long-term follow-up in an HF clinic. Results from the TARGET study demonstrate that targeted left ventricular lead placement using speckle tracking echocardiography is feasible in patients undergoing implantation of a cardiac resynchronization therapy device and is associated with an enhanced response. Two-year follow-up data from EVEREST II show that although a catheter-based mitral valve repair procedure using the MitraClip® system was less effective at reducing mitral regurgitation than conventional surgery, similar improvements in clinical outcomes were observed with fewer short-term adverse events.