Rationale and design of a randomized clinical trial to assess the safety and efficacy of cardiac resynchronization therapy in patients with advanced heart failure: The multicenter InSync randomized clinical evaluation (MIRACLE)

Up to 50% of patients with chronic systolic heart failure have interventricular conduction delays, such as left bundle branch block, that result in abnormal electrical depolarization of the heart. Prolonged QRS duration results in abnormal interventricular septal wall motion, decreased contractility, reduced diastolic filling time, and prolonged duration of mitral regurgitation, which places the failing heart at a significant mechanical disadvantage. Prolonged QRS duration has been associated with poor outcome in heart failure patients. Atrial-synchronized, biventricular pacing or cardiac resynchronization therapy optimizes atrial-ventricular delay, narrows QRS duration, and seems promising in the management of advanced heart failure patients. Initial studies show improved quality of life and functional capacity compared with baseline or with no pacing. These studies, however, were either uncontrolled or poorly controlled, unblinded or only single-blinded, and enrolled small numbers of patients. The Multicenter InSync Randomized Clinical Evaluation (MIRACLE) is a large, prospective, randomized, double-blind, controlled trial designed to more definitively evaluate the clinical efficacy and safety of cardiac resynchronization for heart failure. The study is being completed in 3 phases (an initial pilot phase, a pivotal phase, and an expansion phase), enrolling 500 patients with New York Heart Association (NYHA) class III and IV systolic heart failure and QRS durations of 130 ms or more. Prospectively defined primary end points for the pivotal phase include evaluation of safety (implant success rate, freedom from stimulator- and ventricular-lead-related complications) and effects on functional status (quality of life, NYHA class, 6-minute hall walk distance) at 6 months. A variety of secondary end points will further define the efficacy and mechanism(s) of action of cardiac resynchronization in heart failure. The pivotal phase of MIRACLE will conclude in January 2001.