An innovative new therapy that involves “tuning up” the chambers of the failing heart so they can pump blood more effectively received additional clinical support today, as results of a key European study were reported in the March 22, 2001, issue of the New England Journal of Medicine. The therapy, called cardiac resynchronization, uses a pacemaker-like device to stimulate both chambers of the heart.

Published only days after positive results from Medtronic’s North American MIRACLE (Multi-center InSyncÒ Randomized Clinical Evaluation) trial were reported, data from the MUSTIC (MUltisite STImulation in Cardiomyopathy) study reinforce the MIRACLE trial’s preliminary findings. Both studies suggest that cardiac resynchronization therapy results in functional improvement for a statistically significant number of advanced heart failure patients. The MUSTIC trial was sponsored by the European Society of Cardiology, with financial and technical support from Medtronic, Inc., and ELA Medical, S.A. (France).

Both the MUSTIC study and the MIRACLE trial evaluated therapy involving new implantable systems, similar to pacemakers, that synchronize the beating action of the left and right heart chambers in patients with advanced heart failure. Specialized devices to provide this cardiac resynchronization therapy are commercially available in Europe and Canada but are still under clinical investigation in the United States.

MUSTIC, a controlled, randomized crossover study, compared patients’ exercise tolerance and quality of life when their implanted systems were activated with those indicators during a time when their systems were turned off.

Professor J.C. Daubert, who heads the Department of Cardiology and Vascular Medicine at University Hospital in Rennes, France, led a team of researchers in evaluating 58 heart failure patients at 15 study sites who were divided into two equal-sized groups. The first group immediately received cardiac resynchronization therapy, which paces both the right and left ventricles in synchrony with the heart’s natural rhythm. After 12 weeks, this group “crossed over,” i.e., their cardiac resynchronization systems were turned off for 12 weeks.

Cardiac resynchronization systems were also implanted in the second group, but they were not activated until after 12 weeks. The systems were then turned on for 12 weeks. After 24 weeks, all patients were given the option of receiving resynchronization therapy or not.

The MUSTIC findings suggest that patients whose heart chambers are resynchronized to pump more effectively achieve a significantly improved quality of life. According to Dr. Daubert’s report, the resynchronization therapy “significantly improved symptoms, exercise tolerance and the quality of life and was associated with a reduced number of hospitalizations for decompensated heart failure” in a statistically significant percentage of the study subjects.

Data showed that, during the phase when the implantable cardiac resynchronization systems were activated, patients could walk about 23 percent farther than when the systems were not activated. When asked to compare their quality of life with and without activation of the implanted systems, the patients’ scores indicated a 32 percent improvement when their heart action was optimized with the therapy.

While quality of life and oxygen uptake, as measured by distance walked, were the study’s primary data collection points, the authors noted that only three hospitalizations for heart failure occurred with the systems activated, compared with nine among the 58 patients during periods when their systems were off.

Patients in the study were initially in New York Heart Association Class III, meaning that their lifestyles were seriously restricted or that they were bedridden. All were being treated with two classes of drugs: ACE inhibitors and diuretics at maximal tolerated doses. Enrollment began in March 1998, and the study was completed a year later.

Heart failure affects more than 5 million Americans and 22 million people worldwide with varying degrees of severity. In about a third of patients seriously ill with heart failure, their hearts exhibit major intraventricular electrical conduction delays that disturb the synchronous beating of the left and right ventricles, so that they cannot pump adequate blood to supply the body with necessary oxygen and nutrients. In addition to this study, other formal, randomized, multicenter clinical studies have evaluated cardiac resynchronization. These include:

· The North American MIRACLE trial, which began in November 1998 to evaluate the safety and effectiveness of the Medtronic InSync® cardiac resynchronization system. Used in the MUSTIC study, InSync was commercially released to the European market in 1998 and is currently undergoing clinical evaluation in the United States. The MIRACLE trial results reported at the American College of Cardiology (ACC) meeting this week in Orlando involved 266 patients at 44 U.S. and Canadian centers in a study similar to MUSTIC. The results are from the pivotal first phase of the study, which concluded that cardiac resynchronization therapy dramatically improves exercise function and quality of life in study patients with advanced heart failure.

· The Medtronic-sponsored Multi-center InSync Randomized Clinical Evaluation Implantable Cardioverter Defibrillator (MIRACLE ICD) trial is evaluating therapy for heart failure patients who need resynchronization therapy and who have or may be at risk of experiencing episodes of dangerous accelerated heart rhythms. Patients are implanted with the Medtronic InSync ICD. Effectiveness of the device will be measured by evaluating the system’s effects on patients’ physical capacity and their subjective quality of life. About 35 U.S. and Canadian medical institutions are taking part.

· The Cardiac Resynchronization – Heart Failure (CARE-HF) trial is an 18-month, randomized, controlled study in Europe to evaluate 800 patients for the effect of the new device-based resynchronization therapy combined with drug therapy on hospitalization, mortality and quality of life. Enrollment began in January 2000 at approximately 100 heart centers in 12 European countries. Its 800 patients – 400 receiving cardiac resynchronization associated with optimal pharmacological therapy and 400 who receive optimal pharmacological therapy only – will be in New York Heart Association Classes III or IV, indicating that their chronic heart failure has dramatically progressed.