A randomized, controlled, multi-center trial has found that cardiac resynchronization therapy produced no improvement in peak oxygen uptake during exercise testing, the trial's primary endpoint, in patients with Class III heart failure, including mechanical problems that disrupt the heart's normal rhythm and a moderately prolonged QRS complex as demonstrated on EKG.
The Resynchronization Therapy in Narrow QRS (RethinQ) trial was designed to determine whether cardiac resynchronization therapy (CRT), which currently benefits about 10 to 15 percent of patients with moderate to severe heart failure, could be extended to a much larger group of heart failure patients, about 40 to 50 percent of the 550,000 new cases diagnosed each year.
Although patients in the trial reported increased activity levels and decreased discomfort, the study's results -- presented Nov. 6, 2007, at a late-breaking clinical trial session of the American Heart Association’s Scientific Sessions in Orlando, Florida -- showed that CRT produced no improvement for this population in any of the other objective parameters and endpoints. These parameters included performance on a six-minute walk test, echocardiographic improvement in left-ventricular remodeling, and the secondary endpoint of quality-of-life score.
"While cardiac resynchronization therapy has helped thousands of patients with heart failure caused by electrical dyssynchrony, we did not see that same benefit in patients with mechanical dyssynchrony as determined by echocardiography," said study lead author John F. Beshai, MD, director of pacemaker and defibrillator services at the University of Chicago Medical Center. "This is a valuable therapy for carefully selected patients," he said, "but further research will be necessary to determine which additional groups might benefit from CRT."
CRT devices are surgically implanted in the upper chest with leads to the right and left ventricles. The device delivers electrical impulses to each ventricle simultaneously, which stimulates synchronous contraction. This synchronous contraction improves the heart's pumping efficiency, which improves patients' symptoms.
Current guidelines support the use of CRT in patients with moderate to severe heart failure, an ejection fraction less than or equal to 35 percent, and a prolonged QRS duration, greater than 120 milliseconds, what physicians refer to as a "wide QRS."
The RethinQ investigators followed 172 patients with advanced heart failure, mechanical dyssynchrony (when the heart's main pumping chambers, the ventricles, do not contract together efficiently) and a QRS duration of less than 130 milliseconds, for six months. Eighty-five patients were randomly selected to receive treatment with CRT. The other 87 were followed as controls.
The sub-group of patients with the longest QRS duration, between 120 and 130 milliseconds, did show improvement from CRT, as measured by peak oxygen uptake during exercise testing. This sub-group already is indicated for CRT, said Beshai, and this finding "supports previous research on this patient sub-group." Patients with a QRS duration of less than 120 milliseconds, however, did not show improvement.
"While there may be a group of patients with a narrow QRS who can benefit from CRT therapy, the measures of dyssynchrony used in the RethinQ study did not identify them," Beshai said. "These new data are helpful for all heart failure physicians as we continue to determine the best criteria for assessing who will most benefit from CRT therapy."
Heart failure, one of the leading causes of death in the U. S., is a progressive condition in which the heart weakens and loses its ability to pump an adequate supply of blood to the body. About 5 million Americans suffer from heart failure, with 550,000 new cases diagnosed each year.
This investigator-initiated study was funded by St Jude Medical, makers of the CRT device. Additional authors include Richard Grimm and Patrick Tchou of the Cleveland Clinic Foundation; Sherif Nagueh of the Methodist Hospital, Houston; James Baker of St Thomas Hospital, Nashville; Scott Beau of Arkansas Heart Hospital, Little Rock; Steven Greenberg of St. Francis Hospital, Roslyn, NY; and Luis Pires of St. John Hospital and Medical Center, Detroit.