TORONTO — In patients with mild heart failure, cardiac resynchronization therapy improved composite clinical response scores at 18 months, was associated with left ventricular reverse remodeling, reduced the risk of heart failure hospitalization, and lowered the combined risk of morbidity and mortality, compared with optimal medical therapy.
The 18-month data from the European cohort of the Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) trial supported secondary conclusions from the previously reported 12-month analysis, which, although it indicated that the trial missed its primary clinical composite end point, showed evidence of remodeling and clinical benefit with CRT in mild heart failure (HF).
“Ongoing CRT trials in New York Heart Association class I and II patients may confirm these observations and expand the indication for CRT to this population of heart failure patients,” said Dr. William T. Abraham, who presented the data at the annual meeting of the Heart Failure Society of America.
The REVERSE trial was a multinational prospective effort involving 610 patients with mild or asymptomatic HF and ventricular dyssynchrony. All patients received a CRT device in addition to optimal medical therapy; 191 were randomized to have the device turned on and 419 were randomized to have it turned off.
Eligible patients had left ventricular ejection fractions below 40%, had QRS durations of at least 120 milliseconds, and were already on optimal medical therapy.
The study's main results were published online in the Journal of the American College of Cardiology in September (doi:10.1016/j.jacc.2008.08.027
At this meeting, Dr. Abraham presented the 18-month results from 262 patients in the European cohort, for whom follow-up is continuing to 24 months. These patients, he noted, differed significantly from the North American cohort in their baseline characteristics: They were younger, less likely to have ischemic cardiomyopathy, and less likely to have an implantable cardioverter defibrillator. The European patients had similar ejection fractions to the North American cohort, but had a bit more left ventricular enlargement and slightly longer QRS durations.
In this study population the primary end point significantly favored CRT therapy at 18 months, reported Dr. Abraham, director of the division of cardiovascular medicine at the Ohio State University, Columbus. The proportion of patients who had worsened at 18 months was 29% in the control group vs. 15% in the CRT group, a highly significant difference.
LVESVI improvements seen at 12 months were sustained at 18 months. Also, left ventricular end-diastolic volume index and ejection fraction were both improved in CRT patients, compared with controls.
Furthermore, all-cause mortality did not differ between treatments, while a “remarkable” 58% reduction was seen in the risk of HF hospitalization in the CRT group at 18 months. The absolute rates of hospitalization at 18 months were 13.5% in the control arm and 5.5% in the CRT arm. The combined risk of first HF hospitalization and death was reduced 50% with CRT. Rates of non-HF hospitalization were identical in the CRT on and off groups.
These results “show that there is a favorable impact on remodeling that continues beyond 12 months and that there is a favorable impact on heart failure outcomes … and no signal of an adverse effect on mortality,” commented Dr. William G. Stevenson of Brigham and Women's Hospital in Boston.
REVERSE was sponsored by Medtronic Inc. Dr. Abraham reports research grants, speaker honoraria, and consulting fees from Medtronic, St. Jude Medical Inc., and Biotronik GmbH.