ORLANDO — Cardiac resynchronization therapy was, for the first time, proved to cut mortality in patients with severe heart failure in a controlled study with 813 patients.
With an average follow-up of almost 2.5 years, the results of the Cardiac Resynchronisation Heart Failure Study (CARE-HF) also substantially extended the period that cardiac resynchronization therapy (CRT) has been shown to benefit patients. And the results showed that CRT devices produce a marked improvement in serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of left ventricular dysfunction.
“About 15%–20% of patients returned to normal or near-normal cardiac function,” John G.F. Cleland, M.D., reported at the annual meeting of the American College of Cardiology.
But the study left unanswered a major, lingering question about using CRT devices for treating heart failure: Do patients get incremental benefit from a combined CRT-defibrillator device, or is a CRT-pacemaker device enough? All of the CRT devices used in the new study had pacemaker function only.
“In some patients, a CRT-defibrillator is indicated, because they're at high risk for sudden death, but for many patients a CRT alone is the preferred choice because defibrillators can add a mortality risk,” said Dr. Cleland, chairman of the department of cardiology at Castle Hill Hospital in Kingston-upon-Hull, England.
The CARE-HF trial enrolled patients with New York Heart Association (NYHA) class III or IV heart failure, a left ventricular ejection fraction of 35% or less, a left ventricular end-diastolic dimension of at least 30 mm, and a QRS interval of at least 120 msec. Patients with a QRS interval of less than 150 msec also had to meet at least two of three more criteria of cardiac dyssynchrony.
The study was done at 82 European centers and was funded by Medtronic Inc., the company that makes the devices used in the study. Dr. Cleland has been a consultant to and a speaker for Medtronic.
About 38% of patients had ischemic heart disease, about 45% had dilated cardiomyopathy, and the remainder had other causes of heart disease. About 95% of patients were treated with an ACE inhibitor or angiotensin receptor blocker, about 72% were treated with a β-blocker, and about 55% were treated with spironolactone. Patients were randomized to treatment with optimized medical therapy only, or medical therapy plus implantation of a CRT pacemaker device. The primary end point of the study was combined rate of death from any cause, or an unplanned hospitalization for a major cardiovascular event.
After an average follow-up of 29 months, the primary end point occurred in 39% of patients who received CRT devices, compared with 55% of patients treated with medical therapy only, a statistically significant difference, reported Dr. Cleland. (Results were published concurrent with his presentation at http://content.nejm.org/cgi/reprint/NEJMoa050496.pdf
Death occurred in 20% of patients in the CRT group and 30% of patients treated with drugs only, also a statistically significant difference. Sudden death occurred in 38 of 120 patients who died in the medical therapy group, and in 29 of the 82 patients who died in the CRT group.
After 18 months of treatment, 31% of patients in the CRT group had NYHA class I heart failure, 45% had class II heart failure, and 24% continued to have class III or IV heart failure. In the medical therapy group, 13% improved to NYHA class I heart failure, 37% had class II disease, and 50% continued to have class III or IV disease.
