CRT Plus ICD vs. ICD Alone in Heart Failure and Wide QRS Patients
CRT Plus ICD vs. ICD Alone in Heart Failure and Wide QRS Patients
Abstract & Commentary
By John P. DiMarco, MD, PhD, Professor of Medicine, Division of Cardiology, University of Virginia, Charlottesville. Dr. DiMarco is a consultant for Novartis, and does research for Medtronic and Guidant. This article originally appeared in the November 2009 issue of Clinical Cardiology Alert. It was edited by Michael H. Crawford, MD, and peer reviewed by Ethan Weiss, MD.
Source: Moss AJ, et al. Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med. 2009:361:1329-1338.
Current indications for cardiac-resynchronization therapy (CRT) require that patients have New York Heart Association (NYHA) Class III or Class IV heart-failure symptoms. However, long-standing ventricular dyssynchrony can lead to left-ventricular remodeling and decreased left-ventricular ejection fraction. In this study, the Multicenter Automatic Defibrillation Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) trial, Moss et al tested the hypothesis that prophylactic CRT, in combination with an ICD, would reduce the risk of death or nonfatal heart-failure events in patients with an ICD indication and a QRS duration of 130 milliseconds or more, but only Class I or Class II heart-failure symptoms.
Over a 52-month period, MADIT-CRT enrolled 1,820 patients in the United States, Canada, and Europe. All patients met current guidelines for ICD therapy. Patients with ischemic cardiomyopathy could have Class I or Class II heart-failure symptoms, but those with nonischemic cardiomyopathy had Class II symptoms only. All patients had sinus rhythm, a left-ventricular ejection fraction of 30% or less, and a QRS duration of 130 milliseconds or more. At baseline, a 12-lead electrocardiogram for QRS duration, an echocardiogram for ejection fraction and ventricular volumes, and a six-minute walk test were performed. Patients were randomly assigned in a 3:2 ratio to receive either a biventricular ICD system (CRT-ICD) or a single- or dual-chamber ICD. The primary endpoint was death from any cause or a nonfatal heart-failure event, whichever came first. Heart-failure events required either an outpatient course of intravenous decongestive therapy or a hospital admission with augmented therapy for heart failure. Adjudication of endpoints was carried out by an independent committee unaware of study-group assignment. Analysis used an intention-to-treat approach based on initial randomization.
The study enrolled 1,820 patients with a mean age of 64; 75% were men. There were 821 patients with nonischemic heart disease and 999 patients with ischemic heart disease. The mean left ejection fraction was 0.24, and 65% of the patients had a QRS duration ≥ 150 milliseconds. Follow-up of patients in the trial averaged 2.4 years.
There were 29 patients who did not receive any device for various reasons, 11 in the CRT group (1%) and 19 (2.6%) in the ICD-only group. A total of 173 crossovers occurred. In the ICD-only group, 91 patients (12.4) were upgraded to CRT-ICD therapy during the course of the trial. In the CRT-ICD group, 82 patients (7.5%) achieved an ICD-only device because technical difficulties prevented satisfactory transvenous placement of the left-ventricular pacing lead.
There were 36 deaths (3.3%) and 151 initial heart-failure events (13%) in the CRT-ICD group, compared to 18 deaths (2.5%) and 167 heart-failure events (22.8%) in the ICD-only group. For all patients, the hazard ratio for death or heart failure in the CRT-ICD group compared to the ICD only group was 0.66 (95% confidence interval, 0.52-0.84; p = 0.001). For heart failure only, the hazard ratio was 0.59 (95% CI, 0.47-0.74; p < 0.001). There was no difference in mortality between the groups, with a hazard ratio of 1.0. The hazard ratios for these endpoints were similar for patients with ischemic cardiomyopathy and nonischemic cardiomyopathy. Subgroup analysis revealed a greater benefit of CRT-ICD therapy among women compared to men and among patients with a QRS duration of 150 milliseconds or more compared to those with a shorter QRS duration. At one-year follow-up, the left-ventricular ejection fraction increased by 11% in the CRT-ICD group compared to 3% in the ICD-only group. Favorable changes in the left-ventricular end diastolic and end-systolic volumes were also noted in the CRT-ICD group.
Adverse effects were higher in the CRT-ICD group, with higher rates of pneumothorax, infection, and pocket hematoma requiring evacuation noted. Coronary venous dissection with pericardial effusion occurred in five patients in the CRT-ICD group (0.5%). Left-ventricular lead repositioning was required during the first 30 days in 44 patients (4.0%). After 30 days, serious device-related adverse events, not further defined by Moss et al, occurred with a frequency of 4.5 per 100 device months in the CRT-ICD group, compared to 5.2 per 100 device months in the ICD-only group.
Moss et al conclude that prophylactic use of ICD-CRT therapy in asymptomatic or mildly symptomatic patients with either ischemic or nonischemic heart disease, a reduced ejection fraction, and a wide QRS complex decreases the risk of heart-failure events and improves echocardiographic measures of left-ventricular function.
Commentary
The data from MADIT-CRT are very interesting but should be studied carefully before we change our current practices and guidelines with regard to resynchronization therapy. In MADIT-CRT, the primary endpoint was death and heart-failure events. The data clearly show that CRT decreases heart-failure events in those with the QRS durations over 150 m/sec. However, there were frequent complications associated with implementing CRT therapy that may well cancel out the benefits reported. Moss et al report higher rates of pneumothorax, lead dislodgement, pericardial effusion, and hematoma with CRT therapy and, presumably, many of these complications resulted in prolonged or repeat hospital stays around the time of implant. If data on total cardiac hospital days were reported, there would presumably be a diminution of the benefits seen in the CRT-ICD group. If this is true, then prophylactic CRT therapy is unlikely to be cost-effective since the biventricular ICDs are considerably more costly then single- or dual-chamber systems.
Current data from the national ICD registry indicate that almost 50% of the primary prevention ICD implants in the United States are CRT devices. This suggests that implanting physicians are already using fairly loose criteria for diagnosing Class III functional status in patients with a wide QRS complex in order to stay within current guidelines. MADIT-CRT supports this approach for patients with a QRS duration more than 150 m/sec. For patients with a QRS duration less than 150 m/sec and class I or II functional status, I would argue that a single- or dual-chamber ICD should remain the preferred choice, with later upgrade if symptoms progress.
Current indications for cardiac-resynchronization therapy (CRT) require that patients have New York Heart Association (NYHA) Class III or Class IV heart-failure symptoms.Subscribe Now for Access
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