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Combined Cardiac Resynchronization and Implantable Cardioversion Defibrillator
Abstract & Commentary
Synopsis: Cardiac resynchronization therapy improves quality of life and New York Heart Association Functional class in patients with moderate-to-severe heart failure, wide QRS durations, and indications for an ICD.
Source: Young JB, et al. For The Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE ICD) Trial Investigators. JAMA. 2003;289:2685-2694.
Young and colleagues report a multicenter trial involving the use of cardiac resynchronization therapy (CRT) in patients with accepted indications for an implantable cardioverter defibrillator (ICD). In order to be eligible for the trial, patients had to have a standard indication for ICD placement. The trial enrolled patients with class II, III, and IV heart failure, but in this report only patients with class III and IV heart failure are discussed. The left ventricular ejection fraction had to be £ 0.35 and the QRS duration > 130 msec. Patients also had to have a left ventricular end diastolic diameter of ³ 55 mm, and their medical therapy should have been stable for 1 month prior to enrollment.
In all patients who agreed to participate, an implant was attempted with a Medtronic biventricular ICD. Patients in whom the implant was unsuccessful, usually because of failure to place the coronary sinus lead, are not included in this study. After implant, patients underwent a cardiopulmonary exercise test to measure peak oxygen consumption and exercise duration. After completion of the exercise test, patients were randomized to receive active CRT or just optimal medical therapy and tachyarrhythmia therapy, but without CRT (control group). Most patients in the CRT group were programmed to track native atrial activity with biventricular pacing. Patients in the control group were programmed to a mode in which pacing was not required unless the native rate fell to less than 35 bpm. Follow-up evaluations were performed at 1, 3, and 6 months after enrollment. The 3 primary efficacy end points were changes in New York Heart Association functional class, quality-of-life score and 6-minute walk distance. Secondary end points included peak oxygen consumption, treadmill exercise duration, changes in left ventricular ejection fraction, end systolic and end diastolic volumes, and end diastolic dimensions.
All end points were analyzed according to an intention-to-treat principle. This paper primarily presents data at the 6-month time point.
A total of 369 patients were randomized in the trial. The mean age was about 67 years in both groups. Eighty-nine percent of the patients were New York Heart Association Functional class III, and 11% had New York Heart Association Functional class IV. The average QRS duration at baseline was 163 msec, with a mean ejection fraction of 24%. The indication for the ICD was cardiac arrest in 10%, sustained ventricular tachycardia in 40%, and induction of ventricular fibrillation or ventricular tachycardia at electrophysiologic study in the remainder. ACE inhibitors or an angiotensin blocking agent were taken by 90% of the patients. Sixty percent of the patients were on beta blockers. Ninety-four percent of the patients were on diuretics.
There was a slight imbalance in the form of heart disease in the 2 groups. In the control group, 76% of the patients had ischemic heart disease, whereas in the CRT group only 64% had ischemic heart disease.
During the course of the study, 14 patients crossed over from the control group to CRT before 6 months. Ten patients in the CRT group crossed over to standard therapy because of either lead dislodgement, diaphragmatic stimulation, or programming errors.
Both groups showed some improvement in quality of life. However, the improvement was significantly higher in the CRT group. There was also a significantly greater median decrease in New York Heart Association functional class in the CRT group compared to the control group. However, there was no significant difference in the 6-minute walk test distance change between the 2 groups. The secondary end points also showed a trend toward favoring CRT. Treadmill exercise duration improved in patients on CRT, and CRT patients achieved a higher median increase in peak oxygen consumption. There were nonsignificant trends toward improvement in left ventricular volumes but no change in ejection fraction.
During the 6 months of randomization, 26% of patients in the control group and 22% of the patients in the CRT group experienced at least 1 spontaneous episode of ventricular tachycardia or fibrillation. There were 15 deaths in the control group and 14 deaths in the CRT group during the 6-month follow-up. Three of the deaths in each group were classified as sudden deaths. During the 6-month follow-up, there was no difference in the probability of hospitalization for worsening heart failure or death from any cause (25% control vs 25.7% CRT). The risk of death or all cause hospitalization was 48.3% in the control group vs 47.4% in the CRT group.
Young et al conclude that cardiac resynchronization therapy improves quality of life and New York Heart Association Functional class in patients with moderate-to-severe heart failure, wide QRS durations, and indications for an ICD.
Comment by John DiMarco, MD, PhD
Cardiac resynchronization therapy using biventricular pacing has now become established as an effective therapy for patients with advanced heart failure, left ventricular dysfunction, and prolonged QRS durations. Within the last year, devices capable of providing both biventricular pacing and defibrillation have been released for general use. This paper confirms that combining ICD therapy with resynchronization therapy is feasible. However, the magnitude of changes in functional capacity are less than have been seen in earlier studies on biventricular pacing.
There are several possible reasons for the somewhat lesser degree of benefits seen with CRT in this paper. It must be remembered that the primary indication for device implantation in these patients was for treating their arrhythmias. In earlier CRT trials, the primary indication for device implant was heart failure, and CRT was an intervention used to reverse or slow a steady decline in functional status. Not all of the patients in this trial had recently unstable congestive heart failure. In such patients who were recently stable on optimal medical therapy, it will be harder to show any beneficial effects of device therapy. This will be increasingly true in the future as medical therapy for heart failure improves. Young et al were also careful to minimize any adverse effect of standard ICD implant. The probability of a patient being treated with pacing from the right ventricle only was minimized by careful programming. Therefore, any deleterious effects from RV pacing over and above those associated with the patient’s intrinsic conduction defect were not encountered.
Based on data from this study and from preliminary data from the COMPANION Trial, it seems reasonable to use a cardiac resynchronization device in patients who will receive an ICD and either have a bundle branch block at baseline or will require ventricular pacing. Combined therapy to manage patients’ arrhythmias with the ICD functions of the device and heart failure with CRT seems to be the strategy most likely to produce optimal results.
Dr. DiMarco is Professor of Medicine Division of Cardiology University of Virginia, Charlottesville.