Abstract & Commentary
Synopsis: Patients with class III or class IV heart failure who have an indication for an ICD and have a widened QRS should receive an ICD with cardiac resynchronization.
Source: Higgins SL, et al. J Am Coll Cardiol. 2003;42:1454-1459.
In this report, Higgins and colleagues report on a multicenter trial on the efficacy of cardiac resynchronization therapy in patients with an indication for an implantable cardioverter defibrillator (ICD). All patients in the study had conventional indications for implant of an ICD for either primary or secondary prevention of life-threatening ventricular arrhythmias. In addition, they all had New York Heart Association class II-IV heart failure symptoms, a left ventricular ejection fraction < 35%, and a QRS interval in sinus rhythm > 120 msec. Patients who had an indication for permanent pacing were not eligible. Patients who had atrial arrhythmias, which would preclude effective tracking of atrial activity, were also excluded. Patients underwent implantation of a device with right and left ventricular pacing leads at baseline and then were followed for 30 days with no pacing through the left ventricular lead. Pharmacologic therapy was optimized during this period. There were 2 phases of the study. In phase one, a crossover design was used with randomization 30 days after implant to either resynchronization therapy or no resynchronization therapy with a crossover after 3 months. In phase 2, patients were just randomly assigned to either 6 months of resynchronization therapy or no resynchronization therapy. Initially, the study planned to use oxygen consumption and 6-minute walk distance as the primary end point measures. This was later modified so that the end point was a composite of events including allcause mortality, hospitalization for worsening heart failure, and ventricular tachyarrhythmias requiring device therapy.
The study enrolled 581 patients from 47 centers. Fourteen patients later withdrew consent, were withdrawn by Higgins et al, or were excluded because of inability to place the coronary venous lead. Thus, the final study group was 501 patients with 448 receiving a transvenous left ventricular pacing system and 53 receiving a transthoracic system after an initial transvenous attempt failed. Almost all of the transthoracic leads were implanted during the early portion of the study.
There were 10 deaths and one patient withdrawal in the 30-day postimplant period prior to randomization. Two of the deaths were perioperative; 5 were due to late pump failure, 2 to other cardiac causes, and one to an unknown cause.
The patient’s functional status often changed during the postimplant recovery period. Although patients were not treated with resynchronization therapy during this time, 40% of the patients in New York Heart Association class III or IV improved to New York Heart Association class I or II and 30 of the 162 New York Heart Association class II patients worsened to New York Heart Association class III or IV. Unfortunately, the paper doesn’t specifically state what pacing mode was used during this period. At the time of randomization to resynchronization therapy, 227 patients were in New York Heart Association class III or IV, and 263 were in class I or II. In the entire population, there was a consistent but not statistically significant trend toward fewer heart failure events with resynchronization therapy. Of the 245 patients randomized to CRT, a total of 79 events were observed, including 11 deaths, 32 patients with at least one heart failure hospitalization, and 36 patients with at least one ventricular tachycardia or ventricular fibrillation event. In the control patients, there were 94 events, including 16 deaths, 39 patients with at least one heart failure hospitalization, and 39 patients with at least one VT or VF arrest. Peak oxygen consumption and 6-minute walk distance both improved significantly, but there was only a trend toward improvement in New York Heart Association functional class. Most of this change was seen in patients with class III or IV congestive heart failure symptoms at baseline.
Higgins et al conclude that patients with class III or IV heart failure who have an indication for an ICD and have a widened QRS should receive an ICD with cardiac resynchronization. In this short-term follow-up, they were unable to demonstrate benefits in patients with New York Heart Association class I or II symptoms at baseline. However, longer-term studies may show improvement.
Comment by John DiMarco, MD, PhD
The last several years have shown the introduction of pacing devices that use biventricular pacing for cardiac resynchronization in patients with intraventricular conduction disease. Currently, up to 50% of ICDs being implanted in some centers are devices that can deliver biventricular pacing. Several factors have supported this trend. First, patients with intraventricular conduction defects, particularly left bundle branch block, have been shown to be at very high risk for both heart failure and ventricular arrhythmias. Approximately 25% of patients with advanced heart failure, and perhaps even a greater percent with heart failure and a prior history of ventricular arrhythmias, have intraventricular conduction defects. The possibility that a single device will both improve quality of life and prolong its duration is obviously attractive.
This study reported here shows, however, that short-term benefits will only be seen in patients in whom significant heart failure symptoms are present at baseline. However, as technology improves and it becomes easier and safer to implant left ventricular leads, we may approach a point where it is easier to put in the lead and then use whatever pacing modality is required.
One of the limitations in this paper is that Higgins et al do not describe how the devices were programmed during the "no resynchronization" portion of the trial. It has recently been observed in several trials that unnecessary pacing from the right ventricular apex may actually be harmful. Therefore, it’s hard to know if the findings during resynchronization therapy are being compared to the patients’ native rhythms or some mixture of right ventricular pacing modes.
Dr. DiMarco, Professor of Medicine in the Division of Cardiology at the University of Virginia, Charlottesville, is on the Editorial Board of Clinical Cardiology Alert.