The Neurological Consequences of REMATCH
When the REMATCH (Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure) trial was planned, researchers justifiably focused on comparing long-term treatment with a left ventricular assist device (LVAD) to medical therapy. In this week’s issue of the journal Circulation (Circulation. 2004;109:2423–2427), they look back at the neurological events that struck the study participants. As the researchers, led by Ronald M. Lazar, PhD, of the Columbia University College of Physicians and Surgeons, noted, “Patients in the LVAD arm were significantly more likely to suffer an adverse neurological event than those in the medical arm.”
They found that fewer than half the subjects in the group that received an LVAD experienced a neurological event and that there were “few” deaths attributed to neurological causes.
When a survival analysis that combined stroke and death was done, it demonstrated a benefit for the LVAD over medical therapy, yet the researchers warn that future prospective trials need to be done to determine the true risk of neurological events in this patient group as well as the effects on neurocognition and the role of long-term neuroprotection.
A total of 129 patients were assigned randomly to receive either the LVAD or medical treatment. New neurological events were classified as stroke, transient ischemic attack, toxic-metabolic encephalopathy, or other. A total of 46 neurological events were recorded: 42 in 30 patients who received the LVAD and 4 in 4 patients in the medical management group. In other words, 30 patients of the 68 in the LVAD group suffered a neurological event, compared with 4 of 61 in the medical management group. The average time from implantation of the LVAD until occurrence of the stroke was 221.8 days.
The authors wrote, “Our study represents a starting point in the analysis of neurological complications in patients with long-term circulatory support for heart failure. There were only 129 patients in REMATCH, of whom 68 received the device. Although the device group clearly had more events, including stroke, the trial was not designed to have enough statistical power for analysis of specific risk factors. Our data addressed only outcomes from transplantation-ineligible patients receiving the HeartMate vented electric device (Thoratec). Future studies will determine the neurological outcomes from other devices providing long-term left ventricular assistance. Our patients were extremely sick with end-stage disease; how a younger, less sick population who might not otherwise qualify for transplantation might fare is not known. To make possible the future comparison of brain events across studies, there needs to be prospective measurement of neurological function using standardized instruments and event definitions at an appropriate baseline, at prescribed intervals, and at the time of new events.”
Resynching the Heart
“Resynching” the heart of patients with advanced heart failure and prolonged QRS interval when combined with an implantable defibrillator significantly reduces the risk they will die of their heart disease, said researchers for the COMPANION (Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure) trial in the May 20, 2004, issue of The New England Journal of Medicine (N Engl J Med. 2004;350:2140–2150OpenUrlCrossRefPubMed).
In the large, multicenter study, 1520 patients with advanced heart failure caused by a variety of cardiomyopathies and a QRS interval of at least 120 ms were assigned at random to receive optimal medical therapy alone or in combination with either a pacemaker or pacemaker-defibrillator combination. Both the cardiac resynchronization–with–pacemaker group and the cardiac resynchronization–with–pacemaker-defibrillator groups had a decreased risk of death or admission to the hospital when compared with those who received only medication. The risk was reduced by 34% in the pacemaker group and 40% in the pacemaker-defibrillator group when compared with the medication-alone group. Mortality was reduced by 24% in the pacemaker group and 36% in the pacemaker-defibrillator group.
The authors noted: “These data indicate that, in a population with advanced heart failure and an increased QRS interval, cardiac-resynchronization therapy improves most major factors that affect the quality of life. Moreover, our data demonstrate that adding a defibrillator to cardiac-resynchronization therapy significantly reduces the risk of death. The clinical efficacy of cardiac-resynchronization therapy with a pacemaker-defibrillator is especially noteworthy, since the therapy was delivered in conjunction with the best evidence-based pharmacologic therapy for heart failure. Before our study, the case for defibrillator therapy in patients with left ventricular dysfunction had been based on MADIT II, which was conducted exclusively in a population with ischemic cardiomyopathy. We demonstrated a 36 percent reduction in the risk of death from any cause in the patients who received a pacemaker-defibrillator. The decision of which of these two therapeutic options is appropriate for a particular setting is best determined on an individual basis by patients and their physicians.”
Reducing Risk in Dilated Cardiomyopathy
Implanting a cardioverter-defibrillator in patients with severe, nonischemic dilated cardiomyopathy reduced the risk of dying suddenly from an arrhythmia, said investigators in the DEFINITE (Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation) trial in a report in the May 20, 2004, issue of The New England Journal of Medicine (N Engl J Med. 2004;350:2151–2158OpenUrlCrossRefPubMed).
In a report led by Alan Kadish, MD, of the Northwestern University Medical School in Chicago on behalf of the DEFINITE investigators, the researchers noted that 458 patients with nonischemic dilated cardiomyopathy, a left ventricular ejection fraction of less than 36%, and premature ventricular complexes or nonsustained ventricular tachycardia were enrolled in the study. They randomly assigned 229 patients to receive medical therapy and 229 to receive standard medical therapy plus a single-chamber implanted cardioverter-defibrillator. There were 68 deaths during the 29-month follow-up period. Twenty-eight occurred in the defibrillator group and 40 in the group that received standard medical therapy. At 2 years, the rate of mortality was 7.9% in the defibrillator group and 14.1% in the medical treatment group.
The investigators wrote, “On the basis of our results, the routine implantation of a cardioverter-defibrillator cannot be recommended for all patients with nonischemic cardiomyopathy and severe left ventricular dysfunction. However, our findings of a reduction in sudden death from arrhythmia and an apparent benefit of ICDs [implantable cardioverter-defibrillators] in subgroup analyses suggest that the use of these devices should be considered on a case-by-case basis.”
In an accompanying perspective, Mark A. Hlatky, MD, of Stanford University School of Medicine in California, wrote, “There is a need to bring together the emerging evidence to determine who obtains sufficient benefit from a prophylactically implanted defibrillator to justify its use. Ideally, the clinical-trial investigators will pool their data to determine how the effectiveness of defibrillator treatment varies according to key clinical factors such as ejection fraction, presence or absence of a history of coronary revascularization, and time since myocardial infarction. Pooling trial data offers the best opportunity to establish the efficacy and cost effectiveness of these devices in various segments of the large population of patients who would potentially be eligible for this expensive therapy.”