The REMATCH trial: rationale, design, and end points. Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure.

BACKGROUND: Because left ventricular assist devices have recently been approved by the Food and Drug Administration to support the circulation of patients with end-stage heart failure awaiting cardiac transplantation, these devices are increasingly being considered as a potential alternative to biologic cardiac replacement. The Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial is a multicenter study supported by the National Heart, Lung, and Blood Institute to compare long-term implantation of left ventricular assist devices with optimal medical management for patients with end-stage heart failure who require, but do not qualify to receive cardiac transplantation. METHODS: We discuss the rationale for conducting REMATCH, the obstacles to designing this and other randomized surgical trials, the lessons learned in conducting the multicenter pilot study, and the features of the REMATCH study design (objectives, target population, treatments, end points, analysis, and trial organization). CONCLUSIONS: We consider what will be learned from REMATCH, expectations for expanding the use of left ventricular assist devices, and future directions for assessing clinical procedures.

Vasodepressor syncope due to subclinical myocardial ischemia.

INTRODUCTION: Vasodepressor syncope is a common cause of syncope, but the initiating event that triggers the vasodepressor response remains incompletely understood. Although ischemia due to acute right coronary occlusion may precipitate hypotension and bradycardia through the Bezold-Jarisch reflex, an ischemic precipitant for the common vasodepressor faint has not been previously identified. In the present study, we present evidence for a causal relationship between myocardial ischemia and vasodepressor syncope. METHODS AND RESULTS: Two patients referred for evaluation of syncope underwent upright tilt table testing with either ST segment monitoring, sestamibi scintigraphy and echocardiography during the tilt test, or coronary angiography. Both patients had positive tilt table tests during the control study. Patient 1 was documented to have reproducible ischemic ECG changes during atypical chest pressure induced by upright tilt, despite a normal coronary angiogram with ergonovine provocation. Subsequent tilt testing with simultaneous sestamibi perfusion imaging and echocardiography revealed reversible anterolateral hypoperfusion corresponding with anterolateral hypokinesis during upright tilt that preceded syncope. Ischemic ECG changes during incremental rapid atrial pacing further suggested ischemia on the basis of microvascular disease. Follow-up tilt testing on verapamil was negative. Patient 2 developed ischemic ECG changes during the recovery phase of an exercise stress test, which was followed by a vasodepressor response and frank syncope. Coronary angiography revealed a 90% distal right coronary artery stenosis that was successfully dilated, after which follow-up tilt table testing off all other medication was negative. CONCLUSIONS: These two cases illustrate a previously unrecognized causality between myocardial ischemia and clinical vasodepressor syncope, and demonstrate that subtle manifestations of myocardial ischemia, associated with either atypical angina or silent ischemia, can provoke syncope.

Long-term use of a left ventricular assist device for end-stage heart failure.

BACKGROUND: Implantable left ventricular assist devices have benefited patients with end-stage heart failure as a bridge to cardiac transplantation, but their long-term use for the purpose of enhancing survival and the quality of life has not been evaluated. METHODS: We randomly assigned 129 patients with end-stage heart failure who were ineligible for cardiac transplantation to receive a left ventricular assist device (68 patients) or optimal medical management (61). All patients had symptoms of New York Heart Association class IV heart failure. RESULTS: Kaplan-Meier survival analysis showed a reduction of 48 percent in the risk of death from any cause in the group that received left ventricular assist devices as compared with the medical-therapy group (relative risk, 0.52; 95 percent confidence interval, 0.34 to 0.78; P=0.001). The rates of survival at one year were 52 percent in the device group and 25 percent in the medical-therapy group (P=0.002), and the rates at two years were 23 percent and 8 percent (P=0.09), respectively. The frequency of serious adverse events in the device group was 2.35 (95 percent confidence interval, 1.86 to 2.95) times that in the medical-therapy group, with a predominance of infection, bleeding, and malfunction of the device. The quality of life was significantly improved at one year in the device group. CONCLUSIONS: The use of a left ventricular assist device in patients with advanced heart failure resulted in a clinically meaningful survival benefit and an improved quality of life. A left ventricular assist device is an acceptable alternative therapy in selected patients who are not candidates for cardiac transplantation.