Abstract & Commentary
Synopsis: Left ventricular ejection fraction is the most important risk factor for both arrhythmic events and transplantation-free survival in patients with idiopathic dilated cardiomyopathy.
Source: Grimm W, et al. Circulation. 2003;108:2883-2891.
In this paper, Grimm and colleagues report on the usefulness of noninvasive testing to predict risk for arrhythmias in patients with idiopathic dilated cardiomyopathy. The data are from the Marburg Cardiomyopathy Study, a prospective study of the natural history of patients with idiopathic dilated cardiomyopathy. Patients were eligible for the study if they were aged 16-70 with a left ventricular ejection fraction of £ 45% and a left ventricular end diastolic diameter > 56 mm by echocardiography. They could not be in New York Heart Association class IV heart failure, have a history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF) or unexplained syncope, be receiving class I or class III antiarrhythmic drugs that could not be withdrawn, or be pacemaker dependent. Thorough investigation had revealed no specific etiology for their cardiomyopathy. After enrollment in the study, patients underwent signal-averaged electrocardiography, 24-hour ambulatory ECG monitoring, heart rate variability, and baroreflex sensitivity analyses and testing for microvolt T wave alternans. QTc dispersion was determined from standard electrocardiograms. Patients were then followed perspectively for 52 ± 21 months. Only 3 patients were lost to follow-up during this period. The primary end points were major arrhythmic events, defined as spontaneous sustained VT, VF, or sudden death, and heart transplantation-free survival. Univariate and multivariate Cox regression analyses were used to evaluate the association between these 2 primary outcome measures and the baseline variables.
The study enrolled 343 of 463 screened patients with idiopathic dilated cardiomyopathy. Of these, 263 patients were in sinus rhythm at study entry, and 80 patients were in atrial fibrillation. During follow-up, major arrhythmic events were observed in 46 patients, including sudden death in 23 patients and sustained VT or VF in another 23 patients. There were 49 deaths (14%) during follow-up, and 10 patients underwent heart transplantation. Among the patients in sinus rhythm at study entry, left ventricular end diastolic diameter, left ventricular ejection fraction, nonsustained ventricular tachycardia, and an indeterminate microvolt T wave alternans test showed a significant association with major arrhythmic events during follow-up. However, after multivariate analysis, only left ventricular ejection fraction remained a significant independent predictor of major arrhythmic events. There was an increase in relative risk of 2.28 per 10% decrease in ejection fraction. There was also a trend toward increased risk in patients who were not treated with beta-blockers at study enrollment and for patients with nonsustained VT on the baseline 24-hour ambulatory ECG. On univariate analysis, New York Heart Association class III heart failure, digitalis use, left ventricular end diastolic diameter and left ventricular ejection fraction, an abnormal signal averaged ECG, frequent ventricular premature beats, and decreased baroreflex sensitivity all showed a significant association with death or the need for transplantation. However, multivariate analysis showed that only left ventricular ejection fraction remained a significant predictor of transplantation-free survival with a relative risk of 2.51 per 10% decrease in ejection fraction. As with arrhythmic events, there was a trend toward higher transplantation-free survival in patients with beta-blocker therapy. These predictors were also examined in the 80 patients with atrial fibrillation at study entry. On multivariate analysis, only left ventricular ejection fraction and lack of beta-blocker use were significant predictors of major arrhythmic events and transplantation-free survival.
Grimm et al concluded that left ventricular ejection fraction is the most important risk factor for both arrhythmic events and transplantation-free survival in patients with idiopathic dilated cardiomyopathy. The value of the remaining noninvasive tests was limited.
Comment by John DiMarco, MD, PhD
This important paper by Grimm et al points out once again that ejection fraction is the most powerful predictor of outcome in patients with heart failure. Although all of the noninvasive studies used in this trial have been reported to be effective risk predictors in smaller series, this large prospective study shows that they provide only a small amount of additional information beyond ejection fraction for predicting either arrhythmic events or survival. This both helps and hurts clinicians. Ejection fraction is a simple value that is available in almost all patients. However, all of the patients in this study had depressed ejection fractions. Although it appears that risk increases in inverse proportion to the ejection fraction, there is no cut-off point that identifies high- and low-risk groups. Unfortunately, none of the tests examined seemed to be very helpful in further sorting out individual risks.
Dr. DiMarco, Professor of Medicine, Division of Cardiology, University of Virginia, Charlottesville, is on the Editorial Board of Clinical Cardiology Alert.