The effect of β-adrenergic blockade on T wave alternans in patients with chronic heart failure

Sudden cardiac death is the most common and often first manifestation of atherosclerotic heart disease and is responsible for approximately 50% of the mortality from cardiovascular disease in the developed world. In the United States, 300,000 to 400,000 deaths annually are attributable to sudden cardiac death. This amounts to an overall incidence in the adult population of .1 .2 % per year. In patients who have suffered a large myocardial infarction the incidence of sudden cardiac death approaches 30%. Although this population is easy to identify in order to direct, they represent only a small fraction of total sudden cardiac death victims. Currently, patients only present for treatment of ventricular arrythmias after they have experienced a major arrythmic event. Present tests available to screen patients, such as measuring left ventricular ejection fraction, ventricular ectopy by Holter monitoring, late potentials by signal-averaged electrocardiograms , heart rate variability, and QT dispersion, have limited sensitivity and specificity. Thus, in order to make a significant impact on the problem of sudden cardiac death, a means of identifying the larger group of patients who are at high-risk but have not experienced a ventricular arrythmia is desperately needed. T Wave Alternans is a new and promising technique for the identification of patients at high-risk for sudden cardiac death and ventricular arrythmias. Visual electrical alternans; on the surface electrocardiogram has long been noticed to be associated with ventricular arrythmias and cardiac mortality. However, visually apparent alternans is extremely rare and therefore cannot be used as a sensitive marker of sudden death risk. Recently, techniques have been developed which have made it possible to detect visually inapparent beat-to-beat oscillations of the surface electrocardiogram. In 1994, Rosenbaum et al demonstrated a significant relationship between the presence of microvolt electrical alternans (visually inapparent) measured during atrial pacing with inducibility of ventricular tachycardia and subsequent 20-month arrythmia-free survival. The authors of this study concluded that microvolt T wave alternans may serve as a noninvasive marker of vulnerability to ventricular arrythmias. In 1997, Estes et al. demonstrated that it is feasible to detect T wave alternans with the heart rate elevated by a bicycle exercise protocol rather than atrial or ventricular pacing. This advance has now made it possible to detect T wave alternans in a larger group of patients in order to determine their risk of ventricular arrythmias without the invasive and expensive electrophysiology study. Thus, T wave alternans appears to be a marker of arrythmia vulnerability. However, what is currently unknown is the underlying electrophysiologic pathology that leads to this finding on the electrocardiogram. In addition, could T wave alternans potentially guide therapy if changes of T wave alternans occurred with therapy and correlated with improved survival? Furthermore, the effect of different autonomic stimuli on T wave alternans is also unknown. Patients with congestive heart failure and coronary artery disease are at high-risk for sudden cardiac death. Recent controlled clinical trials have shown that P-blockers reduce cardiovascular mortality and sudden cardiac death in this population. In a study of 21 patients, Kirk et al. looked at the effect of a short-acting intravenous Pblocker on pacing-induced T wave alternans. In this study, intravenous esmolol showed a 50% reduction in the incidence of T wave alternans in a group of patients with inducible ventricular tachycardia. This studies aim is to look at the effect of the oral β-blocker Carvedilol on exercise-induced T wave alternans in patients with congestive heart failure secondary to coronary artery disease. This drug has been shown to reduce the incidence of sudden death in large clinical trials and as a consequence we