Electrophysiologic effects of endothelin receptor-A blockade in patients with coronary artery disease

Selective endothelin receptor-A antagonists are a promising new treatment in patients with heart failure and/or pulmonary hypertension. Animal studies have suggested that these agents may have additional cardiac electrophysiologic actions, however, no data exist in man. We examined the effects of acute endothelin receptor-A blockade on the sinus node, the atrioventricular node and on the ventricular myocardium, in patients with single-vessel coronary artery disease and preserved left ventricular function. The selective endothelin receptor-A antagonist BQ-123 was administered by the intracoronary route, in order to achieve maximum local cardiac effects. After endothelin receptor-A blockade, QT interval increased from 373 +/- 30 msec (mean +/- SD) to 395 +/- 20 msec (p < 0.01) and QTc interval increased from 394 +/- 36 msec to 421 +/- 28 msec (p < 0.01). QT-dispersion, calculated from 12-lead ECG, decreased from 40 +/- 18 msec to 24 +/- 8 msec (p < 0.01) and QTc-dispersion decreased from 44 +/- 20 msec to 26 +/- 9 msec (p < 0.05). These changes were evident only after infusion in the left, but not in the right coronary artery. No effect was found on the sinus node, the atrioventricular node, or the ventricular effective refractory periods. We conclude that selective endothelin receptor A blockade lengthens ventricular repolarization and decreases its inhomogeneity. Further studies are needed to evaluate possible antiarrhythmic actions of this class of agent.