Acute and chronic hemodynamic effects of xamoterol in mild to moderate congestive heart failure

Abstract

Xamoterol, a new β 1 partial agonist, has the potential to modulate cardiac response to variations in sympathetic tone in patients with heart failure. Its properties should result in β-receptor stimulatory effects at low levels of sympathetic tone and β-receptor protective effects at higher levels of sympathetic tone. The acute effects of intravenous (i.V.) xamoterol on hemodynamics at rest and during exercise were studied in 30 patients with mild to moderate heart failure (13 patients in New York Heart Association class II; 17 in class III) due to ischemic (n = 24) or cardiomyopathic (n = 6) heart disease. Cardiac index, stroke volume and stroke work index at rest were significantly improved after i.v. administration of xamoterol and consistent with net agonist effects. During exercise, heart rate and double product were significantly reduced (net antagonist effects), but with preservation of the expected increases in cardiac index and systolic blood pressure. These hemodynamic findings confirm the ability of xamoterol to modulate cardiac response to variations in sympathetic tone. Tachyphylaxis and arrhythmogenicity limit the chronic use of drugs with full β-agonist properties as positive inotropes in heart failure. The patients were therefore entered into a 6-month double-blind, placebo-controlled, crossover study of chronic oral xamoterol therapy, 200 mg twice daily, and the hemodynamic responses to i.v. xamoterol were repeated at the end of the trial. No impairment in either resting or exercise effects was observed, indicative of a maintained response and absence of tachyphylaxis after chronic therapy. Furthermore, 24-hour ambulatory electrocardtographic monitoring showed no change in ventricular arrhythmias during oral treatment. In mild to moderate heart failure, xamoterol improves cardiac performance at rest and during exercise, the changes being consistent with its pharmacologic profile. There was no evidence of tachyphylaxis or exacerbation of ventricular arrhythmias after chronic oral therapy.