Beta, partial agonists to treat heart failure: effects of xamoterol upon cardiac function and clinical status

The presence of systolic dysfunction, diastolic dysfunction, or both is an important consideration in selecting the optimal pharmacologic approach to the treatment of congestive heart failure in an individual patient. Cardiac glycosides and arterial vasodilators act only on systolic function, whereas beta 1-adrenoceptor-stimulating agents, such as beta 1 full and partial agonists, have both inotropic and lusitropic activity. Acute and chronic administration of xamoterol, a new beta 1 partial agonist, to patients with congestive heart failure has been shown to improve myocardial contractility, as indicated by increases in the peak rate of rise in left ventricular pressure, left ventricular ejection fraction, and cardiac output. Improvement in ventricular relaxation and filling, reflected by increases in the peak rate of decline in left ventricular pressure, reductions in the time constant of the decrease in isovolumic pressure, improved left ventricular compliance, and increases in the atrial contribution to diastolic filling, are other beneficial effects of xamoterol on diastolic function. Exercise capacity increases in response to xamoterol therapy, while heart rate at maximum exercise declines. Relief of the signs and symptoms of congestive heart failure and improvement in functional status have also been demonstrated in xamoterol-treated patients. The undesirable effects of beta 1 full agonists, such as tachycardia, arrhythmias, increased myocardial oxygen consumption, and effects on the peripheral vasculature, are not seen with xamoterol. The beta 1 partial agonist also causes no beta-adrenoreceptor down-regulation, a finding that may account for its sustained effectiveness with long-term therapy.