Acute hemodynamic and neurohumoral effects of pindolol: a beta-adrenoceptor antagonist with high intrinsic sympathomimetic activity in patients with dilated cardiomyopathy.

It has been claimed that beta-adrenoceptor antagonists produce clinical improvement and increase longevity in patients with idiopathic dilated cardiomyopathy. Dilated heart is critically dependent upon adrenergic support to maintain forward output. Acute withdrawal of such support, even with small doses of beta-blockers, may worsen myocardial function sufficiently to limit their widespread use. Pindolol (P), a potent beta-adrenoceptor antagonist, possesses high intrinsic sympathomimetic activity. Administration of P to patients with dilated cardiomyopathy may protect against the effects of high circulating catecholamines and at the same time partially maintain intrinsic left ventricular function. We examined the acute hemodynamic effects of P (2.5 mg orally) in seven patients with dilated cardiomyopathy (average ejection fraction, 23%) and resting tachycardia (average, 111 beats/min). As compared to baseline values, P produced a highly significant fall in heart rate (rest, 19%, p less than 0.001; exercise, 24%, p less than 0.01), cardiac output (rest, 20%, p less than 0.01; exercise, 25%, p less than 0.001), and systemic arterial pressure (exercise only, 13%, p less than 0.05). Calculated systemic vascular resistance increased significantly at rest (17%, p less than 0.05). Pulmonary artery pressures did not change. Compared to normal subjects, baseline norepinephrine levels were markedly elevated in patients with dilated cardiomyopathy at rest and during exercise. Pindolol produced a further significant increase in norepinephrine levels. Two of seven patients became appreciably short of breath after P. Despite its substantial intrinsic sympathomimetic activity, pindolol, like other beta-adrenoreceptor antagonists, produces significant hemodynamic impairment in patients with congestive cardiomyopathy. An exaggerated norepinephrine response after the drug may, by increasing peripheral vascular resistance, lead to further deterioration in left ventricular performance.