Increased beta-receptor density and improved hemodynamic response to catecholamine stimulation during long-term metoprolol therapy in heart failure from dilated cardiomyopathy.

TLDR

Severe heart failure is linked to reduced myocardial beta‑adrenergic receptor density and a blunted contractile response to catecholamines. The study aimed to determine whether six months of metoprolol therapy could reverse these abnormalities in patients with dilated cardiomyopathy. Fourteen patients received an average daily dose of 105 mg metoprolol for six months, and myocardial beta‑receptor density, resting hemodynamic output, and peak left‑ventricular dP/dt during dobutamine infusion were measured before and after therapy while patients remained on medication, with the second assessment performed 1–2 h after the morning dose. Metoprolol increased beta‑receptor density from 39 ± 7 to 80 ± 12 fmol/mg, raised stroke work index from 27 ± 4 to 43 ± 3 g/m/m² and ejection fraction from 0.26 ± 0.03 to 0.39 ± 0.03, and amplified dobutamine‑induced peak dP/dt from 21 ± 4 % to 74 ± 18 %, demonstrating restored beta‑adrenergic sensitivity.

Abstract

Severe heart failure is associated with a reduction in myocardial beta-adrenergic receptor density and an impaired contractile response to catecholamine stimulation. Metoprolol was administered during a 6-month period to 14 patients with dilated cardiomyopathy to examine its effects on these abnormalities. The mean daily dose of metoprolol for the group was 105 mg (range, 75-150 mg). Myocardial beta-receptor density, resting hemodynamic output, and peak left ventricular dP/dt response to dobutamine infusions were compared in 9, 14, and 7 patients, respectively, before and after 6 months of metoprolol therapy while the patients were on therapy. The second hemodynamic study was performed 1-2 hours after the morning dose of metoprolol had been given. Myocardial beta-receptor density increased from 39 +/- 7 to 80 +/- 12 fmol/mg (p less than 0.05). Resting hemodynamic output showed a rise in stroke work index from 27 +/- 4 to 43 +/- 3 g/m/m2, p less than 0.05, and ejection fraction rose from 0.26 +/- 0.03 to 0.39 +/- 0.03 after 6 months of metoprolol therapy, p less than 0.05. Before metoprolol therapy, dobutamine caused a 21 +/- 4% increase in peak positive left ventricular dP/dt; during metoprolol therapy, the same dobutamine infusion rate increased peak positive dP/dt by 74 +/- 18% (p less than 0.05). Thus, long-term metoprolol therapy is associated with an increase in myocardial beta-receptor density, significant improvement in resting hemodynamic output, and improved contractile response to catecholamine stimulation. These changes indicate a restoration of beta-adrenergic sensitivity associated with metoprolol therapy, possibly related to the observed up-regulation of beta-adrenergic receptors.