Beneficial effects of metoprolol on myocardial sympathetic function: Evidence from a randomized, placebo-controlled study in patients with congestive heart failure.
BACKGROUND
We sought to investigate whether beta-blockers exert a presynaptic effect in the myocardium as measured by 123I-metaiodobenzylguanidine.


METHODS
The study comprised 59 patients with congestive heart failure, New York Heart Association class II or III, and left ventricular ejection fraction <35%. After an open label titration phase, patients were randomized to their maximal tolerable dose of metoprolol or placebo. Myocardial MIBG uptake was measured before the titration phase and after 6 months of treatment. Other parameters were maximal oxygen consumption, 6-minute walking test, plasma neurohormones, and echocardiographic parameters.


RESULTS
We found a 21.9% increase in mean myocardial MIBG uptake after 6 months of treatment with metoprolol. In contrast, MIBG uptake decreased by 7.8% in the placebo group (P = 0.03 compared with metoprolol). Left ventricular end-diastolic diameter decreased from 74 +/- 11 mm to 67 +/- 10 mm (P <.05, within-group comparison) and LVEF increased from 25.3% +/- 7.4% to 32.6% +/- 9.6% (P <.05, within-group comparison) in the metoprolol group. Placebo-treated patients showed no significant changes. Comparison of changes in left ventricular end-diastolic diameter and LVEF between metoprolol and placebo did not reach statistical significance (P = 0.2).


CONCLUSIONS
This randomized, placebo-controlled study demonstrates that metoprolol has a presynaptic effect as measured by myocardial MIBG scintigraphy in both ischemic and nonischemic cardiomyopathy.
de Milliano
Paul A R
PA
Department of Cardiology, Ziekenhuis Hilversum, Hilversum, The Netherlands. pardemilliano@wxs.nl
de Groot
Andre C
AC
Tijssen
Jan G P
JG
van Eck-Smit
Berthe L F
BL
Van Zwieten
Pieter A
PA
Lie
Kong I
KI
D019797:3-Iodobenzylguanidine / Q000493:pharmacokinetics; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000368:Aged; D004311:Double-Blind Method; D015536:Down-Regulation; D005260:Female; D006321:Heart / Q000187:drug effects / Q000294:innervation; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D017729:Presynaptic Terminals / Q000187:drug effects; D019275:Radiopharmaceuticals; D015899:Tomography, Emission-Computed, Single-Photon
D000319:Adrenergic beta-Antagonists; D019275:Radiopharmaceuticals; D019797:3-Iodobenzylguanidine; D008790:Metoprolol