Effects of carvedilol on myocardial sympathetic innervation in patients with chronic heart failure.
Carvedilol is a beta-blocking agent with antioxidant properties that has been shown to improve survival in chronic heart failure (CHF). Previous open-label studies have suggested that its use may have positive effects on the abnormalities of cardiac sympathetic innervation integrity and functioning. The present study aimed to test the hypothesis that carvedilol exerts its beneficial effects on hemodynamics in parallel with an action on myocardial sympathetic activity and with its antioxidant property.


METHODS
A randomized, multicenter, double-blind, placebo-controlled study of carvedilol was conducted on 64 CHF patients. Patients underwent-before and after 6 mo of therapy with either carvedilol or placebo-measurements of cardiac sympathetic activity, circulating catecholamine level, and hemodynamic indices. Myocardial meta-(123)I-iodobenzylguanidine ((123)I-MIBG) uptake was used to assess the changes in myocardial sympathetic activity. The antioxidant properties of the plasma were assessed by measuring the percentage of nonhemolyzed erythrocytes and the volume of plasma capable of inhibiting 50% of hemolysis after an oxidative stress. Echographic left ventricular (LV) diameters, radionuclide LV ejection fraction (LVEF), and exercise cardiopulmonary capacity were measured to evaluate the hemodynamic response.


RESULTS
End-diastolic and end-systolic LV diameters decreased (both P < 0.05) and LVEF increased (P = 0.03) in the carvedilol group, whereas these parameters remained unchanged in the placebo group. Carvedilol did not alter the submaximal exercise cardiopulmonary capacity or the circulating catecholamine level. The beneficial hemodynamic effects in the carvedilol group were associated with an increase in myocardial (123)I-MIBG uptake as assessed by both planar and tomographic imaging (P < 0.01). Carvedilol had no detectable effect on antioxidant properties of the plasma.


CONCLUSIONS
The benefits of carvedilol on resting hemodynamics appear to be associated with a partial recovery of cardiac adrenergic innervation functioning without detectable antioxidant effect in the plasma.
Cohen-Solal
Alain
A
Department of Cardiology, University Hospital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France.
Rouzet
François
F
Berdeaux
Alain
A
Le Guludec
Dominique
D
Abergel
Eric
E
Syrota
André
A
Merlet
Pascal
P
D000959:Antihypertensive Agents / Q000008:administration & dosage; D002227:Carbazoles / Q000008:administration & dosage*; D000077261:Carvedilol; D002908:Chronic Disease; D004311:Double-Blind Method; D006333:Heart Failure / Q000150:complications / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000294:innervation; D006801:Humans; D008875:Middle Aged; D015990:Placebo Effect; D011412:Propanolamines / Q000008:administration & dosage*; D011877:Radionuclide Imaging; D020127:Recovery of Function / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000000981:diagnostic imaging* / Q000187:drug effects*; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging* / Q000209:etiology / Q000517:prevention & control*
D000959:Antihypertensive Agents; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol