title: Long-term treatment with the beta-blocker carvedilol restores autonomic tone and responsiveness in patients with moderate heart failure.
abstract: The authors performed two studies on the effects of carvedilol on autonomic tone and responsiveness in patients with heart failure. In study 1, the autonomic responses of 25 patients (age, 60 years+/-2; New York Heart Association [NYHA] class, 2.6+/-0.5; pVO2, 16.6 mL/Kg/min+/-1.1) treated with angiotensin-converting enzyme inhibitors, diuretics, and carvedilol (38.0 mg/d+/-2.5) were compared to those of 25 patients of similar age, therapy, NYHA class, and pVO2 in whom carvedilol was not yet administered. In study 2, autonomic tone and responsiveness were studied in 20 patients (age, 57 years+/-9; NYHA class, 2.5+/-0.2; pVO2, 15.6 mL/Kg/min+/-3.4), before and 6 months after additional carvedilol treatment (40.0 mg/d+/-12.5). Autonomic evaluation was performed with autoregressive power spectral analysis of RR variability during 10 minutes of supine rest (control), breathing 20 times per minute (vagal stimulus), and standing (sympathetic activation). The ratio between low-frequency (LF) and high-frequency (HF) components of the autospectra indicated the sympathovagal interaction. In study 1, spectral analysis in controls showed sympathetic hyperactivity which was blunted in patients receiving carvedilol (LF/HF ratio: 10.4+/-1.4 vs. 7.0+/-1.1; P<0.05) who responded to vagal and adrenergic stimuli (LF/HF, -35% with regular breathing and 72% standing). In study 2, left ventricular function, volumes, and exercise performance improved with carvedilol (EF, 31%; EDLV volume, -22%; pVO2, 11%; P<0.05). Sympathetic hyperactivity in control was reduced (LF/HF ratio, 4.9+/-0.8 from 7.9+/-1.3; P<0.05), whereas a response to vagal and adrenergic activation on breathing and standing reemerged (LF/HF ratio, -31% during regular breathing and 88% on standing). Therefore, combined autonomic and hemodynamic effects may determine the favorable effects of beta-blockers in heart failure.
authors.affiliation: Division of Cardiology, Istituto Scientifico Ospedale San Luca, Istituto Auxologico Italiano IRCCS, Milano, Italy. malfi@auxologco.it
authors.forename: Gabriella
authors.initials: G
authors.lastname: Malfatto
authors.forename: Mario
authors.initials: M
authors.lastname: Facchini
authors.forename: Giovanna
authors.initials: G
authors.lastname: Branzi
authors.forename: Beatrice
authors.initials: B
authors.lastname: Riva
authors.forename: Luca
authors.initials: L
authors.lastname: Sala
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Perego
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology*; D002227:Carbazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D002303:Cardiac Output, Low / Q000188:drug therapy* / Q000503:physiopathology; D000077261:Carvedilol; D017079:Exercise Tolerance / Q000502:physiology; D005260:Female; D006321:Heart / Q000294:innervation* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000008:administration & dosage / Q000627:therapeutic use*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol