title: The effect of beta-adrenergic receptor antagonism in cardiac sympathetic neuronal remodeling in patients with heart failure.
abstract: BACKGROUND
  beta-adrenergic receptor antagonism with drugs like carvedilol slows the progression of heart failure by an undefined mechanism. (123)I-metaiodobenzylguanidine (MIBG) is an analog of norepinephrine used to study cardiac sympathetic function.
  
  
  RESULTS
  In this double-blind randomized, placebo-controlled study, we used MIBG imaging to evaluate the effect of carvedilol (n=15) or placebo (n=7) on neuronal norepinephrine reuptake in patients with heart failure due to idiopathic dilated cardiomyopathy, with LVEF less than 35% and functional class II or III. The drug was begun at 6.25 mg b.i.d. and titrated up to 25 mg t.i.d, as tolerated. Thorax planar scintigraphy images were obtained 15 min (Initial) and 4 h (Late) after MIBG injection at baseline (t(0)) as well as 2 months (t(1)) and 6 months (t(2)) after drug initiation. The multifarious statistical technique of profile analysis was applied and p< or =0.05 was considered significant. The heart/mediastinum MIBG uptake (H/M ratio) was calculated from these images. On the Initial images, the H/M ratio was 1.64+/-0.24 (t(0)), 1.71+/-0.21 (t(1)), and 1.87+/-0.34 (t(2)) in the carvedilol group and 1.68+/-0.42 (t(0)), 1.81+/-0.45 (t(1)), and 1.69+/-0.44 (t(2)) in controls (p=0.0455). On the Late images, the H/M ratio was 1.39+/-0.24 (t(0)), 1.53+/-0.23 (t(1)), and 1.64+/-0.36 (t(2)) in the carvedilol group, and 1.49+/-0.45 (t(0)), 1.53+/-0.47 (t(1)), and 1.47+/-0.41 (t(2)) in controls (p=0.0513).
  
  
  CONCLUSIONS
  Compared with placebo, the addition of carvedilol to existing heart failure treatment incites the reverse remodeling of cardiac sympathetic nervous system function.
authors.affiliation: Heart Failure Clinics, Heart Institute São Paulo University Medical School, São Paulo, Brazil. chizzola@incor.usp.br
authors.forename: Paulo Roberto
authors.initials: PR
authors.lastname: Chizzola
authors.forename: Humberto Felício
authors.initials: HF
authors.lastname: Gonçalves de Freitas
authors.forename: Norma Vasconcelos Saldanha
authors.initials: NV
authors.lastname: Marinho
authors.forename: José Alfredo
authors.initials: JA
authors.lastname: Mansur
authors.forename: José Cláudio
authors.initials: JC
authors.lastname: Meneghetti
authors.forename: Edimar Alcides
authors.initials: EA
authors.lastname: Bocchi
mesh_terms: D019797:3-Iodobenzylguanidine; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D002227:Carbazoles / Q000627:therapeutic use*; D002311:Cardiomyopathy, Dilated / Q000150:complications; D000077261:Carvedilol; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000187:drug effects / Q000294:innervation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D011412:Propanolamines / Q000627:therapeutic use*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D013564:Sympathetic Nervous System / Q000000981:diagnostic imaging* / Q000187:drug effects; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000000981:diagnostic imaging* / Q000188:drug therapy*
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D019275:Radiopharmaceuticals; D000077261:Carvedilol; D019797:3-Iodobenzylguanidine; D009638:Norepinephrine