The effect of beta-adrenergic receptor antagonism in cardiac sympathetic neuronal remodeling in patients with heart failure.
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.
Chizzola
Paulo Roberto
PR
Heart Failure Clinics, Heart Institute São Paulo University Medical School, São Paulo, Brazil. chizzola@incor.usp.br
Gonçalves de Freitas
Humberto Felício
HF
Marinho
Norma Vasconcelos Saldanha
NV
Mansur
José Alfredo
JA
Meneghetti
José Cláudio
JC
Bocchi
Edimar Alcides
EA
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*
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D019275:Radiopharmaceuticals; D000077261:Carvedilol; D019797:3-Iodobenzylguanidine; D009638:Norepinephrine