title: Decreased myocardial beta-adrenergic receptor density in relation to increased sympathetic tone in patients with nonischemic cardiomyopathy.
abstract: Cardiac sympathetic function plays an important role in the regulation of left ventricular (LV) function and the pathophysiology of LV dysfunction. (11)C-CGP-12177 ((11)C-CGP) has been used to assess myocardial beta-adrenergic receptor (beta-AR) density in vivo using PET. The aim of this study is to measure myocardial beta-AR density in patients with nonischemic cardiomyopathy and to compare the measurements with various standard parameters of heart failure (HF), particularly with presynaptic function assessed by (123)I- metaiodobenzylguanidine ((123)I-MIBG) imaging.
  
  
  METHODS
  (11)C-CGP PET was performed on 16 patients with nonischemic cardiomyopathy and 8 age-matched healthy volunteers using a double injection method. A (11)C-CGP dynamic scan for 75 min was performed after the injection of (11)C-CGP with a high specific activity. After 30 min, (11)C-CGP with a low specific activity was injected. The beta-AR density of the whole LV was calculated on the basis of the graphical analysis method. Additionally, beta-AR density was compared with LV ejection fraction (LVEF), sympathetic presynaptic function assessed using (123)I-MIBG kinetics, and neurohormonal parameters.
  
  
  RESULTS
  The beta-AR density of patients was significantly lower than that of healthy volunteers (3.80 +/- 0.96 vs. 7.70 +/- 1.92 pmol/mL; P < 0.0001). In the patients, beta-AR density correlated significantly with LVEF (r = 0.62, P < 0.05). Furthermore, beta-AR density correlated significantly with the (123)I-MIBG washout rate (r = -0.68, P < 0.01) and delayed heart-to-mediastinum ratio (H/M ratio) (r = 0.61, P < 0.05). On the other hand, the correlation between beta-AR density and early H/M ratio was not significant (r = 0.40, P = 0.13). The beta-AR density of patients with severe HF (New York Heart Association functional [NYHA] class III) was significantly lower than that of those with NYHA functional class I or class II HF (3.24 +/- 0.96 vs. 4.24 +/- 0.73 pmol/mL; P < 0.05).
  
  
  CONCLUSIONS
  A reduction in beta-AR density measured by (11)C-CGP PET was observed in patients with nonischemic cardiomyopathy. This downregulation may be due to the increased presynaptic sympathetic tone as assessed by (123)I-MIBG imaging.
authors.affiliation: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Tsukamoto
authors.forename: Koichi
authors.initials: K
authors.lastname: Morita
authors.forename: Masanao
authors.initials: M
authors.lastname: Naya
authors.forename: Masayuki
authors.initials: M
authors.lastname: Inubushi
authors.forename: Chietsugu
authors.initials: C
authors.lastname: Katoh
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nishijima
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kuge
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okamoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsutsui
authors.forename: Nagara
authors.initials: N
authors.lastname: Tamaki
mesh_terms: D019797:3-Iodobenzylguanidine; D000368:Aged; D002250:Carbon Radioisotopes; D009202:Cardiomyopathies / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D049268:Positron-Emission Tomography; D017729:Presynaptic Terminals / Q000000981:diagnostic imaging / Q000378:metabolism; D011412:Propanolamines / Q000378:metabolism*; D019275:Radiopharmaceuticals; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000000981:diagnostic imaging / Q000503:physiopathology*; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000378:metabolism
chemical_list: D002250:Carbon Radioisotopes; D007457:Iodine Radioisotopes; D011412:Propanolamines; D019275:Radiopharmaceuticals; D011943:Receptors, Adrenergic, beta; D019797:3-Iodobenzylguanidine; C033394:CGP 12177