Decreased myocardial beta-adrenergic receptor density in relation to increased sympathetic tone in patients with nonischemic cardiomyopathy.
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.
Tsukamoto
Takahiro
T
Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Morita
Koichi
K
Naya
Masanao
M
Inubushi
Masayuki
M
Katoh
Chietsugu
C
Nishijima
Kenichi
K
Kuge
Yuji
Y
Okamoto
Hiroshi
H
Tsutsui
Hiroyuki
H
Tamaki
Nagara
N
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
D002250:Carbon Radioisotopes; D007457:Iodine Radioisotopes; D011412:Propanolamines; D019275:Radiopharmaceuticals; D011943:Receptors, Adrenergic, beta; D019797:3-Iodobenzylguanidine; C033394:CGP 12177