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Decreased Myocardial ß-Adrenergic Receptor Density in Relation to Increased Sympathetic Tone in Patients with Nonischemic Cardiomyopathy

¹ Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan; ² Department of Nuclear Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan; and ³ Faculty of Radiopharmaceutical Science, Health Sciences University of Hokkaido, Sapporo, Japan

Correspondence: For correspondence or reprints contact: Nagara Tamaki, MD, Department of Nuclear Medicine, Graduate School of Medicine, Hokkaido University, Kita15 Nishi7, Kita-ku, Sapporo 060-8638, Japan. E-mail: natamaki{at}med.hokudai.ac.jp

Cardiac sympathetic function plays an important role in the regulation of left ventricular (LV) function and the pathophysiology of LV dysfunction. ¹¹C-CGP-12177 (¹¹C-CGP) has been used to assess myocardial ß-adrenergic receptor (ß-AR) density in vivo using PET. The aim of this study is to measure myocardial ß-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 ¹²³I- metaiodobenzylguanidine (¹²³I-MIBG) imaging. Methods: ¹¹C-CGP PET was performed on 16 patients with nonischemic cardiomyopathy and 8 age-matched healthy volunteers using a double injection method. A ¹¹C-CGP dynamic scan for 75 min was performed after the injection of ¹¹C-CGP with a high specific activity. After 30 min, ¹¹C-CGP with a low specific activity was injected. The ß-AR density of the whole LV was calculated on the basis of the graphical analysis method. Additionally, ß-AR density was compared with LV ejection fraction (LVEF), sympathetic presynaptic function assessed using ¹²³I-MIBG kinetics, and neurohormonal parameters. Results: The ß-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, ß-AR density correlated significantly with LVEF (r = 0.62, P < 0.05). Furthermore, ß-AR density correlated significantly with the ¹²³I-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 ß-AR density and early H/M ratio was not significant (r = 0.40, P = 0.13). The ß-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). Conclusion: A reduction in ß-AR density measured by ¹¹C-CGP PET was observed in patients with nonischemic cardiomyopathy. This downregulation may be due to the increased presynaptic sympathetic tone as assessed by ¹²³I-MIBG imaging.

Key Words: ß-adrenergic receptor • heart failure • sympathetic tone • norepinephrine

COPYRIGHT © 2007 by the Society of Nuclear Medicine, Inc.

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