Decreased Myocardial -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
³ Faculty of Radiopharmaceutical Science, Health Sciences University of Hokkaido, Sapporo, Japan

^* To whom correspondence should be addressed. E-mail: natamaki{at}med.hokudai.ac.jp.

	Abstract

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 -adrenergic receptor (-AR) density in vivo using PET. The aim of this study is to measure myocardial -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 -AR density of the whole LV was calculated on the basis of the graphical analysis method. Additionally, -AR density was compared with LV ejection fraction (LVEF), sympathetic presynaptic function assessed using ¹²³I-MIBG kinetics, and neurohormonal parameters. Results: The -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, -AR density correlated significantly with LVEF (r = 0.62, P < 0.05). Furthermore, -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 -AR density and early H/M ratio was not significant (r = 0.40, P = 0.13). The -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 -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: -adrenergic receptor, heart failure, sympathetic tone, norepinephrine