Decreased myocardial β-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. ¹¹C-CGP-12177 (¹¹C-CGP) has been used to assess myocardial β-adrenergic receptor (β-AR) density in vivo using PET. The aim of this study is to measure myocardial β-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 non-ischemic 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 β-AR density of the whole LV was calculated on the basis of the graphical analysis method. Additionally, β-AR density was compared with LV ejection fraction (LVEF), sympathetic presynaptic function assessed using ¹²³I-MIBG kinetics, and neurohormonal parameters. Results: The β-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, β-AR density correlated significantly with LVEF (r = 0.62, P < 0.05). Furthermore, β-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 β-AR density and early H/M ratio was not significant (r = 0.40, P = 0.13). The β-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 β-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.