Decreased Myocardial  -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 b-adrenergic receptor (b-AR) density in vivo using PET. The aim of this study is to measure myocardial b-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 b-AR density of the whole LV was calculated on the basis of the graphical analysis method. Additionally, b-AR density was compared with LV ejection fraction (LVEF), sympathetic presynaptic function assessed using 123 I-MIBG kinetics, and neurohormonal parameters. Results: The b-AR density of patients was significantly lower than that of healthy volunteers (3.80 6 0.96 vs. 7.70 6 1.92 pmol/mL; P , 0.0001). In the patients, b-AR density correlated significantly with LVEF (r 5 0.62, P , 0.05). Furthermore, b-AR density correlated significantly with the 123 I-MIBG washout rate (r 5 20.68, P , 0.01) and delayed heart-to-mediastinum ratio (H/M ratio) (r 5 0.61, P , 0.05). On the other hand, the correlation between b-AR density and early H/M ratio was not significant (r 5 0.40, P 5 0.13). The b-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 6 0.96 vs. 4.24 6 0.73 pmol/mL; P , 0.05). Conclusion: A reduction in b-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.

Myocardial β-Adrenergic Receptor Density Assessed by 11C-CGP12177 PET Predicts Improvement of Cardiac Function After Carvedilol Treatment in Patients with Idiopathic Dilated Cardiomyopathy

“…Taken together, our study findings suggest that the decrease of myocardial b-AR density implies the presence of higher cardiac sympathetic tone, which in turn predicts benefits from b-blocker treatment. Our findings have extended our own previous finding (8) and that of Spyrou et al (10) that decreased myocardial b-AR density is associated with left ventricular remodeling. Our results are in contrast to those of Gilbert et al, who found that carvedilol improved cardiac function without altering myocardial b-AR density in patients with heart failure (2), indicating that myocardial b-AR density may not predict the efficacy of b-blocker therapy.…”

“…Myocardial b-adrenergic receptor (b-AR) density directly regulates left ventricular systolic function at rest and during dobutamine infusion (8,9). 11 C-CGP12177 PET has been established to allow us to measure myocardial b-AR density noninvasively (8)(9)(10)(11).…”

“…11 C-CGP12177 PET has been established to allow us to measure myocardial b-AR density noninvasively (8)(9)(10)(11). Recently, we demonstrated that a reduction in myocardial b-AR density, as measured by 11 C-CGP12177 PET, in patients with IDC was related to the severity of heart failure (8).…”

“…11 C-CGP12177 PET has been established to allow us to measure myocardial b-AR density noninvasively (8)(9)(10)(11). Recently, we demonstrated that a reduction in myocardial b-AR density, as measured by 11 C-CGP12177 PET, in patients with IDC was related to the severity of heart failure (8). Importantly, myocardial b-AR density inversely correlated with the 123 I-metaiodobenzylguanidine washout rate and positively correlated with a delayed heart-to-mediastinum ratio, indicating that decreased b-AR density was due to the increased presynaptic sympathetic tone.…”

The influence on Dobutamine docking of blood flow around the sinoatrial node

“…There does not appear to be experimental values for the diffusion coefficient (D) for Dobutamine. One method of estimating D is from [11] /sec for diffusion in water. A value of 3.5x10 -10 m 2 /sec will be used.…”