Positron emission tomography with 11C CGP-12177 to assess beta-adrenergic receptor concentration in idiopathic dilated cardiomyopathy.

Merlet, Pascal; Delforge, Jacques; Syrota, A.; Angevin, Eric; Mazièré, B.; Crouzel, C.; Valette, Héric; Loisance, D; Castaigne, A; Randé, Jean Luc Dubois

doi:10.1161/01.cir.87.4.1169

Cited by 149 publications

(48 citation statements)

References 27 publications

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“…Although not statistically significant, it is consistent with the 9% total (14% for b1) BAR density decrease from in vitro assays of biopsy samples of patients with ischemic CHF compared with age-matched healthy subjects (16). In another study, global PET BAR density was decreased in patients with CHF from idiopathic IDCM and correlated with biopsy samples in the same subjects (17).…”

Section: Discussionsupporting

confidence: 61%

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Evidence for Pre- to Postsynaptic Mismatch of the Cardiac Sympathetic Nervous System in Ischemic Congestive Heart Failure

et al. 2008

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Pre-and postsynaptic cardiac sympathetic function is altered in ischemic congestive heart failure (CHF). Whether there is a presynaptic-to-postsynaptic mismatch or whether mismatch is related to adverse cardiac events is unknown. Methods: In 13 patients with ischemic CHF and 25 aged-matched healthy volunteers, presynaptic function was measured by PET of 11 Cmeta-hydroxyephedrine ( 11 C-mHED), a norepinephrine (NE) analog. Postsynaptic function, b-adrenergic receptor (BAR) density (B9 max ), was measured by imaging 11 C-CGP12177. Myocardial blood flow (MBF) was measured by imaging 15 O-water. Each heart was analyzed both globally and regionally, excluding infarcted regions, and a mismatch score, defined as the ratio of B9 max to NE uptake (PS nt ) , was used to indicate mismatch of post-and presynaptic function. Results: Global and regional MBF was not different between CHF and healthy subjects. The global measure of PS nt was lower in CHF (0.32 6 0.34) than that in healthy subjects (0.81 6 0.33, P , 0.0001) and in all 12 regions. Global B9 max tended to be lower in CHF than that in healthy subjects (10.0 6 6.4 pmol/mL vs. 13.4 6 4.2, P 5 0.056) and in all 12 regions. The global mismatch score (B9 max :PS nt ) in CHF patients was significantly greater than that in healthy subjects (50.3 6 50.7 vs. 19.3 6 9.7, P 5 0.005) and also greater in 11 of 12 regions. After 1.5 y of follow-up, 4 individuals had an adverse outcome (CHF death, new or recurrent sudden death, or progressive CHF leading to transplantation). Three of the 4 had mismatch scores . 3 times that of the healthy subjects or the CHF patients without an adverse outcome. Conclusion: Mismatch between pre-and postsynaptic left ventricular sympathetic function is present in patients with severe CHF and may be more marked in those with adverse outcomes.

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Section: Discussionsupporting

confidence: 61%

“…PET has shown that global BAR density is lower in patients with CHF from idiopathic dilated cardiomyopathy (IDCM) compared with that of healthy subjects (17).…”

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confidence: 99%

Evidence for Pre- to Postsynaptic Mismatch of the Cardiac Sympathetic Nervous System in Ischemic Congestive Heart Failure

et al. 2008

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“…PET is an excellent noninvasive tool for investigating the distribution of myocardial b-AR in vivo and provides the possibility of repeated measurements. Studies using PET and the radioligand 11 C-CGP-12177 ( 11 C-CGP) have shown promising results that are in agreement with those of in vitro studies (17). CGP appears to be the most suitable ligand because it is very potent and is a hydrophilic nonselective b-AR antagonist with low nonspecific binding on membranes and slight cellular uptake (18).…”

mentioning

confidence: 75%

“…Increased presynaptic activity in the failing human heart (8,16) and a decrease of postsynaptic b-AR density in failing heart (14,15,17) have been reported. In our study, the degree of b-AR downregulation corresponded to the increase in 123 I-MIBG WR and a decrease in delayed H/M ratio.…”

Section: Discussionmentioning

confidence: 99%

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

Tsukamoto¹,

Morita²,

Naya³

et al. 2007

Journal of Nuclear Medicine

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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.

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PET: Metabolism, Innervation and Receptors

Bengel¹,

Schwaiger²

2006

Cardiac CT, PET and MR

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Positron emission tomography with 11C CGP-12177 to assess beta-adrenergic receptor concentration in idiopathic dilated cardiomyopathy.

Abstract: PET appears to be a safe and reliable method of assessing in vivo changes in the number of left ventricular beta-adrenergic receptor sites of patients with idiopathic cardiomyopathy.

Cited by 149 publications

References 27 publications

Evidence for Pre- to Postsynaptic Mismatch of the Cardiac Sympathetic Nervous System in Ischemic Congestive Heart Failure

Evidence for Pre- to Postsynaptic Mismatch of the Cardiac Sympathetic Nervous System in Ischemic Congestive Heart Failure

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

PET: Metabolism, Innervation and Receptors

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