Muscarinic Receptor Upregulation in Patients With Myocardial Infarction

Mazzadi, Alejandro; Pineau, Julien; Costes, Nicolas; Bars, Didier Le; Bonnefoi, Franck; Croisille, Pierre; Porcher, Raphaël; Chevalier, Philippe

doi:10.1161/circimaging.108.822106

Cited by 28 publications

(14 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As noted by Mazzadi et al, 1 heterogeneity appears to play a major role in the arrhythmias associated with myocardial infarction and ischemia and probably some of the nonischemic cardiomyopathies. Our own observation, using positron emission tomography (PET), that the magnitude of heterogeneity of presynaptic and postsynaptic sympathetic function is associated with adverse outcome in ischemic cardiomyopathy, supports the importance of functional heterogeneity.…”

Section: Article See P 365mentioning

confidence: 76%

Imaging Left Ventricular Muscarinic Receptor Heterogeneity

Caldwell

Link

2009

Circ: Cardiovascular Imaging

View full text Add to dashboard Cite

A s pointed out by Mazzadi et al 1 in this issue of Circulation: Cardiovascular Imaging, parasympathetic tone plays a critical role as modulator of the cardiac sympathetic nervous system in both health and disease. Decreased tone, as reflected by decreased heart rate variability (HRV), has an important role in prognosis after myocardial infarction (MI). 2 HRV is also associated with worse outcome in some patients with heart failure. 3,4 Sudden increases in parasympathetic tone, identified by increase in HRV, may precipitate ventricular fibrillation in selected individuals. 5 Other investigators have not found any of a multitude of HRV components to be predictive of outcome. 6 The predictive value of HRV is insufficient to be used alone and must be part of a multivariate assessment. Article see p 365Given the wealth of data demonstrating that HRV and its derivatives provide useful but not highly predictive clinical information and at a relatively low cost, what added value is gained by the use of a complicated and expensive imaging method? There are limitations to measurement of HRV that generally require the patient to be in sinus rhythm without sinoatrial dysfunction, to have Յ20% ectopic beats, have good quality tracings and, ideally, at least 24 hours of recording. 2 The requirement for sinus rhythm limits it application in the largest population in which it is most likely beneficial, those with heart failure. Also, imaging of presynaptic sympathetic function has been shown to better predict adverse events. 6 The results of the Mazzadi et al 1 study suggest that imaging of parasympathetic function also may be predictive.Probably the most important rationale for the use of imaging to measure muscarinic cholinergic function relates directly to the regional heterogeneity of myocardial perfusion and sympathetic and parasympathetic function. As noted by Mazzadi et al, 1 heterogeneity appears to play a major role in the arrhythmias associated with myocardial infarction and ischemia and probably some of the nonischemic cardiomyopathies. Our own observation, using positron emission tomography (PET), that the magnitude of heterogeneity of presynaptic and postsynaptic sympathetic function is associated with adverse outcome in ischemic cardiomyopathy, supports the importance of functional heterogeneity. 7 HRV and its components reflect both systemic and global cardiac parasympathetic and sympathetic function interaction but do not distinguish between the two. Moreover, HRV cannot measure regional dysfunction. In this report, Mazzadi et al 1 make the case that there are regional differences in muscarinic receptor density in the post-MI patient, even in the absence of significant residual scar, and by inference regional differences in parasympathetic function. Their observations were made in only 11 patients and 9 normal subjects. If their observation of increased receptor density remote from MI location is substantiated in larger populations and can be related to arrhythmic events or other adverse outcome, muscarinic ima...

show abstract

Section: Article See P 365mentioning

confidence: 76%

Imaging Left Ventricular Muscarinic Receptor Heterogeneity

Caldwell

Link

2009

Circ: Cardiovascular Imaging

View full text Add to dashboard Cite

show abstract

“…Although altered cardiac vagal activity has been suggested to have a role in post-infarct arrhythmogenesis, there is a paucity of data on in vivo PET imaging of the PNS in post-infarct patients. One study to date has assessed MR density with [ 11 C]-MQNB PET imaging in post-infarct patients using a modified two-injection protocol [67]. Mazzadi et al [67] reported that MR density was significantly upregulated in the remote and border zone compared to the infarct zone and normal regions in healthy controls, while MR density in the infarct zone was not significantly reduced compared to normal control regions.…”

Section: Alterations In Autonomic Function With Myocardial Ischemia Amentioning

confidence: 99%

Recent Advances and Clinical Applications of PET Cardiac Autonomic Nervous System Imaging

Boutagy

Sinusas

2017

Curr Cardiol Rep

View full text Add to dashboard Cite

Purpose of Review The purpose of this review was to summarize current advances in positron emission tomography (PET) cardiac autonomic nervous system (ANS) imaging, with a specific focus on clinical applications of novel and established tracers. Recent Findings [11C]-Meta-hydroxyephedrine (HED) has provided useful information in evaluation of normal and pathological cardiovascular function. Recently, [11C]-HED PET imaging was able to predict lethal arrhythmias, sudden cardiac death (SCD), and all-cause mortality in heart failure patients with reduced ejection fraction (HFrEF). In addition, initial [11C]-HED PET imaging studies have shown the potential of this agent in elucidating the relationship between impaired cardiac sympathetic nervous system (SNS) innervation and the severity of diastolic dysfunction in HF patients with preserved ejection fraction (HFpEF) and in predicting the response to cardiac resynchronization therapy (CRT) in HFrEF patients. Longer half-life 18F-labeled presynaptic SNS tracers (e.g., [18F]-LMI1195) have been developed to facilitate clinical imaging, although no PET radiotracers that target the ANS have gained wide clinical use in the cardiovascular system. Although the use of parasympathetic nervous system radiotracers in cardiac imaging is limited, the novel tracer, [11C]-donepezil, has shown potential utility in initial studies. Summary Many ANS radioligands have been synthesized for PET cardiac imaging, but to date, the most clinically relevant PET tracer has been [11C]-HED. Recent studies have shown the utility of [11C]-HED in relevant clinical issues, such as in the elusive clinical syndrome of HFpEF. Conversely, tracers that target cardiac PNS innervation have been used less clinically, but novel tracers show potential utility for future work. The future application of [11C]-HED and newly designed 18F-labeled tracers for targeting the ANS hold promise for the evaluation and management of a wide range of cardiovascular diseases, including the prognostication of patients with HFpEF.

show abstract

“…Table 2 provides an overview. Combinations of autonomic imaging agents have, for example, been used to identify an imbalance between presynaptic neuronal integrity and postsynaptic receptor density in progressive heart failure (18), to show that postsynaptic receptor density and downstream signaling may be impaired despite intact presynaptic catecholamine uptake in adriamycin-induced cardiotoxicity (19) or to show that parasympathetic muscarinic receptors may be upregulated after myocardial infarction (20).…”

Section: Beyond Nerve Terminal Functionmentioning

confidence: 99%

Imaging Targets of the Sympathetic Nervous System of the Heart: Translational Considerations

Bengel

2011

J Nucl Med

View full text Add to dashboard Cite

The usefulness of imaging the cardiac sympathetic nervous system is increasingly supported by prospective clinical studies. The future success of this molecular imaging technique, however, will depend on careful design of additional trials. But preclinical and clinical use requires a thorough understanding of the underlying biology, which defines the relationship between neuronal tracer kinetics, disease mechanisms, and appropriate study interpretation. This review focuses on basic methodologic aspects considered relevant for successful continuation of the translation of cardiac neuronal imaging from a research tool toward a clinical test.

show abstract

Muscarinic Receptor Upregulation in Patients With Myocardial Infarction

Cited by 28 publications

References 35 publications

Imaging Left Ventricular Muscarinic Receptor Heterogeneity

Imaging Left Ventricular Muscarinic Receptor Heterogeneity

Recent Advances and Clinical Applications of PET Cardiac Autonomic Nervous System Imaging

Imaging Targets of the Sympathetic Nervous System of the Heart: Translational Considerations

Contact Info

Product

Resources

About