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(Circulation. 2000;101:1552.)
© 2000 American Heart Association, Inc.

Clinical Investigation and Reports

Abnormalities of Cardiac Sympathetic Innervation in Arrhythmogenic Right Ventricular Cardiomyopathy

Quantitative Assessment of Presynaptic Norepinephrine Reuptake and Postsynaptic ß-Adrenergic Receptor Density With Positron Emission Tomography

Thomas Wichter, MD; Michael Schäfers, MD; Christopher G. Rhodes, MSc; Martin Borggrefe, MD, FESC; Hartmut Lerch, MD; Adriaan A. Lammertsma, PhD; Flemming Hermansen, MD; Otmar Schober, MD, PhD; Günter Breithardt, MD, FESC, FACC; Paolo G. Camici, MD, FESC, FACC, FRCP

From the Hospital of the Westfälische Wilhelms-University, Department of Cardiology and Angiology and Institute for Arteriosclerosis Research (T.W., M.B., G.B.) and Department of Nuclear Medicine (MS, H.L., O.S.), Münster, Germany, and the Medical Research Council-Cyclotron Unit and Imperial College School of Medicine, Hammersmith Hospital (C.G.R., A.A.L, F.H., P.G.C.), London, UK.

Correspondence to Dr Thomas Wichter, Medizinische Klinik und Poliklinik, Innere Medizin C (Kardiologie und Angiologie), Westfälische Wilhelms Universität, D-48129 Münster, Germany. E-mail wichtet{at}uni-muenster.de

Background—The frequent provocation of ventricular tachycardia by stress or catecholamines and the efficacy of antiarrhythmic drugs with antiadrenergic properties suggest an involvement of the cardiac adrenergic system in arrhythmogenesis in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Previous studies demonstrated abnormalities of the presynaptic uptake-1 assessed by ¹²³I-MIBG–single-photon emission computed tomography.

Methods and Results—This study investigated neuronal reuptake of norepinephrine (uptake-1) and ß-adrenergic receptor density in 8 patients with ARVC and 29 age-matched control subjects. All subjects underwent positron emission tomography with the volume of distribution (V_d) of [¹¹C]hydroxyephedrine (¹¹C-HED) used to assess presynaptic norepinephrine reuptake, the maximum binding capacity (B_max) of [¹¹C]CGP-12177 (¹¹C-CGP-12177) to assess postsynaptic ß-adrenergic receptor density, and [¹⁵O]H₂O for quantification of myocardial blood flow. Patients with ARVC demonstrated a highly significant global reduction in postsynaptic ß-adrenergic receptor density compared with that in control subjects (B_max of ¹¹C-CGP-12177: 5.9±1.3 vs 10.2±2.9 pmol/g tissue, P<0.0007), whereas the presynaptic uptake-1 tended toward reduction only (V_d of ¹¹C-HED: 59.1±25.2 vs 71.0±18.8 mL/g tissue, NS). There were no differences in myocardial blood flow between the groups, and plasma norepinephrine was within normal limits in patients and control subjects.

Conclusions—The findings demonstrate a significant reduction of myocardial ß-adrenergic receptor density in patients with ARVC. This may result from a secondary downregulation after increased local synaptic norepinephrine levels caused by increased firing rates of the efferent neurons or as the result of impaired presynaptic catecholamine reuptake. These findings give new insights into the pathophysiology of arrhythmogenesis in ARVC, with potential impact on diagnostic evaluation and therapeutic management.

Key Words: cardiomyopathy • ventricular tachycardia • nervous system, autonomic • receptors, adrenergic, beta • tomography

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