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Abnormal Sympathetic Innervation of Viable Myocardium and the Substrate of Ventricular Tachycardia After Myocardial Infarction

Tetsuo Sasano, MD^_*, M. Roselle Abraham, MD^_*, Kuan-Cheng Chang, MD^_*, Hiroshi Ashikaga, MD, PhD^_*, Kevin J. Mills, BS^_*, Daniel P. Holt, BS, John Hilton, PhD, Stephan G. Nekolla, PhD, Jun Dong, MD^_*, Albert C. Lardo, PhD^_*, Henry Halperin, MD^_*, Robert F. Dannals, PhD, Eduardo Marbán, MD^_* and Frank M. Bengel, MD^,_*

^_* Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland
Division of Nuclear Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
Nuklearmedizinische Klinik, Technical University of Munich, Munich, Germany.

Manuscript received November 15, 2007; revised manuscript received February 13, 2008, accepted February 19, 2008.

^_* Reprint requests and correspondence: Dr. Frank M. Bengel, Director, Cardiovascular Nuclear Medicine, Division of Nuclear Medicine/PET, 601 North Caroline Street, Johns Hopkins Outpatient Center 3225, Baltimore, Maryland 21287. (Email: fbengel1{at}jhmi.edu).

Objectives: The aim of this study was to characterize the relationship between impaired sympathetic innervation and arrhythmia with noninvasive biologic imaging in an animal model of post-infarct ventricular tachycardia (VT).

Background: Innervation might be abnormal in the normally perfused borderzone of myocardial infarction, contributing to myocardial catecholamine overexposure and arrhythmogenic risk.

Methods: Myocardial infarction was induced by mid-left anterior descending coronary artery balloon occlusion in 11 pigs. Positron emission tomography (PET) of tissue perfusion and catecholamine uptake and storage was performed with [¹³N]-ammonia and [¹¹C]-epinephrine 4 to 12 weeks later. Magnetic resonance imaging and invasive electrophysiology (electroanatomic mapping, basket catheter, VT inducibility) were performed within 1 week of PET.

Results: When compared with a normal database of 9 healthy animals, reduced perfusion was observed in 37 ± 7% of the left ventricle (LV). Epinephrine retention was reduced in 44 ± 7% of LV, resulting in a perfusion/innervation mismatch of 7 ± 4% LV. Sustained monomorphic VT was inducible in 7 of 11 animals. These animals showed a larger perfusion/innervation mismatch (10 ± 4% vs. 4 ± 2% LV for animals without VT; p = 0.02). Regionally, the degree of perfusion/innervation mismatch did not correlate with wall thickness or thickening but showed a significant correlation with reduced myocardial voltage (r = 0.93; p = 0.001) and with the site of earliest VT activation (chi-square 13.1; p < 0.001).

Conclusions: Noninvasive mapping of cardiac sympathetic nerve terminals reveals regionally impaired catecholamine uptake and storage in the normally perfused borderzone after experimental myocardial infarction. These areas might be useful to characterize the individual risk for ventricular arrhythmia.

Abbreviations and Acronyms   BV = bipolar voltage   EAM = electroanatomical mapping   EPS = electrophysiological studies   ERP = effective refractory period   ICD = implantable cardioverter-defibrillator   LAD = left anterior descending coronary artery   LV = left ventricle/ventricular   MI = myocardial infarction   MRI = magnetic resonance imaging   PET = positron emission tomography   RV = right ventricle   VT = ventricular tachycardia

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