Abnormal sympathetic innervation of viable myocardium and the substrate of ventricular tachycardia after myocardial infarction

Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Journal of the American College of Cardiology (Impact Factor: 15.34). 07/2008; 51(23):2266-75. DOI: 10.1016/j.jacc.2008.02.062
Source: PubMed

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

  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of the study described here was to compare myocardial strains in ischemic heart patients with and without sustained ventricular tachycardia (VT) and moderately abnormal left ventricular ejection fraction (LVEF) to investigate which index could better predict VT on the basis of the analysis of global and regional left ventricular (LV) dysfunction. We studied 467 patients with previous myocardial infarction and LVEF >35%. Fifty-one patients had documented VT, and 416 patients presented with no VT. LV volumes and score index were obtained by 2-D echocardiography. Longitudinal, radial and circumferential strains were determined. Strains of the infarct, border and remote zones were also obtained. There were no differences in standard LV 2-D parameters between patients with and those without VT. Receiver operating characteristic values were −12.7% for global longitudinal strain (area under the curve [AUC] = 0.72), −4.8% for posterior-inferior wall circumferential strain (AUC = 0.80), 61 ms for LV mechanical dispersion (AUC = 0.84), −10.1% for longitudinal strain of the border zone (AUC = 0.86) and −9.2% for circumferential strain of the border zone (AUC = 0.89). In patients with previous myocardial infarction and moderately abnormal LVEF, peri-infarct circumferential strain was the strongest predictor of documented ventricular arrhythmias among all strain quantitative indices. Additionally, strain values from posterior-inferior wall infarctions had a higher association with arrhythmic events compared with global strain.
    Ultrasound in Medicine & Biology 12/2014; 41(2). DOI:10.1016/j.ultrasmedbio.2014.09.025 · 2.10 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this study, we synthesized and characterized N-[11C]methyl-dopamine ([11C]MDA) for cardiac sympathetic nerve imaging. [11C]MDA was synthesized by direct N-methylation of dopamine with [11C]methyl iodide and purified by semi-preparation reverse high pressure liquid chromatography (HPLC). The total synthesis time was 45 min including HPLC purification. The radiochemical yields of [11C]MDA was 20 ± 3 %, without decay correction. The radiochemical purity was >98 % and the specific activity was about 50 GBq/mmol. The biological properties of [11C]MDA were evaluated by biodistribution study in normal mice. PET imaging was performed in healthy Chinese mini-swines. Biodistribution study showed that [11C]MDA had high myocardium uptake. PET/CT imaging showed [11C]MDA had clear and symmetrical myocardium uptake, which was blocked obviously by injecting imipramine hydrochloride. [11C]MDA would be a promising candidate of radiotracer for cardiac sympathetic nervous system imaging.
    Journal of Radioanalytical and Nuclear Chemistry 08/2014; 301(2):469-474. DOI:10.1007/s10967-014-3152-8 · 1.42 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Histological analysis of endomyocardial tissue is still the gold standard for the diagnosis of cardiac amyloidosis, but has its limitations. Accordingly, there is a need for non-invasive modalities to diagnose cardiac amyloidosis. Echocardiography and ultrasound and magnetic resonance imaging can show characteristics which may not be very specific for cardiac amyloid. Nuclear medicine has gained a precise role in this context: several imaging modalities have become available for the diagnosis and prognostic stratification of cardiac amyloidosis during the last two decades. The different classes of radiopharmaceuticals have the potential to bind different constituents of the amyloidotic infiltrates, with some relevant differences among the various aetiologic types of amyloidosis and the different organs and tissues involved. This review focuses on the background of the commonly used modalities, their present clinical applications, and future clinical perspectives in imaging patients with (suspected) cardiac amyloidosis. The main focus is on conventional nuclear medicine (bone scintigraphy, cardiac sympathetic innervation) and positron emission tomography.
    Heart Failure Reviews 11/2014; 20(2). DOI:10.1007/s10741-014-9463-6 · 3.99 Impact Factor