REGIONAL MYOCARDIAL SYMPATHETIC DYSINNERVATION IN ARRHYTHMOGENIC RIGHT-VENTRICULAR CARDIOMYOPATHY - AN ANALYSIS USING I-123 METAIODOBENZYLGUANIDINE SCINTIGRAPHY

Background In patients with arrhythmogenic right ventricular cardiomyo pathy (ARVC), the frequent provocation of ventricular tachycardia duri ng exercise, the sensitivity toward catecholamines, and the response t oward antiarrhythmic drug regimen with antiadrenergic properties sugge st an involvement of the sympathetic nervous system in arrhythmogenesi s. Methods and Results To analyze the presence, extent, and location o f impaired myocardial sympathetic innervation in ARVC, I-123-meta-iodo benzylguanidine (I-123-MIBG) scintigraphy was performed in 48 patients with ARVC. For comparison, 9 patients with idiopathic ventricular tac hycardia and a control group of 7 patients without heart disease were investigated. In patients with ARVC, the clinical sustained (n=25; 52% ) or nonsustained (n=23; 48%) ventricular tachycardia originated in th e right ventricular outflow tract in 38 patients (79%), whereas in the remaining 10 patients (21%), the site of origin was the apical (n=5) or inferior (n=5) right ventricle. In 33 patients (69%), nonsustained or sustained ventricular tachycardia was provocable by exercise (n=28 of 48; 58%) and/or by isoproterenol infusion (n=16 of 37; 43%), wherea s programmed ventricular stimulation induced sustained or nonsustained ventricular tachycardia in 16 patients each (33% each). With I-123-MI BG scintigraphy, the right ventricle was not visible in any patient. N o areas of intense I-123-MIBG uptake (''hot spots'') were observed. Ah patients of the control group and 7 of 9 patients (78%) with idiopath ic ventricular tachycardia showed a uniform tracer uptake in the left ventricle. In contrast, only 8 of 48 ARVC patients (17%) showed a homo geneous distribution of I-123-MIBG uptake, whereas 40 patients (83%) d emonstrated regional reductions or defects of tracer uptake. In 3 of 4 8 patients (6%), the defect area was <15%; in 21 patients (44%), it wa s 15% to 30%; and in 16 patients (33%), it was >30% of the polar map a rea of the left ventricle (mean, 23+/-15%; range, 0% to 57%). In 38 of 40 patients (95%) with an abnormal I-125-MIBG scan, reduced tracer up take was located in the basal posteroseptal left ventricle, involving the adjacent lateral wall in 10, the anterior wall in 2, and the apex in 12 patients. Only 2 patients demonstrated isolated defects of the a nterior or lateral wall; one involved the apex. Perfusion abnormalitie s in the areas of I-123-MIBG defects were excluded by stress/redistrib ution Tl-201 single-photon emission computed tomography scintigraphy a nd by normal coronary angiograms in all patients. Abnormalities in I-1 23-MIBG scintigraphy in patients with ARVC correlated with the site of origin of ventricular tachycardia, demonstrating a regionally reduced tracer uptake in 36 of 38 patients (95%) with right ventricular outfl ow tract tachycardia compared with only 4 of 10 patients (40%) with ot her right ventricular origins of tachycardia. There was no correlation between the results of I-123-MIBG scintigraphy and the extent of righ t ventricular contraction abnormalities, right ventricular ejection fr action, biopsy results, coronary anatomy, or left ventricular involvem ent in ARVC. Conclusions In patients with ARVC, regional abnormalities of sympathetic innervation are frequent and can be demonstrated by I- 123-MIBG scintigraphy. Sympathetic denervation appears to be the under lying mechanism of reduced I-123-MIBG uptake and may be related to fre quent provocation of ventricular arrhythmias by exercise or catecholam ine exposure in ARVC. Therefore, in patients with ARVC, the noninvasiv e detection of localized sympathetic denervation by I-123-MIBG imaging may have implications for the early diagnosis and for the choice of a ntiarrhythmic drugs in the treatment of arrhythmias.