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Head shot of author required Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology THE SEVERITY OF VENTRICULAR ARRHYTHMIA CORRELATES WITH THE EXTENT OF MYOCARDIAL SYMPATHETIC DENERVATION, BUT NOT WITH MYOCARDIAL FIBROSIS EXTENT IN CHRONIC CHAGAS CARDIOMYOPATHY Leonardo Pippa Gadioli, Carlos Henrique Miranda, Antonio Osvaldo Pintya, Alexandre Baldini de Figueiredo, André Schmidt, Benedito Carlos Maciel, José Antonio Marin-Neto, Marcus Vinicius Simões Division of Cardiology – Medical School of Ribeirão Preto – University of São Paulo, Ribeirão Preto, Brazil Head shot of author required Copyright American Society of Nuclear Cardiology

Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology BACKGROUND 1- A peculiar aspect of the natural history of Chronic Chagas Cardiomyopathy (CCC) is the occurrence of severe ventricular arrhythmia in individuals with relatively preserved global left ventricular systolic function that may lead to sudden death in the early phases of disease. 2- Studies that analyzed the electrophysiologic substrate of malignant ventricular arrhythmia in CCC suggested that factors other than the severity of the LV dysfunction and the presence of regional myocardial fibrosis are likely to contribute to the genesis of these arrhythmias. 3- Previous study using myocardial scintigraphy with Iodine-123-metaiodobenzylguanidine (MIBG) in patients with CCC suggested that sympathetic denervation may participate in the arrhythmogenesis mechanism of sustained ventricular tachycardia. 4- However, there is no previous report on the evaluation of the myocardial sympathetic denervation in patients with CCC having less severe forms of ventricular arrhythmia, but which still hold prognostic importance, such as non-sustained ventricular tachycardia (NSVT). Copyright American Society of Nuclear Cardiology

METHODS Study subjects: Study type: C. Study variables Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology METHODS Study type: Prospective observational Study subjects: Chronic Chagas Cardiomyopathy patients with left ventricular ejection fraction (LVEF) ≥35% were included in three groups: SVT group - presenting Sustained Ventricular Tachycardia (SVT, n=15), NSVT group - exhibiting episodes of non-SVT (NSVT, n=11) and control group (n=17)- patients without exhibiting SVT or just only one episode of n-SVT on 24-h Holter monitoring. C. Study variables The extent/severity of myocardial denervation and myocardial fibrosis was assessed in the 3 investigational groups. Copyright American Society of Nuclear Cardiology

Insert a key table or a key figure If figure, insert legend Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology RESULTS Insert a key table or a key figure If figure, insert legend Figure 1. Bar graphs illustrating the results of the summed scores of the Myocardial perfusion, Cardiac MIBG and Myocardial innervation and perfusion mismatch, in the 3 investigated patient groups. NSVT and SVT. NSVT = non Sustained Ventricular Tachycardia; SVT = Sustained Ventricular Tachycardia. Copyright American Society of Nuclear Cardiology

Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology RESULTS Figure 2 – Illustrative examples of MPI and MIBG SPECT images of patients of each study group. Top panel: images of a 40 y.o. female patient of the control group, showing normal MPI (SRS = 0) and mild defects in the MIBG study at the inferior-apical and posterior-lateral walls. The MIBG-MPI mismatch score was 4. Middle panel: images of a 60 y.o. male patient of the non-SVT group showing normal myocardial perfusion (SRS = 0), but severe MIBG defects at the inferior and posterior-lateral walls. The MIBG-MPI mismatch score was 14. Bottom panel: images of a 59 y.o. male patient of the SVT group, showing mild perfusion defects at the posterior-lateral and apical walls (SRS = 3) and severe extensive defects in the MIBG, resulting in a MIBG-MPI mismatch score of 21. The arrows with numbers indicate illustrative examples of myocardial perfusion defects with diverse severity: 1 = mild defect; 2 = moderate defect; 3 = severe defect; 4 = absent uptake. Copyright American Society of Nuclear Cardiology

Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology CONCLUSIONS 1- The extent of regional myocardial sympathetic denervation assessed by MIBG SPECT imaging correlated quantitatively with the presence of ventricular arrhythmia of various degrees of severity in patients with CCC. 2- These results suggest a relevant role played by the regional myocardial sympathetic denervation in triggering severe ventricular arrhythmia in patients with CCC, in addition to the substrate represented by the presence of myocardial fibrosis 3- It is also possible to hypothesize that assessment of cardiac sympathetic innervation could be used for risk stratification of sudden death in CCC. 4- More specific studies in the future should be carried out to elucidate this plausible hypothesis. Copyright American Society of Nuclear Cardiology