Cardiac sympathetic denervation and ventricular arrhythmia are frequently observed in chronic Chagas cardiomyopathy (CCC). This study quantitatively evaluated the association between cardiac sympathetic denervation and sustained ventricular tachycardia (SVT) in patients with CCC. Methods: We prospectively investigated patients with CCC and left ventricular ejection fraction (LVEF) greater than 35% with SVT (SVT group: n 5 15; mean age 6 SD, 61 6 8 y; LVEF, 51% 6 8%) and patients without SVT (non-SVT group: n 5 11; mean age 6 SD, 55 6 10 y; LVEF, 57% 6 10%). Patients underwent myocardial scintigraphy with 123 I-metaiodobenzylguanidine ( 123 I-MIBG) for the evaluation of sympathetic innervation and resting perfusion with 99m Tc-methoxyisobutylisonitrile ( 99m Tc-MIBI) for the evaluation of myocardial viability. A visual semiquantitative score was attributed for regional uptake of each radiotracer using a 17-segment left ventricular segmentation model (0, normal; 4, absence of uptake). A mismatch defect was defined as occurring in segments with a 99m Tc-MIBI uptake score of 0 or 1 and a 123 I-MIBG score of 2 or more. Results: Compared with the non-SVT group, the SVT group had a similar 99m Tc-MIBI summed score (6.9 6 7.5 vs. 4.4 6 5.2, respectively, P 5 0.69) but a higher 123 I-MIBG summed score (10.9 6 7.8 vs. 22.4 6 9.5, respectively, P 5 0.007) and a higher number of mismatch defects per patient (2.0 6 2.2 vs. 7.1 6 2.0, respectively, P , 0.0001). The presence of more than 3 mismatch defects was strongly associated with the presence of SVT (93% sensitivity, 82% specificity; P 5 0.0002). Conclusion: In CCC, the amount of sympathetically denervated viable myocardium is associated with the occurrence of SVT. Myocardial sympathetic denervation may participate in triggering malignant ventricular arrhythmia in CCC patients with relatively well-preserved ventricular function.