OBJECTIVE: More than a century since its discovery, the pathogenesis of Chagas heart disease (CHD) remains incompletely understood. The role of derangements in the autonomic control of the heart in triggering malignant arrhythmia before the appearance of contractile ventricular impairment was reviewed.
RESULTS: Although previous investigations had demonstrated the anatomical and functional consequences of parasympathetic dysautonomia upon the heart rate control, only recently, coronary microvascular disturbances and sympathetic denervation at the ventricular level have been reported in patients and experimental models of CHD, exploring with nuclear medicine methods their impact on the progression of myocardial dysfunction and cardiac arrhythmias. More important than parasympathetic impaired sinus node regulation, recent evidence indicates that myocardial sympathetic denervation associated with coronary microvascular derangements is causally related to myocardial injury and arrhythmia in CHD. Additionally, 123I-MIBG imaging is a promising tool for risk stratification of progression of ventricular dysfunction and sudden death.

Regional myocardial sympathetic denervation is a conspicuous and early disorder in patients with chronic Chagas\' cardiomyopathy (CCC), potentially associated to the progression of myocardial dysfunction OBJECTIVE: To evaluate in a longitudinal study the association between the presence and the progression of regional myocardial sympathetic denervation with the deterioration of global and segmental left ventricular dysfunction in CCC.
18 patients with CCC were submitted at initial evaluation and after 5.5 years to rest myocardial scintigraphy with 123Iodo-metaiodobenzylguanidine and 99mTc-sestamibi and to two-dimensional echocardiography to assess myocardial sympathetic denervation, extent of fibrosis, and the left ventricular ejection fraction (LVEF) and wall motion abnormalities.
In the follow-up evaluation, compared to the initial one, we observed a significant decrease in LVEF (56 ± 11 to 49% ± 12; P = .01) and increased summed defects scores in the myocardial innervation scintigraphy (15 ± 10 to 20 ± 9; P < .01). The presence of regional myocardial sympathetic denervation in ventricular regions of viable non-fibrotic myocardium presented an odds ratio of 4.25 for the development of new wall motion abnormalities (P = .001).
Regional and global myocardial sympathetic denervation is a progressive derangement in CCC. In addition, the regional denervation is topographically associated with areas of future development of regional systolic dysfunction in patients with CCC.

Chronic Chagas\' cardiomyopathy is the most severe and frequent manifestation of Chagas disease, and has a high social and economic burden. New imaging modalities, such as strain echocardiography, nuclear medicine, computed tomography and cardiac magnetic resonance imaging, may detect the presence of myocardial fibrosis, inflammation or sympathetic denervation, three conditions associated with risk of sudden death, providing additional diagnostic and/or prognostic information. Unfortunately, despite its high mortality, there is no clear recommendation for early cardioverter-defibrillator implantation in patients with Chagas heart disease in the current guidelines. Ideally, the risk of sudden cardiac death may be evaluated in earlier stages of the disease using new image methods to allow the implementation of primary preventive strategies.

To investigate the correlation between the extent of myocardial sympathetic denervation and fibrosis and the presence of degrees of severity of ventricular arrhythmias in chronic Chagas cardiomyopathy (CCC).
Forty-three CCC patients with left ventricular ejection fraction (LVEF) ≥ 35% were divided into three groups: SVT group-presenting Sustained Ventricular Tachycardia (SVT) (n = 15), NSVT group-exhibiting episodes of non-SVT (NSVT) on 24-h Holter monitoring (n = 11), and Control group-exhibiting neither SVT nor episodes of NSVT (n = 17). The patients underwent SPECT imaging for myocardial sympathetic innervation with 123Iodine-MIBG (MIBG) and myocardial perfusion with 99mTc-Sestamibi (MIBI) for the evaluation of regional myocardial fibrosis.
The summed rest perfusion scores were similar in the three groups. The summed difference score between MIBG and MPI images, which evaluated the extent of denervated but viable myocardium, was significantly higher in SVT group (20.0 ± 8.0) as compared with the control group (2.0 ± 5.0, P < .0001) and with the NSVT group (11.0 ± 8.0, P < .05).
The occurrence of ventricular arrhythmias of different degrees of severity correlates quantitatively with the extent of cardiac sympathetic denervation, but not with the extent of fibrosis, suggesting that myocardial sympathetic denervation plays a major role in triggering ventricular arrhythmia in CCC.