Evaluation of the Autonomic Nervous System in Chronic Chagasic Cardiopathy: A Systematic Review of the Literature

Rimolo, Lorena dos Santos Marreto; Saraiva, Roberto Magalhães; Cunha, Ademir Batista da

doi:10.36660/ijcs.20190122

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ORIGINAL ARTICLE • Int J Cardiovasc Sci 33 (6) • Nov-Dec 2020 • https://doi.org/10.36660/ijcs.20190122 linkcopy

Evaluation of the Autonomic Nervous System in Chronic Chagasic Cardiopathy: A Systematic Review of the Literature

Authorship SCIMAGO INSTITUTIONS RANKINGS

Background The importance of regional sympathetic denervation in the pathophysiology and prognosis of Chagas disease has been recognized.

Objective To conduct a review of studies that have assessed dysautonomia in chronic Chagas heart disease.

Methods The search was performed on the Medline, Pubmed, Lilacs and SciELO databases. The inclusion criteria were: original articles published in full; studies on individuals with Chagas disease, that used diagnostic methods for chagasic cardiomyopathy, and had clear inclusion and exclusion criteria. Duplicate studies, studies including children (0 to 10 years old), studies involving animals, in vitro experiments, case reports, editorials, theses, and dissertations were excluded.

Results A total of 281 articles were retrieved, and 10 met the inclusion criteria and were analyzed. There was great heterogeneity as to the technique for assessing dysautonomia, groups of patients studied and classification of Chagas disease. The methods used for studying the autonomic system was immunohistochemistry (n=1), Valsalva and tilt-test (n=1), scintigraphy (n=6) and Holter monitoring (n=2). The results indicated dysautonomia in the indeterminate, digestive and cardiac forms of Chagas disease, and sympathetic denervation in the indeterminate and cardiac forms of the disease. There was agreement between areas of denervation, hypoperfusion and fibrosis, but areas of denervation were larger than those of hypoperfusion. The frequency of denervation and its extension increased from the indeterminate to the cardiac form. There was an association between extension of denervation and previous history of malignant ventricular arrhythmia.

Conclusions The evidence presented in this review supports that an early diagnosis of autonomic denervation in chronic Chagas' disease allows the identification of patients with an increased risk of sudden death. Int J Cardiovasc Sci. 2020; [online].ahead print, PP.0-0

Chagas Disease; Chagas Cardiomyopathy; Arrhythmias, Cardiac; Primary Dysautonomias; Autonomic Nervous System

References	Objectives	Design	Techniques	n	Main Results
MARINO et al., 2018¹⁸	To compare cardiac sympathetic dysfunction of patients with HF due to CHD or other etiologies	Cross-sectional	MIBG scintigraphy estimating HMR uptake and cardiac washout	25 CHD patients with HF 25 non-CD HF	The HMR of 123I-MIBG uptake and cardiac washout were similar in patients with HF with or without CD. Late HMR values showed a positive correlation with LVEF in patients with CHD and HF
BARIZON et al., 2018¹⁹	To test the correlation between areas of hypoperfusion, autonomic denervation and fibrosis in patients with CD	Cross-sectional	MIBG SPECT, rest/stress MIBI and MRI	13 CHD	Denervation areas were larger than the areas of rest- or stress-induced hypoperfusion and areas with myocardial fibrosis. In individual patients, there was a strong anatomic correlation between areas of hypoperfusion, denervation, and fibrosis
GADIOLI et al., 2016¹⁷	To investigate the correlation between the extent of myocardial sympathetic denervation and ﬁbrosis and the severity of ventricular arrhythmias in CHD	Cross-sectional	MIBG SPECT, rest/stress MIBI	15 CHD with SVT 11 CHD with NSVT 17 CHD no arrhythmia	The extent of denervated but viable myocardium was higher in SVT group than in the control group and the NSVT group. The occurrence of ventricular arrhythmias correlates 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 CHD
SOUZA et al., 2013¹¹	To evaluate if cardiac rehabilitation improves autonomic function of patients with CHD and dysautonomia on Holter monitoring	Prospective	Heart rate variability on Holter monitoring	18 CHD patients with HF	Heart rate variability parameters in patients with CHD with HF did not show statistically signiﬁcant changes after a six-month cardiac rehabilitation program
MIRANDA et al., 2011¹⁶	To compare the extent of sympathetically denervated viable myocardium between patients with CHD with or without SVT	Cross sectional	MIBG SPECT, rest/stress MIBI	15 CHD with SVT 11 CHD without SVT	The amount of sympathetically denervated viable myocardium is associated with the occurrence of SVT. The presence of more than 3 mismatch defects was strongly associated with SVT. Myocardial sympathetic denervation may participate in triggering malignant ventricular arrhythmia in CHD
LANDESMANN et al., 2007¹⁵	To evaluate if patients with CD IND form present early changes in sympathetic autonomic cardiac innervation	Cross sectional	MIBG SPECT	26 IND 8 controls	The HMR in patients with CD was lower than controls. Patients with CD IND form may have changes in sympathetic cardiac innervation
RIBEIRO et al., 2002¹⁴	To describe heart rate variability patterns in different groups of CD	Cross sectional	Holter monitoring	85 CD with normal echo 49 CHD with wall motion abnormality 26 CHD with LV systolic dysfunction 26 controls	Compared to controls, patients with CD have reduced vagal indexes and abnormal fractal patterns of heart rate variability that are independent of the presence of regional or global LV systolic dysfunction
MACHADO et al., 2000⁸	To assess the densities of sympathetic and parasympathetic nerve terminals in hearts of patients with HF with or without CD	Cross sectional	Histopathology	11 CHD with HF 8 non CD HF	Parasympathetic denervation was more severe in CHD while the degree of sympathetic denervation was similar in both groups
SIMÕES et al., 2000⁵	To detect the regional ventricular sympathetic innervation disturbances and myocardial perfusion abnormalities in various CD forms	Cross sectional	MIBG SPECT, rest/stress MIBI	12 IND 13 CHD with normal LV EF 12 CHD with LV systolic dysfunction 18 controls	Extensive impairment of cardiac sympathetic function at the ventricular level occurred early in CHD and was related to regional myocardial perfusion disturbances, before wall motion abnormalities
MARIN-NETO et al., 1998⁶	To assess cardiac autonomic control and biventricular function in CD patients with no evidence of heart disease	Cross sectional	Radionuclide angiography, Valsalva maneuver, head-up tilt and baroreflex sensitivity	16 IND 15 DIG 14 controls	No significant differences in autonomic functions were found between controls and IND group. CD patients with the DIG form showed abnormally lower Valsalva ratio, baroreflex sensitivity and parasympathetically-dependent heart rate response to tilt and higher Valsalva delay values compared with the controls

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[TFN1] CD: Chagas disease; CHD: Chagas’ heart disease; DIG: CD digestive form; HF: heart failure; HMR: heart-to-mediastinum ratio; IND: CD indeterminate form; LV EF: left ventricular ejection fraction; MIBG: iodine-123 (I-123) meta-iodobenzylguanidine; MIBI: 99mTc-Sestamibi; MRI: magnetic resonance; NSVT: non-sustained ventricular tachycardia; SPECT: single photon emission computed tomography; SVT: sustained ventricular tachycardia; All of the aforementioned studies used a statistical significance level of 5%