ABC | Volume 110, Nº2, February 2018

Original Article Rabelo et al The Presence and Extension of Myocardial Fibrosis in the Undetermined Form of Chagas’ Disease Arq Bras Cardiol. 2018; 110(2):124-131 Table 2 – Characteristics of the indeterminate form versus the cardiac form without left ventricular dysfunction Variables Indeterminate form (n = 17) Cardiac form without ventricular dysfunction (n = 16) p value Rassi Score 2 (0 – 2) 6 (1 – 8) 0.30‡ Area of fibrosis from the CMR (%) 4.1 (2.1 – 10.7) 2.3 (1 – 5) 0.18‡ LV ejection fraction (%) 72 ± 8 67 ± 6 0.09† Ventricular Tachycardia (%) – 20 0.001* METS 10 ± 3 9.4 ± 2 0.60† Maximum VO 2 35 ± 10 33 ± 7 0.47† NT-ProBNP (pg/mL) 125 (34 – 108) 171 (73 – 181) 0.61‡ Ultrasensitive PCR (mg/L) 1.7 (0.35 – 6.5) 1.2 (0.51 – 4.7) 0.40‡ Troponin I (ng/mL) 0.012 (0.0 – 0.012) 0.012 (0.012 – 0.028) 0.31‡ IL-2 (pg/mL) 0.21 (0.03 – 0.55) 0.27 (0.03 – 0.96) 0.14‡ IL-4 (pg/mL) 0.62 (0.00 – 1.6) 0.37 (0.2 – 2.2) 0.83‡ IL-6 (pg/mL) 2.26 (1.39 – 4.35) 3.98 (2.01 – 6.22) 0.50‡ IL-10 (pg/mL) 0.44 (0.19 – 1.06) 0.63 (0.50 – 1.61) 1.47‡ TNF-alfa (pg/mL) 0.48 (0.14 – 1.15) 0.72 (0.58 – 2.71) 1.16‡ IFN-gama (pg/mL) 2.07 (1.30 – 4.35) 2.15 (1.69 – 6.73) 0.51‡ CMR: cardiac magnetic resonance; LV: left ventricular; METS: metabolic equivalent of task; Maximum VO 2 : Maximum Oxygen volume; NT-ProBNP: N-terminal pro B-type natriuretic peptide. *Fisher’s exact test; †Student’s t test; ‡ Mann-Whitney’s test. Data expressed as mean ± standard deviation or percentage (%) for discrete variables and median and interquartile range for continuous variables with non-normal distribution. an indeterminate form was impaired since it was impossible to analyze the electrocardiographic alterations. In 1997, Andrade et al., 24 using a canine model, interpreted that the indeterminate form of the disease is characterized by a self-limited cycle of focal inflammatory alterations, with modulation and suppression of immune responses mediated by cells. Thus, they considered that the indeterminate form of Chagas' disease is characterized by a host-parasite equilibrium instead of a progressive damaging process. 24 As early as 1978, Andrade et al. 13 reported that chronic chagasic myocarditis lesions are not randomly distributed through the atrioventricular conduction system, but rather that there is a clear distribution of lesions in the conduction system. 13 We now know that a large percentage of patients in the indeterminate form show evidence of cardiac involvement in the detailed, non-invasive evaluation. 25 The data from the present study demonstrate that a CMR is not capable of differentiating the indeterminate form from the clinical form without LV dysfunction, since the percentage of fibrosis is similar between the two clinical forms. In this study, the percentage of fibrosis involvement in the indeterminate form (41.2%) was similar to the percentage in the cardiac form without LV dysfunction (43.8%). Some limitations of the study should be recognized. No anatomical tests were performed to definitively rule out ischemic etiology as a cause of myocardial fibrosis. In order to minimize this possibility, an ergometric test was performed with all of the individuals, in addition to including the exclusion criteria of the presence of risk factors for atherosclerosis. Although it is recognized that to rule out coronary artery disease definitively, a coronary angiography would be necessary, the negative predictive value of the exercise test in these circumstances is very high. Coronary artery disease was excluded without performing a coronary angiography in order to avoid radiation and complications resulting from the procedure. Conclusion The presence of fibrosis in the indeterminate form of Chagas' disease has a frequency and extension similar to that of the cardiac form without dysfunction, suggesting that the former is part of a subclinical disease spectrum, rather than lacking cardiac involvement. Thus, indeterminate and cardiac forms without dysfunction resemble each other and differ significantly from cardiac form with dysfunction. Author contributions Conception anddesign of the research: RabeloMMR,Macedo CT, Larocca T, Soares MBP, Correia LCL; Acquisition of data: Rabelo MMR, Macedo CT, Larocca T, Machado A, Pacheco T; Analysis and interpretation of the data and Statistical analysis: Rabelo MMR, Correia LCL; Obtaining financing: Rabelo MMR, Larocca T, Soares MBP;Writing of themanuscript: RabeloMMR, Macedo CT, Soares MBP, Correia LCL; Critical revision of the manuscript for intellectual content: Rabelo MMR, Macedo CT, Souza BSF, Soares MBP, Ribeiro-dos-Santos R, Correia LCL; Interpretation of magnetic resonance data: Torreão J. Potential Conflict of Interest No potential conflict of interest relevant to this article was reported. 129