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 when tested using CMR. 17 However, there is little data available on the degree of myocardial fibrosis presented by these individuals, which demonstrates the potential of this variable in the prediction of evolution to the cardiac form. The purpose of this paper is to describe the frequency and extent of myocardial fibrosis evaluated using CMR in patients in the indeterminate form. In order to contextualize this situation, these patients were compared to other individuals in the chronic cardiac form with and without left ventricular dysfunction. Methods Study population Individuals with Chagas’ disease were recruited between January of 2012 and December of 2013 at the Chagas’ disease outpatient clinic of the Hospital São Rafael, a tertiary referral center in Salvador, Bahia, Brazil. Inclusion criteria were: between 18 and 70 years old and a diagnosis of Chagas’ disease confirmed by two positive serological tests (indirect hemagglutination and indirect immunofluorescence). The exclusion criteria were: an acute form of Chagas' disease; previous myocardial infarction, coronary artery disease, or the presence of two risk factors; primary valve disease; terminal renal disease on dialysis; active hepatitis or cirrhosis; hematological, neoplastic or bone diseases and contraindication to magnetic resonance imaging. The study fulfilled its purpose from the Declaration of Helsinki and was approved by the Ethics Committee of the São Rafael Hospital. All of the individuals signed the Informed Consent Term prior to their participation. The Forms of Chagas’ Disease The indeterminate form was defined by the presence of a Trypanosoma cruzi infection in the absence of clinical manifestations. Signs of cardiac involvement were characterized by normal electrocardiograms, chest X-rays and echocardiograms. The cardiac form without ventricular dysfunction was defined by individuals with cardiac involvement known as abnormal electrocardiograms (typically right bundle branch blocks and left anterosuperior hemiblocks) and without left ventricular dysfunction on the echocardiogram. The cardiac form with ventricular dysfunction was composed of individuals with a reduced left ventricular ejection fraction. Clinical and laboratory data All of the individuals underwent biochemical tests, a 12-lead electrocardiogram, a chest X-ray, 24-hour holter monitoring, a cardiac stress test, a Doppler echocardiogram and a CMR. Scores were calculated as follows: functional classes III and IV by the New York Heart Association (NYHA) (5 points), X-ray cardiomegaly (5 points), left ventricular dysfunction, global or segmental echocardiography (3 points), non-sustained ventricular tachycardia during the 24 hour holter monitoring (3 points), low QRS voltage on the electrocardiogram (2 points) and male (2 points). They were then classified into three risk groups according to the score obtained: low risk (0 to 6 points), intermediate risk (7 to 11 points) and high risk (12 to 20 points). 18 Cardiac magnetic resonance imaging A CMR was performed using the Sigma HDx1,5-T system (General Electric; Fairfield, CT, USA). To evaluate how the functioning of the left ventricular, synchronized images were acquired from the electrocardiogram in the expiratory apnea, including in the short axis, long axis and the four chamber planes, in different sequences. The acquisition parameters applied to the dynamic sequence were: a repetition time (RT) of 3.5 ms, an echo time (ET) of 1.5 ms, a flip angle of 60º, a bandwidth of 125 kHz, a field of view of 35 x 35 cm, a matrix of 256 x 148, a temporal resolution (RT) of 35ms, a cut thickness of 8.0 mmwithout an interval between cuts. Images from the late enhancement technique were acquired with each heart beat 10 to 20 minutes after the administration of a gadolinium‑based contrast agent (0.1 mmol/kg), using a 7.2 ms RT, a 3.1 ms ET, an angle of inclination of 20º, the first phase of cardiac cycle, 16/32 lines per follow-up, a matrix size of 256 x 192, a cut thickness of 8.0 mm, an interval between 2 mm cuts, a field of view of 32 to 38 cm, an inversion time of 150 to 300 ms, a bandwidth of 31,25 kHz, and 2 NEX (number of excitations). The late enhancement technique was used to investigate the presence of myocardial fibrosis, which was estimated by a qualitative (visual) method in accordance with the presence or absence of late enhancement, location and pattern presented; and quantitatively, using percentage values in relation to the total myocardial mass. All analyses were performed with the Siemens Argus program (Simens AG, Munich, Germany). Statistical analysis The categorical data were expressed as numbers (percentages, 95% confidence interval - 95% CI), and continuous data were expressed as mean ± standard deviation (SD) or median and interquartile range (IIQ). Normality was determined by the Kolmogorov-Smirnov test. The comparison of the continuous variables with normal distribution was performed using Student's unpaired t test and Anova (one‑way analysis). The Bonferroni method was used for a post-hoc comparison between the groups. Fisher's exact test was used to compare proportions. The Kruskal-Wallis test was used to analyze non-normal continuous variables. Simple linear regression was used in the associations between fibrotic mass and the fraction of the left ventricular ejection. The analyses were performed using the SPSS program, version 20.0 (IBM), and p values below 0.05 (two-tailed test) were considered statistically significant. As an a priori primary analysis, the frequency and extent of myocardial fibrosis in the indeterminate form was described, and cardiac forms were compared with and without dysfunction. As a post-hoc secondary analysis, the association of fibrosis with the ejection fraction and the Rassi score was tested. Additionally, clinical and laboratory parameters were compared between the indeterminate form and the cardiac form without dysfunction. 125