ABC | Volume 112, Nº2, February 2019

Brief Communication Miranda et al Analysis of iron metabolism in CCC Arq Bras Cardiol. 2019; 112(2):189-192 markers correlate with the degree of ventricular dysfunction of Chagas cardiomyopathy compared to non-chagasic cardiomyopathy (NCh). Methods Study population Forty patients with CCC, 40 chagasic patients with undetermined form (IND), and 40 patients with NCh were consecutively selected according to the inclusion and exclusion criteria. Patients with CCC and with the indeterminate form of Chagas disease showed confirmatory serology for T. cruzi. This study was approved by the Research Ethics Committee of UFMG-COEP with identification number ETIC 359/04. Study design and procedure At the time of inclusion, all patients underwent clinical examination, laboratory examination, 12-lead ECG. Functionalcapacity was assessed by the New York Heart Association (NYHA) scales. The severity of cardiac involvement was determined by echocardiographic indices (ejection fraction [EF], and left ventricular end-diastolic volume, LV). Hematologic evaluation Serum iron dosage (FeSe), transferrin saturation index (TSI), total iron-binding capacity (TIBC), and ferritin were sent to the Central Laboratory of Hospital das Clínicas. Their quantifications were done through the following methods: – serum iron (two-point kinetics) – transferrin saturation index, ferritin (immunoturbidimetry), were quantified by the calculation (serum iron - total iron-binding capacity). – total iron-binding fixation capacity (enzymatic kinetics). – transferrin dosage (immunoturbidimetry). Sample size calculation The work by Jankowska et al. (2012), in which functional classes III and IV HF patients were studied, was the basis for the sampling calculation, and showed alterations in iron metabolism and association with the degree of ventricular systolic dysfunction, and morbidity. Sample size was calculated by the BioStat 5.3 Software, for which the mean and standard deviation [±] of each iron kinetic variable with minimum test power of 0.80 were used, assuming a significance of 0.05% (> 5%) and beta error lower than 20% (test power); we decided to select 40 patients in each IND, CCC and NCh group. Statistical analysis Statistical analysis was performed using SPSS Software version 22.0 (SPSS Inc., Chicago, Illinois, United States). A descriptive analysis of continuous and categorical variables was performed. For the presence or absence of normal distribution of variables, the Shapiro-Wilk test was performed. For the multivariate analysis presented in Table 2, the Cox regression model was used, and the association of variables that were related to death, hazard ratio (HR) and 95% CI was evaluated, assuming a statistical significance of 0.05%. Selection criteria applied to the multivariate model Presence of left ventricular systolic dysfunction (LVEF≤35%). Left ventricular diameter (LVD) < 55mm. FeSe serum iron < 31 μg/dL. When the IST transferrin saturation index is less than 20%. TIBC < 250 μg/dL. Ferritin < 200 mg/dL. Results The demographic, clinical, laboratory and echocardiographic characteristics of the groups are presented in Table 1. There was a predominance of male patients, and most of the patients were NYHA I functional class, with mean left ventricular (LV) FE below 45%. In the univariate analysis, it was found that the variables that were associated with left ventricular systolic dysfunction below 35%were TSI, (OR = 0.89, p = 0.05), iron (OR = 0.97, ferritin (OR = 1.27, p = 0.017), gender (OR = 0.26, p = 0.05), HF etiology (OR = 2.40, p = 0.011), and anemia (OR = 8.97, p = 0.04). In the multivariate analysis, there was an independent association between low left ventricular dysfunction of 35% and TSI (OR = 1.12, p = 0.012), FeSe (OR = 1.02, p = 0.014), gender (OR = 3.94, p = 0.038), and the etiology of HF (OR = 2.6, p = 0.036); 35 individuals with left ventricular dysfunction (87.5%) were identified, who presented the outcome in the sample. Discussion Iron kinetic markers were found to correlate with the degree of ventricular dysfunction of chagasic cardiomyopathy in relation to NCh; the following observations were obtained as main results: (a) CCC patients, when compared with IND and NCh patients, had lower serum levels of iron, ferritin, TSI and TIBC; (b) patients with CCC have lower serum levels of iron, TSI, TIBC, and ferritin than patients with Chagasic and non chagasic cardiomyopathy; (c) lower serum levels of iron, TSI, TIBC, and ferritin are associated with the level of systolic ventricular dysfunction; (d) low serum levels of iron, TSI, TIBC, and ferritin are associated with the degree of cardiac morbidity. As demonstrated by the results presented, we observed that patients with CCC, when comparedwith chagasic patients in the indeterminate form (IND) and those with NCh, present lower serum levels of iron, TIBC, TSI and ferritin. Currently, there are no studies specifically related to CCC and ironmetabolism; thus, we will base our pathophysiological hypotheses on studies performed with other causes of cardiomyopathy. Despite the peculiarities of CCC, there seems to be similarity in the genesis of changes in iron metabolism observed in other pathologies and CCC. As possible pathophysiological mechanisms for iron metabolism alterations in HF, some theories have been described, such as chronic inflammation, intestinal loop edema, and hypoperfusion of the gastrointestinal tract (GIT). 5,6,7 A prospective case control study with 499 patients with chagasic cardiomyopathy reported the persistence of the parasitic element (DNA) through PCR analysis. 7 There was an association between parasite load and disease severity measured from clinical parameters. 7 190