Effects of Selenium treatment on cardiac function in Chagas heart disease: Results from the STCC randomized Trial

Abstract

Background: Chagas disease (caused by Trypanosoma cruzi infection) evolves to chronic chagasic cardiomyopathy (CCC) affecting 1.8 million people worldwide. This is the first randomized, placebo-controlled, double-blinded, clinical trial designed to estimate efficacy and safety of selenium (Se) treatment in CCC.

Methods: 66 patients with CCC stages B1 (left ventricular ejection fraction [LVEF] > 45% and no heart failure; n = 54) or B2 (LVEF < 45% and no heart failure; n = 12) were randomly assigned to receive 100 mcg/day sodium selenite (Se, n = 32) or placebo (Pla, n = 34) for one year (study period: May 2014-September 2018). LVEF changes over time and adverse effects were investigated. Trial registration number: NCT00875173 (clinicaltrials.gov).

Findings: No significant differences between the two groups were observed for the primary outcome: mean LVEF after 6 (β= +1.1 p = 0.51 for Se vs Pla) and 12 months (β= +2.1; p = 0.23). In a subgroup analysis, statistically significant longitudinal changes were observed for mean LVEF in the stage B2 subgroup (β= +10.1; p = 0.02 for Se [n = 4] vs Pla [n = 8]). Se treatment was safe for CCC patients, and the few adverse effects observed were similarly distributed across the two groups.

Interpretation: Se treatment did not improve cardiac function (evaluated from LVEF) in CCC. However, in the subgroup of patients at B2 stage, a potential beneficial influence of Se was observed. Complementary studies are necessary to explore diverse Se dose and/or associations in different CCC stages (B2 and C), as well as in A and B1 stages with longer follow-up.

Funding: Brazilian Ministry of Health, Fiocruz, CNPq, FAPERJ.

Fig. 1

CONSORT 2010 flowchart of study participants indicating the two groups: Selenium (active treatment) and Placebo.

Fig. 2

Adjusted trajectories of LVEF during the follow-up of the two trial groups: Placebo (dashed line) and Selenium (solid line).

Fig. 3

Crude individual LVEF trajectories of patients treated with Placebo (A, C) or Selenium (B, D) during one year of follow-up, shown in the two different subgroups presenting baseline (BL) LVEF ≥ 45% (A, B) or <45% (C, D). Solid black lines highlight patients with rising trajectories, increasing > 5 absolute percentual points in LVEF. Dotted lines show cases with falling trajectories, decreasing > 10 absolute percentual points. Gray lines indicate patients varying < 5 percentual points in LFEV during 12 months of follow-up. Note that all the 6 patients showing an increase in LVEF (solid black lines) are only in the Selenium group (B, D).

Fig. 4

Frequency distribution of patients (percentage) in different ranges of selenium plasma levels measured by ICP-MS, comparing baseline (thin lines) with one-year follow-up (thick lines) in participants treated with Placebo (dashed lines) or Selenium (Solid lines). Note that curves do differ only after treatment with selenium. A shift to the right was detected in the frequency curve of selenium-treated participants, contrasting with the three other conditions. Abnormal low (< 64 mcg/L) was detected only in 10 out of 66 patients at baseline.