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.

Selenium, TGF-Beta and Infectious Endemic Cardiopathy: Lessons from Benchwork to Clinical Application in Chagas Disease

“…Studies in chickens [41] showed that Se deficiency influenced the expressions of 24 selenoproteins and 10 cytokines (including IL-2, IL-4, IL-8, IL-10, IL-12β, TGF-β4, and IFN-γ) in erythrocytes, revealing a relationship between Se and the immune system. These results reinforce the importance of studying immune and antioxidative biomarkers in CD patients during the natural course of CCC development, as well as under the effect of Se treatment [19].…”

“…So far, despite the differences that we observed in Se levels in heathy and CD patients in two Brazilian regions (72 ± 10 ng/mL in Rio de Janeiro city and 55 ± 10 ng/mL in Belo Horizonte city), our studies have shown that there is no systematic endemic Se deficiency in Brazilian areas where CCC is prevalent. The biochemical measurements of serum Se levels in CD patients in the indeterminate form and in the early cardiac form at stages A and B1 were within the ordinary range [19,23], contrasting with the reduction in patients with severe cardiac dysfunction CCC [23]. A meta-regression analysis in a recent systematic review [15] revealed a statistically significant linear dose-response relationship between blood selenium concentration and CVD incidence, but not CVD mortality.…”

“…Translation of science from bench to public health policies is even lower (0.03%) when comparing records retrieved from the Clinical Trials platform. We were proud to deliver the first RCT for CD and Se, which will be further discussed in this review [19].…”

“…Most of these parameters are simultaneously influenced by the supplementation/ deficiency in Se and the modulation of TGF-β−signaling, as summarized in Table 2. However, the possibility of starting clinical trials to test the effect of Se supplementation in CD patients, and the present unavailability of safe TGF-β modulators for studies in humans, drove our focus to Se effects in CD patients [19] and to further analysis of TGF-β modulation in pre-clinical experimental models [27][28][29][30][31]. At this point, the studies were developed according to the following different strategies: (a) basic research concerning TGF-β signaling effects in fibrosis and arrhythmia that generated interesting results [27][28][29][30][31]; (b) efforts to make translational proof-of-concept research on the presumed benefit of Se supplementation in CD patients.…”

“…By that time (1998)(1999)(2000)(2001)(2002), the new classification of CCC stages that are now used in Brazil was not yet developed [47][48][49]. In Table 3, we revisited those data according to the new classification that drove our choices for the RCT designed in 2005-2009 [50] and effectively performed in 2014-2020 [19]. So far, despite the differences that we observed in Se levels in heathy and CD patients in two Brazilian regions (72 ± 10 ng/mL in Rio de Janeiro city and 55 ± 10 ng/mL in Belo Horizonte city), our studies have shown that there is no systematic endemic Se deficiency in Brazilian areas where CCC is prevalent.…”