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Aim: Previous studies showed that granulocyte-colony stimulating factor (G-CSF) improved heart function in a mice model of Chronic Chagas Cardiomyopathy (CCC). Herein, we report the interim results of the safety and efficacy of G-CSF therapy vs. placebo in adults with Chagas cardiomyopathy. Methods: Patients with CCC, New York Heart Association (NYHA) functional class II to IV and left ventricular ejection fraction (LVEF) 50% or below were included. A randomization list using blocks of 2 and 4 and an allocation rate of 1:1 was generated by R software which was stratified by functional class. Double blinding was done to both arms and assessors were masked to allocations. All patients received standard heart failure treatment for 2 months before 1:1 randomization to either the G-CSF (10 mcg/kg/day subcutaneously) or placebo group (1 mL of 0.9% saline subcutaneously). The primary endpoint was either maintenance or improvement of NYHA class from baseline to 6-12 months after treatment, and intention-to-treat analysis was used. Results: We screened 535 patients with CCC in Salvador, Brazil, of whom 37 were randomized. Overall, baseline characteristics were well-balanced between groups. Most patients had NYHA class II heart failure (86.4%); low mean LVEF was 32 ± 7% in the G-CSF group and 33 ± 10% in the placebo group. Frequency of primary endpoint was 78% (95% CI 0.60-0.97) vs. 66% (95% CI 0.40-0.86), p = 0.47, at 6 months and 68% (95% CI 0.43-0.87) vs. 72% (95% CI 0.46-0.90), p = 0.80, at 12 months in placebo and G-CSF groups, respectively. G-CSF treatment was safe, without any related serious adverse events. There was no difference in mortality between both arms, with five deaths (18.5%) in treatment vs. four (12.5%) in the placebo arm. Exploratory analysis demonstrated that the maximum rate of oxygen consumption during exercise (VO2 max) showed an improving trend in the G-CSF group. Conclusion: G-CSF therapy was safe and well-tolerated in 12 months of follow-up. Although prevention of symptom progression could not be demonstrated in the present study, our results support further investigation of G-CSF therapy in Chagas cardiomyopathy patients. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT02154269].
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INTRODUCTION AND OBJECTIVES: Chagas disease is a prevalent cause of heart failure in Latin America, and its prognosis is worse than other etiologies. The Heart Failure Survival Score has been used to assess prognosis in patients with heart failure; however, this score has not yet been studied in patients with Chagas cardiopathy. METHODS: The Heart Failure Survival Score was calculated in 55 patients with severe left ventricular systolic dysfunction due to Chagas disease. Correlations were assessed between the Heart Failure Survival Score and variables obtained from, cardiopulmonary exercise tests, quality-of-life measures, and 6-minute walking tests. RESULTS: Patients were distributed among New York Heart Association classes II-IV; 89% were taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, 62% were taking beta-blockers, 86% were taking diuretics, and 74% were taking aldosterone receptor blockers. The mean Heart Failure Survival Score was 8.75 (0.80). The score correlated well with cardiopulmonary test variables such as peak oxygen uptake (0.662; P<.01), oxygen uptake at the anaerobic threshold (0.644; P<.01), ventilation carbon dioxide efficiency slope (-0.417; P<.01), oxygen pulse (0.375; P<.01), oxygen uptake efficiency slope (0.626; P<.01), 6-minute walking test (0.370; P<.01), left ventricle ejection fraction (0.650; P=.01), and left atrium diameter (-0.377; P<.01). There was also a borderline significant correlation between the Heart Failure Survival Score and quality of life (-0.283; P<.05). CONCLUSIONS: In heart failure patients with Chagas disease, the Heart Failure Survival Score correlated well with the main prognostic functional test variables.