Effects of sacubitril/valsartan versus enalapril on NT-proBNP and hs-troponin T in patients with heart failure due to Chagas disease: insights from the PARACHUTE-HF trial

Background Prognostically important comorbidities such as diabetes, hypertension, and coronary disease are uncommon in patients with heart failure with reduced ejection fraction (HFrEF) secondary to chronic Chagas cardiomyopathy, yet these patients have worse outcomes, including worse survival, compared with other HF etiologies.1 N-terminal pro–B-type natriuretic peptide (NT-proBNP) is a well validated marker of myocardial wall stress and a strong predictor of morbidity and mortality in patients with HFrEF, while cardiac troponins, reflecting ongoing myocardial injury, are also independently associated with worse outcomes.2-4 The underlying mechanisms behind these findings have not been clearly delineated.4 Prior studies have demonstrated that reductions in NT-proBNP levels, particularly achieving concentrations below 1000 pg/mL, are associated with significantly improved clinical outcomes.5 Purpose To evaluate the effects of sacubitril/valsartan versus enalapril on serial changes in NT-proBNP and high-sensitivity troponin T(hsTnT) concentrations in a subset of patients with HFrEF due to Chagas disease enrolled in the PARACHUTE-HF trial. Methods PARACHUTE-HF was a multicenter, randomized, open-label with blinded endpoint adjudication trial enrolling patients with chronic Chagas cardiomyopathy, left ventricle ejection fraction (LVEF) ≤40%, and elevated natriuretic peptides. Patients were randomized to sacubitril/valsartan or enalapril in addition to standard heart failure therapy. NT-proBNP was measured centrally at baseline, Week 12, and Month 8. hsTnT was measured at baseline and Month 8. Due to marked right skewness, NT-proBNP and hsTnT levels were logarithmically transformed before analysis, with results expressed as geometric mean ratios. Results Patients assigned to sacubitril/valsartan had a significantly greater reduction in NT-proBNP compared with enalapril at Week 12 (mean ratio 0.68; 95% CI 0.62-0.75), and this effect was sustained at Month 8 (0.76; 95% CI 0.66-0.88). The proportion of patients achieving NT-proBNP <1000 pg/mL at Week 12 was higher with sacubitril/valsartan (41.3%) versus enalapril (34.5%), chi-square p=0.045. For hsTnT, there was no significant difference between study groups at month 8 (mean ratio 0.96; 95% CI 0.89–1.04). Conclusion In patients with HFrEF due to Chagas disease, sacubitril/valsartan led to a greater and sustained reduction in NT-proBNP compared with enalapril. A decrease in NT-proBNP likely reflects reduced cardiac filling pressures and myocardial wall stress, consistent with favorable hemodynamic effects of sacubitril/valsartan.