Promising Outcomes from First Prospective Study on Heart Failure in Chagas Disease Patients

Recent research presented at ESC Congress 2025 has demonstrated encouraging results from the first prospective clinical trial evaluating the treatment of heart failure (HF) caused by Chagas disease, a parasitic infection primarily affecting Latin America. The trial compared the efficacy of sacubitril/valsartan, an angiotensin receptor–neprilysin inhibitor, against enalapril, an angiotensin-converting enzyme inhibitor, in this specific patient population.

Chagas disease, caused by the protozoan Trypanosoma cruzi, remains a significant health challenge with over 7 million infected individuals worldwide. Transmission occurs mainly through contact with feces or urine of infected triatomine bugs, but can also happen via contaminated food, vertical transmission, blood transfusion, organ transplants, or laboratory accidents. Due to migration, cases are increasingly reported outside Latin America, including North America, Europe, and beyond.

Chagas cardiomyopathy, a severe manifestation of chronic Chagas disease, affects approximately 30-40% of infected individuals over time and is associated with a worse prognosis despite younger age and fewer comorbidities compared to other HF causes.

The PARACHUTE-HF trial, conducted across more than 80 sites in Latin America, involved 922 patients with confirmed T. cruzi infection, reduced left ventricular ejection fraction (≤40%), and symptoms ranging from NYHA class II to IV. Participants were randomly assigned to receive either sacubitril/valsartan or enalapril, with primary endpoints focusing on a hierarchy of cardiovascular death, HF hospitalization, and changes in NT-proBNP levels.

Results showed that patients treated with sacubitril/valsartan had a 52% higher chance of better outcomes compared to those on enalapril. The key positive driver was a significant decrease in NT-proBNP levels by about 30.6% in the sacubitril/valsartan group versus just 5.5% in the enalapril group. Over a median follow-up of 25 months, mortality and HF hospitalization rates were similar between both groups. Safety profiles for both medications were comparable, with fewer discontinuations due to adverse events seen with sacubitril/valsartan.

Professor Renato Lopes emphasized that this trial provides the first robust evidence supporting targeted pharmacological therapy for this high-risk group, highlighting the potential of sacubitril/valsartan to improve outcomes in Chagas-related heart failure. The study also illustrates the feasibility of international collaborations to address neglected tropical diseases and their cardiac complications.

This groundbreaking research opens new pathways for managing Chagas cardiomyopathy and underscores the importance of specialized treatment strategies for infectious causes of heart failure, aligning with the global health priorities discussed at ESC Congress 2025.