Key Inclusion Criteria:
Male or female ≥ 18 years of age
Diagnosis of NYHA Class II-IV HFrEF established by:
LVEF ≤ 40% within 12 months prior to Visit 1 made by any local measurement using echocardiography, multiple gated acquisition scan (MUGA), computerized tomography (CT) scanning, magnetic resonance imaging (MRI), or ventricular angiography, provided no subsequent measurement above 40% AND
NT-proBNP ≥ 600 pg/mL (or BNP ≥ 150 pg/mL) at Visit 1 OR
NT-proBNP ≥ 400 pg/mL (or BNP ≥ 100 pg/mL) at Visit 1 and a hospitalization for HF within the last 12 months
Chagas' disease diagnosis confirmed by at least two different serological tests for anti-Trypanosoma cruzi based on different principles or with different antigenic preparations, such as: enzyme-linked immunosorbent assay [ELISA], indirect immunofluorescence [IFI], indirect hemagglutination [IHA], western blot (WB), chemiluminescent immunoassay (CLIA). If documented history is not available, the tests may be performed during the screening
Key Exclusion Criteria:
Patients with history of suspected or proven angioedema or unable to tolerate ACEIs, ARBs or ARNI (e.g., due to cough, hypotension, renal dysfunction, hyperkalemia)
Use of sacubitril/valsartan in the past 3 months
Patients requiring continuous intravenous inotropic therapy or with indication of advanced support intervention for HF:
already on list for a heart transplantation
with current indication of left ventricular assist device, or cardiac resynchronization therapy (CRT)
Systemic systolic blood pressure lower than 95 mmHg or symptomatic hypotension
Serum potassium > 5.2 mmol/L
Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 of body surface area
Severe gastrointestinal form of chronic Chagas' disease (demonstrated megaesophagus and/or important megacolon, e.g.: with compromised oral intake or surgical indication).
Clinical conditions or systemic diseases limiting proper patient participation
Pregnant or nursing women or women of child-bearing potential unless they are using highly effective methods of contraception
Presence of other cardiac conditions:
Previous cardiac surgery
Heart failure where, in the Investigator's judgement, there is a possible alternative primary etiology e.g., due to coronary artery disease, valve disease, congenital heart disease or other causes.
Untreated arrhythmia or serious conduction disease e.g., bradyarrhythmias, atrial fibrillation with rapid ventricular response, second or third degree atrioventricular block, etc.
Primary uncorrected valvar pathology like moderate to severe aortic stenosis, mitral stenosis and primary mitral regurgitation
Planned organ transplantation (or in listing for transplantation), planned cardiac or other major surgery (including ventricular assist device implantation)
History of malignancy of any organ system within the past 5 years.
Current confirmed COVID19 infection
Past COVID19 infection with persistent symptom burden suspected due to COVID19 (persistent symptoms may include, but are not limited to, continued cough, breathing difficulty, muscle/joint aches, and gastrointestinal symptoms from the time of COVID19 infection onward)