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 2 different serological tests for anti-Trypanosoma cruzi (enzyme-linked immunosorbent assay [ELISA], indirect immunofluorescence [IFI], and indirect hemagglutination [IHA]). 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 or ARBs (e.g., due to cough, hypotension, renal dysfunction, hyperkalemia)
Previous use of sacubitril/valsartan
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
Known gastrointestinal form of chronic Chagas' disease: demonstrated megaesophagus; important megacolon
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.