• Time to the first occurrence of a composite of CV events [ Time Frame: From the date of randomization to the first occurrence (total follow up time up to approximately 36 months) ]
  Time from randomization to the first occurrence of HF hospitalization or CV death
• Time to all-cause mortality [ Time Frame: From date of randomization until the date of death from any cause assessed up to the end of the study, which is estimated to be up to approximately 36 months ]
  The time to all-cause mortality will be determined.
• Time to sudden death or resuscitated sudden cardiac arrest [ Time Frame: From date of randomization until the date of the sudden death or resuscitated sudden cardiac arrest assessed up to the end of the study, which is estimated to be up to approximately 36 months ]
  The time to sudden death or resuscitated sudden cardiac arrest will be determined.
• Number of visits to an ER due to HF (where intravenous therapy is required) [ Time Frame: From the date of randomization up to End of Study (EOS) assessment. Total follow up time up to approximately 36 months. ]
  The rate of visits to an emergency room (ER) due to HF (where intravenous therapy is required) will be determined.
• Number of days alive out of the hospital [ Time Frame: From the date of randomization up to End of Study (EOS) assessment. Total follow up time up to approximately 36 months. ]
  The number of days alive out of the hospital will be determined.
• Number of ventricular fibrillation or sustained ventricular tachycardia [ Time Frame: From the date of randomization up to End of Study (EOS) assessment. Total follow up time up to approximately 36 months. ]
  The number of ventricular fibrillation or sustained ventricular tachycardia needing specific pharmacological, electrical or other treatment will be determined.
• Number of anti-tachycardia pacing or shock therapies [ Time Frame: From the date of randomization up to End of Study (EOS) assessment. Total follow up time up to approximately 36 months. ]
  This will be determined in a subset on a subset of participants who have an ICD or CRT-D at Randomization.

• Chagas Disease
• Heart Failure

• Drug: Sacubitril/valsartan
  50 (24/26) mg, 100 (49/51) mg and 200 (97/103) mg will be available for dose adjustments.
  Other Name: LCZ696; Entresto; Vymada
• Drug: Enalapril
  5 mg and 10 mg will be available for dose adjustments.
  Other Name: Renitec

• Experimental: Sacubitril/valsartan

  Sacubitril/valsartan 200 mg b.i.d.

  Following randomization, patients will receive sacubitril/valsartan in titrated doses from level 1 up to level 3 (50, 100 and 200 mg twice daily).

  Participants taking ACEIs who are randomized to sacubitril/valsartan will do a 36-hour ACEI washout before they start taking the study drug

  Sacubitril/valsartan in dose levels of 50 mg, 100 mg, and 200 mg are equivalent to sacubitril/valsartan 24/26 mg, 49/51 mg and 97/103 mg, respectively

  Intervention: Drug: Sacubitril/valsartan
• Active Comparator: Enalapril

  Enalapril 10 mg b.i.d.

  Following randomization, patients will receive the enalapril in titrated doses from level 1 up to level 3 (2.5, 5 and 10 mg twice daily).

  Intervention: Drug: Enalapril

Key Inclusion Criteria:

• Male or female ≥ 18 years of age

• Diagnosis of NYHA Class II-IV HFrEF established by:

  1. 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
  2. NT-proBNP ≥ 600 pg/mL (or BNP ≥ 150 pg/mL) at Visit 1 OR
  3. 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:

  1. already on list for a heart transplantation
  2. 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:

  1. Previous cardiac surgery
  2. 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.
  3. Untreated arrhythmia or serious conduction disease e.g., bradyarrhythmias, atrial fibrillation with rapid ventricular response, second or third degree atrioventricular block, etc.
  4. Primary uncorrected valvar pathology like moderate to severe aortic stenosis, mitral stenosis and primary mitral regurgitation
  5. 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.