• Composite hierarchical outcome [ Time Frame: Baseline to Weeks 4 and 8 ]
  To determine the effect of sacubitril/valsartan vs. valsartan on the composite hierarchical outcome consisting of: a) time to CV death, b) total HF hospitalizations, c) total urgent HF visits, and d) time-averaged proportional change in NT-proBNP (from baseline to Weeks 4 and 8) using win ratio methodology
• Cumulative number of recurrent composite overtime [ Time Frame: Overtime ]
  To assess the effect of sacubitril/valsartan vs. valsartan on total composite events based on CV death, HF hospitalizations, and urgent HF visits
• Incidences of a composite endpoint of worsening renal function [ Time Frame: Overtime ]
  To assess the effect of sacubitril/valsartan vs. valsartan on the incidences of a composite endpoint of worsening renal function (renal death, reaching ESRD, or decline in eGFR >/= 50%)
• Proportional change in NT-proBNP from baseline to Week 8 [ Time Frame: Baseline to week 8 ]
  To assess the effect of sacubitril/valsartan vs. valsartan on change in NT-proBNP from baseline to Week 8
• Proportional change from baseline in hs-Troponin (high sensitivity) at Weeks 4 and 8 [ Time Frame: Baseline to weeks 4 and 8 ]
  To assess the effect of sacubitril/valsartan vs. valsartan on change from baseline in hs-Troponin (high sensitivity) at Weeks 4 and 8

• Cumulative number of heart failure re-hospitalizations, for a given patient [ Time Frame: Over 8 weeks ]
  To determine the effect of sacubitril/valsartan vs. valsartan on reducing the rate of total heart failure re-hospitalizations at 8 weeks.
• Proportional change in NT-proBNP [ Time Frame: Baseline to week 8 ]
  To determine the effect of sacubitril/valsartan vs. valsartan on change in NT-ProBNP from baseline to week 8.
• Proportional change from baseline at 4 and 8 weeks in the following biomarkers: hs-Troponin (high sensitivity), ST2, and urinary cGMP [ Time Frame: From baseline at 4 and 8 weeks ]
  To determine the effect of sacubitril/valsartan vs. valsartan on change from baseline in biomarkers: hs-Troponin (high sensitivity), ST2, and urinary cGMP at 4 and 8 weeks

• Drug: sacubitril/valsartan

  Sacubitril/valsartan (LCZ696) is available as 24/26 mg, 49/51 mg, and 97/103 mg in tablet form to be taken orally, twice daily, for the double-blind period.

  Valsartan matching placebo is available as 40 mg, 80 mg, and 160 mg in tablet form to be taken orally, twice daily, for the double-blind period.

  Other Name: LCZ696
• Drug: valsartan

  Valsartan is available as 40 mg, 80 mg, and 160 mg in tablet form to be taken orally, twice daily, for the double-blind period.

  Sacubitril/valsartan (LCZ696) matching placebo is available as 24/26 mg, 49/51 mg, and 97/103 mg in tablet form to be taken orally, twice daily, for the double-blind period.

• Experimental: sacubitril/valsartan

  randomized in a 1:1 ratio: sacubitril/valsartan to valsartan for up to approximately 20 months of double-blind treatment.

  Initial dose for patients randomized to sacubitril/valsartan (LCZ696) will be determined by patient's previous dose of ACEi/ARB immediately prior to hospital admission for acute decompensated heart failure. Study treatment will be titrated to the target dose of sacubitril/valsartan (LCZ696) 97/103 mg twice daily (Dose Level 3).

  Patients will be required to take a total of two tablets twice daily (one tablet of active sacubitril/valsartan and one tablet of valsartan matching placebo pack).

  Intervention: Drug: sacubitril/valsartan
• Active Comparator: valsartan

  randomized in a 1:1 ratio: sacubitril/valsartan to valsartan for up to approximately 20 months of double-blind treatment.

  Initial dose at randomization will be based on patient's previous dose of or lack of ACEi/ARB immediately prior to current hospital admission for ADHF, or at the time of out-of-hospital randomization.

  Study treatment will be titrated to the target dose of valsartan 160 mg twice daily (Dose Level 3).

  Patients will be required to take a total of two tablets twice daily (one tablet of active valsartan and one tablet of sacubitril/valsartan (LCZ696) matching placebo pack).

  Intervention: Drug: valsartan

Inclusion Criteria

1. Signed informed consent must be obtained prior to participation in the study
2. Patients ≥40 years of age, male or female

3. Currently hospitalized for or within 30 days following discharge of an acute decompensated HFpEF admission. Patients with a diagnosis of acute heart failure had to have symptoms and signs of fluid overload (i.e. jugular venous distention, edema or rales on auscultation or pulmonary congestion on chest x-ray). Eligible patients will be randomized no earlier than 36 hours and within 30 days post-discharge after presentation with acute HFpEF decompensation and meeting the following definitions of hemodynamic stability:

   In-hospital randomized patients will have been hemodynamically stable defined in this study as:

   1. SBP≥100mmHg for the preceding 6 hours prior to randomization; no symptomatic hypotension
   2. No increase (intensification) in i.v. diuretic dose within last 6 hours prior to randomization
   3. No i.v. inotropic drugs for 24 hours prior to randomization
   4. No i.v. vasodilators including nitrates within last 6 hours prior to randomization

   Out-of-hospital randomization patients will have been hemodynamically stabilized defined in this study as:

   1. SBP ≥100mmHg; no symptomatic hypotension
   2. No increase (intensification and/or change to IV) in diuretic dose within last 24 hours prior to randomization
   3. No i.v. inotropic drugs for 24 hours prior to randomization
4. HFpEF with most recent LVEF >40% (within past 3 months)

5. Elevated NT-proBNP or BNP at the time of screening (and within 72 hours from inhospital screening to out-of-hospital randomization, if applicable)

   1. Patients not in AF at the time of biomarker assessment: NT-proBNP ≥ 500pg/mL or BNP ≥ 150 pg/mL; patients in AF at the time of biomarker assessment: NT-proBNP ≥ 1000pg/mL or BNP ≥ 300 pg/mL
   2. Patients recruited in-hospital will be randomized based on the qualifying local lab value in-hospital NT-proBNP or BNP value. In-hospital is the preferred method of enrollment.
   3. Patients enrolled out-of-hospital can be randomized based on their NT-proBNP or BNP value in the following way:

   if enrolling in out-of-hospital setting then need eligible screening/local NTproBNP/BNP within 72 hours of randomization. The test value could be from recent hospitalization if within 72 hours or would require (re)drawing NT-proBNP or BNP labs in out-of-hospital setting if the lab value is not already available within the last 72 hours

6. Has not taken an ACEi for 36 hours prior to randomization

Exclusion Criteria

1. Any clinical event within the 90 days prior to randomization that could have reduced the LVEF (i.e., MI, CABG), unless an echo measurement was performed after the event confirming the LVEF to be >40%
2. Currently taking Entresto™ (sacubitril/valsartan) or any prior use
3. eGFR < 20ml/min/1.73 m2 as measured by the simplified Modification of Diet in Renal Disease (MDRD) formula at most recent assessment prior to randomization and within 24 hours prior to inpatient randomization or 72 hours prior to outpatient randomization
4. Serum potassium > 5.2 mEq/L at most recent assessment prior to randomization and within 24 hours prior to inpatient randomization or 72 hours prior to outpatient randomization
5. Acute coronary syndrome, stroke, transient ischemic attack; cardiac, carotid or other major CV surgery; percutaneous coronary intervention (PCI) or carotid angioplasty, within 30 days prior to randomization

6. Probable alternative diagnoses that in the opinion of the investigator could account for the patient's HF symptoms (i.e. dyspnea, fatigue) such as significant pulmonary disease (including primary pulmonary HTN), anemia or obesity. Specifically, patients with the following are excluded:

   1. Severe pulmonary disease including chronic obstructive pulmonary disease (COPD) (i.e. requiring home oxygen, oral steroid therapy) or
   2. Hemoglobin (Hgb) < 9.5 g/dL males and < 9 g/dL females within 30 days prior to randomization or
   3. Body mass index (BMI) > 50 kg/m2 at randomization
7. Isolated right HF in the absence of left-sided structural heart disease
8. History of hypersensitivity (i.e. including angioedema), known or suspected contraindications, or intolerance to any of the study drugs including ARNIs (i.e. sacubitril/valsartan), and/or ARBs
9. Patients with a known history of angioedema due to any etiology
10. Patients with a history of heart transplant or LVAD, currently on the transplant list, or with planned intent to implant LVAD or CRT device within the initial three months of enrollment during the trial
11. A cardiac or non-cardiac medical condition other than HF with an estimated life expectancy of < 12 months
12. Known pericardial constriction, genetic hypertrophic cardiomyopathy, or infiltrative cardiomyopathy including amyloid heart disease (amyloidosis)
13. Life-threatening or uncontrolled dysrhythmia, including symptomatic or sustained ventricular tachycardia and atrial fibrillation or flutter with a resting ventricular rate >110 bpm
14. Clinically significant congenital heart disease felt to be the cause of the patient's symptoms and signs of HF
15. Coronary or carotid artery disease or valvular heart disease likely to require surgical or percutaneous intervention within the duration of the trial
16. Any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study
17. Known hepatic impairment (as evidenced by total bilirubin > 3 mg/dL, or increased ammonia levels, if performed), or history of cirrhosis with evidence of portal hypertension such as varices
18. Participation in any other clinical trial involving investigational agents or devices within the past 30 days
19. Current confirmed COVID19 infection
20. 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.
21. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
22. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using basic methods of contraception during dosing of study treatment. Basic contraception methods include:

Total abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.

Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.

Male sterilization (at least 6 months prior to screening). For female patients on the study, the vasectomized male partner should be the sole partner for that patient.

Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps).

Use of oral (estrogen and progesterone), injected, or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example, hormone vaginal ring or transdermal hormone contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS).