Inclusion Criteria:

• Written informed consent by parent(s)/legal guardian(s) for the pediatric patient must be obtained before any study-specific assessment is performed.

* A consent or assent may also be required for some patients depending upon their age and local requirement.

• Male or female, inpatient or outpatient, 1 month (≥ 44 weeks post-conception for pre-term infants) to < 18 years of age.
• Chronic heart failure resulting from left ventricular systolic dysfunction, and receiving chronic HF therapy (if not newly diagnosed).
• NYHA classification II-IV (older children: 6 to less than 18 year old) or Ross HF classification II-IV (younger children: less than 6 year old) any time prior to screening.
  • Note: Age Group 1 patients may be NYHA class I at time of screening if there is a prior history of NYHA class II-IV. Age Group 2 patients must be Ross class II or higher at time of randomization.
• Systemic left ventricular ejection fraction (EF) ≤ 45% or fractional shortening ≤ 22.5% (assessed by echocardiogram, MRI, MUGA or left ventricular angiogram within 1 month before patient begins Part 2).
  • Note: The study will target enrollment of approximately 80% patients with a systemic left ventricular ejection fraction (EF) ≤ 40% or fractional shortening ≤ 20% for Part 2 only.
• Biventricular physiology with systemic left ventricle.
• For Part 1 PK/PD, patients must be treated with an ACEI or ARB prior to screening. For Part 1 PK/PD, patients in Group 1 and 2 must be currently treated with a daily dose equivalent of at least enalapril 0.2 mg/kg prior to the LCZ696 3.1 mg/kg single dose assessment. For Part 1 PK/PD, patients in Group 3 must be currently treated with a daily dose equivalent of at least enalapril 0.1 mg/kg prior to the LCZ696 1.6 mg/kg single dose assessment.
• HF etiologies include: Congenital Cardiac Malformation with systemic ventricular systolic dysfunction; Idiopathic Cardiomyopathy; Familial/Inherited and/or Genetic Cardiomyopathy; History of Myocarditis; Neuromuscular Disorder; Inborn Error of Metabolism; Mitochondrial Disorder; Acquired (Chemotherapy, Iatrogenic, Infection, Rheumatic, Nutritional); Ischemic (e.g., Kawasaki Disease, post-operative); Left ventricular noncompaction

*Assessments of HF (e.g. ECHO) in patients that are done according to current local institutional/hospital standard protocol or that are part of routine clinical care can be used to support patient screening and may have taken place before signing informed consent. An informed consent must be obtained from a patient once they become 18 years old during the study.

Exclusion Criteria:

• Patients with single ventricle or systemic right ventricle.
• Patients listed for heart transplantation as United Network for Organ Sharing (UNOS) Status 1A or hospitalized waiting for transplant while on inotropes or with ventricular assist device at time of entry into the study.
• Sustained or symptomatic dysrhythmias uncontrolled with drug or device therapy.
• For Part 2 only, patients that have had cardiovascular surgery or percutaneous intervention to palliate or correct congenital cardiovascular malformations within 3 months of the screening visit. Patients anticipated to undergo corrective heart surgery during the 12 months after entry into Part 2.
• Patients with unoperated obstructive or severe regurgitant valvular (aortic, pulmonary, or tricuspid) disease, or significant systemic ventricular outflow obstruction or aortic arch obstruction.
• Patients with restrictive or hypertrophic cardiomyopathy.
• For Part 2 only, active myocarditis (diagnosed with presumed or acute myocarditis within 3 months of enrollment).
• Symptomatic hypotension or blood pressures (BPs) below the calculated 5th percentile systolic BP (SBP) for age at screening visit.
• Renal vascular hypertension (including renal artery stenosis).
• Severe pulmonary hypertension (defined by pulmonary vascular resistance (PVR) index > 6 Wood units-m2 ) unresponsive to vasodilator agents (such as oxygen, nitroprusside or nitric oxide).
  • Note: measurement of PVR is not a requirement for study eligibility.
  • History or current clinical evidence of moderate-to severe obstructive pulmonary disease or reactive airway diseases (e.g., asthma).
  • Serum potassium > 5.3 mmol/L at Visit 1 or at Visit 301.
  • Patients with significant renal (eGFR calculated using the modified Schwartz formula < 30% mean GFR for age; hepatic (serum aspartate aminotransferase or alanine aminotransferase > 3 times upper limit of normal); gastrointestinal or biliary disorders (that could impair absorption, metabolism, or excretion of orally administered medications).
  • Concurrent terminal illness or other severe disease (e.g., acute lymphocytic leukemia) or other significant laboratory values that, in the opinion of the Investigator, precludes study participation or survival.
  • Patients with a history of angioedema.
  • Patients with allergy or hypersensitivity to ACEI or ARB.
  • Patients who have parents or legal guardians who do not give consent or allow the child to give assent, or inability of the patient or the parents/legal guardians to follow instructions or comply with follow-up procedures.
  • Pregnant or nursing (lactating) women.
  • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of investigational drug and for 7 days after study drug discontinuation. Highly effective contraception methods include:
    • Total abstinence (when this is in line with the preferred and usual lifestyle of the subject and if acceptable by the local regulation);
    • 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 subjects on the study, the vasectomized male partner should be the sole partner for that subject;
    • Use of oral, (estrogen and progesterone), injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%); for example, hormone vaginal ring or transdermal hormone contraception;
    • In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking investigational drug.
• Use of other investigational drugs within 5 half-lives or within 30 days of enrollment, whichever is shorter.
• History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes.
• Any major solid organ transplant recipient.
• History of malignancy of any organ system, treated or untreated, within the past year with a life expectancy less than 1 year.
• Any advanced severe or unstable disease that may interfere with the primary or secondary study outcome evaluations or put the patient at special risk.
• Any other medical conditions that may put the patient at risk or influence study results in the Investigator’s opinion, or that the Investigator deems unsuitable for the study.
• Patient breastfed by a mother taking ACEI.