This is a multi-center, randomized, double-blind, placebo-controlled study in subjects with stable heart failure with preserved ejection fraction (HFpEF) to evaluate the effects of 4 weeks treatment with subcutaneous MTP-131 (elampretide) on left ventricular function.

Inclusion Criteria:

• Age ≥45 and <80 years.

• Symptomatic heart failure (i.e. NYHA II or III) due to HFpEF for at least 6 months prior to study start

• Evidence of HFpEF: LVEF ≥45% and E/e´>10 and NT-pro-BNP >220 pg/ml (sinus rhythm) / > 600 pg/mL (atrial fibrillation)

• An exercise-induced increase in E/e' of at least 1.5 units during stress echocardiography assessment.

• Heart failure is considered to be stable, in the judgment of the investigator, and no hospitalization for HFpEF or changes in dose regimen of pharmacologic treatment for HF has occurred within 1 month prior to the Screening Visit.

• Treatment with appropriate pharmacologic therapy to manage underlying risk factors according to current guidelines.

• Women of childbearing potential must agree to use 1 of the following methods of birth control from the date they sign the ICF until two months after the last dose of study medication:

  a) Abstinence, b) surgically sterilized male partner, or c) barrier method And hormonal contraception

• Women of child-bearing potential must have a negative serum pregnancy test at baseline

• Willing and able to provide signed informed consent form (ICF) prior to participation in any study-related procedures

Exclusion Criteria:

• Probable alternative diagnoses that in the opinion of the investigator could account for the patient's symptoms e.g. severe pulmonary dysfunction or severe asthma
• LVEF <45% (at the moment of enrollment or in medical history)
• Coronary or peripheral revascularization procedures, valvular procedures, OR any major surgical procedure within 3 months prior to the Screening Visit.
• Acute coronary syndrome (ACS), stroke or transient ischemic attack (TIA) within 3 months prior to the Screening Visit.
• Uncontrolled hypertension defined as a systolic blood pressure (BP) >160 mm Hg or a diastolic BP >100 mm Hg on at least 2 consecutive readings that will require a change in anti-hypertensive treatment during the study period.
• Active cancer or undergoing chemotherapy within previous 6 months
• Total bilirubin >2x the upper limit of normal (ULN) in the absence of Gilbert's Syndrome (M. Meulengracht) and liver enzymes (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST] and/or alkaline phosphatase) elevation >3xULN
• Estimated glomerular filtration rate <30 mL/min, by MDRD
• Known active drug or alcohol abuse within 1 year of the Screening Visit.
• Use of other investigational drugs at the time of enrolment, or within 30 days or 5 half-lives of enrolment
• Treatment with spironolactone or eplerenone for less than 3 months at study start
• Treatment with dabigatran
• Treatment with valsartan/sacubitril
• Female subjects who are pregnant, planning to become pregnant, or lactating.