A Phase 2 Study to Evaluate the Cardiac and Renal Effects of Short Term Treatment With Elamipretide in Patients Hospitalized With Congestion Due to Heart Failure

Inclusion Criteria: * A history of chronic heart failure for at least 1 month * Treated with ≥40 mg/day of furosemide or bumetanide ≥1 mg/day or torasemide ≥10 mg/day for at least 1 month * In-hospital observation/admission and treatment for ≤72 hours and primary cause for admission is heart failure with persistent congestion in the opinion of the Investigator (i.e. at least +2 pitting oedema and/or an estimated 8 kg gain in weight over baseline over the past 4 weeks) requiring intravenous loop diuretic therapy * Sufficiently severe oedema to justify treatment by an intravenous infusion of furosemide of 10 mg/hour for at least 48 hours * Systolic blood pressure \>90 mmHg and considered to be haemodynamically stable, in the opinion of the Investigator * History of left ventricular ejection fraction (LVEF) ≤40% confirmed in the last 18 months * NT-proBNP \>1500 pg/ml or BNP \>500 pg/ml * An eGFR of \>30 mL/min/1.73 m2 using the eGFR (mL/min/1.73 m2) = 175 x (Scr)-1.154 x (Age)-0.203 x (0.742 if female) x (1.212 if African American) Exclusion Criteria: * Acute coronary syndrome, stroke, or transient ischemic attack (TIA), coronary or peripheral revascularization procedures, valve procedures, OR any major surgical procedure within the previous 6 weeks * Invasive cardiac investigation and/or treatment (i.e. coronary angiography, percutaneous coronary intervention \[PCI\] or surgery) or other surgical procedure planned in the next 4 weeks * Use of intravenous radiographic contrast agent within 72 hours prior to screening or planned use during the study * Severe, in the investigators opinion, uncorrected valve disease or congenital heart disease as the cause for cardiac decompensation * Acute mechanical cause of decompensated heart failure such as papillary muscle rupture * Obstructive or infiltrative cardiomyopathy (e.g. amyloid, sarcoid, etc), suspected acute myocarditis, or heart failure related to an untreated metabolic condition (e.g. haemochromatosis) * Second or third degree heart block unless the subject has a ventricular pacemaker * Atrial fibrillation/flutter with sustained ventricular response of \>130 bpm * Placement of a ventricular resynchronization device within the previous 6 weeks * Treatment or planned treatment with intravenous inotropic agents other than digoxin at any time on this admission * Receipt of intravenous vasodilator therapy ≤ 6 hours prior to randomization * The presence of any mechanical assist device or listed for or a history of a heart transplant * Severe respiratory disease or anticipated need for mechanical respiratory support (i.e. mechanical ventilation) * Anuric in the previous 24 hours * Haemoglobin \<9 g/dL at screening or planned blood transfusions in the next 30 days * Serum potassium \>5.5 mEq/L * Marked proteinuria suggestive of nephrotic syndrome * Estimated GFR (eGFR) as per MDRD equation \<30 ml/min * Serum albumin of \< 2.8 g/dL * Liver enzymes (alanine aminotransferase \[ALT\] and/or aspartate aminotransferase \[AST\]) elevation \>5 times the upper limit of normal (ULN) * Total bilirubin \>2.0 times ULN in the absence of Gilbert's Syndrome * Current or planned ultrafiltration, paracentesis, haemofiltration or dialysis