Functional Impact of GLP-1 for Heart Failure Treatment (FIGHT)

Inclusion Criteria

• Age ≥ 18 years
• AHFS as defined by the presence of at least 1 symptom (dyspnea, orthopnea, or edema) AND 1 sign (rales on auscultation, peripheral edema, ascites, pulmonary vascular congestion on chest radiography)
• AHFS is the primary cause of hospitalization
• Prior clinical diagnosis of HF
• Left Ventricular Ejection Fraction(LVEF) ≤ 40% during the preceding 3 months (if no echo within the preceding 3 months, an LVEF ≤ 30% during the preceding three years is acceptable)
• On evidence-based medication for HF (including beta-blocker and ACE-inhibitor/ARB) or previously deemed intolerant
• Use of at least 80 mg or furosemide total daily dose (or equivalent) prior to admission for AHFS (a lower dose of a loop diuretic combined with a thiazide will count as an "equivalent")
• Willingness to provide informed consent

Exclusion Criteria

• AHFS due to acute myocarditis or acute Myocardial Infarction
• Ongoing hemodynamically significant arrhythmias contributing to HF decompensation
• Inotrope, intra-aortic balloon pump (IABP) or other mechanical circulatory support use at the time of consent. Prior use will not exclude a patient.
• Current or planned left ventricular assist device therapy in next 180 days
• United Network for Organ Sharing status 1A or 1B
• B-type natriuretic peptide(BNP) 110 at consent
• Acute coronary syndrome within 4 weeks as defined by electrocardiographic (ECG) changes and biomarkers of myocardial necrosis (e.g. troponin) in an appropriate clinical setting (chest discomfort or anginal equivalent)
• Percutaneous Coronary Intervention, coronary artery bypass grafting or new biventricular pacing within past 4 weeks
• Primary hypertrophic cardiomyopathy
• Infiltrative cardiomyopathy
• Constrictive pericarditis or tamponade
• Complex congenital heart disease
• Non-cardiac pulmonary edema
• More than moderate aortic or mitral stenosis
• Intrinsic (prolapse, rheumatic) valve disease with severe mitral, aortic or tricuspid regurgitation
• Sepsis, active infection (excluding cystitis) or other comorbidity driving the HF decompensation
• Acute or chronic severe liver disease as evidenced by any of the following: encephalopathy, variceal bleeding, International Normalized Ration (INR) > 1.7 in the absence of anticoagulation treatment
• Terminal illness (other than HF) with expected survival of less than 1 year
• Previous adverse reaction to the study drug
• Receipt of any investigational product in the previous 30 days.
• Enrollment or planned enrollment in another randomized therapeutic clinical trial in next 6 months.
• Inability to comply with planned study procedures
• Pregnancy or breastfeeding mothers
• Women of reproductive age not on adequate contraception
• History of acute or chronic pancreatitis
• History of symptomatic gastroparesis
• Familial or personal history of medullary thyroid cancer or multiple endocrine neoplasia type-2 (MEN2)
• Prior weight-loss surgery (i.e., Roux-en-Y gastric bypass) or other gastric surgery associated with increased endogenous GLP-1 production
• Prior or ongoing treatment with GLP-1 receptor agonists
• Ongoing treatment with dipeptidyl peptide-IV inhibitors (1 week washout required)
• Ongoing treatment with thiazolidinedione
• Oxygen-dependent chronic obstructive pulmonary disease
• Diabetic patients with history of 2 or more severe hypoglycemia, Diabetic Ketoacidosis(DKA) or hyperglycemic, hyperosmotic nonketotic coma in the preceding 12 months.
• Diagnosis of Type 1 Diabetes Mellitus
• If diabetic, inadequate glycemic control with glucose level > 300 mg/dL within 24 hours of randomization