Ketone Ester for Treatment Of Acute Heart Failure

Ketones have been suggested to have significant physiological effects in patients with heart failure. Potential mechanisms for these effects include energy provision for the failing heart and direct protective effects on other organs. Despite the strong physiological rationale, the acute effects of ketone therapy in patients with acute heart failure (AHF) is unclear. AHF is a major healthcare issue, with in-hospital mortality exceeding 10%. Therefore, we propose a vanguard randomized controlled trial to assess the effects of ketone esters in patients with AHF. Sixty patients hospitalized with AHF will be randomized to receive either 25 grams of ketone esters three times per day or a matching placebo for five days, or until death or hospital discharge. We hypothesize that ketone therapy will improve markers of systemic congestion and heart failure symptoms. Primary endpoint will be changes in NT-proBNP levels during therapy. Secondary endpoints will be KCCQ scores, and hemodynamic profile as assessed by echocardiogram. Exploratory endpoints will clinical outcomes including mortality, need for intensive care unit admission, among others.

Domain-Specific Inclusion Criteria: 1. Primary diagnosis of AHF with dyspnea on exertion or at rest, and at least two of the following: congestion on chest radiograph, rales on chest auscultation, clinically relevant edema, or an elevated jugular venous pressure \[21\] 2. Admitted to the hospital for less than 48 hours 3. Estimated glomerular filtration rate above 15 mL/min/1.73m² 4. NT-proBNP ≥ 1000 pg/ml Domain-Specific Exclusion Criteria: 1. Type 1 diabetes mellitus 2. Patients on mechanical circulatory support 3. Patients on more than one inotrope or on inopressors 4. Patients on dialysis 5. Patients with non-functioning enteral tracks