Enhancing Cardiac Beta-Hydroxybutyrate Consumption Halts the Progression From Compensated to Decompensated Heart Failure in Dogs With Tachypacing-Induced Dilated Cardiomyopathy

Introduction: Recent Evidence indicates that circulating ketone bodies serve as an alternative myocardial substrate in heart failure (HF). Hypothesis: We tested the hypothesis that enhancing ketones delivery to the heart during early/compensated stages of HF delays the progression towards decompensation. Methods: Eight chronically instrumented dogs were subjected to cardiac tachypacing and infused with the ketone beta-hydroxybutyrate (BHB), starting after 2 weeks of pacing (HF+BHB group), i.e. during the early stages of cardiac dysfunction. A group of 8 dogs was subjected to cardiac pacing without BHB infusion (HF group). In 5 dogs per group, paired blood samples were withdrawn from aorta and coronary sinus to measure cardiac substrate utilization. 3H-oleate and 14C-glucose were co-infused to track the metabolic fate of free fatty acids (FFA) and glucose. Results: Blood BHB concentrations reached 190.3±19.7 microM in HF+BHB, approximately 4-fold the normal baseline values. This enhanced cardiac ketone upt...