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Preliminary research presented at the American Heart Association’s Basic Cardiovascular Sciences Scientific Sessions 2024 suggests that increasing ketone supply to the heart could significantly enhance energy production in cases of heart failure with preserved ejection fraction (HFpEF).
HFpEF occurs when there are signs or symptoms of heart failure with a high left ventricle filling pressure even when there is normal or near-normal ventricle ejection fraction higher than 50%. A normal ejection fraction is between 50% and 70%. Heart failure with reduced ejection fraction (HFrEF) is when the heart’s pumping power is less than 40%. HFrEF has been meticulously studied and has well-established methods of treating it, whereas HFpEF has no current evidence-based treatment regimens.
“Humans typically rely on carbohydrates and fats for energy, but ketones become crucial when glucose levels are low, such as during fasting or intense exercise,” said study author Qiuyu (Violet) Sun, a PhD candidate at the University of Alberta, Canada. “Our study shows that increasing ketone supply in HFpEF mice improves the heart’s ability to produce adenosine triphosphate (ATP), the energy currency of cells, without disrupting glucose or fat utilization.”
For their research, the University of Alberta team induced HFpEF in mice through a high-fat diet and chemical treatment to mimic human conditions. They then administered varying levels of β-hydroxybutyrate, a major ketone body, to observe its impact on cardiac metabolism and discovered that increasing ketone supply led to a notable increase in ATP production derived from both ketones and glucose oxidation. This resulted in improved overall cardiac function.
“This increase in ketone utilization didn’t interfere with the heart’s ability to use glucose or fats, which is critical in maintaining balanced energy production,” Sun said. “This finding suggests a potential avenue for developing therapies that optimize cardiac energy metabolism in HFpEF.”
Heart failure affects millions globally, with HFpEF becoming increasingly prevalent due to aging populations and rising obesity rates. Despite these trends, effective treatments have not yet been developed. Sun noted the urgency of developing targeted therapies for HFpEF, stating, “Identifying key proteins involved in cardiac energy metabolism could pave the way for future drug development to treat this condition effectively.”
While the study is promising, the authors noted the limitation of its focus on a specific metabolic phenotype of HFpEF, while there are a range of HFpEF subtypes including fibrotic type or the diastolic dysfunction phenotypes. These are also of importance and should be studied. Future studies should also seek to develop models that more closely align with and translate to human physiology.
“The prevalence of heart failure with preserved ejection fraction is rising, driven by an aging population and increasing obesity rates. Unfortunately, there is still a lack of clinically effective treatment for this condition,” Sun said. “We hope our study can help us better understand this condition. Identifying key proteins involved in cardiac energy metabolism could potentially lead to identification of druggable targets for future development of medications to treat HFpEF.”
