HMN 2026: How Distinct metabolic signature is found in patients with heart failure with preserved ejection fraction

What exactly happens in the hearts of patients with heart failure with preserved ejection fraction (HFpEF)—and how can this knowledge be used to develop new therapies? A research team led by Dr. Gabriele Schiattarella from the Deutsches Herzzentrum der Charité and a guest researcher at the Max Delbrück Center now has an answer: The heart muscle of patients with HFpEF and obesity shows a very distinct metabolic pattern—a kind of “metabolic fingerprint.” This fingerprint, the researchers found, is distinct from people with obesity but who do not have symptoms of cardiometabolic diseases. The study is published in Cardiovascular Research.

To uncover the fingerprint, the researchers—in collaboration with Drs. Stefan Kempa and Philipp Mertins, Group Leaders of the Proteomics and Metabolomics and Proteomics Technology Platforms respectively—analyzed biopsied tissue from 19 patients with HFpEF who were severely overweight or obese. They then compared the results to heart tissue from four people who were also severely overweight or obese but did not suffer from heart failure. They examined various types of molecules—including lipids, proteins and metabolic products. This approach (also known as multiomics) makes it possible to obtain a particularly comprehensive picture of the dynamic processes that take place in heart tissue.

The results showed that although fat metabolism in the hearts of obese patients with HFpEF remained largely normal, glucose metabolism was disrupted. At the same time, certain metabolic products accumulated, and they found signs indicating that the heart lacked energy. These changes were closely linked to the extent of structural changes in the heart and the severity of the disease.

HFpEF and obesity as distinct diseases

The study highlights that these metabolic changes are not simply a consequence of obesity. HFpEF—incidentally, the most common form of heart failure—is, in fact, a distinct condition with specific molecular characteristics. This brings new therapeutic and preventive approaches into focus—particularly treatments that specifically target the heart’s metabolism.

“Our findings highlight metabolic pathways as potential targets for therapy, including improving cardiac glucose metabolism and reducing harmful by-products, pointing toward more targeted treatments and early prevention strategies in HFpEF,” explains Schiattarella, senior author of the paper.

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