Dr. Gemma Vilahur, head of the Molecular Pathology and Therapeutics of Atherothrombotic and Ischemic Diseases research group at the Institut de Recerca Sant Pau (IR Sant Pau) and member of the Steering Committee of the Spanish Biomedical Research Network Center for Cardiovascular Diseases (CIBERCV), has participated in an international review published in Nature Reviews Cardiology that explores how the interaction between inflammation and metabolism contributes to the development and progression of heart failure. In the article, the IR Sant Pau researcher served as corresponding author.
Heart failure is one of the leading causes of hospitalization and mortality in developed countries, and its incidence increases with population aging and improved survival after myocardial infarction. It is a chronic condition in which the heart is unable to pump enough blood to meet the body’s needs, leading to fatigue, shortness of breath, and fluid accumulation.
The paper, titled “Immunometabolism in Heart Failure,” compiles the latest scientific evidence on the role of immunometabolism—the interaction between metabolism and the immune system—in heart dysfunction within the context of heart failure and proposes new research directions aimed at improving diagnosis and prognosis for patients.
In heart failure, damage to heart tissue triggers an initial inflammatory response necessary to repair the myocardium. However, often this reaction does not fully resolve and turns into chronic low-grade inflammation that progressively impairs heart function.
At the same time, both cardiac cells and immune cells modify their ways of obtaining and using energy. When the heart becomes less efficient at producing energy—such as after a myocardial infarction or under metabolic stress conditions like diabetes or obesity—alternative pathways are activated that consume more resources and generate by-products that perpetuate inflammation. In this process, immune cells switch their main energy source (“metabolism”) from oxidative phosphorylation, which depends on oxygen and the availability of fatty acids and takes place in the mitochondria, to glycolysis, a faster pathway that converts glucose into pyruvate but is less efficient in terms of ATP production.
The review also emphasizes that the bone marrow and spleen act as reservoirs of immune cells that are released and directed toward the injured heart. The continued arrival of these cells—especially when inflammation persists over time—contributes to the progression of heart failure.
This constant and bidirectional interaction between immune cells and cardiac tissue cells generates a true metabolic dialogue—or crosstalk—through which both influence each other. Immune cells alter the energetic environment of the myocardium by releasing inflammatory molecules that modify the metabolism and function of cardiomyocytes and fibroblasts. In turn, damaged cardiac cells send metabolic signals that again modify the immune response. This ongoing exchange of signals promotes adverse cardiac remodeling, characterized by fibrosis, loss of elasticity, and progressive deterioration of contractile function.
“The failing heart doesn’t just beat with less strength—it also changes the way it obtains and uses energy,” explains Dr. Gemma Vilahur. “This metabolic alteration stimulates an immune response that, in turn, worsens the damage. Understanding this dialogue is essential to breaking this vicious cycle.”
The review notes that these processes are detectable from the very early stages of heart failure and may even be present before clinical symptoms appear. Detecting these changes early could enable action before heart damage becomes irreversible, opening the door to more effective prevention and treatment strategies.
The article also highlights that research in immunometabolism paves the way for new therapeutic strategies to prevent and treat heart failure. Understanding how immune and cardiac cells manage energy, and how these processes influence the inflammatory response, allows researchers to identify specific metabolic pathways that could be modulated with drugs.
In this regard, the authors suggest that adjusting the balance between glucose and fatty acid consumption or regulating mitochondrial activity—the organelles responsible for energy production—could help improve cardiac function and slow disease progression. Similarly, controlling the metabolic activation of immune cells could help limit the chronic inflammation that accompanies heart failure.
“Immunometabolism allows us to understand heart failure from a broader perspective,” adds Dr. Vilahur. “It’s not just about treating symptoms—it’s about targeting the cellular mechanisms that cause them.”
In addition, this integrated perspective opens new opportunities for developing biomarkers capable of reflecting the metabolic and inflammatory status of the heart. These biological indicators—detectable in blood or through advanced imaging techniques—could identify at an early stage which patients are at risk of disease progression, anticipate decompensations, and monitor treatment response. In the future, their clinical use could help select the most appropriate therapies for each patient profile, advancing toward truly personalized medicine in heart failure.
The use of advanced molecular imaging techniques, such as positron emission tomography (PET) or magnetic resonance imaging with specific tracers, will also make it possible to noninvasively track the trafficking and activation of immune cells in the heart. These tools provide a new way to observe the inflammatory process in real time, helping to assess disease progression and directly evaluate the effects of metabolism- or inflammation-targeted therapies.
Taken together, these strategies—far more precise than conventional treatments focused solely on improving pump function—represent a paradigm shift in the management of heart failure. By integrating the immune and metabolic components into diagnosis and therapy, they open the door to treating the disease at its biological root with a more effective, preventive, and personalized approach.
Dr. Vilahur’s participation in this publication reinforces IR Sant Pau’s leadership in researching the cellular mechanisms that link inflammation, metabolism, and cardiovascular disease. Her group has long focused on studying how the metabolic environment and the immune system contribute to the development of atherosclerosis, myocardial infarction, and heart failure.
“Our goal is to translate this knowledge into clinical practice to improve diagnosis and treatment for patients,” says Dr. Vilahur. “The future of cardiology lies in integrating molecular biology with personalized medicine and cardiovascular prevention strategies.”
Andreadou I, Ghigo A, Nikolaou P-E, Swirski FK, Thackeray JT, Heusch G, Vilahur G. Immunometabolism in heart failure. Nat Rev Cardiol October 2025;22:751–72. https://doi.org/10.1038/s41569-025-01165-8.
