The Mystery of Heart Failure Revealed

Heart failure with preserved ejection fraction, known as HFpEF, has stumped medical professionals for years. Affecting nearly four million Americans and over 30 million people globally, patients with this condition struggle with limited treatment options.

Unlike conventional heart failure, where the heart muscle weakens, HFpEF appears normal in scans. The heart can still pump blood, but it can't relax and fill adequately, leading to feelings of breathlessness, exhaustion, and swelling in the legs, abdomen, or lungs.

Revolutionary Theory Challenges Old Beliefs

For a long time, high blood pressure was considered the main cause of HFpEF. However, a groundbreaking theory from Dr. Milton Packer, a leading cardiologist at Baylor University Medical Center, suggests that the real issue might not originate from the heart at all.

His team's research proposes that unhealthy fat tissue could be the hidden antagonist behind much of the disease. This idea, known as the Adipokine Hypothesis, was recently featured in the Journal of the American College of Cardiology and presented at the 2025 European Society of Cardiology Congress.

Fat: An Active Player, Not Just Storage

While many view fat merely as stored calories, it's actually a dynamic organ that emits chemical signals throughout the body. These signals, called adipokines, can influence heart health, blood circulation, metabolism, and immune response.

When fat is healthy, adipokines offer protective benefits, reducing inflammation and assisting in fluid regulation. But unhealthy fat alters this dynamic, releasing harmful adipokines that can cause inflammation and stress on the heart.

Understanding How Fat Affects Your Heart

Dr. Packer's theory links these unhealthy fat signals to the onset of HFpEF through various pathways. Chronic inflammation, triggered by stressed fat tissue, attracts immune cells that release more inflammatory substances, damaging blood vessels and heart muscle.

Moreover, as arteries lose flexibility, blood pressure rises, leading to the formation of scar tissue that disrupts the heart's ability to relax.

Unifying the Evidence: A New Perception of HFpEF

The Adipokine Hypothesis brings together disparate research findings, indicating that patients with HFpEF typically possess excess visceral fat around vital organs like the heart. Laboratory experiments reveal that adipokines can damage heart muscle relaxation, while other studies confirm that these signals can cause blood vessels to constrict, raising blood pressure.

This theory links obesity, hypertension, and diabetes—not as separate entities—but as interconnected conditions influenced by the signaling of fat tissue.

A Shift in Medical Perspectives

If Dr. Packer's hypothesis holds water, HFpEF may not be just a heart issue but a widespread bodily concern. This could redefine diagnostic and treatment strategies, focusing on fat distribution, inflammation markers, and waist-to-height ratios, rather than just cardiac function.

Dr. Packer emphasizes that body mass index (BMI) is misleading; instead, a waist-to-height ratio below 0.5 is more indicative of health. Most HFpEF patients fall above this threshold.

Potential Treatments Already in Our Hands?

An exciting implication of this hypothesis is that certain medications could alter fat biology to combat HFpEF. Drugs like semaglutide and tirzepatide, initially developed for diabetes and weight loss, may hold potential for reshaping adipokine profiles, reducing harmful fat while restoring healthy signaling.

Lifestyle changes—diet, exercise, or even surgery—could also become vital components in managing this condition.

The Future of Heart Failure Treatment

While the Adipokine Hypothesis is still under investigation, it's generating considerable optimism. Dr. Packer recalls proposing a hypothesis for another heart condition 33 years ago that revolutionized treatment, and there's hope this new framework could do the same for HFpEF.

If validated, this new understanding could transform both prevention and treatment of heart failure. By focusing on waist-to-height ratios, doctors might catch risks earlier, and patients could receive targeted therapies that address the heart's underlying problems.

At a public health level, these findings underscore the critical need to confront rising obesity rates. Addressing fat as an active organ could usher in new avenues for prevention and care, changing lives as we know them.