What is HFpEF?

Heart failure with preserved ejection fraction ‍(HFpEF) is the most common form of heart failure, ⁢affecting an⁢ estimated nearly 4⁤ million⁢ people in the United States and 32 million people worldwide. Unlike other ⁤types of heart failure where the heart muscle⁢ weakens, in HFpEF the heart muscle becomes stiff, hindering its ability to ‍fill properly with blood. This leads to increased pressure within the heart and symptoms like shortness of⁣ breath, particularly during exertion, and fluid retention in the lungs, abdomen, or legs.

The Adipokine Hypothesis: A New Framework

Traditionally, high blood pressure has been considered the primary cause of HFpEF. Though, ⁢a‍ new hypothesis, the Adipokine Hypothesis, proposes a different mechanism.this framework, ⁢published in JACC and presented at⁣ ESC Congress 2025, suggests that ⁤excess internal fat tissue – fat surrounding vital organs, including the heart – plays a central role in the development ⁣of HFpEF.

The hypothesis centers around adipokines, signaling molecules released by fat tissue. In a healthy ⁢individual, adipokines have protective effects on the heart and‍ kidneys. However,in the context of excess internal fat,adipokine signaling becomes disrupted,contributing directly to the development of HFpEF.

“Up to now,ther has been no unifying hypothesis to explain HFpEF. That has resulted⁣ in⁤ meaningful misunderstanding and a lack of direction in both⁤ diagnosis and therapy,” explains Dr. Milton Packer,Distinguished Scholar in Cardiovascular Science ⁤at Baylor University Medical ⁤Center at⁣ Dallas and Visiting Professor at⁤ Imperial College in London,and author of the⁢ paper. “This bold new framework helps to identify‍ the true cause of HFpEF in most people. That should make ⁣an enormous difference in guiding ⁤effective treatments.”

How Do adipokines Contribute to HFpEF?

The precise‍ mechanisms by which altered ‍adipokine ⁤signaling leads to‍ HFpEF are still being investigated, but research suggests several key pathways:

• Inflammation: Dysfunctional adipokines can promote chronic, low-grade inflammation, damaging the heart muscle and impairing its ability to relax.
• Fibrosis: Adipokines can stimulate the deposition of collagen in⁢ the heart ⁢muscle, leading to stiffness⁤ and reduced filling capacity.
• Metabolic Dysfunction: ⁤Altered adipokine signaling can disrupt glucose and lipid metabolism, further contributing to heart muscle dysfunction.

It’s⁢ important to note ⁤that this isn’t simply about the *amount* of fat, but the *function* of ⁣the fat tissue and the signals it’s sending.⁤ Even ⁤individuals with a normal body mass index (BMI) can have significant⁤ amounts of⁤ internal fat and experience disruptions in adipokine signaling.

Implications for Diagnosis ⁣and Treatment

The Adipokine Hypothesis has⁤ significant implications for how HFpEF is diagnosed and treated. Currently