New hope for heart failure: a drug blocks a signal sent by fat around the heart

If you or someone you love lives with heart failure, here is news worth a second sip of coffee. Researchers have pinned down a signal that fat around the heart sends out, and a drug that blocks that signal improved heart pressures in a clinical trial.

It applies to one form of heart failure, called HFpEF, where the heart pumps normally but is stiff and fills poorly. When high pressure in the lung vessels comes along with it, treatment has been hard. Now there is a clear new target, and a drug already being tested against it.

How the study worked

This is a review, a paper in which experts bring together lab, animal and human evidence. It was published Oct. 26, 2026, in Circulation. It leans on the CADENCE trial in people with HFpEF and high lung pressure, and a larger phase III trial is now running to see whether the drug slows the disease over time.

What they found

The story starts with fat that sits right on the heart, called epicardial fat. It lies next to two key spots: the left atrium, the upper left chamber of the heart, and the veins that carry blood back from the lungs.

When that fat expands, it releases substances that stir up inflammation. The best known is activin A. It causes fibrosis (a scar-like stiffening), makes heart tissue stiffer and pushes heart cells to age.

People show this pattern in real life. Activin A in the blood is higher in people with HFpEF who have an enlarged left atrium, high pressure in the lung veins and more resistance in the lung vessels.

In experimental models of obesity-related disease, drugs that trap activin signals eased HFpEF. They also improved problems in both the lung vessels and the left side of the heart.

That led to a test in people. The drug is sotatercept, which traps activin signals and is already used for a different lung blood pressure condition, pulmonary arterial hypertension. In the CADENCE trial, it lowered pulmonary artery wedge pressure, which reflects how much pressure is backed up on the left side of the heart. It also lowered the left atrial volume index, a measure of how big that upper left chamber is.

The authors say those gains could not be explained by lower resistance in the lung vessels alone. In plain words, the drug appeared to be working on the heart itself, just as the fat-signal idea predicted.

What is fat around the heart, and why does it matter?

You may know belly fat and the fat under your skin. This is a different layer, a thin coat of fat on the surface of the heart. Because it touches the heart and the lung veins, what it releases reaches them directly.

That is why the finding ties HFpEF to obesity in a concrete way. It also explains why a drug aimed at one specific signal could help.

What you can do today

Spend five minutes on ClinicalTrials.gov, the free U.S. government database of studies. Search “sotatercept heart failure” and see which trials are listed and where they are recruiting. Then jot down two questions for your next cardiology visit: whether your heart failure is the HFpEF type, and whether your lung pressure has been checked. You will walk in with a clear picture of where this research is heading.