Right Ventricle Emerges as Key Clue in Hidden Heart Failure

About 3 million people in the United States live with heart failure with preserved ejection fraction, or HFpEF — a hard-to-diagnose condition in which the heart squeezes normally but grows too stiff to fill properly. Even walking to the mailbox can leave patients breathless. HFpEF is more common in women and grows more common as aging, hypertension, diabetes and obesity rise.

More than 80% of HFpEF patients also develop high blood pressure in the lungs' blood vessels, a complication called pulmonary hypertension. The combined illness, PH-HFpEF, brings severe breathlessness, repeated hospitalizations and an annual mortality rate of 15%. "HFpEF is incredibly common," said Farhan Raza, a cardiologist and researcher at the University of Wisconsin-Madison's Cardiovascular Research Center. "Many patients feel profoundly breathless and have dramatically poor quality of life from this disease."

HFpEF typically begins in the left ventricle, which pumps oxygen-rich blood to the body; its walls stiffen and thicken, and pressure backs into the lungs, causing pulmonary hypertension. Over time, that strain can weaken the right ventricle (RV), which sends blood to the lungs for oxygen. Raza says standard tests cannot show how this differs between patients — which may help explain why sildenafil and, more recently, oral levosimendan both failed trials for PH-HFpEF.

A new study led by Raza, with researchers from the University of Wisconsin-Madison and the Morgridge Institute for Research, published in the American Heart Association journal Circulation: Heart Failure, found that right ventricular function strongly indicates a PH-HFpEF patient's outlook. The researchers also identified molecular changes involving cellular energy production that could become targets for precision treatments.

The team studied 48 patients with PH-HFpEF who underwent extensive cardiac evaluation, including invasive testing and cardiac magnetic resonance imaging; 29 had normal right ventricular function, while 19 had right ventricular dysfunction. Subsets also underwent catheter-based measurements inside the pulmonary arteries, imaging that tracked blood flow changes over time, and heart tissue biopsies for molecular and genetic analysis.