CU Researchers IdentifyPotential Treatment for Diastolic Dysfunction in Heart Failure

(May 2018) Researchers at the University of Colorado School of Medicine have identified a potential treatment target for patients with diastolic dysfunction, which is a heart relaxation abnormality.

According to a study published in the February 7 issue of the journal Science Translational Medicine, the researchers tested the effect of an investigational drug called givinostat in treating diastolic dysfuction, an abnormality that contributes to heart failure with preserved ejection fraction (HFpEF).

HFpEF refers to cases where the heart can pump blood normally, but is not able to fill as efficiently as a healthy heart. Millions of people worldwide suffer from HFpEF, which can be caused by hypertension, diabetes, aging or other conditions. To date, there have been no effective drugs identified to treat this form of heart failure.

Studying of the hearts of patients with diastolic dysfunction and HFpEF, the research team found that fibrosis, the commonly suspected culprit in these cases, is not the sole cause of diastolic dysfunction.

Instead, their findings indicated that there was a defect in the ability of the muscle cells of the heart to relax.

Mark Y. Jeong, MD, assistant professor of medicine, and Timothy A. McKinsey, PhD, associate professor of medicine, tested whether givinostat might improve the heart’s ability to relax in the face of hypertension or aging. They found that the investigational drug, tested in rat and mouse models, helped the heart relax properly.

“These are exciting findings because we may be able to help patients with a form of heart failure that has been recalcitrant to standard-of-care therapies,” said McKinsey. “Givinostat is currently in clinical development for the treatment of muscular dystrophy. Our data suggest the possibility that givinostat could be ‘repurposed’ for the treatment of HFpEF.”

Further study is needed to determine whether it could be an effective treatment, said McKinsey, who is also director of the Consortium for Fibrosis Research & Translation (CFReT), which is one of the programs supported through the CU School of Medicine’s Transformational Research Funding initiative (www.cfret.org).