Approximately 3 million people in the United States are living with heart failure with preserved ejection fraction, or HFpEF, and their prognosis can be daunting. Debilitating symptoms and frequent hospitalizations lead to deteriorating quality of life and the annual mortality rate is 15%. The number of people with this form of heart failure, which is more common in women than men, is growing alongside a rise in risk factors like aging, hypertension, diabetes, and obesity. Yet clinicians can struggle to detect the disease in early stages when it’s most treatable.
A study by clinicians and scientists from the University of Wisconsin School of Medicine and Public Health and the Morgridge Institute for Research, led by associate professor of medicine Farhan Raza, has led to new insights about HFpEF. The condition develops when the walls of the heart’s left ventricle, the chamber responsible for pumping blood through arteries, become stiff and thicken, leading to severe fatigue, pulmonary hypertension and dysfunction of the heart’s right ventricle (RV), which pumps blood into the lungs to get oxygenated. Using long-read RNA sequencing allowed researchers to detect particular variants of genes that might be expressed in longer or shorter versions. They found that a handful of genes are differently expressed between patients with and without RV dysfunction. While these results are preliminary, it’s possible that some of these gene expression variants might be tied to HFpEF, including GATD3, which has a variant expressed much more highly in right ventricular dysfunction and is also involved in mitochondrial function. Previous research has linked RNA metabolism and mitochondrial dysfunction to the development of heart disease, and in analyzing biopsied tissue from HFpEF patients, the UW researchers detected diminished function in mitochondria and an increase in RNA metabolism and transport. Based on these findings, GATD3 could be a target for future study and potential treatment development.
The team plans to conduct larger studies that develop a clearer picture of the molecular and cell-level variation between the heart tissue of patients with normal RV function versus those with dysfunction.
Learn more about a possible pathway to precision treatments for HFpEF
