Mutations in gene linked to heart failure discovered

New York: Researchers have identified new mutations in a gene commonly associated with non-ischemic dilated cardiomyopathy (NIDC), a disease that weakens the heart muscle, making it more difficult to adequately circulate blood to meet the body’s needs.

Patients with NIDC struggle because the heart’s ability to pump blood is decreased, as the heart’s main pumping chamber, the left ventricle, is enlarged and dilated.

Unlike other kinds of heart conditions, NIDC often isn’t related to or a symptom or sign of a known cardiovascular disease or disease risk factor.

In the study, researchers from the Intermountain Healthcare Heart Institute in the US, have identified 22 mutations in 27 of 229 NIDC patients in a gene called TITIN — 15 of them not previously discovered.

These TITIN mutations are of a type called “truncating variants”, or TTN-tv, which are linked with the development of cardiomyopathy and heart failure.

“Truncating mutations in TITIN are common in NIDC, so we wanted to know: if we find one, should we be more, or less worried about the patient’s prognosis? The answer is yes,” said principal investigator of the study Jeffrey L. Anderson.

In the study, the DNA samples of the 229 Intermountain patients diagnosed with NIDC were analysed.

Researchers also identified lifestyle, environmental and other disease factors documented in the medical records that are associated with heart problems, like high blood pressure, diabetes, a history of alcohol or drug abuse, or previous chemotherapy treatment.

Patients were evaluated when they first presented and then were followed for five years.

Patients with a TTN-tv mutation more often had severe cardiomyopathy at presentation, and by five years they were less likely to have recovered (11 per cent of those with a mutation versus 30 per cent of those without).

These patients also were more likely to have shown progressive disease, such as a heart transplant, implant of a permanent heart assist device, or death if they had a TTN-tv mutation (41 per cent) than if they didn’t (25 per cent).

TTN-tv mutation patients also commonly were found to have non-genetic predisposing factors, suggesting that these other factors may act in concert with genetic factors to precipitate heart failure.

The study was presented at the 2019 American Heart Association Scientific Sessions in Philadelphia, US.