Genetic Variant Causing Heart Failure in Patients of African Descent Largely Goes Undiagnosed

Hereditary transthyretin amyloid cardiomyopathy (hATTR-CM), which is caused by a genetic variant significantly associated with heart failure in individuals of African descent, is underdiagnosed, according to a new study published in JAMA.

hATTR-CM is now treatable after the FDA approved the first drug for it in May 2019. Prior to the approval, treatment consisted of supportive care and heart transplants. hATTR-CM is caused by the buildup of amyloid, a transthyretin protein, in the walls of the heart. This causes the walls to become stiff, so it is difficult to pump blood out of the heart. This type of heart failure is common, but diagnosis of hATTR-CM is often not considered.

“Our findings suggest that hATTR-CM is a more common cause of heart failure than it’s perceived to be, and that physicians are not sufficiently considering the diagnosis in certain patients who present with heart failure,” author Daniel J. Rader, MD, chair of the Department of Genetics at Penn Medicine, said in a statement. “With the recent advances in treatment, it’s critical to identify patients at risk for the disease and, when appropriate, perform the necessary testing to produce an earlier diagnosis and make the effective therapy available.”

The researchers assessed the association between the hereditary transthyretin TTR V122I variant and heart failure, as well as diagnoses of heart failure among carriers of the gene, with a cross-sectional analysis of individuals of African ancestry who were at least 50 years old and had been enrolled in the Penn Medicine Biobank between 2008 and 2017.

A total of 3724 individuals (median age of 64 years) were included in the study. The majority (78%) had a diagnosis of hypertension and only 20% had a history of myocardial infarction or coronary revascularization. A total of 116 (3.1%) participants were TTR V122I carriers.

There was also a case-control study of participants of African and Hispanic/Latino ancestry with and without heart failure. They were enrolled in the Mount Sinai BioMe Biobank between 2007 and 2015. In the case-control study, there were a total of 2307 people of African ancestry and 3663 Hispanic/Latino individuals (median age of 73 years). Similar portions had hypertension (79%) and a history of myocardial infarction or coronary revascularization (17%).

The authors found that the gene variant was associated with higher rates of heart failure (44% of carriers vs 30% of noncarriers in the cross-sectional analysis and 2.6% of heart failure cases vs 1.8% of controls in the case-control study). While 44% of carriers had heart failure, only 11% had been diagnosed with hATTR-CM.

“This study suggests that workup for amyloid cardiomyopathy and genetic testing of TTR should be considered, when appropriate, to identify patients at risk for the disease and intervene before they develop more severe symptoms or heart failure,” said the study’s lead author Scott Damrauer, MD, an assistant professor of surgery at Penn Medicine and a vascular surgeon at the Corporal Michael J. Crescenz VA Medical Center.

Reference

Damrauer SM, Chaudhary K, Cho JH, et al. Association of the V122I hereditary transthyretin amyloidosis genetic variant with heart failure among individuals of African or Hispanic/Latino ancestry. JAMA. 2019;322(22):2191-2202. doi: 10.1001/jama.2019.17935.