Image of a heart with a DNA double helix in front of it to indicate genetic heart diseases such as transthyretin amyloid cardiomyopathy.
Credit: iStock/SvetaP DNA double helix: iStock/Kagenmi

Researchers have linked a rare genetic mutation in TTR V142I, which affects mostly people of African descent, to an earlier onset of heart failure and a higher risk of hospitalization. The findings suggest screening for the mutation could lead to faster treatment and improved outcomes, the researchers said.

The results of the study appear this week in the Journal of the American College of Cardiology: Heart Failure.

“This is the most comprehensive evaluation of the association between this mutation and measures of cardiac structure, heart function, and heart failure risk in an exclusively Black population,” said lead study author Ambarish Pandey, M.D., assistant professor of internal medicine in the Division of Cardiology at University of Texas Southwestern Medical Center in Dallas. “The results also highlight the importance of early genetic screening in patients at higher risk for carrying the mutation.”

Heart failure affects about 6.5 million people in the United States alone. Black Americans are at higher risk for the condition than any other racial/ethnic group in the U.S., and they experience worse outcomes.

TTR V1421 has long ago been linked to a higher risk of heart failure in people of African ancestry. Mutations in this gene can cause a condition called transthyretin amyloid cardiomyopathy, which is potentially fatal because protein builds up inside the heart. However, little was known about the impact of the mutation on important clinical-related factors such as heart structure, heart function, hospitalization rates, and blood biomarkers.

This team studied TTR V142I in a group of middle-aged participants from the 20-year-long Jackson Heart Study, the largest and longest investigation of cardiovascular disease in Black Americans. Of the 2,960 participants selected from the study, about 119 (4%) had the genetic mutation, but none had heart failure at the start. The researchers followed the participants for about 12 years between 2005 and 2016.

During the study period, the researchers observed 258 heart failure events. They found that patients who carried the genetic mutation were at significantly higher risk of developing heart failure, compared to those without it. These patients also developed heart failure nearly four years earlier and had a higher number of heart failure hospitalizations. Researchers found no significant difference in death rates between the two groups during this study period.

During follow-up studies, however, they observed significant increases in blood levels of troponin, a protein complex that is an important marker of heart damage, among carriers of the genetic mutation. They did not see any significant associations between the genetic mutation and changes in heart structure and function as evaluated by echocardiographic and cardiac MRI assessments.

“What that means is that the gene is causing heart damage slowly over time,” said Amanda C. Coniglio, M.D., the lead author of the study and a physician with Duke University School of Medicine in Durham, North Carolina. “The changes are subtle but significant.”Adolfo Correa, M.D., Ph.D., study co-author and former director of the Jackson Heart Study, said, “About half of Black American men and women living in the United States today have some form of cardiovascular disease, but the root causes are poorly understood. This study brings us a step closer to better understanding this particular form of gene-related heart failure, as well as the life-saving importance of early screening.”

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