Genes Linked to Heart Disease Unexpectedly Found in Genetics Tests – Now What?

The growing prevalence of genetic testing among healthcare professionals, researchers, and consumers has led to the discovery of incidental genetic abnormalities linked to cardiovascular diseases. However, the AHA warns that not all identified single gene variants necessarily indicate risk factors. To address this issue, a new scientific statement provides a framework for healthcare professionals to accurately assess genetic variants, communicate results with patients and their families, and establish robust multidisciplinary teams for tailored care when necessary.

A new American Heart Association scientific statement helps interpret incidentally found gene variants that may be associated with cardiovascular disease risk.

Increasing use of genetic testing means people may discover they have a gene variant associated with some types of cardiovascular disease (CVD). A new scientific statement, published today (March 27, 2023) in the American Heart Association (AHA) journal Circulation: Genomic and Precision Medicine, aims to help individuals and healthcare professionals understand what to do when a variant is discovered.

An American Heart Association scientific statement is an expert analysis of current research and may inform future guidelines. The new statement, “Interpreting Incidentally Identified Variants in Genes Associated with Heritable Cardiovascular Disease,” suggests the next steps to determine whether a variant truly carries a health risk, provides support to healthcare professionals on how to communicate with people and their families, and suggests the appropriate follow-up actions to care for people with variants deemed higher risk for CVD.

Variants associated with cardiovascular disease risk are often found “incidentally” when people undergo genetic testing for non-cardiac reasons, including screening or diagnosis of other diseases. These unexpected genetic variants may also be discovered with genetic testing through direct-to-consumer DNA testing kits.

Pretest genetic counseling is strongly encouraged to prepare patients for the possibility of incidental findings, how and whether findings will be communicated, and potential implications for themselves and family members.

“The scope and use of genetic testing have expanded greatly in the past decade with the increasing ease and reduced cost of DNA sequencing,” said Andrew P. Landstrom, M.D., Ph.D., FAHA, chair of the scientific statement writing committee and associate professor of pediatrics and cell biology at Duke University School of Medicine in Durham, North Carolina. “Where we would once look for genetic changes in a handful of genes, we can now sequence every gene and, potentially, the whole genome, allowing us to make genetic diagnoses that would have been impossible in the past. However, with increased genetic testing comes more surprises, including finding unexpected variants in genes that might be associated with cardiovascular disease.

“If we interpret these incidental variants incorrectly, it may lead to inappropriate care, either by suggesting patients have a risk of cardiac disease when they do not, or by not providing care to those with increased risk for a serious condition.”

This statement is the first to focus on inherited monogenic, or single-gene, diseases for CVD that can be passed on within families, such as hypertrophic cardiomyopathy or long QT syndrome. There are currently 42 clinically treatable, secondary variant genes that increase the risk of sickness or death from sudden cardiac death, heart failure and other types of cardiovascular disease, according to the American College of Medical Genetics and Genomics. Genetic variants that cause long QT syndrome cause the heart to electrically reset slower than normal after each contraction, which may cause electrical instability of the heart and may lead to fainting, arrhythmias or even sudden death.

Once an incidental genetic variant for CVD is found, the statement authors suggest a framework for interpreting the variant and determining whether it is classified as benign, uncertain, or pathogenic (disease-causing):

“The list of incidental variants related to cardiovascular disease continues to evolve. This statement provides a foundation of care that may help people with a CVD-related genetic variant and their health care professionals take the next step in determining the individual and familial risk that a variant may or may not carry,” Landstrom said. “It’s also important to consult with genetics specialists to custom-tailor an evaluation and treatment plan to both the individual and the genetic variant in order to ensure the highest level of care possible.”

Reference: “Interpreting Incidentally Identified Variants in Genes Associated With Heritable Cardiovascular Disease: A Scientific Statement From the American Heart Association” 27 March 2023, Circulation Genomic and Precision Medicine.
DOI: 10.1161/HCG.0000000000000092

Co-authors are Anwar A. Chahal, M.B.Ch.B., Ph.D., M.R.C.P., vice chair; Michael J. Ackerman, M.D., Ph.D.; Sharon Cresci, M.D.; Dianna M. MIlewicz, M.D., Ph.D.; Alanna A. Morris, M.D., M.S., FAHA; Georgia Sarquella-Brugada, M.D., Ph.D.; Christopher Semsarian, M.B.B.S., Ph.D., M.P.H., FAHA; Svati H. Shah, M.D., M.H.S., FAHA; and Amy C. Sturm, M.S., L.C.G.C. Authors’ disclosures are listed in the manuscript.

The Association receives funding primarily from individuals. Foundations and corporations (including pharmaceutical, device manufacturers, and other companies) also make donations and fund specific Association programs and events. The Association has strict policies to prevent these relationships from influencing the science content.

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