New Statement Suggests Next Steps for Interpreting Incidentally Identified Gene Variants Associated with Heart Disease

The increasing use of genetic testing means that people may be found to have genetic mutations associated with certain cardiovascular diseases (CVDs). A new scientific statement published today in the American Heart Association journal Circulation: Genomic and Precision Medicine aims to help individuals and health professionals understand what to do when a mutation is discovered. increase.

The American Heart Association Scientific Statement is an expert analysis of current research that may inform future guidelines. The Interpretation of Variants” suggests next steps for determining whether a variant really poses a health risk, provides support to health professionals on how to communicate with people and their families, and provides guidance for CVD. Appropriate follow-up actions to care for people with variants considered at high risk.

Variants associated with cardiovascular disease risk are often discovered ‘incidentally’ when undergoing genetic testing for non-cardiac reasons, such as screening or diagnosing other diseases. These unexpected genetic mutations may also be found during genetic testing with consumer DNA test kits.

Pre-test genetic counseling is strongly recommended to prepare patients about the possibility of incidental findings, how and whether findings are communicated, and the potential impact on themselves and their families.

“The reach and use of genetic testing has expanded significantly over the past decade, as DNA sequencing has become easier and less expensive.” Associate Professor of Pediatrics and Cell Biology, Duke University School of Medicine, Durham, North Carolina. “Whereas we used to look for genetic alterations in a handful of genes, now we can sequence every gene, or even the entire genome, making genetic diagnoses that were impossible in the past. Yes, but the increase in genetic testing brings additional surprises, such as the discovery of unexpected variants in genes that may be associated with cardiovascular disease.

“Misinterpretation of these incidental variants could suggest that patients are at risk for heart disease when they are not at risk, or could result in the withholding of care from patients at increased risk for serious conditions. , can lead to inadequate care.”

This statement is the first to focus on inherited monogenic or monogenic disorders of CVD that can be passed on in families, such as hypertrophic cardiomyopathy and long QT syndrome.American College of Medical According to Genetics and Genomics, there are now 42 clinically treatable secondary mutation genes that increase the risk of morbidity and mortality from sudden cardiac death, heart failure, and other types of cardiovascular disease. Genetic mutations that cause long QT syndrome cause the heart’s electrical reset to be slower than normal after each contraction, leading to cardiac electrical instability that can lead to syncope, arrhythmias, and even sudden death.

When an incidental genetic variant of CVD is discovered, the authors of the statement interpret the variant and use it to determine whether it is classified as benign, uncertain, or pathogenic (causing disease). Suggest a framework.

• HCWs should advise if the incidentally identified variant falls within a cardiovascular disease gene with a known association with CVD, and if the patient is informed about the incidental finding during pretest genetic counseling. Patients should only be informed if they have consented to be notified.
• Incidentally, variants in genes of uncertain association with CVD should not be reported.
• If the variant found may increase the risk of CVD, family history and medical evaluation by an expert health care professional are recommended. Preferably, a specialist working with or within a multidisciplinary team to address the disease in question is recommended. The purpose of this evaluation is to determine whether the individual has evidence of the disease, such as symptoms and related laboratory results, or whether there are warning signs in the family history.
• The genetic variant itself should be periodically re-evaluated by an expert or team of experts to confirm whether the CVD link is accurate. As knowledge about variants evolves over time, their association with disease may be reclassified.
• Finally, medical evaluation and genetic re-evaluation should guide the next steps, from dismissing an incidental variant as unlikely to cause CVD to initiating medical intervention. This may include periodic reassessment with appropriate tests (echocardiogram, blood tests, etc.) and possibly screening of other family members for the variant.

The list of incidental variants associated with cardiovascular disease continues to evolve. This statement provides a basis for care that may help people with CVD-associated genetic mutations and their health care professionals to assess individual and family risks that mutations may or may not have. We also consult a genetics expert to tailor the assessment and treatment plan to both the individual and the genetic mutation to ensure the highest possible level of care. It is also important to adjust

Andrew P. Landstrom, MD, Ph.D., FAHA, Chair of the Scientific Statement Committee

This scientific statement was prepared by a volunteer writing group on behalf of the Genomics and Precision Medicine Council of the American Heart Association and the Data Science and Precision Medicine Committee of the Clinical Cardiology Council. Council on Cardiovascular and Stroke Nursing. Hypertension Council; Council on Lifelong Congenital Heart Disease and Heart Health in Youth: Council on Peripheral Vascular Disease. and the Stroke Council. Scientific statements from the American Heart Association help raise awareness and facilitate informed health care decisions about cardiovascular disease and stroke issues. A scientific statement outlines what is currently known about the topic and areas where additional research is needed. Scientific statements inform the development of guidelines but do not make treatment recommendations. The American Heart Association guidelines provide the association’s official clinical practice recommendations.