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American Heart Association Develops Genetic Testing Guidelines for Cardiovascular Disease

NEW YORK – The American Heart Association has developed guidelines for cardiovascular practitioners who may be looking to incorporate genetic testing into the care of patients with inherited cardiovascular diseases.

In a scientific statement published in the journal Circulation: Genomic and Precision Medicine on Thursday, researchers and clinicians on behalf of the American Heart Association Council on Genomic and Precision Medicine; the Council on Arteriosclerosis, Thrombosis and Vascular Biology; the Council on Cardiovascular and Stroke Nursing; and the Council on Clinical Cardiology said that genetic testing could be useful in the management of a variety of cardiovascular conditions, including cardiomyopathies, arrhythmic disorders, thoracic aortic aneurysms and dissections, and familial hypercholesterolemia (FH).

However, not all cardiovascular practitioners are fully aware of the utility and challenges of incorporating genetic test results into the care of patients and their families, the authors noted. The statement they released summarized current best practices with respect to genetic testing and its implications for the management of these diseases.

For example, the authors wrote, "Genetic testing typically should be reserved for patients with a confirmed or suspected diagnosis of an inherited cardiovascular disease, or for individuals at high a priori risk resulting from a previously identified pathogenic variant in their family." This involves rigorous, disease-appropriate phenotyping, and a comprehensive family history that spans at least three generations. If these two elements together establish or strongly suggest an inherited cardiovascular disease, then the next step is to identify the most appropriate person for genetic testing.

Next, the authors said, if the decision is made to proceed with genetic testing, the clinician should decide what scope of genetic testing should be performed. The choice of testing ranges from targeted sequencing of a single gene or a few genes most likely to be involved in the disease, to large gene panels that include limited-evidence genes, to unbiased exome or genome sequencing that queries all genes. While a clinician's inclination might be to test all genes possible, this may not increase the likelihood of clinically actionable results in adult patients, the authors noted.

Further, expanded test panels may increase the number of variants of uncertain significance (VUS) that are identified. And in the case of exome or genome sequencing, expanded testing may increase the chance of picking up secondary or incidental findings that are not relevant to the disease in question, which can lead to confusion.

"Providers should also be aware that genetic testing might not reveal a cause or confirm a diagnosis of the patient's disease because the yield of genetic testing for any inherited cardiovascular disease remains less than 100 percent, usually much less than 100 percent," the authors wrote.

If testing is performed, the experts said, clinicians must also be aware of how they plan to return results to patients. This should be done in the presence of a genetic counselor, so that the patient has a full understanding of the implications of the results for their health.

The authors also noted the possibility for secondary or incidental findings from genetic testing. Secondary or incidental findings are becoming particularly relevant because patients are increasingly undergoing genetic testing with exome or genome sequencing in order to maximize the chance of identifying causal pathogenic variants and because costs between gene panels and exomes or genomes are narrowing.

The current recommendation is that patients should be notified of pathogenic or likely pathogenic variants in any of the 59 genes deemed medically actionable by the ACMG, if they have not opted out of receiving these results, the AHA experts said. However, VUS are not typically returned when discovered as incidental findings. Importantly, 30 of the ACMG 59 genes are related to cardiovascular diseases.

"The field of clinical genetics is in rapid flux. We anticipate that this scientific statement will need to be updated to reflect new advances in the field and new disease-specific guidelines, expert consensus documents, and other statements that are published," the authors wrote. "Reliable classification of variants identified in genetic testing will remain a preeminent challenge for the practice of clinical genetics. Ongoing efforts by ClinGen to refine gene-specific variant classification criteria will be critical, as will laboratory-based functional platforms to reliably interpret variants in a medium-throughput or high-throughput fashion."