Advances in genetic testing are improving the understanding of a variety of inherited cardiovascular diseases, but not all cardiologists are aware of the benefits and risks of incorporating genetic test results into clinical practice.
To improve their understanding, the American Heart Association issued its first scientific statement summarizing current best practices for genetic testing and its implications for the management of cardiovascular conditions with a strong genetic component, including cardiomyopathies, arrhythmic disorders, thoracic aortic aneurysms and dissections, and familial hypercholesterolemia.
“This is a resource that is geared toward cardiologists and cardiovascular providers, like myself, who really should know more about the genetics because it’s becoming part of everyday practice and is just going to increase over time,” Kiran Musunuru, MD, PhD, chair of the writing group and professor of cardiovascular medicine and genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, told theheart.org | Medscape Cardiology.
“So the aim is to inform, educate, and help clinicians who don’t have much exposure to genetics because it’s such a new thing, and also to point them to more detailed resources.”
Knowing that a patient has a genetic mutation for a specific cardiovascular disease can influence how a physician manages the patient, and has implications for immediate family as well, Musunuru said. “Testing and finding the mutation could be an important clue to detecting disease early, and perhaps stave off bad symptoms before they occur.”
The document highlights the importance of genetic professionals, the appropriate use of genetic testing, and how to select patients in whom there is a high suspicion or a clinical diagnosis of an inherited cardiovascular disorder.
Genetic testing has seen explosive growth in the past few years, both in the clinical setting and with direct-to-consumer testing, but its use for heart disease should be reserved for specific patients, Musunuru emphasized.
“Your suspicions should be triggered if a patient has a phenotype that is consistent with one of these inherited diseases, such as extremely high cholesterol levels or structural heart diseases, cardiomyopathies, abnormal rhythm disorders, thoracic aorta disorders,” he said. “Some of them are spontaneous, some don’t have much to do with genetics, but many of these cases are clearly driven by genetics. It is important that providers target specific patients for genetic testing, and not start doing genetic testing in everyone routinely.”
Cardiologists should try to get a family medical history that ideally goes back three generations to determine if there is a pattern of inherited CVD.
“We don’t always routinely go the extra mile to look at three generations and ask about grandparents, uncles, and aunts,” Musunuru said. “But if you do this very carefully and are very detailed, you will realize that what is affecting the patient in front of you has affected quite a few family members, which then raises the suspicion that this is an inherited condition.”
Genetic counseling is essential before genetic testing to make sure patients understand not only the benefits, but also the risks and uncertainties related to testing. However, this can be challenging, particularly in rural areas, because of a shortage of trained genetic professionals, Musunuru observed.
Telehealth is a promising option that could make genetic counseling more accessible, he suggested. “There’s a lot of excitement nowadays about telehealth, especially with COVID-19. Genetic counselors don’t have to be in the same room with the patient; they’re not doing examinations or listening to the heart or doing clinical testing. Telehealth provides a way for them to advise patients and explain the benefits and harms before you do the testing.”
When a genetic variant is identified, all first-degree relatives should consider undergoing genetic testing and counseling for that specific mutation whenever possible. Communicating that news to family members is up to the patient because of privacy laws, but healthcare professionals can provide written letters that explain the genetic findings, which patients can then give to their family.
What We Still Don’t Know
Testing results may confirm the diagnosis of an inherited cardiovascular disease, but they may also be inconclusive.
“We are very good at reading the genome. Unfortunately, we’re not so good at understanding or interpreting the genetics,” Musunuru observed.
Often, a mutation is classified as uninterpretable or a variant of uncertain significance (VUS). It could be pathologic or benign, and the uncertainty can pose a real dilemma for the clinician. There have been anecdotal cases where clinicians have inappropriately implanted defibrillators because they were concerned about a mutation thought to be suspicious for an arrhythmia, which later turned out to be benign, Musunuru observed.
“So genetic testing can almost be like opening a can of worms,” he said. “That’s why part of the intent of the statement is not to provide precise recommendations but more to alert physicians to the fact that there is some uncertainty associated with genetic testing. And that it is important to have genetics professionals involved, even if they may not necessarily know if something is pathogenic or not, but that they can help guide providers away from those irrevocable decisions they may later come to regret.”
Additionally, the full spectrum of genes responsible for various inherited cardiovascular diseases has not yet been clarified, Musunuru said.
“We are still very much in discovery mode and research is ongoing,” he added. “Genetic testing methods are evolving and reliable classification of variants identified in genetic testing will remain a challenge for the practice of clinical genetics.”
Musunuru reports no relevant financial relationships.
Circ Genom Precis Med. 2020;13:e000067. Abstract