Frequently Asked Questions

Genetic and genomic testing can both play roles in diagnosing cardiovascular disease. Broadly speaking, genetics refers to the study of genes while genomics refers to the study of the entirety of a person’s genes, known as the genome. Genetic testing is the study of specific, individual genes and whether they are passed from one generation to the next. Genetic tests help determine if a patient has a specific altered gene that can lead to an inherited heart condition. Genomic testing looks broadly for gene alterations, or harmful changes, anywhere in the genetic code. Genomic testing looks at the make-up of genes a person is born with that can affect cardiovascular risk.

The CardioGenomic Testing Alliance is committed to raising awareness and utilization in both genetic and genomic testing in cardiology. CGTA is encouraged by the progress of genomic testing for inherited cardiovascular disease as actionable genes related to cardiovascular diseases continue to grow.

CGTA will consider genomic testing in cardiology to be an inclusive term that refers to both genetic testing and genomic testing in cardiology.

Cardiologists should offer genomic testing in cases where patients are at a high risk of developing cardiovascular disease as a result of a confirmed or suspected diagnosis of an inherited cardiovascular disease or pathogenic variant in their family. This identification should depend on a comprehensive evaluation of at least three generations’ worth of the patient’s family history. After this history is sufficiently examined, providers should refer the patient to genetic specialists and/or counselors if a patient’s medical record suggests they may have inherited a form of cardiovascular disease. ¹

Genomic testing in cardiology allows patients to learn if they have an inherited cardiovascular condition passed down from previous generations. In addition to providing actionable insights into the health of first-degree family members, genomic testing also empowers patients to make informed decisions for their families. Genomic testing is especially useful for assessing patients with complex medical histories, as it provides a comprehensive view of the patient’s condition. Genomic testing in cardiology can provide a deep insight into genetic risk of cardiovascular disease and can assist with appropriate therapy selection, if needed.

Genetic and genomic testing provide cardiologists with additional information about a patient’s hereditary cardiovascular condition, improving the effectiveness with which often underdiagnosed single-gene mutations are identified and treated.³ Additionally, genomic testing can help providers identify specific relatives at risk of developing certain cardiovascular conditions.⁴ By targeting the specifically identified mutation within the genome in patients with inherited cardiovascular conditions, genetic counselors can more effectively test for the presence of the mutation in the patient’s family members.

Genetic testing can provide critical information to support diagnosing and managing “inherited cardiovascular diseases such as:

• cardiomyopathies, heart muscle diseases that can lead to heart failure;
• thoracic aortic aneurysms and dissections, syndromes that cause the body’s major artery to balloon and rupture;
• arrhythmic disorders that predispose people to potentially fatal abnormal heart rhythms; and
• familial hypercholesterolemia, or highly LDL elevated cholesterol levels that greatly increase the risk of heart attack.⁵

There are several practice guidelines and consensus statements that provide clear guidance for recognizing and targeting patients with likely inherited cardiovascular disease. The AHA Scientific Statement on Genetic Testing for Inherited Cardiovascular Diseases summarizes several of these guidelines and statements, providing a robust overview and clear expectations for genetic testing.⁶

Check out CGTA’s resource page to learn more about this Scientific Statement and stay tuned for additional guideline resources.

Cascade testing is a predictive approach for identifying relatives at risk for inherited cardiac conditions. Cascade testing is an essential component of genetic testing and determines whether the pathogenic variant identified in the original family member is present or not in relatives at risk.⁷ Early detection through cascade testing can reduce morbidity and mortality of family members potentially carrying the same variant.⁸ The United States Centers for Disease Control Office of Public Health Genomics classifies cascade genetic testing as Tier 1 genomic application, which means there is strong and clear evidence supporting its implementation into clinical practice.⁹

Cascade testing is able to separate relatives that are at-risk for an inherited cardiac condition who require ongoing screening from those who do not. Relatives who test positive through early detection cascade testing are able to identify the most appropriate approach for medical management, which could include ongoing testing, medical therapy, or device implantation.

Relatives who test negative for the variant can, in most cases, be released from lifelong screening and clinical surveillance knowing they are not at increased risk for the inherited cardiac condition. This also means their children or any future children are not at an increased risk.

Genetic counselors are in a unique position within the healthcare continuum, supporting patients’ medical, genetic, and psychological needs. Specifically, a clinical genetic counselor is an allied healthcare professional with specialized training in medical genomics, education, and counseling. Genetic counselors support patients and families seeking more information about how inherited diseases and conditions might affect them and help interpret genetic test results.¹⁰

Genetic counselors that specialize in cardiovascular disease provide guidance to individuals and families experiencing the diagnosis or prospective diagnosis of an inherited cardiovascular condition.¹¹ Cardiovascular genetic counseling activities include:

• Family history risk assessment
• Selecting the most informative relatives for genetic counseling
• Selecting the most appropriate genetic test
• Educating the patient and family members about genetic testing
• Ensuring accurate variant interpretation
• Communicating results to the patient and any necessary family members

Genetic counselors support patients and their families both pre and post genetic testing. Prior to genetic testing, counselors discuss how the testing might impact patients and their families while gathering any relevant family health history and presenting available testing options. If a patient chooses to move forward with testing, genetic counselors will help each patient understand their test results and treatment options while answering any questions the patient may have. Please visit the National Society of Genetic Counselors website to learn more.

https://www.nsgc.org/

Providers are encouraged to refer patients for genetic counseling. Below are helpful resources available to find a genetic counselor near you or virtually:

• The National Society of Genetic Counselors directory offers access to over 3,300 genetic counselors.¹²
• The American Board of Genetic Counselor Certified Genetic Counselor Directory assists providers in locating genetic counseling services.¹³

Similar to other medical tests, providers can order genetic and genomic tests for inherited cardiovascular disease through testing companies, including several CGTA members companies. Please visit their websites to learn more about ordering these tests for your patients.

A blood sample stored in ethylenediaminetetraacetic acid (EDTA) is the gold standard for genetic and genomic testing in cardiology. However, depending on the testing laboratory, other samples may be acceptable, including:

• cultured cells (from skin or different organs, as well as chorionic villus sampling (CVS) and amniotic liquid in prenatal cases)
• buccal swabs
• dried blood spots
• DNA extracted from another laboratory

Yes, samples obtained postmortem can be used for genomic testing. Several types of samples can be accepted in this situation, but sample type and sample collection information (date, time of collection after death, storage conditions, etc.) may play a very important role in successfully obtaining DNA from such samples. Further discussion with the testing lab is recommended.

Once genomic testing has been completed, a health care provider can expect to receive a report from the performing laboratory that summarizes all reportable variants. The specific test results will dictate how and if the patient’s medical management will change and if other family members should be tested.

Broadly, results of genomic testing in cardiology may be positive, negative, or inconclusive.¹⁴ These results are specific to patients receiving genomic testing and do not apply to cascade testing of relatives.

• Positive results include genetic variants that are classified as pathogenic or likely pathogenic. These results may have direct implications for the medical care of your patient and their family.
• Inconclusive results include variants that are of uncertain clinical significance; these should not be used to direct patient care.
• Negative results include results with no actionable or uncertain results.

In addition to results regarding a patient’s cardiovascular risks, genomic testing may also include secondary, or incidental, findings associated with health risks for non-cardiovascular conditions.

A negative result cannot rule out a genetic risk for a patient. It is possible that a patient has a genetic risk that could not be identified on the testing based on the technology used or due to the interpretation of variant(s) identified, or that the patient has genetic risk related to many genomic variants (polygenic disease).

Genetic testing panels targeting only genes associated with cardiovascular disease would not be expected to identify health risks unrelated to cardiovascular disease. Genetic tests help determine if a patient has a specific altered gene that can lead to an inherited heart condition. Genomic testing looks broadly for gene alterations, or harmful changes, anywhere in the genetic code. Genomic testing may identify health risks that are unrelated to cardiovascular disease such as cancer or metabolic conditions, although these findings are uncommon.^15,16 Patient preferences regarding these types of results may be reviewed in pretest counseling/consenting.¹⁷ In some cases, patients may opt out of receiving results that are unrelated to their personal or family history of cardiovascular disease.

While guidelines from the College of American Pathologists (CAP) establish which information must be included in genomic test reports, labs vary in the depth of information they choose to include and in how the information is displayed. The specific genetic variants reported typically follow HGVS nomenclature for consistency across labs, but information regarding how a variant was classified, the medical significance, inheritance, and next steps for the patient can vary by laboratory. Labs also may offer different options regarding the reporting of secondary/incidental findings.

Like other medical tests and procedures, genetic and genomic testing for cardiovascular disease may be covered by insurance, including Medicare. Coverage is dependent on several factors, so it is recommended that each health care provider check with the corresponding insurance provider and testing laboratory for each patient.

The Genetic Information Nondiscrimination Act (GINA) protects patients from discrimination based on information obtained from genetic testing.¹⁸ GINA prohibits health insurers and employers from making decisions based on genetic information. Specifically, insurers cannot request or purchase genetic information to use in eligibility or coverage decisions. For more information on how the GINA protects patients from genetic discrimination in health insurance and employment, visit ginahelp.org.

Cardiovascular genetic and genomic testing in children has an important diagnostic role in determining the risk of developing heritable cardiovascular disease. A Scientific Statement from the American Heart Association was released in 2021, outlining the key points and recommendations for pediatric cardiovascular genetic and genomic testing. Please refer to “Genetic Testing for Heritable Cardiovascular Diseases in Pediatric Patients: A Scientific Statement From the American Heart Association” for details.¹⁹