Cardiovascular diseases are a leading cause of death with significant financial burden for patients, their families, and the society at large.
Towards our journey to deliver precision medicine, we gained a deep understanding of the various behavioral and lifestyle risk choices, such as smoking and poor diet. Only recently started working towards addressing socio-economic risk factors, such as access to care, malnutrition. The last component is the genetics of the patient and the disease. For over a decade, clinical guidelines have recommended genetic testing for patients with specific cardiovascular diseases. However, uptake of this testing among cardiologists has been extremely slow.
Recently, experts discussed the clinical utility of cardiogenomic testing and how to overcome barriers to adoption.
- Michael Ackerman, MD, PhD, Mayo Clinic
- Alice Lara, RN, Sudden Arrhythmia Death Syndromes (SADS) Foundation
Patients with inherited cardiovascular diseases and their families need cardiogenomic testing
Cardiogenomic testing is recommended for four broad categories of cardiovascular diseases.
- Cardiomyopathies or heart muscle diseases. These include dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM) and arrhythmogenic cardiomyopathy (ACM).
- Channelopathies or genetic electrical diseases. Although a patient's heart may look normal, the heart's electrical system has issues. Examples include long QT syndrome (LQTS), Brugada syndrome, short QT syndrome and catecholaminergic polymorphic ventricular tachycardia (CPVT).
- Aortopathies. The aorta exhibits structural problems and is at high risk for rupture. One example is Marfan syndrome.
- Familial lipidemias or lipid disorders, such as familial hypercholesterolemia (FH).
The clinical utility of genomic testing across the triad of medicine — diagnostic, prognostic and therapeutic — is different for the different types of inherited cardiovascular diseases. There are two critical aspects for care quality: the patient in front of the physician and the patient's family.
According to Dr. Ackerman, "Cardiologists must recognize that a patient's genetic type influences treatment plans," and added, "For example, I treat patients with long QT syndrome type 1 differently than I treat people with long QT syndrome type 3. The treatment for sarcomeric HCM is fundamentally different from treatment for a mimic that is actually Fabry disease."
And when genetic testing uncovers a patient's disease-causing variant, the Class 1 recommendation is for first-degree relatives to be offered genetic testing. Based on published work, this critical cascade testing confirms additional at-risk family members in over 40% of those tested.
"We talk to families every day who have had a disease in their family, but it didn't pass to them. But we also hear from people who have had cardiac events, and they wish someone had done genetic testing so they could have been treated appropriately," Ms. Lara said.
Unfortunately, many cardiologists aren't ordering these tests due to misconceptions
A study led by Illumina offered dramatic insights into clinical adoption of cardiogenomic testing. Briefly, utilization of guideline-directed genetic testing in inherited cardiovascular diseases among diagnosed patients was 0.8% for DCM, 1.6% for HCM, 1.2% for LQTS, and 1.5% for FH. The highest percentage of genetic testing was among patients with hereditary amyloidosis at 6%, potentially due to the availability of targeted medications for patients with amyloidogenic transthyretin (TTR) variants. This is a significant underutilization of precision medicine.
"I'd give clinical utilization of cardiogenomic tests across the country a grade of a C minus or D plus," Dr. Ackerman said. "Doctors often say, 'I know that my patient has HCM, why do I need the genetic test?' That shows a level of ignorance with respect to these conditions."
Part of the problem is that genetic testing has been expensive in the past and payers used to classify the tests as "investigational."
"Around 2003, the first clinical genetic test for long QT syndrome was released in the United States and it cost $5,400," Dr. Ackerman said. "Blue Cross Blue Shield led the way among payers, stating that these tests had bona fide clinical utility. Now they are increasingly available, covered by insurance companies in a favorable manner, and the price has dropped dramatically. Today cardiogenomic tests are less expensive than an echocardiogram."
Myths about the cost of cardiogenomic testing also need to be debunked among patients. "The number one barrier among patients is that they think genetic tests are too expensive and that insurance won't cover it," Ms. Lara said. "They don't realize that the world has changed. What we hear from our genetic testing partners is that the average person with health insurance will pay less than $200 out of pocket for a genetic test."
Test ordering represents an additional barrier to cardiogenomic testing. Cardiologists may be dependent on genetic counselors for pre- and post-testing support, mistakenly believing that they can't use these tests without their help. For broader access to cardiogenomic testing, we may need pathways to become genetic counselor independent for test acquisition. Dr. Ackerman added “That doesn't mean that [genetic counselor] role isn't mission critical in other phases, but I don't need the genetic counselor for the acquisition of the test, and most of our patients don't. There are mechanisms of doing the genetic counseling and all of the guidelines recognized it.” According to Ms. Lara, most patients surveyed by the SADS Foundation that have had genetic testing didn't see a genetic counselor in advance.
Another challenge is test result interpretation. Physicians need a basic skill set to assess the phenotype and genotype and make sure they are concordant. "These are competencies that most cardiologists simply don't have yet," Dr. Ackerman said. "If a test is hard to obtain, they don't try hard to get it — especially if they aren't good at assimilating the results."
In addition to training, one potential solution is to flip the conversation to focus on the percentage of cardiogenomic test results that are clear. "There are a lot of things in genetic tests that are easy, but we inadvertently spooked cardiologists," Dr. Ackerman said. "Many think the tests are too complicated, when they're actually straightforward and actionable in many cases. A lot of times the results are a slam dunk. You get an irrefutable classic variant, then you figure out how to treat the patient and determine who else in the family has the disease."
For test results that are ambiguous with variants of uncertain significance, cardiologists need the right resources to interpret them. This is where genetic counselors can play an important role.
Partnerships, training and patient education are effective ways to increase cardiogenomic testing
Cardiologists need to commit to conducting cardiogenomic testing for patients with potentially inherited cardiovascular conditions.
"The first step is to acknowledge that you need to get in the game," Dr. Ackerman said. "If you label a patient with one of these conditions, you need to order the genetic test, no excuses. The next step is to figure out the roadblocks at your campus."
Partnering with genetic test companies and other colleagues can be powerful.
"Genetic test companies are more than happy to help — they recognize that this may be uncharted territory for you and your organization," Dr. Ackerman said. "Also, find a partner on your team — don't feel like you have to do this alone. By tag-teaming with a colleague, you can share the burden."
Clinician training is also essential. For six years, Mayo Clinic has offered a continuing medical education course called "Genetics of Heart and Vascular Disease." The objective of this course is to improve literacy in the field of genetic cardiology among cardiologists, nurse practitioners and physician assistants.
Finally, the value of patient education cannot be overlooked. The SADS Foundation has developed an infographic about cardiogenomic testing that patients can bring to their physicians. The organization also offers online resources related to insurance, genetic counseling, genetic testing labs and research.
Lack of testing adds to the outcome inequities. A study on FH alone found that limited-variant screening would have missed 64% of white/Caucasian, 85% of Hispanic, and 94% of black/African American individuals positive for FH- associated variants vs Comprehensive Genetic Testing. "We have to say it loud and clear," Dr. Ackerman said. "If care providers and cardiologists are diagnosing someone with one of the said genetic heart conditions and they aren't doing genetic testing, they aren't practicing standard-of-care medicine."
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