Heart of the matter

Genetic testing helps confirm or rule out diagnoses of inherited cardiovascular disease

Mark Deakyne was watching a TV comedy with friends when he started laughing hysterically and uncontrollably. Standing up to get a drink, his heart began racing and he became so lightheaded he felt like he might pass out. Scared, Deakyne didn’t say anything to anyone. 

The incident, however, did not pass unnoticed. Deakyne, who lives in Dubuque, Iowa, was wearing a Holter monitor to track his heart’s electrical activity. After receiving the monitor’s report, Deakyne’s doctor, Ferhaan Ahmad, MD, PhD, called the very next night to strongly encourage Deakyne to have a cardioverter defibrillator implanted to help control the abnormal rhythms. It was a procedure Deakyne had been resisting.

“What doctor calls a patient at 9:30 at night to talk about a notable arrhythmic activity?” Deakyne recalls. “Dr. Ahmad said the cardioverter defibrillator was ‘a good insurance policy.’ Guess who now has an internal defibrillator implanted in his chest?” 

For Deakyne, the episode confirmed his decision two years earlier in 2014 to get his heart care from Ahmad, a cardiologist and associate professor of internal medicine, and the specialized team of providers at University of Iowa Heart and Vascular Center.

At the time, Deakyne, who was very active and an avid RVer who hiked and biked many campground trails, had been diagnosed with the progressive heart disease hypertrophic cardiomyopathy (HCM). He received care at the Iowa City Veterans Affairs Medical Center, where his doctor, also a fellow from UI Health Care, told him about ongoing research into the genetic causes of HCM. Deakyne got tested, which brought him to Ahmad, director of the UI Cardiovascular Genetics Program, one of only a few broad-based cardiovascular genetics programs that currently exist at academic medical centers.

Benefits of genetic testing

Mutations in over a dozen genes are known to cause HCM, a disorder that leads to abnormal thickening of the muscle in the heart, disrupting normal blood flow through the heart. Symptoms of HCM include chest pain, shortness of breath, and dizziness. More seriously, HCM can also cause abnormal heart rhythms that can lead to strokes and sudden cardiac death. 

“The most common benefit of genetic information is that if you identify a pathogenic variant, one that you know causes disease, it means that family members can be screened for the variant to identify people at risk of developing the disease, which allows providers to manage symptoms and reduce the risk of life-threatening complications,” Ahmad says. “Genetic testing can also help confirm a true diagnosis or identify ‘look-alike’ conditions that should be treated differently.”

HCM is just one of a growing list of inherited heart conditions for which genetic information is increasingly used to care for patients. To maximize the benefit to patients and families affected by inherited heart problems, the American Heart Association (AHA) recently recommended the creation of more specialized clinical cardiovascular genetics programs, like the one at the UI, that combine expertise in cardiovascular medicine with expertise in genetic testing and counseling for heart disease.

Test, but also teach

Genetic testing is seldom simple, and using it to improve patient care requires expertise to understand the nuances of the test results and their interpretation as well as the dynamic nature of genetic science. 

“The majority of people come to the clinic thinking testing will provide black-and-white results. But in fact, there is often more of a gray area,” says Maggie Freese, MS, CGC, certified genetic counselor in the UI Cardiovascular Genetics Program. “It is really important that we provide counseling pre- and post-testing to make sure patients understand that results aren’t always definitive, and to explain what the result means.”

Initial analysis indicated that Deakyne had a mutation in the MYH7 gene, one of two genes most commonly associated with HCM. This variant was classified as “likely pathogenic” on the American College of Medical Genetics and Genomics’ five-point scale: pathogenic, likely pathogenic, uncertain significance, likely benign, and benign.

This initial interpretation did not change how Ahmad and his team managed Deakyne’s care, but it did suggest that his family members might benefit from screening for the variant to ensure they were not at risk of developing HCM. However, genetic science constantly evolves, and new information can update understanding of the disease-causing nature of different variants. The variant that Deakyne has was subsequently downgraded to a variant of “uncertain significance,” meaning it is not known if this particular mutation causes HCM.

According to Freese, cases involving uncertain findings occur frequently. Genetic counselors can help clarify what new interpretations of test results mean for patients and help them come to terms with the findings.

“It doesn’t mean Mark’s disease is not genetic, but we still don’t have enough evidence to say what the exact genetic cause is for him,” she says.

Although the genetic test did not identify a causative mutation, Deakyne continues to benefit from a multidisciplinary team with expertise across all aspects of heart care. Recently he started to experience palpitations and painful chest pressure, and these symptoms actually appeared during a clinic visit. Ernesto Ruiz Duque, MD, a fellow training in Ahmad’s clinic at the time and now a heart failure faculty member at UI, immediately ordered an electrocardiogram to determine what was happening. The on-the-spot diagnosis and a simple reprogramming of the implanted defibrillator solved the problem.

“The painful chest pressure has not returned since,” Deakyne says.