By Steve Spencer
Back in the early 2000s when Pankaj Arora, MD was training in population genomics at the Massachusetts Institute of Technology’s Broad Institute, he got his first inkling of the possibilities that genetic testing could do for medicine. “Those were the early days of genome-wide association studies, where we realized that we could scan through the genomes of individuals in an unbiased fashion to look at genetic variations contributing to a disease,” he said.
Years later, he put his vision to work with the founding of the UAB Cardiogenomics Clinic in 2021. The clinic, which is just one of two in the southeast, provides patients with a cardiovascular assessment that includes genetic testing, genomic counseling, and a personalized treatment plan for patients who are at risk of inherited cardiovascular diseases.
“Inherited cardiovascular conditions include abnormally high cholesterol, cardiomyopathy and arrhythmias. Many of these conditions can be managed through screenings, follow-ups, prevention and other treatment options,” said Arora, who serves as director of the Cardiogenomics Clinic.
The clinic sees referral patients from across the southeast, particularly with people who have family histories of heart disease. In many cases, patients receive whole genome sequencing to seek out critical spelling mistakes inside their DNA code, using gene panels to look for specific genetic variations. “There is a gene panel for heart failure and arrhythmias, for early heart attack, and for diseases of the blood vessels,” Arora said.
High blood pressure is determined by a composite of common genetic variations summarized as a polygenic risk score. These genetic risk scores help accurately predict the risk of cardiovascular events in the future which allows the clinic team to tailor the patient’s treatment plan.
Genetic results can lead to other types of treatments, as well. “One common consequence of congenital cardiovascular defects is aortopathy, or dilation of the aorta, when the big vessel coming out of the heart is enlarged,” Arora said. “My surgical colleague Kyle Eudailey, MD and others are interested in us letting them know when this condition in a patient is genetic in etiology so they can operate before it grows too large and leads to fatal outcomes.”
Once the results of the genetic tests are in, the next step is to help patients understand what this means for their cardiac care and help them create a plan. For that, the clinic has two genetic counselors on staff who specialize in translating the complex vocabulary of genetic testing and disease into a language everyone can understand. “We want to help them understand what to do if they have a genetic variation, and how it impacts them, their children, and their significant others,” said Taylor McClinchey, one of the counselors.
Research by the Cardiogenomics Clinic team has uncovered some information that sheds light on different cardiac vulnerabilities between population groups. In a paper published last year in the Journal of the American Medical Association, Arora and co-authors reported that people carrying the Val122lle variation in the transthyretin gene were at significantly higher risk of heart failure and death. Notably, this Val122lle genetic variant is more common among those of African ancestry. Those carrying this genetic variation had a nearly 2.5-fold higher risk of heart failure and a 40 percent higher risk of death from any cause than non-carriers.
In addition to caring for patients, Arora and Vibhu Parcha, MD lead the UAB Cardiovascular Clinical and Translational Research Program, which has created a biobanking effort known as UAB CARBON (for Cardiovascular Research Biobank) that is building a database of de-identified samples to help researchers uncover new connections between genetic variations and heart conditions. Advancing research and bettering the lives of patients and their families is central to the work being done in the UAB Cardiogenomics Clinic. As advances in genetic medicine continue leading to more gene-based therapeutics, the clinic’s value to the community will grow, hopefully leading to better quality of life for people with inherited cardiovascular conditions.