VIDEO: Using genetics in cardiology to enable earlier interventions

"My work for many years has been to understand genetic basis for heart muscle diseases, in particular cardiomyopathy," Seidman said. "These are devastating disorders, and they are the most common cause of sudden death, in particular on the athletic field when young people die. For years we have understood that these disorders have a genetic cause, and they can run in families."

Her research, and that of other genetic researchers, has been to identify the genetic mechanisms that cause diseases and then develop small molecules that can address the consequences of an abnormal gene to help the function of the heart. She said genetic testing allows cardiologists to intervene earlier before the diseases cause damage to the heart.

"That is a really big accomplishment that has taken scores of investigators, not just me, to be able to have that success," Seidman explained.

Seidman receives AHA's highest honor for scientific research

The same research looking at the mechanisms of genetic diseases also offers an opportunity potentially develop genetic therapies to cure the diseases as well. "There is real promise that we can move from treatment to cure, and that is an amazing opportunity not just for cardiomyopathies, but also for all sorts of disorders that we now recognize have a genetic substrate," she explained.

Seidman said that is really the substance for why she was given the 2022 Research Achievement Award. She accepted the award as a representative of a large group of researchers who have contributed as a team to these discoveries. 

The award is given each year in recognition of outstanding lifetime contributions to cardiovascular research and/or teaching. The AHA said Seidman, along with a team of research scientists in her lab, discovered molecular base of both hypertrophic and dilated cardiomyopathy. Working from this discovery point, she was further able to identify pathways that would allow targeted disease treatment. She identified dominant cell mutations that can be linked to 75% of inherited hypertrophic cardiomyopathy. Using experimental models of human heart cells, she was able to demonstrate how these altered biophysical changes affect outcomes such as increased incidents of atrial fibrillation and heart failure. 

Her work led to the development of mavacamten, a drug that clinical trials have found to be an effective treatment to normalize cell function if they have mutated as a result of cardiomyopathy. The clinical trial results led to the FDA market approval of the drug in May 2022.

Building from her successful breakthroughs in hypertrophic cardiomyopathy, she and her team began the work that would lead to the identification of multiple disease genes that cause inherited dilated cardiomyopathy. Seidman’s work made gene-based diagnostics for cardiomyopathy possible, which makes early intervention possible, delaying the onset of heart failure. Research within her lab is credited for identifying gene mutations in cardiac factors related to congenital heart disease, a condition occurring in 1% of live births.

Real-world implementation of cardiac genetic testing

Numerous genetic tests for cardiac disorders are now commercially available in the U.S. to screen patients, Seidman explained. Most of these tests are covered by insurance, and the ones that are not are offered at a cost of a couple hundred dollars. 

"This enables patients to get early and accurate diagnosis, and that is really key to early interventions and treatments," she said. "For example, we know hypertrophic cardiomyopathy and other cardiomyopathies put people at risk for sudden cardiac death. If we know the people at the highest risk, we can intervene with medicines and devices like implantable defibrillators that can save lives."

Family history is one of the biggest predictors of future events and disease development in other family members, and these tests can be used to cascade test other family members for these genes once problems are detected in a family member.   

A patient with one of these genes has a 50% chance of giving it to their children. She said it also means their siblings have a 50% chance of having the genes as well. 

"We want to find these patients and prevent the bad outcomes, and we have the opportunities to do that today," Seidman explained. "The future is to be able to actually prevent them from getting these diseases, and we are on the cusp of seeing that happen."

She said there is a movement toward more genetic testing, including genetic testing at birth. American guidelines for genetic testing have been very "laissez faire" toward genetic testing, she said. In Europe, guidelines put more emphasis on genetic testing to improve patient screening and prevention. Seidman feels it makes sense to put more weight behind genetic testing because it can help improve patient outcomes.