Researchers at Brigham and Women’s Hospital are investigating genetic drivers of vascular disease to help prevent aortic dissection and aneurysm in patients with a familial risk. Using a simple blood draw, they are testing patients for genetic abnormalities that can cause the often-deadly condition.

“Aortic dissection is one of the most emergent diagnoses we see as cardiologists,” said Rajat M. Gupta, MD, a Brigham cardiologist and member of the Heart and Vascular Genetics Program. “Unfortunately, it is typically diagnosed only after the patient dies suddenly or presents at the emergency department with a ruptured aorta. Quite often, patients and their families are left wondering why it happened to them.”

Until recently, cardiologists had a hard time answering the family’s question of why this happened. It was generally believed that a person’s risk for aortic dissection was based on a mix of genetic and environmental factors. However, with the cost of genetic sequencing dropping significantly over the past five years, more patients and families now can be tested cost-effectively to understand how much genetic factors contribute to a dissection.

Aortic Genetic Testing for At-Risk Families

Through its Heart and Vascular Genetics Program, the Brigham offers aortic genetic testing to patients and their family members who have an observable vascular problem — such as aortic dissection; aortic aneurysm; or an aneurysm in the brain, kidney or other organ — and a family history of vascular problems.

In addition to panel testing done as part of the patient’s clinical care, over the last year the Brigham has made genetic testing available to about 30 families as part of a project funded by a Harvard Medical School/Brigham and Women’s Hospital Khoury Innovation Award. Since familial mutations were found in about five of those families, Brigham’s genetic counselors will have the opportunity to guide family member expectations around risk factors and increase their understanding of the causes of aortic disease.

“As we continue to expand genetic testing, we will identify new mutations that cause aortic aneurysm and dissection,” Dr. Gupta said. “We will also identify the patients who can benefit from whole genome sequencing, which generates much more data and can help identify other types of mutations that increase disease risk.”

From Bench, to Bedside, to Bench

According to Dr. Gupta, offering sequencing to more patients is one thing. Interpreting the results is another. He said findings can be confusing, with variants of uncertain significance. The Heart and Vascular Genetics Program grapples with these mutations daily in the lab, making the Brigham ideally suited to interpret and communicate the implications to patients and their families.

“Clinically, we often move from the bench to the bedside and back to the bench again,” Dr. Gupta said. “Not only do insights from the research lab drive sequencing strategy, but we also take genetic abnormalities from individual patients back to the lab to look for new mechanisms of disease.”

These insights make it possible for Dr. Gupta and his colleagues in the program to speak honestly with patients about what they currently know about a particular genetic mutation and what they may learn in the future with more research.

Interdisciplinary Approach to Optimize Patient Care

According to Dr. Gupta, the Brigham was one of the first academic centers to establish an aorta genetics specialty. He credits Christine Edry Seidman, MD, director of the Heart and Vascular Genetics Program, for leading the Brigham’s research into the molecular basis for genetic cardiac disease and applying that knowledge to the clinical setting, enhancing the care of patients and their families.

Dr. Gupta called Dr. Seidman “an incredible scientist and role model” who has been instrumental in the Brigham’s long history of using genetics successfully for patients with heart failure. He also praised the interdisciplinary nature of the clinic, which includes:

• Genetic counselors who coordinate annual aorta imaging tests and communicate with patients to make sure their questions are answered
• Vascular medicine specialists who manage follow-up care
• Cardiothoracic surgeons who ultimately will intervene if an aortic loop replacement is needed

The Brigham’s leadership and expertise in research, genetic counseling and the interpretation of genetic sequencing results offers hope to families who have a condition without a cure.

“Because we currently don’t have any therapies to eliminate the risk of aortic dissection, early diagnosis is the best key to prevention,” Dr. Gupta said. “The families we treat are extremely motivated to participate in genetic testing.”