Study Shows Increased Genetic Burden in Advanced Dilated Cardiomyopathy and Heart Failure Risk to Families.

New research published in Circulation and led by the MedStar Heart and Vascular Institute has demonstrated the benefits of routine genetic testing for patients with advanced heart disease from dilated cardiomyopathy.  

A five-year cross-sectional study led by MedStar Heart & Vascular Institute has found that a diverse group of patients with advanced heart disease due to dilated cardiomyopathy (DCM) were nearly 2.5 times more likely to have a disease-causing genetic variant.

DCM is one of the most common causes of heart failure, affecting almost 400,000 people in the U.S. in 2019. It is rarely subject to clinical genetic testing, often due to barriers including cost and stigma. 

DCM is a progressive disease in which the heart muscle becomes enlarged and less effective at pumping blood. Symptoms can include shortness of breath, fatigue, swelling of the legs and feet, and irregular heartbeat. DCM can lead to heart failure or sudden cardiac death.

The DCM Precision Medicine Study demonstrates the benefits of routine genetic testing for patients and their families. Our researchers examined the genetic profile of patients with advanced DCM to learn whether we could identify a genetic variant that might be passed down to family members. 

First-degree relatives and heart failure risk.

The DCM Precision Medicine Study involved 25 leading academic U.S. heart failure and heart transplant programs in the Dilated Cardiomyopathy Consortium. We analyzed clinical and genetic sequence data from 1,265 patients with advanced DCM.

For analysis, these patients were divided into three groups:

• Patients who had a heart transplant or a pump called a left ventricular assist device (LVAD)
• Patients who had a pacemaker or defibrillator
• Patients with advanced heart disease and no transplant or device

Among the transplant/LVAD group, 26% of patients had genes we could identify as pathogenic or likely pathogenic. In both other groups, just 15% of patients had pathogenic genes we could locate.

After statistical analysis controlling for factors such as demographics, social determinants of health, and medical issues, our research revealed that patients with an LVAD or transplant had nearly 2.5 times greater likelihood of a pathogenic or likely pathogenic variant. 

While our cross-sectional study was short-term, these findings indicate that first-degree relatives of people with advanced heart failure from DCM, such as siblings and children, are much more likely to be at risk of heart failure and even sudden cardiac death. 

Related reading: A “Nearly Indestructible” Man Gets a New Heart.

The importance of diversity in this research.

This study was unique because 42% of our participants were of African ancestry, and 44% were female. Most genetic information scientists have studied before now comes from patients of European ancestry, so we were eager to diversify our participants. 

Most of the human genome has roots in Africa, yet structural racism, social and economic barriers, and generational trauma place obstacles between historically minoritized communities and access to clinical trials. The DCM Precision Medicine Study needed to include the broadest possible cross-section of patients, and by design included patients who identified as African ancestry and Hispanic ethnicity.

At MedStar Health, we conducted a simple feasibility study and found that almost all our minority patients were interested in participating in this genetic study and recruiting family members to help. Along with participation from the Dilated Cardiomyopathy Consortium at 25 sites, this study features ancestral, gender, and geographic diversity to cast a wider net and enroll more patients. 

Got risk? Get screened.

Our research reveals the value of targeted screening programs for families of patients with DCM. 

If your family member has DCM at any stage, we know you may have a higher genetic risk, so your screening recommendation will change. You should receive an echocardiogram and EKG annually if you are younger than 20, with decreasing frequency as you age if the disease does not develop. 

Now that genetic testing is more affordable and widely available, family members of patients with DCM should speak with their doctor about screening. Early detection is always best. Patients can often begin taking medications when their disease is mild to help blunt the progression of disease with the aim to avoid progression to advanced heart failure. 

These results are exciting, and they’re just the beginning. Our next steps involve broadening our research. Currently, there is little data on the genes of people of Asian ancestry and genes from large portions of the African subcontinent. In the U.S., people of Hispanic ancestry are a large and growing population with a diverse ancestral genetic background that is critical to our understanding of the human genome. 

By involving more people in genetic research, we may be able to help develop early treatment for diseases like DCM that can help all of us lead healthier, longer lives.