Director, Cardiovascular Genetics Center, Brigham and Women’s Hospital
Thomas W. Smith, Professor of Medicine and Genetics, Harvard Medical School
Genes and Heart Failure
We've known for a long time that some families appear to have too many types of heart diseases than occur in the general population. That increase within a family makes us think that there is a genetic underpinning or cause for their heart disease. Over the years, my research group has been very involved in finding these families and understanding the cause of this increased rate of heart disease within their particular family. We now know the cause is due to a change in the DNA structure or the genes that encode important proteins that are made in the heart.
Diagnosis and Treatment of Genetic Heart Disease
Here at Brigham and Women's Hospital, we were one of the first institutions around the country and around the world to pioneer the diagnostic testing of patients who are at risk for genetic forms of heart disease, including hypertrophic and dilated cardiomyopathies. From a simple blood test we can now determine if an individual has one of these very damaging variants in their genetic material. If they do, we can help them to recognize the likelihood that they will develop that condition or not and we can intervene.
For example, my colleagues in the subspecialties of arrhythmias have devices and medications to prevent arrhythmias. Our colleagues in imaging have the opportunity and capacity to identify individuals who are at increased risk for their heart muscle to fail and we have treatments that can reduce those risks even though we have not directly addressed the genetic cause of the disease.
For some cardiomyopathies, in particular hypertrophic cardiomyopathy, the disease thickens the heart muscle in a way that really inhibits normal blood flow out of the heart and to all of the organs. We can treat that in two ways. We have a superb group of cardiothoracic surgeons who can remove a small piece of that tissue and improve the flow of the blood and reduce symptoms quite dramatically or we can do a less invasive procedure through the cardiac catheterization laboratory.
In addition, in people who have dilated cardiomyopathy, we know that their heart function is reduced and sometimes they need additional support. We can introduce an assist device to have their heart pump more normally and allow them to go on with their daily living activities. In extreme cases we can do cardiac transplantation. Both of those treatments are available here at Brigham and Women's Hospital by highly skilled and really dedicated physicians.
Reducing Risk of Heart Disease in Family Members
Traditionally, when we recognized that a person had heart failure, we would take care of that individual alone. Today, when we know that there's a genetic cause for their heart condition, we can begin to ask whether other family members are also at risk for the condition; in particular, the patient's sisters, brothers, and their children. The reason that's important is that sometimes we can recognize that the first presentation of a disease could be quite devastating, an arrhythmia, a heart attack, a stroke, a sudden death event. If we know that an individual is at risk for a condition even if they don't have symptoms, we have the capacity to intervene and to prevent those very devastating events.
The other reason why it's important is that we know that lifestyle definitely impacts the way in which our heart responds. In many instances, some very simple preventative measures are very beneficial. For example, we know that adverse events are more common to occur when people are very strenuously exercising, such as occurs in competitive athletics. And so for young people at risk for these conditions, we sometimes don't allow them to participate as vigorously in competitive sports as we do others.
Genetic Heart Disease Research
There's a lot of work going on in the research laboratories of Brigham and Women's Hospital. Our goal is ultimately to not only define the genetic variants that cause these diseases, but to understand the mechanism and to find new treatments that will directly take care of the problems that are caused by these genetic variations. We've been able to do that by building prototypes of molecules that prevent some of those processes from reducing heart function. Those are now being spearheaded through the development of targeted therapies that are specific for genes that are altered by mutations. These treatments aren't yet widely available, but the progress that's been made in the past four to five years is absolutely phenomenal. Within the next couple of years, clinical trials will begin to really understand if these molecules can prevent the development of disease or delay the progression of these genetic forms of heart disease.