There’s been increasing recognition that our genetic background plays an important role in heart disease, specifically disease that affects the heart muscle and heart rhythm. Over the past 25 years, research that has been pioneered at Brigham and Women’s Hospital, particularly by the Seidman Research Laboratory, has helped to foster the development of the field of cardiovascular genetics.
The Cardiovascular Genetics Center is composed of a multidisciplinary team of physicians, scientists, genetic counselors and nurses, all working together to provide the best possible care to patients and families with inherited heart disease. Also, to bring genetics to medicine, to translate the discoveries from basic science to clinical medicine and to clinical practice.
An important, distinguishing feature of genetic or inherited disease, including inherited heart disease, is that instead of focusing on care for an individual patient, care must extend to their family as well. So if you are related to a person that has genetic heart disease, you may also be at risk for developing that same condition.
In the Cardiovascular Genetics Center we see patients and families with a variety of different, potentially genetic or inherited heart conditions. That includes hypertrophic cardiomyopathy (HCM), familial dilated cardiomyopathy, inherited arrhythmias, inherited sudden death, Marfan syndrome and other diseases that affect the aorta along with other, less-defined conditions with a genetic or familial basis.
Hypertrophic cardiomyopathy is one of the diseases that we really focus on in the Cardiovascular Genetics Center. It is an inherited cardiomyopathy or an inherited heart muscle disease where the heart muscle becomes too thick or hypertrophied. The groundbreaking research conducted at Brigham and Women’s Hospital back in the 1980s and 1990s led to the discovery that mutations, or changes in the DNA sequence, and the genes that make up a structure called the sarcomere actually cause hypertrophic cardiomyopathy. HCM is one of the most common genetic heart diseases. It’s present in about one in 500 to about one in 1,000 people in the general population.
The manifestations of HCM can be highly variable. It can range from patients who have no symptoms at all to those who have severely limiting symptoms or life threatening arrhythmias. Most people with HCM do very well. They have manageable symptoms and live a normal life expectancy. But there can also be very serious consequences. For instance, patients with HCM are at higher risk for suffering sudden cardiac death and having dangerous arrhythmias than people in the general population. And there is also a subset of individuals with HCM who can develop refractory heart failure and need either heart transplantation or, unfortunately, develop end-stage heart failure.
We also need to remember to care for their family as well. So we usually start with the closest or the first-degree relatives related to the patient that’s been diagnosed with HCM. So that means their parents, their siblings and their children also have about a 50 percent risk of having HCM as well. Because HCM can develop at any time in life, it’s important not to just have a one-time evaluation but to follow people over time to see if manifestations can develop as people grow older.
Genetic testing can now be done to identify the cause of disease in a particular family. So with genetic testing we start with the person in the family that has the most clear diagnosis of disease. Ideally, we start with a family member that has the most serious consequences.
At times we can find changes in that person’s DNA or mutations in their DNA that we are quite confident causes the disease in question. And if that’s the case, then we have been able to establish the genetic cause of the disease in that family. We can also extend a much more focused type of genetic testing to their family member.
Genetic testing and interpreting the results of genetic testing appropriately can be very complicated. The results are oftentimes ambiguous and therefore it’s important to make sure that the family really knows what they are getting into so they can understand the potential benefits of genetic testing as well as the limitations and the implications for the whole family. So it’s important that genetic testing be pursued in collaboration with genetic counselors who can have these detailed conversations with patients.
Right now treatment is only available to try to mask or palliate symptoms of HCM. We don’t currently have any treatments that can fundamentally change how the disease develops or to prevent its development.
We recently finished a pilot, clinical trial where we targeted relatives of patients with HCM that were known to carry the mutation that causes HCM in their family but have not yet developed clinically diagnosable changes in their heart. We randomized them to receive either diltiazem or a placebo agent for anywhere from one to three years and looked to see if there were any changes. There were hints that it may be able to subtly improve some of the early changes in heart structure that are present early in the development of HCM.
And so with this information and with new experiments in the basic science laboratory, we’re now in the process of leading a bigger clinical trial, partnering with other HCM centers in the US and Canada to study this strategy of disease modification.
When patients come to our center we will give them the best possible clinical care as well as the potential to be involved in cutting edge research where we’re really trying to translate these basic science discoveries to clinical medicine.