What is a DCM Precision Medicine study, and why have I chosen to be a participant?

In a previous post, I discussed a number of heart failure clinical studies that are ongoing.  These studies seek patients who can participate in efforts to develop advances in heart medications and heart devices.    Researchers also look for participants to help them develop new tests that can aid doctors in the diagnosis of heart failure at an earlier stage, and tests to track the progress of a heart failure patient.
 
In fact, about 10 months ago, I was interested in participating in a study that would determine if the Type 2 Diabetes drug, Farxiga, could be beneficial in the treatment of heart failure.  Alas, one of the qualifications was that the patient must have a blood pressure above a certain level.  If you have been reading my posts for a while, you know that my blood pressure is always very low.  I did not meet the blood pressure qualification and was not eligible for this study.
 

But several months ago, my heart failure doctor advised me that the Heart and Vascular Institute where he practices is participating in what is known as the Dilated Cardiomyopathy (DCM) Precision Medicine Study.  The sponsor for the study is Ohio State University.  He asked me if I was interested, as I appeared to be an excellent candidate.  I said yes. 

As it turns out, the study has been around for quite some time.  It all began with Dr. Ray Hershberger of Ohio State University.  According to the website dcmproject.com, Dr. Hershberger chose this area of research following the 1992 report that 20% of cases of DCM of unknown cause (idiopathic DCM also known as IDC) could be shown to be familial with the clinical screening of family members. This evidence indicated a genetic cause for DCM. 

Dr. Hershberger and his team commenced studying DCM genetics in the Familial Dilated Cardiomyopathy (FDC) Study in 1993. In 2013 the study was renamed the Dilated Cardiomyopathy (DCM) Study.  With the activation of the Precision Medicine Study in 2015 the DCM study was renamed the DCM Discovery Study.  It appears to me that the DCM Precision Medicine Study is a separate and distinct study from the DCM Discovery Study.  But I suspect that the studies benefit and relate to each other, and I believe the original FDC study provided much data so that other genetic studies related to DCM could move forward.

DCM Precision Medicine Study is quit a mouthful.  Let’s break it down to the basic elements.  I have dilated cardiomyopathy (DCM).  Cardiomyopathy is a word that means “disease of the heart.”  What happens to a patient with this disease?  The American Heart Association says:   “Frequently the disease starts in the left ventricle, the heart's main pumping chamber.  The heart muscle begins to dilate, meaning it stretches and becomes thinner. Consequently, the inside of the chamber enlarges. ***   As the heart chambers dilate, the heart muscle doesn't contract normally and cannot pump blood very well. As the heart becomes weaker heart failure can occur.”

What is precision medicine?  According to the Dilated Cardiomyopathy Research Project:  Precision medicine, most simply, is when clinical medicine uses or leverages genetic and genomic knowledge for risk prediction and intervention.  The National Institute of Health defines precision medicine as “an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person”.  

So very simply put, I am participating in a study to see if I have a gene that is the cause of my dilated cardiomyopathy, which in turn led to my heart failure.  Fortunately for me, there was no blood pressure minimum requirement to be eligible for this study.  But there were other eligibility requirements.  Participants had to have a left ventricular ejection fraction of 50 or less.  Since mine is around 15, I met this criteria.  Participants must have a left ventricular enlargement which I do.   

There were also exclusion criteria listed below.  I do not know what some of these criteria relate to, but I do know that I do not have any of them.

• Coronary artery disease (CAD) causing ischemic cardiomyopathy (> 50% narrowing, any major epicardial coronary artery)
• Primary valvular disease
• Adriamycin or other cardiotoxic drug exposure
• Other forms of cardiomyopathy: Hypertrophic, Restrictive, or Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy
• Congenital heart disease
• Other detectable causes of dilated cardiomyopathy, including sarcoid and hemochromatosis.
• Other active multi-system disease that may cause DCM (e.g., active connective tissue disease).
• Severe and untreated or untreatable hypertension (systolic blood pressures routinely greater than 180 mm Hg and/or diastolic blood pressures greater than 120 mm Hg, and if resistant to multidrug treatment).

 
How likely is it that I will be found to have a gene variant that caused my DCM?  According to the brochure on the study that I received from the INOVA Fairfax Heart and Vascular Institute, “variants (changes) in the DNA of several genes can cause DCM.  DCM-causing variants have been found in about 40% of people with familial DCM.  While variants have also been found in individuals without a family history of DCM, the role of genetics in apparently non-familial DCM is unclear.  To help answer this question, the DCM Consortium will conduct the Precision Medicine Study. Our goal is to determine how much of DCM is familial, the genes involved, and how families communicate about this inherited condition. This will help us to better test for DCM so we can predict who may develop it, and ultimately, how to prevent it.”

Each family member who enrolls in the study at a consortium site will have a cardiac check-up that includes a cardiac exam with a doctor, an ECG, an echocardiogram and a blood draw.  However, the blood will not be tested for variant genes unless the blood of the family member with DCM has evidence of a variant gene. 

So you are probably asking, as we did, why the family members have to go through all the cardiac tests if I do not prove to have any variant genes and their blood will not be tested.  According to the brochure the reason is:  “To better understand the genetic cause of DCM, it is helpful to compare results from family members with and without the condition. Because DCM can be present but silent for years, it is difficult to know with certainty if a family member does or does not have DCM unless a cardiac check-up is performed.”

So what will I, as well as other family members, get from participating in the study?  According to the DCM Precision Medicine Study website: 

• By participating in this research study, you may contribute new information, which may benefit patients in the future. We cannot be sure that this study will benefit you or your family directly, but it should improve our understanding of the genetics of DCM and hopefully lead to eventual development of effective treatments or therapies. The analysis of your DNA and/or tissue sample could lead to new information about the nature of your or your family’s condition and the genes involved. This information might be useful in the accurate diagnosis of the disorder, may provide opportunities for early diagnosis and intervention in at‐risk family members, and may lead to insights on how to approach treatment.

I think those are huge benefits.  Looking back on the awful period of not knowing what was causing my blackouts, dizziness and intense bouts of fatigue, I have concluded the opportunity to have an advance warning of heart failure is incredibly valuable.  If I can give that advance warning to my family by participating in this study, I feel I will have given them the most precious gift ever.  Plus insights are always a good thing, especially if they can help the medical community learn how to treat those of us who have heart failure resulting from genetically induced DCM. 

​I suspect that my family members and I are gaining a better understanding of cardiovascular issues in general through answering the questions posed by the study researchers.   I would venture to say that each of my family members will be very committed to make sure that they have their annual physical exams, to include an ECG, right on schedule.  Because it is only through screening and identifying heart and other issues early that we have a fighting chance to defeat these conditions.