Researchers at the University of Rochester School of Medicine and Dentistry are part of a team that received $9 million from the National Institutes of Health to study a group of heart muscle disorders that account for up to 20 percent of cases of sudden death in young people. Called arrhythmogenic ventricular cardiomyopathies or AVCs, they run in families and are frequently diagnosed in athletes. Genes are responsible for approximately 40 percent of cases, but what’s behind the remaining 60 percent remains a mystery.
The Rochester team, led by Wojciech Zareba, M.D., Ph.D., professor of Cardiology and director of the University’s Heart Research Follow-up Program, will receive $2.9 million for their contributions to the study. They’ll join physicians and scientists from the University of Cincinnati, University of Arizona, University of Colorado and Harvard University in searching for new genes that cause AVCs and biomarkers that can help physicians better identify and treat these notoriously hard-to-diagnose disorders.
Zareba describes AVCs as diseases of cardiac glue. In a healthy heart the “glue” keeps the muscles together and ensures they work in a central way, allowing the heart to pump blood throughout the body. In an AVC patient the glue is missing and the muscle tissue is loose and in disarray. The result is uncoordinated muscle contractions that cause arrhythmias – irregular and potentially fatal heart rhythms – and hamper the heart’s pumping action, which is a sign of impending heart failure.
Unlike most forms of heart disease, AVCs strike young patients, with a peak appearance in the mid 30’s. Many athletes who die suddenly have a form of the disease, and animal models have confirmed that it is triggered by exercise: In mice with an established AVC gene, those that exercised on a running wheel showed clear signs of disease while those that were sedentary did not experience any changes or symptoms. In a past study by Zareba of 143 AVC patients, 45 percent were very active individuals.
Zareba says AVCs are a rare but underappreciated group of disorders. In Europe they are considered the third greatest reason for sudden death in people below the age of 65 and the fourth in the United States. All patients get an implantable cardioverter defibrillator or ICD – a device that detects potentially fatal arrhythmias and shocks the heart back into a normal rhythm – and are encouraged to abandon competitive sports. There is no other treatment at the moment – something the group hopes to change with their new study.
Zareba believes the study’s greatest importance lies in the fact that it might help physicians and scientists better understand more common cardiomyopathies – any weakening of the heart muscle that keeps it from pumping blood as well as it should. Cardiomyopathies often develop following a heart attack and are found in most patients with heart failure. According to the American Heart Association, about 5.1 million people in the United States have heart failure.
The study includes ten enrolling centers across the country and Spencer Z. Rosero, M.D., a practicing cardiologist at UR Medicine’s Strong Memorial Hospital, will enroll patients from Rochester and surrounding areas. Researchers will evaluate more than 1,000 patients with arrhythmogenic cardiomyopathies in the study. Zareba’s team is also in charge of the database that will house all patient data, the assessment of patient electrocardiograms and arrhythmia activity and the final analysis when data collection is complete.
In addition to Zareba, study principal investigators include Jeffrey Towbin, M.D., University of Cincinnati, Frank Marcus, M.D., University of Arizona, Luisa Mestroni, M.D., University of Colorado, and Jeffrey Saffitz, M.D., Ph.D., Harvard University. Under a previous NIH grant, this group conducted a successful study that led to new and improved diagnostic criteria for AVCs and the identification of genes that account for about 40 percent of cases.