Defusing a time bomb
Dr. Brenda Gerull gives teenagers and others who are at risk for a particular heart disorder a chance for longer life
Story by Sheelagh Matthews/Photo by Veer
Serious heart diseases can come as a surprise or appear slowly over a lifetime. In some cases, the younger the patient, the more sudden and severe the onset can be. We tend to picture teenagers as bundles of energy who empty out the refrigerator, sleep until noon on Saturdays, and hang out with friends at every other possible moment. But some teens have a different story. Some have to undergo heart surgery to get an implant that could save their lives. AHFMR Clinical Investigator Dr. Brenda Gerull’s research on the genetics of a debilitating form of heart disease provides teens and their parents, as well as patients of other age groups, information that can help them make difficult decisions on how to proceed.
Dr. Gerull investigates the genetic causes and underlying molecular mechanisms of heart muscle disorders (cardiomyopathies) with a strong genetic component, particularly those that result in irregular heart beats (arrhythmias). She is most interested in a disorder known as arrhythmogenic right ventricular cardiomyopathy (ARVC). As its name implies, ARVC predominantly affects the right ventricle (chamber) of the heart. During the course of ARVC, fibrous fatty tissue builds up in the heart muscle of the right ventricle. This impairs the function of the heart muscle, which can cause arrhythmia and poor cardiac performance characterized by ventricular tachycardia (rapid heart beats) and heart failure. People with ARVC are at increased risk of sudden cardiac death, even young people like teenagers.
To prevent sudden cardiac death from ARVC, an electrical device called an internal cardiac defibrillator is implanted in the heart, and patients must live with it for the rest of their lives. According to Dr. Gerull, when a teenager shows such symptoms as rapid heart beats (even while resting) and fainting (especially during exercise), ARVC is likely the culprit.
Although ARVC can affect people of all ages, it is an especially difficult decision to put such a device in to the heart of a young person, as participating in sports and other exercise activities will be severely limited or no longer possible. Because of the implications the treatment has for a patient’s lifestyle, the decision is easier to make if there is genetic confirmation that the patient actually has ARVC; this is particularly true for teenagers.
The trouble is that not all patients with ARVC have the same symptoms, and not everyone who carries the gene will develop the disease. Dr. Gerull’s research demonstrated that ARVC is caused by genetic mutations that result in abnormal cellular junction proteins. Cellular junctions are mechanical structures that hold beating heart cells together, preventing them from tearing apart. Considering an average, healthy human heart beats about 70 times a minute—or about 100,000 times a day—that’s a lot of mechanical strain. But we still don’t know how the mutated junctional proteins cause the heart failure and sudden death seen in ARVC. Dr. Gerull is investigating just that.
Accelerating her efforts is what Time Magazine named the 2008 Invention of the Year: the retail DNA testing service 23andMe, co-founded by Anne Wojcicki and Linda Avey. This test analyzes individual genomes at a very low price, making it possible for Dr. Gerull to include in her study the genetic information of her patients and their family members. (A genome is all the genetic information in an organism’s chromosomes.) The test will also allow Dr. Gerull to genetically confirm that a patients has ARVC.
A newcomer to Calgary, Dr. Gerull was raised, educated, and worked as a cardiologist in Berlin, Germany. She was attracted to the University of Calgary because of the opportunities she had to conduct translational research there. Translational research, often called “bench-to-bedside” research, bridges the gaps between a researcher’s work in the lab (at the “bench”) and a clinician’s application of this knowledge when treating patients (the “bedside”).
After arriving in Calgary at the beginning of the Calgary Stampede in 2009, one of the first things she bought was a new pair of cowboy boots to wear to work. Since her first week in Cowtown, Dr. Gerull has concentrated on setting up her lab and assembling her team at the new, state-of-the art Health Research Innovation Centre located in the Foothills Medical Centre. Dr. Gerull hopes her research will, one day, be used as a model to study what causes arrhythmias, which are a common feature of many heart diseases, and to help develop new ways to diagnose and treat them.