5 minute read
The Power Of Knowing: How SickKids Is Shining New Light
THE POWER OF KNOWING:
How SickKids Is Shining New Light on ARVC
In fall 1990, 20-year-old Heather Cartwright was rowing in the annual regatta at Trent University in Ontario, Canada. She was in the best shape of her life. She’d been training all summer and had her sights on making the national team someday. But in the final thousand meters of the race, Heather’s body started to shut down. She could hardly see. She was dizzy. Her legs went limp. As the boat crossed the finish line, she was slumped over her oar, barely conscious.
(L-R) SIBLINGS BRIAN, MEREDITH AND HEATHER CARTWRIGHT. MEREDITH AND HEATHER WERE BOTH DIAGNOSED WITH ARVC AFTER EXPERIENCING A MAJOR CARDIAC EVENT. BRIAN IS BEING TESTED YEARLY. TOGETHER, THEY SUPPORT ARVC RESEARCH AT TORONTO’S HOSPITAL FOR SICK CHILDREN AND TORONTO GENERAL HOSPITAL.
At the local hospital, Heather was stabilized and told she’d had an exerciseinduced tachycardia, meaning her heart rate had become so fast it couldn’t pump blood to her body. It wasn’t a diagnosis but a symptom of something more serious. At the time, her cardiologist didn’t know exactly what.
As a young athlete in her prime, Heather thought her collapse was a fluky symptom of overexertion. “I thought I was healthy, I thought I was fine,” she remembers. “I thought the problem was to be easily explained and easily fixed.” But it was neither. It would take four years for Heather to get a diagnosis: arrhythmogenic right ventricular cardiomyopathy, or ARVC, a rare, hereditary heart disease that the medical community had only just officially defined.
The main feature of ARVC is frequent arrhythmias, spells of erratic or fast heartbeats that, if severe enough, can cause cardiac arrest and sudden death. The symptoms are brought on by intense exercise, so athletes are disproportionately affected. As this story was going to print, Danish soccer player Christian Eriksen was revived with a defibrillator after collapsing inexplicably during a Euro Cup match, a chilling scene that looks a lot like an arrythmia-induced cardiac arrest.
“This disease kills suddenly and unexpectedly,” says Heather. “Seemingly healthy, athletic, happy kids who are just out on a soccer field or in a hockey rink or on a basketball court or on a rowing course.”
But this shadow may be lifting. With help from donors like Heather and her family, researchers at Toronto’s Hospital for Sick Children (SickKids) are casting
DR. HAMILTON AND KEY MEMBERS OF HIS LAB TEAM, DIPTENDU CHATTERJEE AND MEENA FATAH
new light on ARVC and exposing this once-invisible disease.
It’s estimated that 80% of people with ARVC are undiagnosed. Many people die of the disease, not knowing they had it. Unless you have a known family history, you wouldn’t necessarily think to get tested. Even if you do, the process is arduous and not always definitive. It requires a detailed series of clinical tests every year: MRI, ECG recordings, an exercise stress test, blood work. Heather’s brother Brian has been getting the full workup every year for several years (so far, so good). His daughter is six—too early for ARVC to show up in the clinical tests.
“The tests are probably only about 70% sensitive,” says Dr. Robert Hamilton, cardiologist and researcher at the Labatt Family Heart Centre at SickKids. “Unfortunately, there's no perfect gold standard for the disease, and we think we’re probably missing 30%.”
Even with the discovery of ARVC gene mutations in the last 20 years, genetics only accounts for roughly 60% of ARVC patients. Heather’s sister Meredith had tested negative for the known genes, but a few years later, she landed in the hospital after a major cardiac event. She, too, was diagnosed with ARVC.
The most common ARVC mutations affect the proteins that make a structure called a desmosome. “This holds heart muscle cells together at their ends, very much like a hitch on a train,” says Dr. Hamilton. “If you can think about a hitch being made up of several different pieces of metal, if any one of those pieces of metal are deformed, then that hitch may be weak and allow the train cars to separate.” When these cells separate, they’re replaced by scar tissue and fatty deposits, which affect how well the heart pumps and weaken the electrical connections between cells, thought to cause arrhythmias.
In 2013, Dr. Hamilton learned about a group of skin-blistering diseases called pemphigus caused by autoantibodies, immune proteins that mistakenly attack the body’s own tissue. In pemphigus, autoantibodies attack the desmosomes in the skin, causing blistering and rashes. “So I really got to thinking maybe there's an autoantibody to the heart's desmosome,” says Dr. Hamilton. “And we went searching for that.”
Dr. Hamilton and his team began testing blood samples of their ARVC patients. They were astounded to discover that every single sample had the autoantibody. “It didn't matter whether you had a gene cause or not, or whether you even knew which gene it was,” says Dr. Hamilton. This simple blood test result was the strongest, clearest indication of ARVC out there. It also identified the trigger of the disease: autoantibodies attacking desmosomes in the heart.
Being able to easily and accurately detect ARVC will no doubt save countless lives. Sudden death is rare among people who’ve been diagnosed. They can be monitored, educated about exercise, and if needed, fitted with an implanted defibrillator. Family testing could be expanded and easily deployed anywhere in the world. Dr. Hamilton and his team aim to have a clinical test within two years, so hospitals and commercial labs everywhere can include the ARVC test in routine blood work.
Implicating autoantibodies in this heart disease and others like it will likely lead to their classification as autoimmune diseases (along with genetic), which opens up all kinds of new treatment directions already in use.
In their lifetimes, Heather and Meredith, who already have their diagnosis, might be able to receive a treatment that stops the autoantibodies from doing more damage to their hearts. Their brother Brian may know quickly and definitively if his young daughter has ARVC. The next generation of Cartwrights—and scores of other affected people—will have the power of knowing.
To learn more about ARVC research and the Cartwrights’ powerful story, listen to the SickKids VS podcast episode:
