In their quarter-century campaign to accurately diagnose one of the most mysterious causes of sudden cardiac death, scientists are closing in on their quarry with the aid of improved genetic screening. “In many cases,” says cardiologist Hugh Calkins, “we can now pin it down.” One of every 5,000 people has arrhythmogenic right ventricular dysplasia, or ARVD. Its presence too often becomes clear only after an autopsy reveals telltale signs of the condition, such as a severely dilated right ventricle whose walls are thinned and replaced with fibro-fatty tissue. While getting an accurate early diagnosis can avert deaths in affected people, the condition’s genetic links also give it a ripple effect: A third of an afflicted person’s children will likely get it. That link further magnifies the value of accurate early diagnosis. Confirmed cases can trigger prudent family-wide screening, but cases that are merely suspected can bring unnecessary worry and, worse, unnecessary treatment that often includes an implanted device. |  |
The concern is no minor detail. Calkins describes one recent study that scrutinized cases of reported ARVD in which patients were treated. After an elaborate battery of tests using the full gamut of established criteria, most of the suspected diagnoses proved incorrect.
The process of diagnosing ARVD has always been taxing, says Calkins, who has been immersed in the chase for eight years and now heads up a team of 10 specialists here. The current criteria include various combinations of six different factors, ranging from the major dilation of the right ventricle (reducing ejection fraction) to EKG readings that show arrhythmias characterized by inverted T waves in the right precordial leads.
While a family history of ARVD is obviously a strong indicator, Calkins, who serves on a task force charged with revising the condition’s diagnostic criteria, says one genetic mutation has recently come to the fore—in a protein known as plakophilin-2. Calkins says this PKP2 error is associated with up to 45 percent of ARVD patients.
What’s more, Calkins adds, is that patients with PKP2 are also more likely to develop ARVD at an early age, which hints at the condition’s especially tragic distinction—its disproportionate toll on young athletes.
ARVD is responsible for 5 percent of sudden cardiac deaths in young people in the United States, and it is often the culprit behind the abrupt collapses of athletes at the height of competitive performances. Calkins says this is due to the natural dilation of the heart during exercise, which pushes an undiagnosed ARVD patient’s already enlarged right ventricle past its pumping capacity.
If ARVD is caught in advance, patients are advised against strenuous activity. Their arrhythmias can be temporarily relieved with ablation therapy, but Calkins says the more optimal long-term solution currently resides with the implantation of a defibrillator, which can detect and correct dangerous arrhythmias whenever they strike.
Calkins hopes the revised criteria for ARVD will be published in early 2008.