Promises to make diagnosis simpler for disease than can strike younger adults
Researchers are reporting a promising new test for quick diagnosis of a rare but potentially deadly heart condition that is a leading cause of sudden death in young people.
The disease is arrhythmogenic right ventricular cardiomyopathy (ARVC), in which a genetic flaw causes the muscle cells of one of the heart’s main pumping centers to be replaced by fatty deposits. The end result can be a sudden loss of regular heartbeat that is often fatal.
ARVC affects about one in 5,000 people worldwide, said study senior author Dr. Jeffrey E. Saffitz, chairman of pathology at Beth Israel Deaconess Medical Center in Boston. “Most cardiologists with active practices have seen cases of it,” he said.
ARVC is more common in Mediterranean populations. It is the leading cause of sudden cardiac death among Italians under the age of 35, according to background information in the study, published in the March 12 issue of the New England Journal of Medicine.
Diagnosis of ARVC now requires a battery of tests, including an electrocardiogram, an echocardiogram and a magnetic resonance imaging procedure, Saffitz said. But with all those tests, “you have to have pretty advanced disease for it to show up,” he said. “People who have the disease that is not advanced and not overtly manifest are still at risk of sudden death.”
The new test looks for abnormally low levels of a protein called plakoglobin, an essential component of the structures that bind heart cells together so they beat in rhythm. Laboratory studies by Saffitz and his colleagues identified low levels of plakoglobin as a possible marker for ARVC, and the new study was designed to verify that possibility.
It did — comparing heart tissue biopsies from 11 people with ARVC and 10 people with no heart disease. “All ARVC samples but no control samples showed a marked reduction in immunoreactive signals for plakoglobin,” the journal report said.
Once the condition has been diagnosed, it can be treated by implanting a defibrillator to maintain a normal heartbeat.
The test is still being validated in an international research network, but “at some point in the relatively near future, we expect to apply to the U.S. Food and Drug Administration for its use as a clinical test,” Saffitz said. That application will be made “in the next year or so,” he said.
ARVC usually is the result of an inherited genetic mutation. But about a third of cases occur in people with no family history but who have a mutated form of the plakoglobin gene, Saffitz said.
Candidates for the test include young people in a family where someone has been diagnosed with the condition, Saffitz said, but also “young people who have signs or symptoms of arrhythmia, who pass out and recover, who often feel lightheaded and go to a primary care doctor because of that.”
Family doctors usually refer such people to large medical centers, where the current battery of tests can be done, Saffitz said. “Many will not have ARVC,” he said. “It would be useful to have a simple test that can help decide whether they have it or not.”
Dr. Frank Marcus, professor emeritus of medicine at the University of Arizona and an authority on ARVC, said, “I have been following this work carefully and am most enthusiastic about the possibility of making an accurate diagnosis in this disease, which has been very difficult to diagnose with a high degree of certainty.” Marcus was a leader of the group that first described the condition in 1982.
Obtaining a tissue sample from the heart is “an invasive procedure with a small but definite risk,” Marcus noted. “Nevertheless, if the results can be confirmed by others or by these investigators in a larger series of patients in the early stages of the disease, it would be a significant medical advance,” he said.