New Test May Identify Deadly Cardiovascular Disease

Researchers at Beth Israel Deaconess Medical Center have discovered a new diagnostic test for a severe heart condition that now often goes undetected before causing sudden death.

Before the study, scientists had not been able to formulate an effective way to identify the disease, known as Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), until it progressed to deadly stages.

“This is a disease, more than any other we know of, where the risk of dying suddenly is the greatest,” said Jeffrey E. Saffitz, one of the authors and a professor of pathology at the Medical School.

Often the first and only manifestation of the disease is when an individual “drops dead,” only to be diagnosed with ARVC at the autopsy, Saffitz said.

Since the disease runs in families, the test will likely serve shocked relatives wanting to know whether they are also at risk.

Previous diagnostic tests relied on characteristic changes that occur when the disease is already far advanced, at which point the patients are near death or require a heart transplant, Saffitz said.

The new diagnostic test consists of obtaining a sample of tissue from a heart biopsy and then looking for a specific protein that the researchers found exists in smaller quantities in patients with ARVC, said Angeliki Asimaki, the study’s lead author and a research fellow at the Medical School.

Most of the mutations that cause ARVC are in genes encoding components of a type of cell junctions called “desmosomes,” which are particularly abundant in tissues that experience great mechanical force, such as the heart.

The Beth Israel researchers showed that one desmosomal protein—plakoglobin—turned up in lower quantities in the tissues of ARCV patients.

“We then needed to know whether this result was confined to our samples, if it is specific for this disease, and then if it can be used for diagnosis,” Asimaki said.

The researchers found that every sample from a patient with ARVC had less plakoglobin and that in other types of heart disease plakoglobin was normal.

“It appears that this diagnostic approach is specific and sensitive,” Asimaki said. “It also appears that this test will show us the protein is expressed even when the disease has progressed very little.”

Although the test will involve a heart biopsy, the researchers believe that cardiologists and patients will be more willing to undergo the procedure if they believe a clear-cut diagnosis can be made, said Saffitz.

“We are hoping it may lead not only to diagnosis of ARVC but also treatment in the near future,” said Shiva P. Gautam, one of the authors and an associate professor at the Medical School.

—Staff writer Alissa M. D'Gama can be reached at adgama@fas.harvard.edu

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