Researchers Identify Protein for Early Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy

Investigators at Beth Israel Deaconess Medical Center (BIDMC) have developed an immunohistochemical test to diagnose arrhythmogenic right ventricular cardiomyopathy (ARVC).

Several years ago, the team discovered that a desmosomal protein known as plakoglobin was diminished in tissue samples of ARVC. In the current study, the authors determined that a reduced plakoglobin signal serves as an early biomarker for ARVC.

“ARVC has been linked to genetic mutations in proteins that form desmosomes, subcellular structures responsible for cell-to-cell adhesion,” explains Jeffrey E. Saffitz, M.D., Ph.D., chairman of the department of pathology at BIDMC. “In many individuals, ARVC has no symptoms or warning signs, meaning that the first and only manifestation of disease is sudden death,”

After ascertaining that the protein was indeed diminished in cases of ARVC and not in other types of heart disease, the scientists performed blinded immunohistochemical analysis of heart-biopsy samples, obtained from an ARVC registry located at Johns Hopkins University School of Medicine.

“On the basis of clinical criteria, we made the correct diagnosis in 10 of 11 subjects with definite ARVC and correctly ruled out ARVC in 10 of 11 subjects who did not have the condition,” says Saffitz. “There was no question that the plakoglobin signal level was reduced diffusely in the ARVC samples.”

Previous studies have found that MRI electrocardiography and echocardiography accurately identifies patients with advanced AVRC, but those tests are much less sensitive for patients with earlier or less conspicuous disease. Beth Israel Deaconess Medical Center has filed patents covering methods of diagnosing ARVC.

The report appears in the March 12 issue of The New England Journal of Medicine.