Plakoglobin May Test for Arrhythmogenic Right Ventricular Cardiomyopathy
Last Updated: 2009-03-11 17:07:02 -0400 (Reuters Health)
NEW YORK (Reuters Health) - In endomyocardial biopsy samples, reduced levels of plakoglobin are associated with arrhythmogenic right ventricular cardiomyopathy (ARVC), but not with other forms of heart-muscle disease, and may for the basis of a new diagnostic test.
“The diagnosis of ARVC can be challenging because the clinical presentation is highly variable and genetic penetrance is often low,” Dr. Jeffrey E. Saffitz at Harvard Medical School, Boston, and his team note in the March 12 issue of the New England Journal of Medicine.
ARVC is associated with a high frequency of arrhythmias and sudden cardiac death, and the researchers’ goal is to develop an immunohistochemical test to diagnose the condition at earlier stages than is now possible with imaging studies and clinical workup.
The desmosomal protein plakoglobin links adhesion molecules at the myocardial intercalated disk to the cytoskeleton, Dr. Saffitz and co-investigators explain.
The team conducted immunohistochemical analysis using a single antiplakoglobin antibody on conventional endomyocardial biopsy or autopsy samples from 11 subjects with ARVC, 10 control subjects with no evidence of heart disease, and 5 subjects each with hypertrophic cardiomyopathy, dilated cardiomyopathy, or ischemic heart disease.
The immunoreactive signal levels for plakoglobin were reduced in all 11 subjects with ARVC but in none of the other 25 subjects.
The researchers also conducted a blinded analysis of 30 biopsy samples from an ARVC registry, which, based on clinical criteria, included 11 diagnosed with ARVC, 14 not considered to have ARVC, and 5 considered to be “borderline.”
Plakoglobin signal levels were reduced in samples from 12 subjects, including 10 diagnosed with ARVC, one borderline case, and one case believed to not have ARVC. Five samples were of poor tissue quality that could not be analyzed.
Statistical analysis indicated that plakoglobin testing had a sensitivity of 95%, specificity of 90%, positive predictive value of 91%, and negative predictive value of 95%.
Diffuse plakoglobin reductions even in normal-appearing specimens “suggest that it is not necessary to biopsy the heart in areas showing structural changes in order to diagnose ARVC,” Dr. Saffitz and colleagues say. “A conventional endomyocardial biopsy of the right side of the interventricular septum would reliably show this diagnostic change.”
“Our results are promising in terms of developing a sensitive and specific immunohistochemical test for the diagnosis of ARVC,” they conclude.
Tags: arrythmia, ARVC, cardiomyopathy, plakoglobin, sudden death