Ischemic Cardiac Myocytes Express Membranous CD56 in the Setting of Cardiac Allograft Vasculopathy (CAV): A Potential Predictor of CAV in Endomyocardial Biopsies
Kammi J Henriksen, Anthony Chang, Aliya N Husain. The University of Chicago, Chicago, IL
Background: CAV is an accelerated, diffuse form of coronary artery disease, characterized by concentric intimal proliferation and progressive luminal stenosis, which is a major cause of morbidity and mortality after cardiac transplantation. Since the process primarily affects the large epicardial coronary vessels, a histologic diagnosis cannot be rendered until the time of explant or autopsy. Interestingly, it has been reported that CD56 is upregulated in ischemic cardiac myocytes, and might play a cardioprotective role in metabolic stress. Considering that the development of CAV results in progressive cardiac myocyte ischemia, we hypothesized that the presence and intensity of CD56 expression in post-transplant endomyocardial biopsies might predict the development of CAV.
Design: A retrospective review of autopsy cases was conducted to identify cardiac transplant patients with CAV at the time of death, who had undergone serial endomyocardial biopsies at our institution. Using the archived formalin-fixed, paraffin-embedded tissue blocks, immunohistochemical staining for CD56 was performed on 3-5 serial endomyocardial biopsies and autopsy heart from each patient. Control was autopsy heart without any pathology.
Results: Six patients were identified who had undergone cardiac transplantation (age range 6-57 years) and had serial endomyocardial biopsies over the course of 14 months to 18 years (average: 8 years) prior to death. In 5 of 6 patients, the initial biopsy examined at 3-6 months post-transplantation showed CD56 staining isolated to the intercalated discs, with minimal cytoplasmic or membranous staining. Over time, the cardiomyocytes developed membranous CD56 expression, and eventual membranous and cytoplasmic CD56 as seen in the autopsy specimens. In one control autopsy heart without cardiac pathology, CD56 expression was primarily seen in the intercalated discs.
Conclusions: The detection of CAV in cardiac transplant recipients is heavily reliant on invasive procedures, which are often non-diagnostic. By utilizing immunohistochemical staining for CD56, a marker which is expressed in ischemic cardiomyocytes, we were able to track the progression of ischemic changes in serial endomyocardial biopsies of multiple patients who developed CAV. We propose that upregulation of CD56 expression in post-transplant endomyocardial biopsies might help predict which patients will develop CAV, thus enabling earlier detection and guiding appropriate management.
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 34, Wednesday Afternoon