Background
Coronary angiography remains the most widely used tool for routine screening and diagnosis
of cardiac allograft vasculopathy (CAV), a major pathologic process that develops
in 50% of cardiac transplant recipients beyond the first year after transplant. Given
the invasiveness, expense, discomfort, and risk of complications associated with angiography,
a minimally invasive alternative that is sensitive and specific would be highly desirable
for monitoring CAV in patients.
Methods
Plasma proteomic analysis using isobaric tags for relative and absolute quantitation–matrix-assisted
laser desorption ionization double time-of-flight mass spectrometry was carried out
on samples from 40 cardiac transplant patients (10 CAV, 9 non-significant CAV, 21
possible CAV). Presence of CAV was defined as left anterior descending artery diameter
stenosis ≥ 40% by digital angiography and quantitatively measured by blinded expert
appraisal. Moderated t-test robust-linear models for microarray data were used to identify biomarkers that
are significantly differentially expressed between patient samples with CAV and with
non-significant CAV. A proteomic panel for diagnosis of CAV was generated using the
Elastic Net classification method.
Results
We identified an 18-plasma protein biomarker classifier panel that was able to classify
and differentiate patients with angiographically significant CAV from those without
significant CAV, with an 80% sensitivity and 89% specificity, while providing insight
into the possible underlying immune and non-alloimmune contributory mechanisms of
CAV.
Conclusion
Our results support of the potential utility of proteomic biomarker panels as a minimally
invasive means to identify patients with significant, angiographically detectable
coronary artery stenosis in the cardiac allograft, in the context of post-cardiac
transplantation monitoring and screening for CAV. The potential biologic significance
of the biomarkers identified may also help improve our understanding of CAV pathophysiology.
Keywords
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© 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
