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Updated: Aug 25, 2026
Mouse Model of Alloimmune-induced Vascular Rejection and Transplant Arteriosclerosis
Published on: May 17, 2015
Changes in coronary endothelial function predict progression of allograft vasculopathy after heart transplantation
Steven M Hollenberg1, Lloyd W Klein, Joseph E Parrillo
1Cardiology Division, Cooper Hospital/University Medical Center, Camden, New Jersey 08103, USA. Hollenberg-Steven@cooperhealth.edu
Insights
Serial studies show that a faster decline in coronary endothelial function predicts cardiac allograft vasculopathy (CAV) after heart transplantation. This suggests monitoring endothelial function changes is key for early CAV detection and prognosis.
Area of Science:
- Cardiology
- Transplantation immunology
- Vascular biology
Background:
- Coronary endothelial dysfunction is an early indicator of cardiac allograft vasculopathy (CAV).
- Previous studies linked annual decrements in endothelial function to progressive intimal thickening using IVUS and Doppler flow wire measurements.
Purpose of the Study:
- To evaluate serial changes in coronary endothelial function.
- To identify early markers for cardiac allograft vasculopathy (CAV) in heart transplant recipients.
Main Methods:
- 45 heart transplant patients were studied annually post-transplantation until reaching endpoints (angiographic CAV or cardiac death).
- Coronary endothelial function was assessed via intracoronary infusions of adenosine, acetylcholine, and nitroglycerin.
- Intravascular ultrasound (IVUS) images and Doppler velocities were simultaneously recorded.
Main Results:
- Patients reaching endpoints (6 with CAV, 3 deaths) showed a significantly greater mean annual decrease in area response to acetylcholine (-4.5% vs -0.9%, p=0.04).
- A trend towards a greater annual decrement in flow response to acetylcholine was observed in patients with endpoints (-31% vs -5%, p=0.08).
- No significant differences in responses to adenosine or nitroglycerin were found between groups.
Conclusions:
- Rapidly declining endothelial function, rather than absolute intimal thickening, may be more critical in early CAV development.
- Serial assessment of endothelial function provides prognostic information for CAV development post-heart transplantation.
- Endothelial dysfunction is implicated in the pathogenesis of clinically significant cardiac allograft vasculopathy.
Objective:
Coronary endothelial dysfunction may be an early marker for cardiac allograft vasculopathy (CAV) in orthotopic heart transplant recipients. We used serial studies to evaluate changes in coronary endothelial function in patients with and without clinically evident CAV.
Background:
In serial studies with intravascular ultrasound (IVUS) and Doppler flow wire measurements, we previously demonstrated that annual decrements in coronary endothelial function are associated with progressive intimal thickening.
Methods:
We studied 45 patients annually, beginning at transplantation until pre-specified end-points (angiographic CAV or cardiac death) were reached. At each study, we measured coronary endothelial function using intracoronary infusions of adenosine, acetylcholine, and nitroglycerin. We simultaneously recorded IVUS images and Doppler velocities.
Results:
Of the 45 patients studied, 9 reached end-points during the study (6 had CAV and 3 died). The mean annual change in area response to acetylcholine was -4.5% +/- 3.0% in patients who reached end-points and -0.9% +/- 1.5% in those who did not (p = 0.04). The mean annual decrement in flow response to acetylcholine was greater in patients who reached end-points (-31% +/- 11% vs -5% +/- 5%, p = 0.08). Responses to adenosine and nitroglycerin did not differ.
Conclusions:
When serial responses were evaluated, patients with end-points had more rapid decreases in endothelial function. The rate of disease progression may be more important than the absolute degree of intimal thickening in early CAV. These data implicate endothelial dysfunction in the development of clinically significant vasculopathy and suggest that serial studies of endothelial function may provide important prognostic information about the development of CAV after heart transplantation.
