Related Experiment Video
Updated: May 11, 2026
Murine Cervical Heart Transplantation Model Using a Modified Cuff Technique
Published on: October 12, 2014
Coronary endothelial dysfunction after heart transplantation predicts allograft vasculopathy and cardiac death
S M Hollenberg1, L W Klein, J E Parrillo
1Section of Cardiology, Rush-Presbyterian-St Luke's Medical Center, Chicago, Illinois, USA.
Insights
Endothelial dysfunction in heart transplant recipients predicts future cardiac events like death or cardiac allograft vasculopathy (CAV). Serial endothelial function tests can identify patients at risk.
Area of Science:
- Cardiology
- Transplant Medicine
- Vascular Biology
Background:
- Coronary endothelial dysfunction is an early indicator of cardiac allograft vasculopathy (CAV) in heart transplant recipients.
- Previous studies showed annual decrements in endothelial function correlate with intimal thickening.
Purpose of the Study:
- To determine if endothelial dysfunction predicts clinical events, including cardiac death and CAV development.
- To assess the predictive value of serial endothelial function measurements.
Main Methods:
- Seventy-three heart transplant patients were monitored annually post-transplant.
- Coronary endothelial function was assessed using intracoronary infusions of acetylcholine, adenosine, and nitroglycerin.
- Intravascular ultrasound and Doppler velocities were measured simultaneously to evaluate epicardial and microvascular responses.
Main Results:
- Fourteen patients reached an endpoint (CAV or cardiac death) during the study.
- Patients with endpoints showed significantly impaired endothelium-dependent epicardial and microvascular responses to acetylcholine compared to those without endpoints.
- Responses to adenosine and nitroglycerin did not differ significantly between groups.
Conclusions:
- Abnormal acetylcholine responses, indicating endothelial dysfunction, preceded clinical endpoints in heart transplant recipients.
- Endothelial dysfunction is implicated in the development of clinically significant cardiac allograft vasculopathy.
- Serial assessment of endothelial function holds clinical utility for risk stratification in heart transplant patients.
Background:
Coronary endothelial dysfunction may be an early marker for cardiac allograft vasculopathy (CAV) in orthotopic heart transplant recipients. Using serial studies with intravascular ultrasound and Doppler flow-wire measurements, we have previously demonstrated that annual decrements in coronary endothelial function are associated with progressive intimal thickening. The present study tested whether endothelial dysfunction predicts subsequent clinical events, including cardiac death and CAV development.
Methods And Results:
Seventy-three patients were studied yearly beginning at transplantation until a prespecified end point was reached. End points were angiographic evidence of CAV (>50% stenosis) or cardiac death (graft failure or sudden death). At each study, coronary endothelial function was measured with intracoronary infusions of adenosine (32-microgram bolus), acetylcholine (54 microgram over 2 minutes), and nitroglycerin (200 microgram) into the left anterior descending coronary artery; intravascular ultrasound images and Doppler velocities were recorded simultaneously. Of the 73 patients studied, 14 reached an end point during the study (6 CAV and 8 deaths, including 4 with known CAV, 1 graft failure, and 3 sudden). On the last study performed, the group with an end point had decreased epicardial (constriction of 11.1+/-2.9% versus dilation of 1.7+/-2.2%, P=0.01) and microvascular (flow increase of 75+/-20% versus 149+/-16%, P=0.03) endothelium-dependent responses to acetylcholine compared with the patients who did not reach an end point. Responses to adenosine and nitroglycerin did not differ significantly.
Conclusions:
Endothelial dysfunction, as detected by abnormal responses to acetylcholine, preceded the development of clinical end points. These data implicate endothelial dysfunction in the development of clinically significant vasculopathy and suggest that serial studies of endothelial function have clinical utility.
