Coronary Endothelial Dysfunction After Heart Transplantation Predicts Allograft Vasculopathy and Cardiac Death
Open Access
- 17 December 2001
- journal article
- clinical trial
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation
- Vol. 104 (25), 3091-3096
- https://doi.org/10.1161/hc5001.100796
Abstract
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-μg bolus), acetylcholine (54 μg over 2 minutes), and nitroglycerin (200 μg) 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.Keywords
This publication has 13 references indexed in Scilit:
- Intravascular ultrasound imaging after cardiac transplantation: advantage of multi-vessel imagingThe Journal of Heart and Lung Transplantation, 2000
- The registry of the international society for heart and lung transplantation: sixteenth official report—1999The Journal of Heart and Lung Transplantation, 1999
- Simultaneous intracoronary ultrasound and Doppler flow studies distinguish flow-mediated from receptor-mediated endothelial responsesCatheterization and Cardiovascular Interventions, 1999
- Atherosclerosis — An Inflammatory DiseaseNew England Journal of Medicine, 1999
- Endothelial dysfunction: Clinical implicationsProgress in Cardiovascular Diseases, 1997
- Predictive model to assess risk for cardiac allograft vasculopathy: An intravascular ultrasound studyJournal of the American College of Cardiology, 1995
- Epicardial vasomotor responses to acetylcholine are not predicted by coronary atherosclerosis as assessed by intracoronary ultrasoundJournal of the American College of Cardiology, 1995
- Nitric oxide: an endogenous modulator of leukocyte adhesion.Proceedings of the National Academy of Sciences, 1991
- Responses of coronary arteries of cardiac transplant patients to acetylcholine.JCI Insight, 1988
- Paradoxical Vasoconstriction Induced by Acetylcholine in Atherosclerotic Coronary ArteriesNew England Journal of Medicine, 1986