Incidence, progression and functional significance of cardiac allograft vasculopathy after heart transplantation

Background, Cardiac allofraft vasculopathy after heart transplantation le:l ds to an accelerated form of atherosclerosis with mar ked and often diffuse vessel wall changes that limit Long-term survival. Previous studies showed contradictory results relating vessel wall changes to endothelial vasodila tor response. Methods. A total of 30 cardiac transplant recipients were studied 3, 12, an d 24 months after heart transplantation. Coronary angiography was performed at rest, during supine bicycle ergometry, and after 1.6 mg sublingual nitr oglycerin. Coronary cross-sectional area (biplane coronary angiography) and coronary artery wall changes (intravascular ultrasound) were assessed and extent of intimal changes correlated to vasodilator responses to nitroglyce rine and bicycle ergometry, Results, Intravascular ultrrasound showed significant intimal thickening in 43, 64, and 58% of patients at 3, 12, and 24 months. Intimal thickening 3 months after transplantation was related to donor age (r=0.70, P<0.01) but did not predict progression of disease that manifested itself angiographica lly as a decrease in coronary cross-sect;iona]: area at 12 and 24 months (P <0.005) and significant coronary stenosis in 12% of patients after 24 month s. Endothelium-independent vasodilatation after nitroglycerin (33+/-15, 44/-20, and 43+/-24%) was normal. Endothelium-dependent, flow-induced vasodil atation during exercise was decreased (14+/-11, 18+/-14, and 16+/-17%) but did not correlate to intimal changes assessed by ultrasound. Conclusions. The study confirms the high incidence of intimal thickening af ter heart transplantation as assessed by intravascular ultrasound. Impaired exercise-induced vasodilatation suggests diminished bioavailability of end othelium-derived nitric oxide to physiological stimulation but the lack of relationship between coronary wall changes and this functional impairment s uggests intermittent and presumably reversible endothelial injury in graft atherosclerosis.