Transplant Coronary Artery Disease

Since the fIrst successful orthotopic cardiac transplantation in 1967. the survival after transplantation has gradually been improved due to the introduction of cyclosporin-A, the monitoring of acute rejection by cndomyocardial biopsies and optimized patient carel, In the last decade, clinical studies indicate that coronary artcry disease ill the graft is the most common cause of death in the first postoperative years. The earliest change consist of concentric fibrosis and smooth muscle cell proliferation with collagen accumulation creating diffuse intimal thickening. Tills process involves not only the large epicardial vessels but also the intramyocardial branches. The specific fillgiographic morphology of the lesions found after transplantation was described by the group of Stanford, distinguishing 3 categories: type A, discrete or short tubular stenosis in the proximal, middle or distal segments of major coronary arteries or their branches, type B; diffuse concentric luminal narrowing in the middle to distal segment branches; and type C, diffusely narrowed irregular distal branches that are squared of and end abruptly, the latter two groups both unique to the post-transplant patients • Despite this clear categorization, pathological examinations showed that the process of accelerated coronary artelY disease is underestimated by visual interpretation of coronmy angiography7. Thus, visual interpretation of coronary angiography has limitations for both clinical and research purposes. The aim of this thesis is to describe the changes in the coronary vasculature in the first six years after cardiac transplantation and to correlate these changes with previously identified risk factors. In addition to morphological epicardial coronary artery changes, assessed by quantitative coronary angiography, myocardial flow reserve and atrial pacing stress were used to assess the influence of accelerated coronary artery disease on myocardial flow and cardiac function. Chapters II-V describe the results of quantitative analysis of serial coronary angiograms at different postoperative stages. The influence of changes in coronary microvasculature on myocardial flow reserve is described in chapters VI and VII. Chapter VIII describes the functional correlates of diffuse coronary artelY disease using atrial pacing stress at the time of routine angiography.

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