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J Thorac Cardiovasc Surg 2003;126:238-239
© 2003 The American Association for Thoracic Surgery
Surgery for congenital heart disease |
Dr David R. Clarke (Denver, Colo). Congratulations to Dr Baskett and his coauthors are certainly in order for an excellent clinical study and presentation.
This study clearly puts yet another nail in the coffin of the theory that cryopreserved allografts do not elicit an immune response. It also goes further and irrefutably links ABO and HLA incompatibility to graft failure determined by the need for reoperation or echocardiographic evidence of progressive regurgitation or significant stenosis. Two other risk factors identified could also be associated with an immune phenomenon: Use of an aortic homograft and shorter warm ischemic time could presumably lead to the implantation of a higher antigenic load. Are there other possible explanations for the appearance of these risk factors?
Dr Baskett. It is a hard group of patients to look at, as I know you are well aware. There is so much we do not know about how the preservation affects the valves. I think some of the clinical factors, such as the diagnosis of pulmonary atresia, which often goes along with peripheral pulmonary stenosis, probably unmask failure sooner than you may see in a patient, for example, with a Ross procedure (in which there is not the same need for a competent valve). But as you point out, there seems to be a consistent association among several factors that are known to increase the antigenic load and valve failure. This seems to keep coming through in everybody’s work.
Dr Clarke. You also have identified age at operation as a risk factor that has been identified in previous studies. In previous studies, it seems that stenosis in younger patients was very common. Did you find a difference in the failure mode related to the age of the patient at implantation?
Dr Baskett. That is a very good question. We did not look specifically at that when we were constructing our statistical models. The different variables presented and how one chooses to present them, including age and so forth, affects this. Statistically, there is a lot of interaction with age and weight, and so forth. Anecdotally, yes, the younger patients do tend to develop stenosis, but I do not have specific data to prove that.
Dr Clarke. You have not referred to any technical considerations specifically. Was operative technique important in any of your patients, in terms of contributing to the failure of the valve?
Dr Baskett. People have looked before at whether proximal extensions with Dacron or autologous pericardium affects failure. We had only 4 patients who had a Dacron graft, and that was early on in the experience, so there was not enough variability to look at that. We chose instead to use primary diagnosis as a way of getting at operative technique.
Dr Clarke. I thank you once again for a superb presentation of an excellent study and for providing further support for the use of a minimally antigenic valve conduit in the pediatric population. I also thank the association for the privilege of discussing this work.
Dr John Hawkins (Salt Lake City, Utah). This has been an excellent presentation of data showing that the failure of cryopreserved allografts is multifactorial. I have just 1 question about ABO incompatibility. There have been numerous studies showing (in a multifactorial analysis similar to yours) that ABO mismatch is actually not important in valve failure and then a couple of studies that have shown it is important. A recent article also demonstrated that these ABO antigens are poorly expressed, if at all expressed, on the endothelium of cryopreserved allografts. Have you performed any analysis of actual ABO receptors on the endothelium of these cryopreserved allografts using your preservation method?
Dr Baskett. Thank you for your question. Certainly the literature is very confusing in terms of the different variables. Part of this is because most of the literature is from Europe, where they tend to use the so-called fresh or homovital valves, which are stored at 4° for approximately 1 month and then used. Clearly, these are very different valves compared with cryopreserved valves (which we are looking at), so some studies will say ABO is not important. Also, depending on what you are looking at, most studies include adults, and clearly the response in adults and children is completely different. We have not looked specifically at explanted valves; we did a few years ago but did not perform any immunohistochemical staining on them. We have performed quite a bit of work in the laboratory in the rat model looking at just that sort of thing. It also depends on the data you have. We are fortunate in that we have quite detailed data on all the valves, particularly the preservation data. I believe when you have so many variables that you can put in and account for, you are going to see different things coming out. Some of the bigger studies have had only 3 or 4 different variables, so certain things jump out and overwhelm other variables that one may not have the data to support. Looking at the literature, I find that it is a very muddy field.
Dr Andrew S. Wechsler (Philadelphia, Pa). I have a technical question to help me understand your data a little bit better. How did you perform your analysis accounting for the fact that there were only approximately half the valves for which you had histocompatibility data available? When you performed your analysis, did you include data from all of the valves with missing data from the valves in which you did not have a tissue match, or did you look only at the valves in which you had the tissue matching and not analyze the other valves? That may have influenced the assessment you performed.
Dr Baskett. I only included the HLA subset, so there were 47 that had HLA, and I removed the other valves. So it is a subanalysis, and obviously the confidence intervals are much bigger and the numbers smaller.
Related Article
J. Thorac. Cardiovasc. Surg. 2003 126: 232-238.
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