APPENDIX. CONFERENCE DISCUSSION
Dr M. Hazekamp (Leiden, Netherlands): Actually, I think that the aortic homograft is underestimated at the moment. A decrease has been shown in the use of homografts, and I think Mr. Pepper will discuss this topic shortly hereafter. Anyway, in Hannover you have shown us that the process of decellularization is technically feasible, without deterioration of the aortic homografts and the pulmonary homografts also, that surgical implantation is feasible, and that there is no later dilatation of these homografts up to 7.5 years. That is something that you should be congratulated on. I am a little bit biased as a participant in ESPOIR and hopefully in the HORIZON study. I hope you forgive me for this.
I am interested in two things. I have two questions. One of the questions is, did you see on CT or on chest X-rays any calcification in the aortic wall, both in the short and in the long homografts?
Dr Tudorache: Our follow-up, in most of the patients is around 2 years, the mean follow-up, and in these patients we didn't see it. Moreover, last week we performed CT scan and MRI in our oldest patients, and even in these patients, 7.5 years after the operation, we didn't see calcification inside. We performed as well some operations in the sheep model and sporadically implanted allografts in the aortic position, and we had some spots inside, but 2.5 years after the implantation. I think it should be enough.
Dr Hazekamp: My other question is, you showed us these histology slides of the explanted homograft, but can you explain a little bit more, go a little bit more into detail about what cells did you see and how they were aligned? For example, did you see a true endothelial lining on this homograft and was it uniformly covering the homograft, and the myofibroblasts, which I think you saw them because you wrote it in the paper, were they scattered or were they in a uniform way introducing themselves in these homografts?
Dr Tudorache: Actually, this is not normal. It has already changed tissue, and of all 3 cusps, only one, the non-coronary cusp, had a normal macroscopic view. The non-coronary cusp already had hypogenesis because of probably turbulence in this graft, because we had progressive aortic valve degeneration in this, with consequent insufficiency, and the insufficiency was actually caused by a missing left coronary cusp. The right coronary cusp had as well some modification and thickening. That's why it is very difficult to say whether the recellularization of this graft after the implantation takes the normal course, as probably in the autograft. Nevertheless, we saw a lot of myofibroblasts. The endothelial lining of the cusps has been seen, as well in the proximal part of the cusps. The tip of the cusp, of the non-coronary cusp, which was macroscopically the normal one, was sporadically covered with some cells, but this was not comparable with a perfect native cusp. But once again, this is not a normal decellularized homograft and we explanted because of another cause.
Dr Hazekamp: No, I agree, I agree. Of course, the key question is do you think that these decellularized homografts, when they get repopulated by the recipient cells, that they will behave like a normal aortic valve? It's speculation, I know, because there are no explants, but what do you think?
Dr Tudorache: That's why we started this multicentre study now.
Dr Hazekamp: Just speculate.
Dr Tudorache: We don't want to speculate. We show now our data. Unfortunately, we don't have the explants, and maybe this is a good answer to your question, but that is why we are trying now to implant more in several centres, and maybe in several years we will have the response to your question.
Dr F. da Costa (Curitiba, Brazil): We have a similar experience; by the way, the longest. We have now 103 decellularized aortic allografts implanted. Follow-up is extending up to 10 years. The mean follow-up is 4.8 years. I don't think those valves will grow, to tell you the truth, but there is one striking feature of those valves, that up to 10 years, and we have several above 7 or 8 years, the CT scan shows no calcification, and the only patient that we had to redo was secondary to patient out growing the valve with subsequent stenosis—and I think you had 2 of those. We implanted a small homograft in a small kid and the kid outgrew the graft—the cusps were absolutely normal, the conduit with no calcification at all, but there was no growth. So I believe decellularized aortic allografts are going to be major advances in aortic valve surgery, but it is not going to be a living graft, as the pulmonary autograft. That is my belief at the moment.
Dr Tudorache: I can't answer this question as well. We performed some operations in growing sheep and compared the Ross procedure with implantation of decellularized aortic homografts, and we saw in decellularized homografts the increase of the diameter of the grafts from 18 to 22 mm without loss of the functionality. This data will be published in the journal, I think next month. Also comparing the homograft, we have less of an increase in diameter as compared with the autograft in these sheep. Nevertheless, the increase in the diameter was more physiological in the decellularized group when compared with the autograft group. In normal sheep, the increase was comparable with the decellularized graft and the autograft was a little bit bigger. This is the answer to your question.