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Dr Vaughn A. Starnes (Los Angeles, Calif). Dr Morales and associates are to be congratulated on an excellent paper retrospectively reviewing 21 years of experience at the TCH. During that time, they performed 165 transplants on 155 recipients. As noted in the paper, children with cardiomyopathy made up more than 50% of the patients, another approximately 40% were children with CHD, and 7.9% were children with graft failure.

As noted by the author, this series compares favorably with the International Registry of Heart and Lung Transplant survival statistics and the causes for transplant.

As we see in this report, as also true of the registry, our improvement in survival over time has been primarily related to our early graft survival, particularly in the first year after the transplant event. As noted by these authors, an increase of 20% over this decade between 1995 and after 1995, it increased from 71% to 91% during that period of time; that survival statistic paralleled the course over the next 5 to 10 years.

The authors bring up some interesting findings that are also true in the registry, that ethnicity does affect survival, with the pediatric white population faring better than the African American or Hispanic transplant recipients.

The other interesting factor was that the mismatch between genders was very compelling. The mismatch of a male recipient receiving a female donor heart had a significant importance over time and, in fact, at 10 years the survival difference was 49% versus 70%. I thought that was a very compelling argument about trying to match gender.

I have three questions.

The ISHLT reported a significant negative impact with an odds ratio of 2.1 on the influence of CHD as a pretransplant diagnosis on the outcome of the recipient. You found no statistical difference between the cardiomyopathy group and the CHD group. Could you explain that?

Dr Morales. I think if we look into the two different eras, in the pre-1995 era it was a risk factor. In the post-1995 era, in which we now have a dedicated congenital heart surgery center, including surgeons, anesthesiologists, and intensivists, CHD is no longer a risk factor because of the large improvement in early survival. I believe that this is why, overall, it did not come out as a risk factor in our analysis.

Dr Starnes. My second question concerns the negative impact of prolonged intubation. With your odds ratios on 1- and 5-year survivals (7.4 and 3.8, respectively) as a negative impact of this factor, I would view this more as a surrogate for a very sick pretransplant patient with other comorbidities. Are you suggesting that intubation is an independent risk factor outside of the comorbidities that might go along with that?

Dr Morales. I agree with you that it probably has something to do with their pretransplant status; however, the statistical analysis would say that prolonged intubation is itself an independent risk factor for mortality.

Dr Starnes. Again, regrettably, the long-term outcome has remained the same over the past 20 years, and the survival beyond 3 years is still affected by coronary artery disease, with death due to coronary disease representing 30% to 35% in most series and 34% in your series. Given this, has your group taken on any novel immunosuppressive approaches? I noted in your manuscript that some 5% of your patients were receiving rapamycin.

Dr Morales. When a patient has transplant artery coronary disease, one thing that we have changed in the past 5 to 8 years is prescribing rapamycin. Almost all of our applications of rapamycin are for transplant coronary disease. We have also started prescribing pravastatin (Pravachol) as possible prophylaxis against transplant coronary disease once the patients reach adolescence.

Dr Roland Hetzer (Berlin, Germany). I want to congratulate the Houston group for this enormous experience. Our own activities among more than 1500 heart transplants include 140 infants and children under the age of 18 years during the past 20 years. Our 10-year survival in this transplanted group was 70%. We have attributed this to very close, meticulous monitoring of rejection by electrophysiologic telemetric methods.

I would like you to comment on several issues: the mode of rejection monitoring in children and infants, the impact of chronic renal failure at long term, the obvious lack of compliance in adolescents, and the diagnostics of transplant vasculopathy, which we have found to be an important factor for survival beyond 10 years after transplantation.

Dr Morales. In terms of how we monitor these children for chronic rejection or acute rejection, we do myocardial biopsies every 2 weeks during the first 3 months, then every 3 months for the first year, then every 6 months for the next 4 years, and yearly thereafter. Our cardiology colleagues also do a great job at clinically following these children quite frequently and often will diagnose a change in their clinical status. At 3 months, we do coronary angiography as a baseline and then follow that up with yearly angiograms to diagnose coronary disease.

Renal failure played a significant cause in only 1 of the 59 deaths in this series, so it actually has not played a major role in our series in regard to mortality. However, it certainly is a widely known morbidity in these patients, whose renal function we follow closely. Two of our patients have required renal transplant.

Adolescent noncompliance has always been a problem, and as you have seen in our slide on conditional 5-year survival, it definitely has a negative impact on late survival. As do most programs, we pride ourselves in developing close and strong relationships with our patients, so through our counseling we try to improve compliance.

Dr Cooley. In that initial operation that we did on an 8-month-old infant, our concern was, then, about the possibility of the influence of immunosuppressive drugs on growth and development. It was very gratifying to see how that little girl grew and became intelligent; she was a good student in school and so forth. It was a real tragedy when she did pass away from coronary occlusive changes.

I missed it in the donors involved. The situation with the donor in our first transplant was rather complex. The donor was another infant from Dallas, Texas. The mother and father, in a fit of anger, had thrown the child out of a second-story window and the child sustained severe brain injury. To get the permission for the donation, we had to go to the jail in Dallas where the mother and father were incarcerated. We brought the baby down to Houston and had the little recipient available. The recipient was an adopted child. So the situation became rather complicated.

I missed it in your policy now at TCH about ABO mismatch in candidates for transplantation. I hear reports of other institutions that are using ABO mismatch. What is the policy at the Children’s Hospital in Houston?

Dr Morales. Thank you, Dr Cooley, for your comments. It is quite an honor to have you here at this presentation to give all of us perspective on this field. I am aware that Toronto has had good success with the ABO mismatch. However, we have not performed any ABO mismatch transplants at TCH. It is something that our cardiologists are interested in and they have been investigating this option, but as of this time we have not applied this donor management strategy.

Dr Lucio Parenzan (Bergamo, Italy). To find a small heart, as you know, is difficult. Many times you have to fly many hours. What do you think about the new system they have in Germany where they are perfusing the heart during the transplantation? Do you have any data? Do you have any knowledge? Do you think it is a good idea?

Dr Morales. I am not aware of the new system in Germany.

I can say that we did analyze ischemic time, with maximum ischemic time being 7.5 hours, as a continuous variable to see whether it was a risk factor for mortality. Our analysis demonstrated that at no time was ischemic time a risk factor for death. However, having said that, there obviously is an ischemic time in which graft function and mortality would be affected negatively, but it is unclear to me that it is at 4 hours, as we have always been taught.

Dr Adnan Cobanoglu (Cleveland, Ohio). I would like to find out more about the retransplants. There were 13 patients. How was the outcome in the retransplantation group?

Dr Morales. We calculated Kaplan–Meier survival curves of the 13 retransplants and of all the primary grafts, and we compared the two groups. We did not find a statistical difference between the cohorts. However, I do not know how much can be gathered from that analysis, since there were only 13 retransplants. Having said that, our belief now is that their survival is about the same, but we will have to see whether that is true as our numbers and length of follow-up increase.

Dr William A. Baumgartner (Baltimore, Md). You said ischemic time is not related to rejection or survival. Increasing evidence suggests that there is a relationship between ischemic time, or injury at the time of procurement, and the future development of coronary artery disease. Have you looked at this correlation?

Dr Morales. We did not look at the issue of ischemic time and chronic rejection in particular. We did show that, at least in our series, ischemic time was not related to death or graft failure in general. This issue of ischemic time and chronic rejection is an interesting one that we should investigate in our series.