T dren s Hospital of Pittsburgh was started in 1982 as a

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1 ORIGINAL ARTICLES Lessons Learned in Pediatric Heart Transplantation Alfred0 Trento, MD, Bartley P. Griffith, MD, Frederick J. Fricker, MD, Robert L. Kormos, MD, John Armitage, MD, and Robert L. Hardesty, MD Department of Thoracic and Cardiovascular Surgery, Cedars-Sinai Medical Center, Los Angeles, California, and Departments of Surgery and Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania Between February 1,1982, and June 30,1988,32 children underwent cardiac transplantation for treatment of congenital heart disease (10) and other cardiomyopathies (22). The &year actuarial survival was a disappointing 36% because of a high perioperative mortality (12 of 32, 37.5%) and because of five late deaths due to uncontrollable rejection. The perioperative mortality was a staggering 60% (6 of 10) for the patients with congenital heart disease. Four of the 6 recipients with congenital heart disease died because of acute failure of the donor right ventricle. This included 2 patients who required reconstruction of the pulmonary arteries for stenosis secondary to previous systemic-to-pulmonary shunts and 2 others in whom the pulmonary vascular resistances were underestimated because of undetected recent pulmonary emboli (1) and complicated pulmonary vascular anatomy (1). Five of the six late deaths were due to rejectionrelated events, and all were patients with acquired cardiomyopathy. (Ann Thorac Surg ) he Pediatric Heart Transplant Program at the Chil- T dren s Hospital of Pittsburgh was started in 1982 as a natural extension of the Adult Transplant Program that had already been in progress for the previous 2 years [l]. Pediatric patient selection, perioperative care, and longterm follow-up have been under the direction of the same physicians involved in the adult cardiac transplant program. This has allowed us to take advantage of the substantial experience accumulated over the past 6 years with the much larger number of adults who underwent heart transplantation, and it has also assured a homogenicity of care that makes possible meaningful comparisons of the results of heart transplantation in adult and pediatric patients. Results obtained in our 32 pediatric patients, as compared with the 363 adults who underwent transplantation in Pittsburgh during the same period of time, have been similar in terms of life expectancy of the patients who survived the procedure, side effects of immunosuppressive therapy, and quality of life [2]. However, the children have suffered a high perioperative mortality and a disproportionate incidence of late death owing to rejection or rejection-related events. Patient Population and Recipient Selection Criteria for pediatric patient selection for transplantation have been similar to those followed for adult recipients (31 and include end-stage heart disease with a life expectancy of less than 6 months. Between February 1, 1982, and June 30, 1988, 32 children aged 3 months to 17 years (average age, 9 years) have undergone heart or heart-liver transplantation. Idi- Presented at the Twenty-fourth Annual Meeting of The Society of Thoracic Surgeons, New Orleans, LA, Sep 26-28, Address reprint requests to Dr Trento, Department of Thoracic and Cardiovascular Surgery, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Suite 6215, Los Angeles, CA opathic cardiomyopathy (15 patients) and palliated congenital heart disease with irreversible myocardial dysfunction (10 patients) are the most frequent causes of end-stage cardiac disease (Table 1). Two patients were treated for acute viral myocarditis. Three others were treated by combined heart-liver transplantation: 2 for primary hypercholesterolemia with ischemic cardiomyopathy and 1 for intrahepatic biliary atresia and dilated cardiomyopathy. A 12-year-old girl required heart transplantation because of end-stage cardiomyopathy caused by adriamycin, and a 12-year-old boy received transplantation because of a primary angiosarcoma of the heart. Contraindications to heart transplantation in children are the same as in adult patients and have been described previously [4]. As we learned from the adult program, selection of recipients has an obvious impact on survival. Patients with high pulmonary vascular resistance (PVR), previous pulmonary emboli, or complicated pulmonary artery anatomy requiring reconstruction at the time of mansplantation have been accepted in our program, but these patients often had a bad outcome, which has significantly affected our overall results. Survival The 6-year actuarial survival for the 32 patients who underwent heart transplantation is a disappointing 36%. This is significantly (p < 0.05) different from the actuarial survival of the adult population (50%) (Fig 1). Fourteen patients are surviving 4 months to 6 years after transplantation. Three have been alive for more than 4 years, 9 are alive after 3 years, and 2 were transplanted less than 1 year ago. The difference in survival between the adult and pediatric populations is due to the high perioperative mortality in the latter group (37.5% versus 20%). Children with congenital heart disease had a much higher perioperative mortality (6 of 10, 60%) than those with acquired cardiomyopathy (6 of 22, 27%) by The Society of Thoracic Surgeons OOO

2 618 TRENTOETAL Ann Thorac Surg Table 1. Pediatric Heart Transplantation Between February 1, 1982, and June 30, 1988: Patient Population Diagnosis Number Alive Dead 0 Idiopathic cardiomyopathy Congenital heart disease Acute viral myocarditis Ischemic cardiomyopathy " Adriamycin toxicity Cardiac angiosarcoma Total Four of the 6 recipients with congenital heart disease died of acute failure of the donor right ventricle (Table 2). Of these 4 patients, 2 required reconstruction of the pulmonary arteries due to stenosis secondary to previous systemic-to-pulmonary shunts (Pott's shunt and bilateral Blalock-Taussig shunts), and 2 had PVR underestimated because of unrecognized recent pulmonary emboli and complicated pulmonary vascular anatomy, respectively. The other 2 recipients with congenital heart disease also were complicated cases as they required total circulatory support by extracorporeal membrane oxygenation for two and three days, respectively, before transplantation. One of these patients died of biventricular failure of the transplanted heart, and the other died of severe pulmonary hemorrhage (Table 2, patient 6). Extracorporeal membrane oxygenation was instituted in these 2 patients because of inability to wean them from cardiopulmonary bypass at the time of repair of their congenital anomalies (anomalous origin of left coronary artery and ventricular l Years Fig 1. Actuarial survival of pediatric and adult population between Februay 1982 and Iune The difference is statistically significant and is due to the high perioperative mortality of the pediatric population (37.5% versus 20%). septal defect with anomalous muscle bundle, respectively). Of the 22 patients with cardiomyopathy who underwent heart transplantation, 6 died in the perioperative period and 6 died after hospital discharge (Table 3). Of the 6 early deaths, 2 were secondary to technical problems related to simultaneous multiple organ transplantation (heart-liver), 2 were due to Pseudomonas infections, 1 was due to a brain hemorrhage, and 1 was due to a diffuse lymphoproliferative disorder. Of the 6 patients who died after hospital discharge (9 months to 3 years after transplantation), 1 died of lymphoproliferative disease; the other 5 deaths were related to acute or chronic rejection. Two of these 5 patients had documented extensive coronary atherosclerosis (Figs 2, 3) 2 and 3 years after transplantation, as well as chronic myocardial inflammation and fibrosis, and died suddenly of acute coronary occlusion. The other 3 died of uncontrollable rejection several months after transplantation. 0 Table 2. Early Death After Pediatric Heart Transplantation in Patients With Congenital Heart Disease Patient No. Age 1 16 yr Diagnosis Time of Death Cause of Death Single ventricle Pott's shunt, Third postoperative day Right heart failure, left PA stenosis thrombosis of left PA Right heart failure, failure of bilateral PA reconstruction 17 yr Double-inlet left ventricle Third postoperative day Right heart failure, 15 yr Norwood procedure, bilateral Intraoperative PA stenosis after ventricular septation, cardiomy opathy 9 Y' Tricuspid atresia, bilateral BT shunts, MVR 3 mo Anomalous left coronary artery, attempted repair, ECMO support Intraoperative Intraoperative recent pulmonary emboli Right heart failure, high PVR Biventricular failure 6 4 Y' VSD and anomalous muscle Intraoperative Lung hemorrhage bundle, attempted repair, ECMO support BT = Blalock-Taussig; ECMO = extracorporeal membrane oxygenation; MVR = mitral valve replacement; PA = pulmonary artery; PVR = pulmonary vascular resistance; VSD = ventricular septal defect.

3 Ann Thorac Surg TRENTO ET AL 619 Table 3. Causes of Death After Pediatric Heart Transplantation in Patients With Acquired Cardiomyoputhy Cause of Death Early Late ~ ~~ Rejection Technical problems Infections Lymphoprolifera tive disease Brain hemorrhage Total 6 6 Immunosuppression and Rejection The immunosuppressive therapy in our pediatric program, always based on cyclosporine, has undergone the same evolution as in the adult program. In the last 3 years we have used a regimen of triple-drug therapy to reduce the toxic effects of cyclosporine [3]: azathioprine is started preoperatively with a loading dose of 4 mgkg intravenously, methylprednisolone (20 mg/kg) is administered intraoperatively, and prophylactic antithymocyte globulin (1.5 mgkg/day) is administered for three to five days postoperatively. Cyclosporine, prednisone, and azathioprine are used for chronic immunosuppression. The maintenance dose of cyclosporine has varied from 4 to 20 mgkg/day to maintain a whole blood radioimmunoassay cyclosporine level that is greater than 700 mg/ml initially. After 6 months, the cyclosporine dose is decreased to target levels of 500 mg/ml by radioimmunoassay and 150 to 250 mg/ml by high-performance liquid chromatography. Prednisone dose has varied between 0.1 and 0.3 mg/kg/day. The same immunosuppressive regimen is used for our adult transplant patients. In our pediatric patients, the linearized rejection rate was 2.3 episodes per Fig 2. Coronary angiogram shows a tight stenosis of the proximal left anterior descending artery in a 16-year-old boy 3 years after transplantation. B Fig 3. Histological appearance of the circumflex coronary artery (A) and of the left anterior descending coronary artery (B) in the same 16-year-old boy whose angiogram is shown in Figure patient-days in the first month; this decreased to 0.3 episodes per 100 patient-days in the sixth month. Despite the finding that rejection was the principal cause of late death in our children, the incidence of rejection was not different from that of the adult population. Analysis of actuarial rejection rate shows that during the first postoperative year only 25% of the surviving patients were rejection-free versus 31% of the adult patients. The difference does not reach statistical significance. As in the adult population, the frequency of rejection tends to decrease with time, but two episodes of serious and symptomatic rejection occurred 15 months and 2 years after transplantation, both associated with reduction or discontinuation of corticosteroids. Although the reported experience of newborns undergoing heart transplantation indicates that they appear to tolerate an immunosuppressive therapy without steroids well [4, 51, we have not yet been able to withhold steroids from our older transplant patients because of recurrent rejection. Quality of Life Follow-up data on the surviving children wert? reported recently [6]. Growth parameters in children surviving longer than 1 year have shown that linear growth is

4 620 TRENT0 ET AL Ann Thorac Surg maintained in most of these patients. In contrast, most patients have shown a marked increase in weight, with only 4 patients on the same weight percentile. Hypertension and abnormalities in renal function related to cyclosporine represent serious long-term concerns. Essentially all surviving children have required antihypertensive therapy, and 8 of the 12 children surviving more than 1 year are currently on a chronic antihypertensive regimen. Combination of diuretics with angiotensin blocking agents have been useful even in the most refractory case. Long-acting calcium channel blockers and a- and blockers have also been used with success. Serum creatinine level usually returns to baseline at about 1 month after transplantation and then increases slowly to reach a plateau at about 1 year. Only 1 patient had a serum creatinine level greater than 1 mg/100 ml, but all the other children had an increase of up to 200% in the serum creatinine level from the baseline level. The abnormalities in serum creatinine level that we have observed are clinically significant, and we are concerned that long-term use of cyclosporine may cause progressive and irreversible renal dysfunction in children. Despite these side effects of immunosuppression, the surviving children enjoy an excellent physical and emotional rehabilitation, as documented by a follow-up study of 10 of our children who survived transplantation [7]. The study used standardized psychological tests, projective drawings, exercise testing, and parents interviews to determine the child s daily activities before and after transplantation. In many areas, function improved drama tically after transplantation. Comment Our intention in this article was to focus more on the patients who did not survive to determine if the factors responsible for the significant difference between the results of the pediatric and adult programs are specific to our experience and possibly avoidable. An elevated perioperative mortality and a high incidence of late deaths due to rejection have emerged as important features of our review. The long-term survival for patients who survived operation is very similar in the pediatric and adult population. There is no statistically significant difference in the actuarial survival curves of the two groups after the first 2 months. Improvement in the overall survival of the transplanted children thus can be achieved by decreasing perioperative mortality. Four of the 6 patients with congenital heart disease died of acute right heart failure. Two of these 4 patients had very unfavorable pulmonary artery anatomy and, retrospectively, we would have been wise not to accept them for transplantation. The other 2 patients had undetected high PVR; a more rigorous perioperative work-up might have influenced the decision to select a donor of bigger size or to perform a heterotopic transplantation [%lo]. In reality, the response of the donor right ventricle to increased PVR is unpredictable, and the upper limit of PVR at which orthotopic heart transplantation can still be successful is not known. Cri- teria developed from the adult transplantation experience suggested that a PVR of more than 6 Wood units or a transpulmonary gradient of more than 15 mm Hg [8, 10, 111 was a contraindication to orthotopic heart transplantation. These criteria are not necessarily valid for the variable body size of children. Therefore, we use a PVR index, which is PVR corrected for body surface area. Recently, the problem of PVR was reviewed by Addonizio and colleagues [lo]. In their experience, no mortality occurred if PVR index was greater than 6 Wood units. We successfully performed transplantation in 2 children with PVR index of 9 and 10 U, respectively. Both had reactive pulmonary vasculature, as demonstrated by a decrease in PVR index to 6 during administration of dobutamine. Therefore, a decrease in PVR after administration of pulmonary vasodilators or inotropic agents can be an indication that the patient will be able to accept a heart transplant in orthotopic position, especially if an oversized heart is used. Heterotopic transplantation has been used only once in our pediatric population, in a 14-year-old boy with idiopathic cardiomyopathy and fixed, elevated PVR. He has survived for 3 years, and follow-up cardiac catheterizations have shown that most of his right-sided output still comes from the native right ventricle and most of the left-sided output comes from the donor left ventricle. On the basis of the good results of heterotopic transplantation in the adult population [ll], perhaps we should explore the use of this procedure more frequently even in the younger children. But in contrast to what is reported in the adult patients [ll], in whom PVR tends to decrease with time after heterotopic transplantation, in the pediatric population elevated PVR, which does not respond to pulmonary vasodilators preoperatively, may continue to be elevated even after heterotopic transplantation, as was the case in our 14-year-old boy. The transplanted heart will then function mostly as a chronic left ventricular assist device. The other 2 patients were bridged to the transplant procedure with extracorporeal membrane oxygenation. At present, because of size constraints, extracorporeal membrane oxygenation is the only form of mechanical cardiac support that can be used in the pediatric population [12]. Both of our patients in whom extracorporeal membrane oxygenation was used because of the postpump left ventricular failure died in the operating room at the time of transplantation because of preexisting pulmonary failure (pulmonary hemorrhage and pulmonary edema) and would not today be candidates for even a heroic transplantation attempt. The other important aspect emerging from our review is the cause of late deaths, almost all of which were due to rejection. This is significantly different from the experience with our adult population, in which rejection and coronary artery disease were responsible for only 50% of the late deaths; the other 50% being due to infections, malignancy, stroke, liver failure, and other causes. Considering the overall experience between 1982 and 1988, the linearized and actuarial rejection rate of our pediatric population was not different from that of the adult group.

5 Ann Thorac Surg 1989;4& TRENTO ET AL 621 But if we consider only the last 3 years, during which the current triple-drug immunosuppressive protocol has been used, the actuarial rejection rate in the pediatric group has shown that only 36% of the pediatric patients are free of rejection during the first postoperative year versus 47% of the adult population. Two episodes of serious and symptomatic rejection occurred 15 months and 2 years after transplantation, and both were associated with reduction or discontinuation of corticosteroids. For this reason, we have been reluctant to withdraw steroids uniformly from our chronic immunosuppressive therapy. Accelerated coronary vascular disease in our children remains the major obstacle to long-term graft survival [6]. Prevalence of atherosclerosis in the adult cardiac transplant recipients is estimated to be approximately 20% at 1 year, increasing to 50% at 3 years after transplantation [13, 141. Data gathered by Pennington and colleagues [15] did not identify coronary atherosclerosis as a major problem in children. This may reflect the short follow-up of most children receiving cardiac transplantation. Coronary atherosclerosis has been a major factor in five of our six late deaths. Two children died of documented acute occlusion of the left anterior descending coronary artery, and 3 died of recurrent or chronic rejection, but autopsy showed that all had severe diffuse coronary artery disease causing ischemic cardiomyopathy. Although pathogenesis of transplant atherosclerosis has not been determined, overwhelming evidence points to an immunological basis [ We (141 have related the occurrence of two or more major rejection episodes with the development of coronary artery disease. Other factors such as hypertension, lipid metabolism, and obesity may play a substantial role, but a more effective immunosuppressive regimen appears to be the first step in achieving better graft survival. Lymphoproliferative disease in children receiving cyclosporine has been well described [17]. In our experience, 2 pediatric patients died 2 months and 1 year postoperatively with lymphoproliferative disease involving multiple organs. In both patients, the disease was associated with Epstein-Barr virus infection and with an increased immunosuppressive therapy. The incidence of Epstein-Barr virus-related lymphoma in immunosuppressed children was recently reviewed by Ho and associates [18] at the University of Pittsburgh School of Medicine. It is somewhat higher than in the adult population and is more frequently associated with primary Epstein- Barr virus infection. In our 2 patients, autopsy showed a diffuse lymphocytic infiltration of all organs, including the heart. This diffuse form of the disease appears to be more frequent than the localized form in the pediatric population. The usual treatment of reducing or discontinuing immunosuppression has achieved complete cure in about half of the patients. Finally, the best aspect of our experience has been the excellent quality of life of the surviving patients. These children have adapted very well to their new situation and are extremely grateful for their new life-style. They can experience and do things that they were never able to do before because of their chronic cardiac illness, which quite often was congenital. But despite these rewarding results, the long-term prognosis of heart transplantation in this age group is, at best, unknown. In conclusion, even in the pediatric population, heart transplantation is becoming a viable procedure for endstage congenital or acquired heart diseases. In our experience, the difference between adult and pediatric mortality has been related to acceptance of patients with elevated PVR, previous pulmonary emboli, and severe pulmonary artery anomalies. With proper patient selection and rigorous preoperative evaluation, we can achieve for the pediatric population a perioperative mortality rate approaching that of adult patients. Long-term problems that affect survival, such as hypertension, renal dysfunction, and coronary artery disease, are still unsolved but can probably be addressed by development of new immunosuppressive regimens. References 1. Griffith BP, Hardesty RL, Trento A, Bahnson HT. Five years of heart transplantation in Pittsburgh. Heart Transplant 1985;4: Kormos RL, Trento A, Hardesty RL, et al. Avoidance of perioperative renal toxicity by a modified immunosuppression protocol. Transplant Proc 1987;19: Griffith BP, Hardesty RL, Thompson ME, Drummer JS, Bahnson HT. Cardiac transplantation with cyclosporine: the Pittsburgh experience. Heart Transplant 1983;2: Bailey LL, Neilsen-Cannarella SL, Concepcion W, et al. Baboon-to-human cardiac xenotransplantation in a neonate. JAMA 1985;254: Bailey LL, Neilsen-Cannarella SL, Doroshow RW, et al. Cardiac allotransplantation in newborns as therapy for hypoplastic left heart syndrome. N Engl J Med 1986;315: Fricker FJ, Trento A, Griffith BP, et al. Experience with heart transplantation in children at the University of Pittsburgh and Children's Hospital. Presented at the Symposium for Heart Transplantation in Children, St. Christopher's Hospital, Philadelphia, PA, Oct Fricker FJ, GrSith BP, Hardesty RL, et al. Experience with heart transplantation in children. Pediatrics 1987;79: Griepp RB, Stinson EB, Dong E, et al. Determinants of operative risk in human heart transplantation. Am J Surg 1971;122: Rabinovitch M, Haworth SG, Castaneda AR, et al. Lung biopsy in congenital heart disease: a morphometric approach to pulmonary vascular disease. Circulation 1978;58: Addonizio LJ, Gersony WM, Robbins RC, et al. Elevated pulmonary vascular resistance and cardiac transplantation. Circulation 1987;76(Suppl5): Cooper DKC, Hassoulas G, Novitsky D, et al. The results of orthotopic and heterotopic heart transplantation at Gisote Schuur Hospital, Capetown: Heart Transplant 1982;1: Rogers AJ, Trento A, Siewers RD, et al. Extracorporeal membrane oxygenation for postcardiotomy cardiogenic shock in children. Ann Thorac Surg 1989; Billingham ME. Cardiac transplant atherosclerosis. Transplant Proc 1987;19: Uretsky BF, Murali S, Reddy PS, et al. Development of coronary artery disease in cardiac transplant patients receiving immunosuppressive therapy with cyclosporine and prednisone. Circulation 1987;

6 622 TRENTO ET AL Ann Thorac Surg 15. Pennington DG, Sarafrin J, Swartz M. Heart transplantation in children. Heart Transplant 1985;4: Hess ML, Hastillo A, Mohanakumar T, et al. Accelerated atherosclerosis in cardiac transplantation: role of cytotoxic B-cell antibodies and hyperlipidemia. Circulation 1983;68(Suppl2): Starzl TE, Porter KA, Iwatsuki S, et al. Reversibility of lymphomas and lymphoproliferative lesions developing with cyclosporine-steroid therapy. Lancet 1986;1: Ho M, Gaffe R, Miller T, et al. The frequency of Epstein-Barr virus infection and associated lymphoproliferative syndrome and its manifestation in children. Transplantation 1988; 45: DISCUSSION DR LEONARD L. BAILEY (Loma Linda, CA): I thank Dr Trento for sending me a preliminary copy of the manuscript, which I read with considerable interest. Both the manuscript and his presentation have engendered in me a response that is more emotional than intellectual. I'm filled with a combination of astonishment and empathy for my Pittsburgh friends and colleagues who are, I believe, clearly better at what they do than this report implies. This is, after all, a preliminary report, and its utility has to do with teaching the rest of us where the pitfalls might lie in a pediatric heart transplant program. I believe there must be a better way to effect organ transplantation even in this most difficult of all age groups. I have at least two profound impressions from this presentation. First, the recipient selection in this preteen and teenage group must be very objective and based on valid, reliable, and current data. Children with more than 5 Wood units of pulmonary arteriolar resistance ought not to have orthotopic heart transplantation in its usual form. I know that Dr Eric Rose at Columbia has been able to see a few children with higher resistances through transplantation. I know also that Dr Magdi Yacomb's group has done the same by using so-called conditioned hearts. But, on the average, results are poor when pulmonary resistance is up. I believe that elevated PVR is a nonnegotiable issue. It is better for every one of us to stay out of that physiological hornet's nest and thereby improve operative survival. Second, I learned from this report that this age group of recipients on this immunosuppressive protocol may have a higher than expected rate of accelerated coronary atherosclerosis and lethal rejection. There are probably many reasons for this, but I believe that steroids accelerate the condition. Like the Harefield Hospital group, we believe strongly that chronic steroid administration has no place in maintenance immunosuppression of transplanted infants and children. We have been generally successful in achieving this goal, and Dr Yacomb's group never really initiates chronic steroid use in their transplanted children. At last report, Dr Yacomb's group had a 75% overall survival in 36 children operated on since They have not observed accelerated atherosclerosis, chronic hypertension, and chronic renal failure in anything like the magnitude reported in the present study, and neither have we. I am sure that the recipient compliance in this difficult age group factors into late survival, and these youngsters require the closest of medical and psychological surveillance. Finally, I wish to add a word about philosophy of management with regard to structural heart disease. If donor supply permits, I believe that babies born with incurable congenital heart disease and normal lungs preferentially should have a heart transplant. The sooner after birth it occurs, it seems to me, the better. Operative survival, quality of life, and durability of therapy may all be enhanced by this approach if our experience at Loma Linda is an indication. Palliative interventions, although frequently necessary, postpone the need for transplantation and thus increase the surgical, immunological, and infectious risks. I believe we must amplify our interest in infants and children who need heart transplantation. We must learn all we can from candid and honest reports such as the one we have heard today and not be discouraged by these results. Infants and children with end-stage heart disease need our commitment to make heart transplantation not only palliative therapy, but also curative therapy in every sense of the word. We believe we may be edging near to that reality in the newborn and early infant age group. With the help of some of the phenomenal new monoclonal antibodies being studied presently in our laboratory and others, transplantation cures seem inevitable for the older children. DR CRAIG R. SMITH (New York, NY): I congratulate Dr Trento and associates on another great contribution from their enormous experience. Our experience has been somewhat different at Columbia Presbyterian in New York, where Dr Rose, Dr Reemtsma, and I have performed transplantation in 30 patients between the ages of four days and 18 years. Although our overall results are quite similar to those of the present study, with a 28% perioperative mortality and a 60% 1-year survival, we differ somewhat in our experience, with 9 patients with congenital heart disease. In this group, there were two perioperative deaths (a 22% mortality), with one death owing to sepsis at 2 weeks and one death in the operating room owing to unequivocal donor failure. With regard to the discussion in the abstract of what constitutes unfavorable pulmonary anatomy, 4 of our patients had pulmonary arterial anatomy requiring reconstruction at the time of transplantation, accomplished with no perioperative mortality and one late death of rejection. I will briefly describe two examples. One child with a single ventricle and transposition of the great arteries was treated in infancy with atrial septectomy and pulmonary artery (PA) banding, and underwent transplantation at age 4 years by Dr Rose. At the time of transplantation, the tight band behind the aorta was divided and the arteriotomy was extended into the constricted left PA, with the area patched open with the donor's PA bifurcation. This child is alive and well 4 years later. Another patient, born with a single ventricle and pulmonary atresia, had a Waterston shunt at age 4 months. When I performed transplantation on this patient at age 17 months, his pulmonary angiogram showed kinking and partial obstruction of the right PA and only trace filling of the left PA. At operation, the Waterston shunt was resected and both PAS were reconstructed with a long pericardial patch. A pulmonary angiogram obtained 3 months later was essentially normal, and this patient is alive and well at 2 years. Knowing the experience of Dr Trento and his colleagues, when we hear thunder and lightning from Pittsburgh it may be presumptuous to forecast anything but rain. Nonetheless, in this very small subsegment of the transplant population, in which each patient tends to present a unique set of problems, perhaps we should be cautious about making lists of anatomical exclusions. I think patients who are otherwise satisfactory should

7 Ann Thorac Surg TRENTOETAL 623 undergo transplantation if surgical correction has a reasonable chance of achieving acceptable PVR. My only question for Dr Trento is how do you define unfavorable PA anatomy; isn t it really a matter of achieving an acceptable PVR? DR TRENTO: I thank Dr Bailey for his kind comments and I compliment the New York group for their excellent results. It is so difficult to say what is unfavorable PA anatomy. Our 2 patients obviously had difficult PA anatomy. One of them had a previous Norwood procedure followed by bilateral modified Blalock-Taussig shunts, which distorted both PAS at the hilum. Probably at present we would not have considered him a transplant candidate. But I do agree that it is difficult to decide, on the basis of anatomy, whether a patient can undergo an orthotopic heart transplantation. As far as patient selection, we obviously had a painful experience, and many of those patients that we have transplanted and lost would not now be accepted as candidates. I am referring particularly to the 2 patients who were supported with extracorporeal membrane oxygenation for 3 or 4 days. After this period of extracorporeal membrane oxygenation support, they certainly were not viable candidates for the transplant procedure, because of the severe pulmonary edema and fluid overload.