Cardiac transplantation has become an accepted

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1 Cardiac Retransplantation in Children Kirk R. Kanter, MD, Robert N. Vincent, MD, Alexandria M. Berg, MSN, William T. Mahle, MD, Joseph M. Forbess, MD, and Paul M. Kirshbom, MD Division of Cardiothoracic Surgery, Department of Surgery, and Children s Healthcare of Atlanta at Egleston, Division of Pediatric Cardiology, Emory University School of Medicine, Atlanta, Georgia Background. Experience with pediatric cardiac retransplantation is limited. Outcomes should be inspected to insure proper use of donor hearts. Methods. Of 152 pediatric heart transplantations, we performed 20 retransplants in 17 children (3 had a second retransplant). The retransplant children were older than the primary transplant children ( years versus years; p 0.005). Excluding 1 early retransplant, the interval from primary transplant to retransplant was years (range, 1.1 to 11.1). The retransplant patients were clinically more ill than the primary transplant patients (United Network for Organ Sharing status I, 75% versus 63%; mechanical circulatory support or dialysis, 20% versus 3.8%). Results. Donor ischemia time (188 versus 165 minutes) and cardiopulmonary bypass time (127 versus 127 minutes) were not significantly different for the retransplant patients. Excluding 1 retransplant patient who required a tracheostomy, days on the ventilator (2.7 versus 2.7), days Cardiac transplantation has become an accepted treatment for end-stage or inoperable heart disease in children [1]. With time, increasing numbers of children who have undergone heart transplantation will have transplant coronary artery disease or chronic graft dysfunction for which the only current successful treatment is cardiac retransplantation [2 4]. The experience with cardiac retransplantation in adults, however, often has been disappointing [5 13]. Some have even advocated the elimination of the option of cardiac retransplantation [14]. In view of the ongoing critical shortage of suitable cardiac donors, it is therefore important to examine outcomes with pediatric cardiac retransplantation to determine whether it is a reasonable use of scarce resources (ie, donor hearts). With this in mind, we have examined our results with 20 cardiac retransplantations in 17 children and that forms the basis of this report. Patients and Methods Patient Population Since the inception of our heart transplant program in 1988, of 152 pediatric heart transplants performed at our Accepted for publication Feb 18, Presented at the Fiftieth Annual Meeting of the Southern Thoracic Surgical Association, Bonita Springs, FL, Nov 13 15, Address reprint requests to Dr Kanter, Division of Cardiothoracic Surgery, Emory University School of Medicine, 1365 Clifton Rd, Atlanta, GA 30322; kkanter@emory.edu. on inotropic support (3.0 versus 3.2), intensive care unit days (7.2 versus 6.7), and hospital days (15.9 versus 13.8) were similar in the retransplant group. Freedom from rejection at 90 days and 1 year was not different in the retransplant patients. Actuarial patient survival in the patients undergoing first retransplant was similar to the primary transplant patients at 30 days (95% versus 94.7%), 1 year (94.1% versus 80.7%), and 3 years (78.4% versus 73.1%). Two of 3 children receiving a third transplant died within 1 year of redo retransplantation. Conclusions. Cardiac retransplantation can be performed in children with results comparable with those for primary transplantation despite increased clinical acuity. These early results suggest that cardiac retransplantation in children is a reasonable therapeutic option. Children with repeat retransplantation do not fare as well. (Ann Thorac Surg 2004;78:644 9) 2004 by The Society of Thoracic Surgeons institution, 17 children underwent 20 retransplant procedures (3 children had a second retransplant). The number of cardiac transplant procedures performed each year at our institution divided into primary transplants and retransplants is shown in Figure 1. Our first pediatric retransplantation was performed in Since then, the number of retransplants has become an increasing proportion of our total transplant volume. The clinical characteristics of the children at the time of retransplantation are shown in Table 1 as compared with the 132 children undergoing a primary transplant procedure. The retransplant patients were significantly older than the patients undergoing primary transplantation. The percentage of retransplant patients who were United Network for Organ Sharing (UNOS) status I was higher than in the primary transplant group, but that did not achieve statistical significance. Nonetheless, the percentage of patients requiring mechanical assistance (defined as the use of a ventricular assist device, extracorporeal membrane oxygenation, an intraaortic balloon, continuous venovenous hemofiltration, or dialysis) at the time of transplantation was significantly greater in the retransplant group (Table 1). The retransplant group also had higher levels of preformed antibodies compared with the primary transplant patients. Only 1 child in this series required early retransplantation for acute graft failure. For the remaining 19 retransplants, the interval from primary transplant to retransplant (or from first retransplant to second retransplant 2004 by The Society of Thoracic Surgeons /04/$30.00 Published by Elsevier Inc doi: /j.athoracsur

2 Ann Thorac Surg KANTER ET AL 2004;78:644 9 RETRANSPLANTATION IN CHILDREN 645 Abbreviations and Acronyms CPB cardiopulmonary bypass CTRD Cardiac Transplant Research Database CVVH continuous veno-venous hemofiltration ECMO extracorporeal membrane oxygenation ICU intensive care unit ISHLT International Society for Heart and Lung Transplantation NS not significant UNOS United Network for Organ Sharing for the 3 children who had 3 transplants) ranged from 1.1 to 11.1 years (mean, ; median, 4.6). The indications for retransplantation for the 19 nonacute retransplants were transplant coronary artery disease in 11, chronic graft failure in 6, and graft failure associated with acute rejection in 2. During this same time, 7 other children were listed for cardiac retransplantation but were not retransplanted. Two of the children improved clinically; they were removed from the transplant waiting list and continue to do well. The other 4 died before a suitable donor could be located 2 were listed for their first retransplant and 2 were listed for a redo retransplant (their third transplant). The remaining patient remains on the heart transplant waiting list. Table 1. Patient Characteristics at Time of Transplantation Retransplant (n 20) Primary (n 132) p Value Age, years UNOS status I 75% 63% 0.33 Mechanical support 20% a 3.8% Days listed Class I PRA 10% 25% 15.4% 0.33 Class II PRA 10% 69% 31% a One patient was supported with extracorporeal membrane oxygenation, 1 with continuous venovenous hemofiltration (CVVH) for renal failure, 1 with an intra-aortic balloon pump (IABP), and 1 with both CVVH and IABP. PRA panel reactive antibodies; UNOS United Network for Organ Sharing. Operative Strategy and Patient Management The operative and postoperative management of the retransplant patients was no different from that received by the primary transplant patients and has been described previously [1]. We required a negative prospective crossmatch before transplantation for patients with high levels of preformed antibodies (defined as class I panel reactive antibodies [PRA] 20%). Recently, for sensitized recipients who are clinically acutely ill (UNOS status IA), our institutional policy has been to treat these patients with mycophenolate and intermittent intravenous immunoglobulin before transplant, then with plasmapheresis at the time of transplant and after transplant for 2 weeks. None of the 4 patients who were listed for retransplantation but died before a suitable donor was available required a prospective crossmatch. Induction immunotherapy was not used routinely. All patients were maintained on triple-drug immunosuppression therapy (cyclosporin or tacrolimus, azathioprine or mycophenolate, and a weaning dose of steroids). Periodic surveillance endomyocardial biopsies were obtained from all patients, as were routine annual coronary arteriograms. Efforts were made to wean patients from steroids entirely within a year of transplantation based on negative endomyocardial biopsies. Rejection episodes were treated with pulsed steroids. Only recurrent, refractory, or hemodynamically compromising rejection episodes were treated with monoclonal antibodies such as OKT-3. Diagnostic intravascular ultrasonography of the coronary arteries was not used routinely. Statistics Continuous variables were compared by analysis of variance and are presented as the mean standard deviation. Nominal variables were compared by 2 analysis with Fisher s exact test. Life-table analysis was done by the Kaplan-Meier survival method with significance determined by log-rank analysis. Significance was defined as a p value of 0.05 or less. Fig 1. The total number of pediatric transplants performed at the authors institution by year (x-axis) broken down into primary transplants (gray bars) and retransplants (black bars). *Numbers for 2003 are through October Results A tabulation of the early perioperative results comparing the retransplant procedures to the primary transplant procedures is shown in Table 2. Donor ischemia time was slightly but not significantly longer in the retransplant group, but cardiopulmonary bypass times were the same. Various measurements during the hospital stay were also similar after one excludes 1 redo retransplant patient who had respiratory failure requiring a tracheostomy (Table 2). She was eventually discharged home 5 months after retransplantation on home ventilation. There was 1 death within 30 days of transplantation in the retransplant group (95% 30-day survival). This was in 1 of the 2

3 646 KANTER ET AL Ann Thorac Surg RETRANSPLANTATION IN CHILDREN 2004;78:644 9 Table 2. Comparison of Early Perioperative Results of Retransplant and Primary Transplant Groups Retransplant (n 20) Primary (n 132) p Value Donor ischemia (minutes) CPB time (minutes) Days ventilated a Days on inotropes ICU days a Hospital days a Day survival 95.0% 94.7% NS a Excludes one redo retransplant patient who had respiratory failure necessitating a tracheostomy. CPB cardiopulmonary bypass; ICU intensive care unit; NS not significant. patients undergoing retransplantation for graft dysfunction associated with acute rejection. At the time of retransplant, he was on a ventilator with an intraaortic balloon requiring continuous venovenous hemofiltration for renal failure. He died 15 days after retransplantation of multisystem organ failure. The other patient who underwent retransplantation associated with acute rejection died of transplant coronary artery disease 3.5 years after retransplant while on the waiting list for a third transplant. Despite higher levels of preformed antibodies before retransplantation defined as a PRA of 10% or greater (Table 1), the retransplant patients were no less likely to be free of acute cellular rejection in the first year postoperatively than were the primary transplant patients (Fig 2). The retransplant patients have been followed up a mean of years (range, 15 days to 8.4 years). Two of the 3 redo retransplant patients died of chronic graft dysfunction 8.7 and 9.4 months after retransplantation. The third redo retransplant patient is currently doing well 2 months after her third transplant. The patient who underwent retransplantation for acute graft failure survived 7 years before undergoing a redo retransplant for transplant coronary artery disease (she was the patient who required a tracheostomy for respiratory failure, and she died 8.7 months after her third transplant). Actuarial patient survival comparing the 17 patients undergoing first retransplantation with the 132 children undergoing primary transplantation is shown in Figure 3. Survival among the retransplant patients was similar to that of the primary transplant patients at 1 year (94.1% versus 80.7%) and 3 years (78.4% versus 73.1%). Fig 2. Percentage of patients in the primary transplant group (gray bars) and the retransplant group (black bars) who were free of acute rejection at different time intervals after transplantation. (NS not significant.) Since the first published report of cardiac retransplantation from Stanford [15], the outcomes of retransplanted patients compared with outcomes of patients undergoing primary transplantation have been reported to be suboptimal, particularly in adults. Subsequent reports from Stanford have continued to confirm these early disappointing findings [5, 16, 17]. The most recent update from Stanford in 1999 analyzed 69 retransplants in 67 patients over a 30-year period. They reported 1-, 5-, and 10-year actuarial survival rates of 49%, 27%, and 15%, respectively [11]. Other individual centers have confirmed these poorer results with cardiac retransplantation in adults. Mullins and colleagues [6] from Papworth Hospital in Great Britain reported a 33% 1-year survival with 13 retransplants in 12 patients. The Utah transplant group had a 1-year survival rate of 74% in 20 retransplant patients compared with an 88% 1-year survival with primary transplantation [8]. In Paris, Schnetzler and others [10] performed 24 retransplants of 1,063 transplant procedures with a 45.5% 1-year survival and a 31.2% 5-year survival rate. Early results with retransplantation in multi-institutional studies have echoed these single-institution results. The Registry of the International Society for Heart and Lung Transplantation (ISHLT) examined 449 retransplant procedures mainly in adults with a 1-year actuarial survival of 48% [7]. Another report in 2000 from the combined ISHLT/UNOS database continued to show inferior outcomes in 514 adult retransplantations with a 1-year survival of 65% and a 3-year survival of 55% [12]. More Comment Fig 3. Patient survival using the Kaplan-Meier method with a mean follow-up interval of years for the patients undergoing first retransplant (dotted line) compared with the primary transplant patients (solid line). (NS not significant; Re-Tx retransplant.)

4 Ann Thorac Surg KANTER ET AL 2004;78:644 9 RETRANSPLANTATION IN CHILDREN 647 recently, investigators from the Cardiac Transplant Research Database Group (CTRD) compared 106 retransplants with 7,290 primary transplants and found an actuarial survival of 56% at 1 year and 38% at 5 years for the retransplant patients [13]. There have been, however, a few reports concerning adult cardiac retransplantation that are more promising. The Columbia group reported results with adult cardiac retransplantation similar to primary transplantation [18, 19]. After 1993, they adopted a policy of not performing retransplantation for acute graft failure or for acute rejection within 6 months of primary transplantation. With this policy, they achieved an amazing 94% survival at 1, 2, and 4 years in 19 retransplant patients [19]. Interestingly, the most recent report of the ISHLT Registry analyzed 5,923 adult transplants from 1999 to 2001 and found that retransplantation was no longer a risk factor for 1-year mortality [20]. The authors speculate that these improved results are due to avoiding retransplantation for acute graft failure or for early acute rejection. Other investigators also have shown that results with adult cardiac retransplantation are improved if the retransplant procedure is remote from the primary procedure or if it is performed for transplant coronary artery disease [2, 7 10, 12, 13, 16, 21]. There are very few publications looking specifically at pediatric cardiac retransplantation. The only singleinstitution papers with reasonable numbers of pediatric retransplant patients have come from the pioneering team at Loma Linda. They have shown no difference in survival rates between children undergoing retransplantation and those with primary transplantation [3, 22]. Their most recent report of 22 retransplants of 347 total pediatric transplants revealed a 3-year actuarial survival in the retransplant group of 81.9% compared with 77.3% in the primary transplant group [23]. Two of their 3 early retransplant deaths were from the group who underwent early retransplantation for acute graft failure (n 5). There was only 1 late death in their series. However, owing to the nature of the patient population of the Loma Linda transplant group, most of their retransplant patients had their primary transplant in infancy. This emphasis on neonatal transplantation differs from our program and that of many other busy pediatric transplant centers. Michler and colleagues [24] performed a multiinstitutional study looking at 17 pediatric cardiac retransplantations excluding children who had their primary transplant in the neonatal period. The actuarial 1-year and 3-year survivals in their study were 71% and 47%, respectively, even though only 1 patient required retransplantation for acute graft failure. The most recent pediatric report of the ISHLT did not identify retransplantation as a risk factor for 1-year or 5-year mortality on multivariate analysis [25]. However, retransplantation did prove to be a significant risk factor for mortality within 5 years, considering only those children who survived the first posttransplant year (odds ratio 4.68; p 0.003) [25]. The current study demonstrates that retransplantation in children can be performed with early results comparable to those of children undergoing primary transplantation (Table 2) despite higher clinical acuity in the retransplant group (Table 1). Although the retransplant patients more often had increased levels of preformed antibodies (Table 1), they were just as likely to be free of acute cellular rejection at different time intervals during the first posttransplant year (Fig 2). This apparent paradox of similar or fewer early rejection episodes after retransplantation has been observed previously both in adults [16, 18] and in children [24]. The explanation for this phenomenon in our series is not obvious. Certainly, our retransplant patients did not receive enhanced immunosuppression therapy compared with the primary transplant patients. The 30-day survival in our series of 95% for the retransplant patients was comparable with that for the primary transplant patients (94.7%) despite a significantly higher use of mechanical assistance (20% versus 3.8%; p 0.018). Although the Loma Linda group reported equivalent early survival statistics with retransplant and primary transplant patients (operative mortality 9.0% versus 8.3%), only 1 of their initial retransplant group required high-dose inotropic support and dialysis [3]. One explanation for our satisfactory early results is that only 1 of the 20 retransplants in our series was performed for acute graft failure (that patient actually survived 7 years before undergoing a third heart transplant). Although several authors have identified a short interval between primary transplantation and retransplantation as a marker for poor outcome [12, 13, 18, 21], we have not made a conscious effort to avoid early retransplantation in our series. We have been fortunate to have only rare patients who needed an early retransplant for acute graft dysfunction. The actuarial patient survival of our patients undergoing a first retransplant is not statistically different from that of the primary transplant group (Fig 3), recognizing that the mean follow-up in the retransplant patients is only 2.6 years. Naturally, there is concern that these children who need a second transplant have an unfavorable immunologic milieu that predisposes them to the development of transplant coronary artery disease or chronic graft dysfunction. It is disturbing to note that an early report from Stanford found that in 5 of 11 patients retransplanted for transplant coronary artery disease who survived 1 year, transplant coronary artery disease developed in the new graft [5]. On the other hand, others have shown that if a patient survives 6 months after retransplantation, then the risk of death is no different from that of primary transplant patients [7]. Certainly, our cohort of pediatric retransplant recipients needs to be observed long term to discover what their fate will be. Of concern in our series was the observation that 2 of the 3 redo retransplant patients (their third transplant) died within a year of retransplantation. The third patient currently is doing well although she has been followed up only 2 months since redo retransplantation. There are no significant series of third time heart transplantations in the literature. Most series of retransplan-

5 648 KANTER ET AL Ann Thorac Surg RETRANSPLANTATION IN CHILDREN 2004;78:644 9 tation list at most 2 or 3 redo retransplants, making it difficult to form an informed opinion about the fate of these patients. Even though our numbers are small, this apparent propensity for poor outcome is alarming. We have taken a very conservative approach to retransplanted children who may need a third heart transplant. We will list for retransplantation only those candidates who have no other comorbidities such as chronic renal, hepatic, or respiratory insufficiency, which even without cardiac problems would be life-limiting. Also, currently we would not list for third transplantation a child who has significant graft dysfunction or graft arteriosclerosis of the retransplanted heart within 3 years of retransplantation. In summary, we have found that cardiac retransplantation in children can be performed with reasonable early morbidity and mortality rates. Their midterm survival appears to be equivalent to children undergoing primary transplantation. Of concern in our series is the apparent poor outcome of children who need a third transplant. References 1. Kanter KR, Tam VK, Vincent RN, et al. Current results with pediatric heart transplantation. Ann Thorac Surg 1999;68: Musci M, Loebe M, Wellnhofer E, et al. Coronary angioplasty, bypass surgery, and retransplantation in cardiac transplant patients with graft coronary disease. Thorac Cardiovasc Surg 1998;46: Razzouk AJ, Chinnock RE, Dearani JA, Gundry SR, Bailey LL. Cardiac retransplantation for graft vasculopathy in children: should we continue to do it? Arch Surg 1998;133: Mulla NF, Johnston JK, Vander DL, et al. Late rejection is a predictor of transplant coronary artery disease in children. J Am Coll Cardiol 2001;37: Gao SZ, Schroeder JS, Hunt S, Stinson EB. Retransplantation for severe accelerated coronary artery disease in heart transplant recipients. Am J Cardiol 1988;62: Mullins PA, Scott JP, Dunning JJ, et al. Cardiac transplant waiting lists, donor shortage and retransplantation and implications for using donor hearts. Am J Cardiol 1991;68: Ensley RD, Hunt S, Taylor DO, et al. Predictors of survival after repeat heart transplantation. The Registry of the International Society for Heart and Lung Transplantation and Contributing Investigators. J Heart Lung Transplant 1992;11 (Suppl):S Karwande SV, Ensley RD, Renlund DG, et al. Cardiac retransplantation: a viable option? The Registry of the International Society for Heart and Lung Transplantation. Ann Thorac Surg 1992;54: Martinelli L, Rinaldi M, Goggi C, et al. Emergency and elective cardiac retransplantation. Eur J Cardiothorac Surg 1993;7: Schnetzler B, Pavie A, Dorent R, et al. Heart retransplantation: a 23-year single-center clinical experience. Ann Thorac Surg 1998;65: Robbins RC, Barlow CW, Oyer PE, et al. Thirty years of cardiac transplantation at Stanford university. J Thorac Cardiovasc Surg 1999;117: Srivastava R, Keck BM, Bennett LE, Hosenpud JD. The results of cardiac retransplantation: an analysis of the Joint International Society for Heart and Lung Transplantation/ United Network for Organ Sharing Thoracic Registry. Transplantation 2000;70: Radovancevic B, McGiffin DC, Kobashigawa JA, et al. Retransplantation in 7,290 primary transplant patients. A 10- year multi-institutional study. J Heart Lung Transplant 2003; 22: Collins EG, Mozdzierz GJ. Cardiac retransplantation: determining limits. Heart Lung 1993;22: Copeland JG, Griepp RB, Bieber CP, et al. Successful retransplantation of the human heart. J Thorac Cardiovasc Surg 1977;73: Dein JR, Oyer PE, Stinson EB, Starnes VA, Shumway NE. Cardiac retransplantation in the cyclosporine era. Ann Thorac Surg 1989;48: Smith JA, Ribakove GH, Hunt SA, et al. Heart retransplantation: the 25-year experience at a single institution. J Heart Lung Transplant 1995;14: Michler RE, McLaughlin MJ, Chen JM, et al. Clinical experience with cardiac retransplantation. J Thorac Cardiovasc Surg 1993;106: John R, Chen JM, Weinberg A, et al. Long-term survival after cardiac retransplantation. A twenty-year single-center experience. J Thorac Cardiovasc Surg 1999;117: Taylor DO, Edwards LB, Mohacsi PJ, et al. The registry of the International Society for Heart and Lung Transplantation: twentieth official adult heart transplant report J Heart Lung Transplant 2003;22: Novick RJ. Heart and lung retransplantation: should it be done? J Heart Lung Transplant 1998;17: Fortuna RS, Chinnock RE, Bailey LL. Heart transplantation among 233 infants during the first six months of life: the Loma Linda experience. Loma Linda Pediatric Heart Transplant Group. Clin Transpl 1999: Dearani JA, Razzouk AJ, Gundry SR, et al. Pediatric cardiac retransplantation: intermediate-term results. Ann Thorac Surg 2001;71: Michler RE, Edwards NM, Hsu D, et al. Pediatric retransplantation. J Heart Lung Transplant 1993;12(Suppl):S Boucek MM, Edwards LB, Keck BM, et al. The registry of the International Society for Heart and Lung Transplantation: sixth official pediatric report J Heart Lung Transplant 2003;22: DISCUSSION DR W. STEVES RING (Dallas, TX): That is an excellent series, Dr Kanter. You are to be congratulated on really outstanding results in this pediatric group, which, in general, tend to have worse results than the adult counterparts. One of the things that struck me about this and one of the issues that we seem to face all the time is identifying patients with severe graft vasculopathy. They are not always sick in the hospital, on mechanical support. The question I ask you is, since 75% of your patients are status I at the time of transplant, what do you use for the timing of your relisting for transplant in patients in whom you identify graft coronary artery disease, because we know the incidence of sudden death is very high once these patients have been identified with severe coronary artery disease? DR KANTER: We take our lead from the Pediatric Heart Transplant Study Group, which looked at children who were identified as having moderate or severe graft coronary artery disease on routine annual coronary arteriography. Once they are identified, their median survival is less than 8 months. Therefore, it is our institutional policy, unless there are contraindica-

6 Ann Thorac Surg KANTER ET AL 2004;78:644 9 CURRENT STRATEGIES IN HEART FAILURE 649 tions, to list them for retransplantation at the time of identification of moderate or severe graft coronary artery disease. DR RING: Under what status? DR KANTER: Whatever status into which they fit using UNOS criteria. Most of them start off as status II because they are at home, but once they get sick enough to come into the hospital, require ventilation, inotropic support or mechanical support, then of course they become status I. We do not purposely put them on inotropic support unless they hemodynamically need it. DR RING: Well, this is the paradox we face because that 80% one-year mortality, a large portion of those deaths are sudden deaths out of the hospital. In other words, they are doing well, they are not hospitalized patients, and they just suddenly drop dead from a silent MI. DR KANTER: You are exactly right. During the same time period we have listed five other patients for retransplantation who for one reason or another did not undergo retransplantation. Either they died or became noncompliant, and one patient actually got better and came off the list. DR RING: Thanks. DR CLIFFORD VAN METER (New Orleans, LA): Outstanding work. You are to be congratulated. At what level of preformed antibody do you do prospective cross matching and have you tried to immunomodulate any of your patients and what success have you had in doing that without infectious complications? DR KANTER: Our standard technique is to perform a prospective cross match if the class I PRA is greater or equal to 20%. However, once they become status I in the hospital and therefore sick, we will take a donor that is not local without a cross match and we will plasmapherese the patient intraoperatively. For immunomodulation preoperatively, we put them on methotrexate and give them periodic doses of IVIG in hopes of reducing their antibody load. The Thoracic Surgery Foundation for Research and Education 2004 Awards TSFRE Research Grants provide operational support of original research efforts by thoracic surgeons who have completed their formal training, and who are seeking initial support and recognition for their research program. Awards of up to $30,000 a year for up to two years are made each year to support the work of an earlycareer thoracic surgeon (within five years of first faculty appointment). Peter S. Dahlberg, MD, PhD University of Minnesota Robert S. Poston, MD University of Maryland TSFRE Research Fellowships provide support of up to $35,000 a year for up to two years for surgical residents who have not yet completed thoracic surgical training. Allen Cheng, MD Stanford University Danny Ramzy, MD University of Toronto Nathalie Roy, MD Children s Hospital Boston Nina Starr Braunwald Research Fellowships provide up to $35,000 a year for up to two years of support for young women in academic thoracic surgery who have not yet completed surgical training. Bao-Ngoc Nguyen, MD University of Maryland TSFRE/NHLBI Mentored Clinical Scientist Development Award (K08) Kenneth R. McCurry, MD University of Pittsburgh Cytoprotective Effect of CO in Lung Ischemia/Reperfusion Y. Joseph Woo, MD University of Pennsylvania Angiogenesis and Cardiac Growth as Heart Failure Therapy 2004 by The Society of Thoracic Surgeons Ann Thorac Surg 2004;78: /04/$30.00 Published by Elsevier Inc