Renal insufficiency is associated with early mortality in pediatric lung re-transplantation

The Journal of Heart and Lung Transplantation Volume 23, Number 2S

month, 91% at 6 months, and 91% at 1 year following infection. The major risk factor for CMV was D⫹/R- (p ⬍ 0.0001). Among all other D/R combinations, the freedom from CMV infection ranged from 90 –98% at 6 months. In all D/R combinations (including D⫹/R-), there was no significant reduction in CMV infection with any form of prophylaxis. Conclusions: CMV infection is infrequent except in CMV negative recipients with CMV positive donors. Death from CMV infection is uncommon. There does not appear to be a demonstrable benefit of any type of CMV prophylaxis in our study. 251 BASILIXIMAB IN CRITICALLY ILL CHILDREN UNDERGOING HEART TRANSPLANTATION: INITIAL DATA K.A. Ford,1 C.M. Cale,2 P.G. Rees,3 M.J. Elliott,3 M. Burch,3 1 Pharmacy Department, Great Ormond Street Hospital for Children, London, United Kingdom; 2Immunology Department, Great Ormond Street Hospital for Children, London, United Kingdom; 3Cardiology Department, Great Ormond Street Hospital for Children, London, United Kingdom Rationale: More children are coming to heart transplantation (HTx) on extracoporeal membrane oxygenation (ECMO), or inotropic support and/or renal impairment. The use of basiliximab, a chimaeric monoclonal antibody against CD25 (IL2Ralpha) has not been previously reported in critically ill paediatric heart transplant patients. Basiliximab has potential advantages in the management of patients with renal impairment. Patients: Basiliximab was given to 29 patients (median age: 7.8y; 0.4-16y) on ECMO, with renal impairment or on intravenous inotropes preceeding transplantation. Children normally received two doses on day 0 and day 4 post-transplant. Calcineurin inhibitor (CI) was given in low dose or withheld altogether in patients with renal impairment. Flow cytometry was used to monitor CD25. Results: At transplantation, 12 patients were on ciclosporin, the remaining 17 were on tacrolimus. All but 3 patients had subtherapeutic levels of CI in the first post-operative week. There were 21 patients who had more than 2 consecutive doses of CI cancelled in the first week (median consecutive cancelled doses: 8; 3-40doses). There were 64 surveillance biopsies and 3 episodes of severe acute rejection in the first 6 months. In all children, serum creatinine had returned to within normal limits for age by 1 month post-tx. Infections rates were low and acceptable. CD25 was undetectable at first assessment, and in all but two patients (on ECMO) thereafter. There were no adverse effects. Conclusion: Basiliximab can be used safely in critically ill children undergoing HTx. In children with pre- or post- operative renal dysfunction, basiliximab provided adequate immunosuppression to allow delay of CI for up to 40 consecutive doses without increase risk of rejection. These preliminary results are encouraging yet need confirmation in a large prospective trial. 252 ASSOCIATION OF GROWTH HORMONE THERAPY WITH THE DEVELOPMENT OF BRONCHIOLITIS OBLITERANS SYNDROME IN PEDIATRIC LUNG TRANSPLANT RECIPIENTS S.C. Sweet,1 M.T. de la Morena,1 P.M. Schuler,1 C.B. Huddleston,2 E.N. Mendeloff,2 1Department of Pediatrics, Washington University, St. Louis, MO; 2Department of Cardiothoracic Surgery, Washington University, St. Louis, MO Background: Many pediatric lung transplant recipients suffer from somatic growth failure. The majority have growth failure prior to transplant due to chronic respiratory failure and factors related to

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underlying disease. The use of corticosteroids is felt to be the primary post-transplant factor. However, some patients fail to improve their somatic growth when steroids are weaned during the first year after transplant. In these instances growth hormone (GH) has been considered. Studies of GH use in renal transplant have raised questions about its contribution to chronic rejection of the transplanted kidney. Therefore, we reviewed our experience with GH administration to determine the impact of GH on development of bronchiolitis obliterans syndrome (BOS). Methods: Computerized records of patients who underwent lung transplantation at St. Louis Children’s Hospital between June 1990 and July 2003 were reviewed. Of 236 recipeints, nine received GH after transplant. Outcomes in this group of patients were compared to 71 patients of similar age and diagnosis who underwent lung transplant during the same period. Results: Of the nine patients who received GH, eight developed BOS subsequent to beginning GH therapy. The ninth patient was well at last follow-up at our center 2 years ago. Compared to the group of patients with similar age at transplant and pre-transplant diagnosis, patients who received GH were more likely to develop BOS (RR 8.7, p ⫽ 0.03, Fisher’s Exact Test). In contrast, Kaplan-Meier analysis of the freedom from BOS in the GH population compared to control was not significantly different. There was no difference in Kaplan-Meier graft survival between the two groups. Conclusions: Patients who received GH treatment following lung transplant had a higher incidence of OB compared to a control cohort. Survival and freedom from BOS was not different. Analysis of a larger group of patients is necessary to clarify these findings. However, based on this analysis, we recommend that GH be used cautiously in pediatric lung transplant recipients. 253 RENAL INSUFFICIENCY IS ASSOCIATED WITH EARLY MORTALITY IN PEDIATRIC LUNG RE-TRANSPLANTATION M.T. de la Morena,1 S.C. Sweet,1 K. Schechtman,3 P.M. Schuler,1 E.N. Mendeloff,2 C.B. Huddleston,2 1Pediatrics, Washington University School of Medicine, St. Louis, MO; 2Cardio-Thoracic Surgery, Washington University School of Medicine, St. Louis, MO; 3 Biostatistics, Washington University School of Medicine, St. Louis, MO Introduction: Early survival is lower in patients undergoing lung re-transplantation. We sought to identify risk factors associated with mortality in pediatric patients that receive a second lung transplant. Material and Methods: We reviewed the charts of all pediatric patients undergoing bilateral lung transplantation (BLT) between June of 1990 through November 2002. Demographic, physiologic, operative and outcome data were collected and categorized as variables prior to transplant, at time of transplant and post-transplantation. Data corresponding to a first transplant in those patients receiving a second transplant were excluded to avoid bias. Results: 203 transplants were performed: 175 patients (pts) received 1st transplant (Txp); 28 pts received a 2nd Txp; median follow up was 667days. Both cadaveric BLT and living donor lobar transplants (LDLT) were included. A higher proportion of patients received LDLT as a second transplant (p ⫽-0.002). No statistical difference were noted for gender, primary diagnosis, infectious colonization, mechanical ventilation at time of transplant, height and weight z-scores, need for re-operation, bypass time, rejection episodes in first year, development of bronchiolitis obliterans or post transplant lymphoproliferative disease for either transplant. The differences in survival between 1st and 2nd Txp is accounted for by mortality during the first year (p ⬍ 0.01). Donor CMV status and operative bleeding were predictors of mortality for both 1st and 2nd Txp (p ⬍ 0.05). However,

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in this pediatric population, renal function at second transplant was an independent predictor of mortality (p ⬍ 0.05). Conclusion: In contrast to adult experience, mechanical ventilation at time of second transplant was not a predictor for mortality in pediatric lung re-transplantation. Instead, renal insufficiency was the unique predictor of mortality in this pediatric population. Based on these findings, we have adopted creatinine clearance ⬍50ml/min/m2 as a contraindication for pediatric lung re-transplantation. 254 PEDIATRIC LUNG TRANSPLANT: DO PRIMARY PULMONARY HYPERTENSION PATIENTS HAVE WORSE OUTCOME? S. Koulouri,1 M.S. Woo,1 M.V. Horn,1 E. Perez,1 V.A. Starnes,1 J.R. Szmuszkovicz,1 1Cardiothoracic Transplant Program, Childrens Hospital Los Angeles, Los Angeles, CA High mortality risk has been reported for primary pulmonary hypertension (PPH) pts undergoing lung transplantation (LTx). Do PPH children have worse outcomes after LTx than cystic fibrosis (CF) children? All pediatric PPH pts undergoing LTx at our institution were compared to CF pts undergoing LTx in the same period. Data collected: demographics, echocardiograms, ischemic times, cardiopulmonary bypass times (CPB), perioperative and 1-year survival. From 1994-2002, 10 PPH children (3M:7F; mean age at Tx 13.7 ⫾ 3.4 years) underwent LTx. Seven were on IV prostacyclin and 3 took oral beraprost prior to Tx. There were 5 living donor double lobar lung (LDL) Txs and 5 cadaveric double LTxs. Prior to Tx, all PPH pts had severe right ventricular and right atrial dilatation with pancaking of the left ventricle. Mean tricuspid regurgitation gradient prior to Tx was 102.5 ⫾ 18.4 mmHg (range 74-140 mm Hg). Six pts were NYHA Class III and 4 were NYHA Class IV. Mean PPH ischemic times were 148.1 ⫾ 83.4 min (range 52.5- 294 min). Mean CPB times were 139.9 ⫾ 40.6 min (range 85-214 min). 9 PPH pts survived the perioperative period (90%); 1 pt expired from non-specific graft failure. Of the 9 surviving pts, 1 pt is ⬍6 months post-Tx and 8 pts have survived ⬎1 year (100%). During the same period, 41 CF pts (22M:19F; mean age at Tx 14.9 ⫾ 3.5 years) were transplanted. There were 34 LDL and 7 cadaveric LTxs. Mean CF ischemic times were 99.7 ⫾ 52.6 min (range 44.5-249 min). Mean CPB times were 124.2 ⫾ 36.2 min (range 75-260 min). Of 41 CF pts, 38 survived the perioperative period (93%). One-year CF Tx survival was 92%. There was no difference between groups in age (p ⫽ 0.33), gender distribution (p ⫽ 0.29), CPB time (p ⫽ 0.25), perioperative mortality (p ⫽ 1.0), or 1-year survival (p ⫽ 1.0). There was a significant difference in ischemic times (p ⫽ 0.02) and type of Tx surgery (p ⫽ 0.04). We conclude that pediatric PPH pts have similar perioperative and 1-year survival compared to CF pts undergoing LTx. Our findings support lung transplantation as a viable therapeutic option for pediatric PPH pts who fail to respond to medical therapy. 255 IMPACT OF SIROLIMUS ON LIPID PROFILES IN PEDIATRIC THORACIC ORGAN RECIPIENTS A. Byno,1 Y. Law,1 G. Boyle,1 S. Miller,1 P. Fitzgerald,1 S. Gandhi,1 R. Sindhi,1 S. Webber,1 1Cardiology and Transplantation, Children’s Hospital, Pittsburgh, PA Background and Aims: Sirolimus is an effective immunosuppressant with good safety profile. However, its propensity to cause hyperlipidemia in adults has raised concerns about its use in heart Tx. We sought to assess the impact of sirolimus on lipid profiles in children, and to determine the response of elevated lipids to statins. Methods: Pediatric thoracic recipients commenced on sirolimus for refractory acute rejection, chronic rejection or for CI sparing under-

The Journal of Heart and Lung Transplantation February 2004

went prospective safety monitoring that included fasting lipid profiles at baseline, 1, 2 and 6 months, then every 6 months thereafter. Pravastatin was commenced when hyperlipidemia developed (LDL ⬎ 130, TC ⬎ 220) but was not used prophylactically. Results: 21 patients aged 15 ⫾ 5.3 yrs were commenced on sirolimus at 3.6 ⫾ 3.7 yrs after Tx (12 male; 15 heart, 6 lung). 20 were on tacrolimus and 1 on cyclosporine. Baseline total cholesterol (TC) was 164 ⫾ 45 mg/dl and rose to 190 ⫾ 50 at 1mo with minimal additional rise by 6 mos 197 ⫾ 56 (p ⬍ 0.02). Overall increase in TC reflected increases in HDL, LDL and VLDL (% change from baseline to peak value prior to any statin use of 25, 33, 23 and 66% respectively). Triglycerides (TG) also increased early from baseline of 154 ⫾ 95 mg/dl to 195 ⫾ 134 at 3 mos (p ⬍ 0.03). 7 pts (35%) developed TC ⬎ 250 or TG ⬎ 300 at some point during sirolimus therapy. Five of these 7 were diabetic and all were receiving corticosteroids. Statin therapy was introduced in 8 patients. Response to therapy was rapid with significant fall over first month sustained over 6 months. Decrease in LDL was significantly greater than that for HDL: median lipid levels at 0, 1 and 6 mo after start of statin: TC 242, 218, 188; LDL 173, 119, 86; HDL 70, 56, 61; TG 445, 337, 251. Conclusion: Significant rises in all fractions of standard fasting lipid profile were seen after introduction of sirolimus with greatest rise in the first month. Lipid abnormalities with sirolimus were most severe in patients on steroids, especially if diabetic. Response to statin therapy was usually rapid and was most marked for LDL. 256 PREPONDERANCE AND IMPLICATIONS OF ETIOLOGICAL MISCLASSIFICATION IN ADVANCED HEART FAILURE: A CLINICAL-PATHOLOGICAL INVESTIGATION P.A. Uber, Z.M. N’Dandu, M.H. Park, R.L. Scott, H.O. Ventura, M.R. Mehra, Ochsner Clinic Foundation, New Orleans, LA Background: Etiology of heart failure is typically demarcated into ischemic and non-ischemic cardiomyopathy. This classification allows us to focus on strategies for modification of ischemic substrates when ventricular dysfunction results from sequelae of coronary artery disease (CAD). Purpose: We sought to determine correlative accuracy of clinical etiological classification of ventricular dysfunction with subsequent pathological diagnosis and to ascertain significance of concomitant CAD. Methods: Between 1/1992-8/2003, 112 patients classified as nonischemic cardiomyopathy by a heart failure specialist, underwent heart transplantation. Patients were excluded for age ⬍35, congenital heart disease, myocarditis, primary valvular heart disease or infiltrative disease. Explanted hearts were examined by a blinded pathologist, who reclassified the etiology of heart failure. Ischemic cardiomyopathy was defined as the presence of severe 3-vessel CAD with extensive myocardial scar. In those accurately classified, presence of co-morbid CAD and myocardial ischemia was also evaluated. Results: The cohort included patients (age 57 ⫾ 9 years, 60% men) with severe ventricular dysfunction (LVEF 19 ⫾ 11%) and nonischemic cardiomyopathy as the listing diagnosis at cardiac transplantation. Pathological analysis resulted in reclassification of 21% (23/ 112) as ischemic cardiomyopathy. Of those accurately classified (89/112), 33% (29/89) had at least moderate-severe CAD in ⫽ 1 vessel territory (⫾ infarction). Additionally, 18% (16/89) had areas of recent ischemia (occlusive thrombus or ischemic infarction). Those with inaccurate classification were older (59 ⫾ 7 vs 53 ⫾ 8 years, p 0.001) with shorter time to transplantation (44 vs 58 months, p 0.05). Conclusions: This investigation suggests a high prevalence of etiological mis-diagnosis in advanced heart failure. Furthermore, the clinical classification of non-ischemic cardiomyopathy etiology underestimates contribution of concomitant coronary arteriopathy to dis-