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660: Outcomes with Asymptomatic Antibody-Mediated Rejection in Pediatric Heart Transplant Patients
S294
Abstracts
N.P. van der Kaaij1, J. Kluin2, R.A. Lachmann3, M.A. den Bakker4, J.J. Haitsma3, R.W.F. de Bruin5, B. Lachmann3, A.J.J.C. Bogers1 1 Erasmus MC, Rotterdam, Netherlands; 2UMC Utrecht, Utrecht, Netherlands; 3Erasmus MC, Rotterdam, Netherlands; 4Erasmus MC, Rotterdam, Netherlands; 5Erasmus MC, Rotterdam, Netherlands Purpose: Lung ischemia reperfusion injury (LIRI) contributes to morbidity and mortality after lung transplantation. The objective was to investigate the effect of open lung concept (OLC) ventilation on LIRI as compared to conventional ventilation (CV) after reperfusion. Methods and Materials: Male Sprague-Dawley rats (n⫽63) underwent 150 minutes warm ischemia of the left lung. At reperfusion, animals received conventional ventilation (tidal volume 6 ml/kg, 4 cm H2O positive end-expiratory pressure (PEEP)), OLC ventilation (collapsed alveoli were recruited by applying high peak inspiratory pressures combined with high levels of PEEP) for 3 hours or were directly extubated. Animals were killed directly after 3 hours of ventilation (day 0), day 1 or day 3 postoperatively. Blood gas values were measured and lung compliance was recorded. The level of alveolar protein and leukocyte infiltration (by flowcytometry) was assessed in broncho-alveolar-lavage-fluid (BALf). Histological analysis was performed in 3 animals per group. Results: No difference in PaO2 and lung compliance was seen between conventional ventilated and directly extubated rats on day 1. OLC ventilation resulted in higher PaO2 (day 0 and 1), less infiltration of granulocytes, macrophages, and lymphocytes in the BALf of the left lung, superior lung compliance, and less injury on HE slides as compared to CV and directly extubated rats. Conclusions: OLC ventilation at reperfusion decreases LIRI and may hereby prevent the development of ARDS and decrease the risk on long-term organ dysfunction. 658 The Impact of Aspergillus Colonization on Acute Rejection and Lymphocytic Bronchiolitis in Lung Transplant Patients S.S. Weigt1, C.-H. Tseng2, C. Huang1, D.J. Ross1, R. Saggar1, R. Saggar1, J.P. Lynch1, A. Gregson3, B.M. Kubak3, A. Ardehali4, R.M. Elashoff2, J.A. Belperio1 1David Geffen School of Medicine at UCLA, Los Angeles, CA; 2David Geffen School of Medicine at UCLA, Los Angeles, CA; 3David Geffen School of Medicine at UCLA, Los Angeles, CA; 4David Geffen School of Medicine at UCLA, Los Angeles, CA Purpose: While acute rejection (AR) is considered the principal risk factor, multiple infections have also been linked with the development of bronchiolitis obliterans syndrome (BOS). We have previously demonstrated that Aspergillus colonization is a risk factor for BOS, separate from the effects of AR. Others have recently shown that lymphocytic bronchiolitis (LB) may be a more important risk factor for BOS than AR. We hypothesized that Aspergillus colonization would be associated with an increased risk of LB in lung transplant recipients. Methods and Materials: For this study, we examined the same cohort of lung transplant recipients in whom we previously studied the impact of Aspergillus colonization on BOS (201 lung transplant recipients at UCLA between 1/2000 and 6/2006). We defined Aspergillus colonization as a positive BAL culture or two positive sputum cultures with the same Aspergillus species from patients without evidence of invasive disease. AR and LB episodes were defined strictly by histopathologic findings according to standard ISHLT criteria. We evaluated the risk of recurrent AR, LB and the composite of either AR or LB using a modified Anderson-Gill model with allowance for correlation of recurrent events.
The Journal of Heart and Lung Transplantation February 2009
Results: AR was more common after the development of Aspergillus colonization, however this increase was not statistically significant (HR ⫽ 1.19, p ⫽ 0.49). There was a non-significant trend for increased risk of LB recurrence (HR ⫽ 1.44, p ⫽ 0.062). We did find an elevated risk for the combined recurrence of AR and LB after the development of Aspergillus colonization at borderline significance (HR ⫽ 1.39, p ⫽ 0.056). Conclusions: Because AR is characterized by a perivascular lymphocytic infiltrate, the mechanism linking AR and small airways obliteration is not well understood. However, Aspergillus colonization and LB both affect small airways, the sight of BOS. Aspergillus colonization of the lung allograft appears to increase the risk of subsequent LB and may in part explain the association between Aspergillus and BOS. 659 Strain and Strain Rate in Pediatric Cardiac Transplant Recipients: Comparison to Normal Children J. Bodtke, T.H. Best, R. Sachdeva, E.A. Frazier, W.R. Morrow Arkansas Children’s Hospital, Little Rock, AR Purpose: Strain (S) and Strain Rate (SR) are known to be sensitive measures of regional myocardial function. Prior to evaluating their role in detection of acute rejection, it is important to establish baseline values in the absence of rejection. Purpose: To determine differences in regional myocardial velocities between normal children and pediatric heart transplant (HTx) recipients without acute rejection. Methods and Materials: Twenty pediatric HTx recipients (age ⱕ 18 years) with no acute rejection by biopsy (HTx) and 36 normal children (controls) were prospectively enrolled. Tissue Doppler Imaging of the lateral free wall of the right ventricle (RV), inferoseptal wall (Septum), and the anterolateral wall of the left ventricle (LV) was performed. Tissue velocity (TV), strain (S), and strain rate (SR) were obtained from basal, mid, and apex segments. Values were compared between HTx recipients and controls adjusted for age, weight, height and heart rate. Results: There was no difference in mean age or shortening fraction between groups. Mean TV values were significantly reduced in HTx vs. controls in RV mid and apex as well as basal and mid-septum. Mean S values were all significantly reduced in HTx vs controls (pⱕ0.01). Mean SR values were reduced in all segments except in basal septum and LV mid and apex in HTx compared to controls. Conclusions: Regional longitudinal myocardial velocities are significantly reduced in pediatric HTx recipients compared to normal children in the absence of cellular rejection by biopsy. Longitudinal studies are needed to determine whether changes in TV, S, or SR could detect acute or chronic rejection.. Myocardial Strain
Base Mid Apex
RV Control
HTx
Septum Control
Htx
LV Control
HTx
-36.8 -33.8 -29.6
-22.2 -20.0 -20.5
-25.5 -25.2 -27.1
-19.3 -18.3 -19.3
-27.6 -26.9 -24.1
-20.5 -20.9 -18.6
All Values in percent, All significant at less than p⬍⫽0.01
660 Outcomes with Asymptomatic Antibody-Mediated Rejection in Pediatric Heart Transplant Patients E.L.P. Chan, D.S. Levi, J.C. Alejos, G.S. Perens Mattel Childrens’ Hospital at UCLA, Los Angeles, CA Purpose: Antibody-mediated rejection (AMR) has become a significant problem in pediatric orthotopic heart transplants (OHT). Unfor-
The Journal of Heart and Lung Transplantation Volume 28, Number 2S
tunately, the sequelae and outcomes of asymptomatic pediatric OHT patients with AMR are unknown. Methods and Materials: All patients under 21 years that underwent OHT between April 2000 and July 2007 were retrospectively reviewed. Patients that were asymptomatic at the time of biopsy with AMR or a negative result fit inclusion criteria. Biopsy specimens from routine endomyocardial biopsies were evaluated for AMR based on ISHLT criteria. The diagnosis of coronary artery vasculopathy (CAV) was defined by angiography or positive nuclear PET scan, and graft failure was defined as need for re-transplantation or death due to heart failure. These outcomes were determined for patients after development of AMR, and compared post-OHT for patients with and without AMR. Results: A total of 57 pediatric heart transplants (23 females, ages 2 months-21 years) were followed for at least 3 years during the study period. 20 grafts (35%) developed asymptomatic AMR. No patients were treated at diagnosis of asymptomatic AMR. Of the 20 asymptomatic patients with AMR, 30% developed CAV at one year postdiagnosis and 20% had graft failure. At 3 years post-AMR diagnosis, cumulatively there was no new CAV, and 35% with graft failure. Comparing AMR and non-AMR recipients, at 1 year post –OHT, 0% of the AMR patients and 3% of non-AMR patients developed graft failure (p⫽0.649). At 3 years post-OHT, 15% of AMR patients vs. 14% of non-AMR patients developed CAV (p ⫽0.3), while 40% vs. 8%, respectively, had graft failure (p ⫽ 0.005). Conclusions: A significant percentage of children with asymptomatic, biopsy-proven AMR develop CAV and graft failure within 3 years of developing AMR. These patients have an increased incidence of graft failure compared to AMR-negative patients by 3 years post-OHT. These results suggest that treatments should be considered even for asymptomatic patients if AMR is present. 661 Heart Transplantation Against a Positive Crossmatch in Highly Sensitized Children S.F. Chandler1, C. Almond1, T.P. Singh1, H. Mah2, E. Milford2, G.S. Matte3, H. Bastardi1, J. Mayer3, F. Fynn-Thompson3, E.D. Blume1 1Children’s Hospital Boston, Boston, MA; 2Brigham & Women’s Hospital, Boston, MA; 3Children’s Hospital Boston, Boston, MA Purpose: Sensitization to human leukocyte antigens (HLA) is a risk factor for adverse outcomes after heart transplantation (HT). Traditional approaches of awaiting a negative crossmatch donor result in longer waiting times and increased mortality on the waitlist. We report our institutional experience following HT in highly sensitized pediatric patients undergoing HT against a positive crossmatch (⫹CM). Methods and Materials: A retrospective review of 134 patients transplanted from 1996-2008 revealed 23 (17%) highly sensitized children (pre-HT PRA⬎10%). ⫹CM pts received an institutional protocol involving antibody depletion prior to transplant, followed by plasmapheresis for five days and IVIG for six months, in addition to standard immunosuppression. Clinical outcomes were analyzed for ⫹CM pts and compared to -CM sensitized pts and to non-sensitized controls. Results: Among the 23 highly sensitized pts, 11 (47%) had a ⫹CM at the time of HT. Median age was 8.9 years (range: 0.4-19.3) and 2 (18%) were female. Diagnosis prior to HT included congenital heart disease (7), cardiomyopathy on mechanical support (2), and re-HT(2). There was no difference between the ⫹CM and -CM (n⫽12) groups in pre-transplant risk factors. One ⫹CM pt died of multi-organ system failure 2 weeks post HT. During median follow-up of 2.3 yrs (2 wks-9.6yrs), there was no significant difference in patient survival or rejection episodes between ⫹CM
Abstracts
S295
and –CM pts. The ⫹CM pts had significantly more infections in the first year post-HT compared to non-sensitized pts (4/11 vs 12/111, p⫽0.03), however there was no difference in patient survival. Conclusions: Sensitized children with a positive crossmatch treated with a standardized perioperative antibody-depletion protocol at HT followed by IVIG have survival and rejection profiles similar to that of sensitized pts with a negative CM. The protocol is associated with higher infection rates during the first year compared to non-sensitized pts. Larger multi-center studies are needed to better understand the impact of sensitization on pediatric HT outcomes.
662 Volume-Outcome Relationships in Pediatric Heart Transplantation R.R. Davies1, M.J. Russo1, J.M. Quaegebeur1, S.R. Mital3, K.N. Hong1, R.S. Mosca1, J.M. Chen2 1Children’s Hospital of NewYork-Prebyterian, New York, NY; 2Weill Medical College of Cornell University, New York, NY Purpose: The interaction between volume and outcome in many complex surgical procedures has been well-established. No published data has examined this relationship in pediatric cardiac transplantation. Methods and Materials: There were 5,218 transplants performed on patients ⬍ 19 years old in the UNOS database 1987-2006. Patients were stratified into 3 groups based on the volume of transplants performed that year at that center: low (⬍ 5 per yr: n⫽1,388), medium (5-14 per yr: n⫽2,457), and high (ⱖ 15 per yr: n⫽1,373). A logistic regression model for postoperative mortality was developed and observed:expected (O:E) mortality rates calculated for each group. Results: Long-term survival decreased with decreasing center volume (p⬍0.0001). Low volume centers had O:E ratio of postoperative mortality of 1.54 (p⬍0.0001), compared to high volume centers (0.86, p⫽0.0761) (Figure 1). At low volume centers, high-risk patients (O:E ratio 1.58, p ⬍0.0001)— especially younger patients (O:E ratio 1.79, p⬍0.0001) or those with congenital heart disease (O:E 1.52, p ⬍ 0.0001)— did poorly, but the observed mortality at high volume centers was lower than expected (Figure 2). Similar results were obtained in the subset of patients transplanted after 1996 (Figure 1). Conclusions: The volume of transplants performed at any one center has a significant impact on outcomes. Regionalization of care is one option for improving outcomes in pediatric cardiac transplantation.
Abstracts
N.P. van der Kaaij1, J. Kluin2, R.A. Lachmann3, M.A. den Bakker4, J.J. Haitsma3, R.W.F. de Bruin5, B. Lachmann3, A.J.J.C. Bogers1 1 Erasmus MC, Rotterdam, Netherlands; 2UMC Utrecht, Utrecht, Netherlands; 3Erasmus MC, Rotterdam, Netherlands; 4Erasmus MC, Rotterdam, Netherlands; 5Erasmus MC, Rotterdam, Netherlands Purpose: Lung ischemia reperfusion injury (LIRI) contributes to morbidity and mortality after lung transplantation. The objective was to investigate the effect of open lung concept (OLC) ventilation on LIRI as compared to conventional ventilation (CV) after reperfusion. Methods and Materials: Male Sprague-Dawley rats (n⫽63) underwent 150 minutes warm ischemia of the left lung. At reperfusion, animals received conventional ventilation (tidal volume 6 ml/kg, 4 cm H2O positive end-expiratory pressure (PEEP)), OLC ventilation (collapsed alveoli were recruited by applying high peak inspiratory pressures combined with high levels of PEEP) for 3 hours or were directly extubated. Animals were killed directly after 3 hours of ventilation (day 0), day 1 or day 3 postoperatively. Blood gas values were measured and lung compliance was recorded. The level of alveolar protein and leukocyte infiltration (by flowcytometry) was assessed in broncho-alveolar-lavage-fluid (BALf). Histological analysis was performed in 3 animals per group. Results: No difference in PaO2 and lung compliance was seen between conventional ventilated and directly extubated rats on day 1. OLC ventilation resulted in higher PaO2 (day 0 and 1), less infiltration of granulocytes, macrophages, and lymphocytes in the BALf of the left lung, superior lung compliance, and less injury on HE slides as compared to CV and directly extubated rats. Conclusions: OLC ventilation at reperfusion decreases LIRI and may hereby prevent the development of ARDS and decrease the risk on long-term organ dysfunction. 658 The Impact of Aspergillus Colonization on Acute Rejection and Lymphocytic Bronchiolitis in Lung Transplant Patients S.S. Weigt1, C.-H. Tseng2, C. Huang1, D.J. Ross1, R. Saggar1, R. Saggar1, J.P. Lynch1, A. Gregson3, B.M. Kubak3, A. Ardehali4, R.M. Elashoff2, J.A. Belperio1 1David Geffen School of Medicine at UCLA, Los Angeles, CA; 2David Geffen School of Medicine at UCLA, Los Angeles, CA; 3David Geffen School of Medicine at UCLA, Los Angeles, CA; 4David Geffen School of Medicine at UCLA, Los Angeles, CA Purpose: While acute rejection (AR) is considered the principal risk factor, multiple infections have also been linked with the development of bronchiolitis obliterans syndrome (BOS). We have previously demonstrated that Aspergillus colonization is a risk factor for BOS, separate from the effects of AR. Others have recently shown that lymphocytic bronchiolitis (LB) may be a more important risk factor for BOS than AR. We hypothesized that Aspergillus colonization would be associated with an increased risk of LB in lung transplant recipients. Methods and Materials: For this study, we examined the same cohort of lung transplant recipients in whom we previously studied the impact of Aspergillus colonization on BOS (201 lung transplant recipients at UCLA between 1/2000 and 6/2006). We defined Aspergillus colonization as a positive BAL culture or two positive sputum cultures with the same Aspergillus species from patients without evidence of invasive disease. AR and LB episodes were defined strictly by histopathologic findings according to standard ISHLT criteria. We evaluated the risk of recurrent AR, LB and the composite of either AR or LB using a modified Anderson-Gill model with allowance for correlation of recurrent events.
The Journal of Heart and Lung Transplantation February 2009
Results: AR was more common after the development of Aspergillus colonization, however this increase was not statistically significant (HR ⫽ 1.19, p ⫽ 0.49). There was a non-significant trend for increased risk of LB recurrence (HR ⫽ 1.44, p ⫽ 0.062). We did find an elevated risk for the combined recurrence of AR and LB after the development of Aspergillus colonization at borderline significance (HR ⫽ 1.39, p ⫽ 0.056). Conclusions: Because AR is characterized by a perivascular lymphocytic infiltrate, the mechanism linking AR and small airways obliteration is not well understood. However, Aspergillus colonization and LB both affect small airways, the sight of BOS. Aspergillus colonization of the lung allograft appears to increase the risk of subsequent LB and may in part explain the association between Aspergillus and BOS. 659 Strain and Strain Rate in Pediatric Cardiac Transplant Recipients: Comparison to Normal Children J. Bodtke, T.H. Best, R. Sachdeva, E.A. Frazier, W.R. Morrow Arkansas Children’s Hospital, Little Rock, AR Purpose: Strain (S) and Strain Rate (SR) are known to be sensitive measures of regional myocardial function. Prior to evaluating their role in detection of acute rejection, it is important to establish baseline values in the absence of rejection. Purpose: To determine differences in regional myocardial velocities between normal children and pediatric heart transplant (HTx) recipients without acute rejection. Methods and Materials: Twenty pediatric HTx recipients (age ⱕ 18 years) with no acute rejection by biopsy (HTx) and 36 normal children (controls) were prospectively enrolled. Tissue Doppler Imaging of the lateral free wall of the right ventricle (RV), inferoseptal wall (Septum), and the anterolateral wall of the left ventricle (LV) was performed. Tissue velocity (TV), strain (S), and strain rate (SR) were obtained from basal, mid, and apex segments. Values were compared between HTx recipients and controls adjusted for age, weight, height and heart rate. Results: There was no difference in mean age or shortening fraction between groups. Mean TV values were significantly reduced in HTx vs. controls in RV mid and apex as well as basal and mid-septum. Mean S values were all significantly reduced in HTx vs controls (pⱕ0.01). Mean SR values were reduced in all segments except in basal septum and LV mid and apex in HTx compared to controls. Conclusions: Regional longitudinal myocardial velocities are significantly reduced in pediatric HTx recipients compared to normal children in the absence of cellular rejection by biopsy. Longitudinal studies are needed to determine whether changes in TV, S, or SR could detect acute or chronic rejection.. Myocardial Strain
Base Mid Apex
RV Control
HTx
Septum Control
Htx
LV Control
HTx
-36.8 -33.8 -29.6
-22.2 -20.0 -20.5
-25.5 -25.2 -27.1
-19.3 -18.3 -19.3
-27.6 -26.9 -24.1
-20.5 -20.9 -18.6
All Values in percent, All significant at less than p⬍⫽0.01
660 Outcomes with Asymptomatic Antibody-Mediated Rejection in Pediatric Heart Transplant Patients E.L.P. Chan, D.S. Levi, J.C. Alejos, G.S. Perens Mattel Childrens’ Hospital at UCLA, Los Angeles, CA Purpose: Antibody-mediated rejection (AMR) has become a significant problem in pediatric orthotopic heart transplants (OHT). Unfor-
The Journal of Heart and Lung Transplantation Volume 28, Number 2S
tunately, the sequelae and outcomes of asymptomatic pediatric OHT patients with AMR are unknown. Methods and Materials: All patients under 21 years that underwent OHT between April 2000 and July 2007 were retrospectively reviewed. Patients that were asymptomatic at the time of biopsy with AMR or a negative result fit inclusion criteria. Biopsy specimens from routine endomyocardial biopsies were evaluated for AMR based on ISHLT criteria. The diagnosis of coronary artery vasculopathy (CAV) was defined by angiography or positive nuclear PET scan, and graft failure was defined as need for re-transplantation or death due to heart failure. These outcomes were determined for patients after development of AMR, and compared post-OHT for patients with and without AMR. Results: A total of 57 pediatric heart transplants (23 females, ages 2 months-21 years) were followed for at least 3 years during the study period. 20 grafts (35%) developed asymptomatic AMR. No patients were treated at diagnosis of asymptomatic AMR. Of the 20 asymptomatic patients with AMR, 30% developed CAV at one year postdiagnosis and 20% had graft failure. At 3 years post-AMR diagnosis, cumulatively there was no new CAV, and 35% with graft failure. Comparing AMR and non-AMR recipients, at 1 year post –OHT, 0% of the AMR patients and 3% of non-AMR patients developed graft failure (p⫽0.649). At 3 years post-OHT, 15% of AMR patients vs. 14% of non-AMR patients developed CAV (p ⫽0.3), while 40% vs. 8%, respectively, had graft failure (p ⫽ 0.005). Conclusions: A significant percentage of children with asymptomatic, biopsy-proven AMR develop CAV and graft failure within 3 years of developing AMR. These patients have an increased incidence of graft failure compared to AMR-negative patients by 3 years post-OHT. These results suggest that treatments should be considered even for asymptomatic patients if AMR is present. 661 Heart Transplantation Against a Positive Crossmatch in Highly Sensitized Children S.F. Chandler1, C. Almond1, T.P. Singh1, H. Mah2, E. Milford2, G.S. Matte3, H. Bastardi1, J. Mayer3, F. Fynn-Thompson3, E.D. Blume1 1Children’s Hospital Boston, Boston, MA; 2Brigham & Women’s Hospital, Boston, MA; 3Children’s Hospital Boston, Boston, MA Purpose: Sensitization to human leukocyte antigens (HLA) is a risk factor for adverse outcomes after heart transplantation (HT). Traditional approaches of awaiting a negative crossmatch donor result in longer waiting times and increased mortality on the waitlist. We report our institutional experience following HT in highly sensitized pediatric patients undergoing HT against a positive crossmatch (⫹CM). Methods and Materials: A retrospective review of 134 patients transplanted from 1996-2008 revealed 23 (17%) highly sensitized children (pre-HT PRA⬎10%). ⫹CM pts received an institutional protocol involving antibody depletion prior to transplant, followed by plasmapheresis for five days and IVIG for six months, in addition to standard immunosuppression. Clinical outcomes were analyzed for ⫹CM pts and compared to -CM sensitized pts and to non-sensitized controls. Results: Among the 23 highly sensitized pts, 11 (47%) had a ⫹CM at the time of HT. Median age was 8.9 years (range: 0.4-19.3) and 2 (18%) were female. Diagnosis prior to HT included congenital heart disease (7), cardiomyopathy on mechanical support (2), and re-HT(2). There was no difference between the ⫹CM and -CM (n⫽12) groups in pre-transplant risk factors. One ⫹CM pt died of multi-organ system failure 2 weeks post HT. During median follow-up of 2.3 yrs (2 wks-9.6yrs), there was no significant difference in patient survival or rejection episodes between ⫹CM
Abstracts
S295
and –CM pts. The ⫹CM pts had significantly more infections in the first year post-HT compared to non-sensitized pts (4/11 vs 12/111, p⫽0.03), however there was no difference in patient survival. Conclusions: Sensitized children with a positive crossmatch treated with a standardized perioperative antibody-depletion protocol at HT followed by IVIG have survival and rejection profiles similar to that of sensitized pts with a negative CM. The protocol is associated with higher infection rates during the first year compared to non-sensitized pts. Larger multi-center studies are needed to better understand the impact of sensitization on pediatric HT outcomes.
662 Volume-Outcome Relationships in Pediatric Heart Transplantation R.R. Davies1, M.J. Russo1, J.M. Quaegebeur1, S.R. Mital3, K.N. Hong1, R.S. Mosca1, J.M. Chen2 1Children’s Hospital of NewYork-Prebyterian, New York, NY; 2Weill Medical College of Cornell University, New York, NY Purpose: The interaction between volume and outcome in many complex surgical procedures has been well-established. No published data has examined this relationship in pediatric cardiac transplantation. Methods and Materials: There were 5,218 transplants performed on patients ⬍ 19 years old in the UNOS database 1987-2006. Patients were stratified into 3 groups based on the volume of transplants performed that year at that center: low (⬍ 5 per yr: n⫽1,388), medium (5-14 per yr: n⫽2,457), and high (ⱖ 15 per yr: n⫽1,373). A logistic regression model for postoperative mortality was developed and observed:expected (O:E) mortality rates calculated for each group. Results: Long-term survival decreased with decreasing center volume (p⬍0.0001). Low volume centers had O:E ratio of postoperative mortality of 1.54 (p⬍0.0001), compared to high volume centers (0.86, p⫽0.0761) (Figure 1). At low volume centers, high-risk patients (O:E ratio 1.58, p ⬍0.0001)— especially younger patients (O:E ratio 1.79, p⬍0.0001) or those with congenital heart disease (O:E 1.52, p ⬍ 0.0001)— did poorly, but the observed mortality at high volume centers was lower than expected (Figure 2). Similar results were obtained in the subset of patients transplanted after 1996 (Figure 1). Conclusions: The volume of transplants performed at any one center has a significant impact on outcomes. Regionalization of care is one option for improving outcomes in pediatric cardiac transplantation.