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Risk Factors for Sudden Death in Children with Cardiac Allograft Vasculopathy
S122
The Journal of Heart and Lung Transplantation, Vol 32, No 4S, April 2014
Conclusion: The proposed risk score appears to discriminate 1-yr survival in ACHD HTx recipients. If validated, this risk score may help in defining acceptable thresholds of risk among ACHD patients undergoing evaluation for HTx. Future research will focus on validating this risk score in an additional cohort to determine its predictive value.
3( 18) Evaluating Pediatric Heart Re-transplant Candidates: Using a Risk Prediction Model to Estimate Early Mortality after Re-Transplant S.L. Siehr ,1 S.A. Hollander,1 K. Gauvreau,2 D.N. Rosenthal,1 T.P. Singh,2 B. Kaufman,1 J. Yeh,1 C.S. Almond.2 1Pediatric Cardiology, Stanford University School of Medicine, Palo Alto, CA; 2Pediatric Cardiology, Harvard Medical School, Boston, MA. Purpose: Pediatric heart transplant (HT) centers may be reluctant to offer re-transplant to children within 6 months of primary HT because of studies suggesting graft survival is poor. The purpose of this study was to explore an alternate method for risk-stratifying re-transplant candidates by determining whether a previously validated pediatric post-transplant risk-prediction model can accurately predict early mortality in heart re-transplant candidates. Methods: All children listed for heart re-transplantation between 2004 and 2010 were identified using Organ Procurement and Transplant Network (OPTN) data. Using standard model discrimination and calibration statistics, the observed in-hospital mortality of the re-transplant cohort was compared to their predicted in-hospital mortality using a validated risk-prediction model originally developed in a cohort of primary HT candidates. Results: Of 137 children who underwent heart re-transplantation during the 6-year study period, the median age was 13 years (Interquartile range (IQR) 9, 15), the median weight was 41 kg (IQR 26, 54); 4% were supported on Extra-corporeal membrane oxygenation (ECMO) at transplant, 7% a ventilator, 34% were listed UNOS status 1A, 46% had an abnormal estimated creatinine clearance, and 13% had a bilirubin level ≥ 2 mg/dL. Overall, 9 of 137 patients (7%) died prior to hospital discharge. When the original risk prediction model was applied to the re-transplant cohort, the C-statistic (0.71) and Hosmer-Lemeshow goodness-of-fit (P= 0.37) suggested acceptable prediction of post-transplant in-hospital mortality. Conclusion: Overall unadjusted in-hospital mortality for children undergoing heart re-transplant is relatively similar to patients undergoing primary HT. A risk-prediction model validated previously in children undergoing primary HT performs reasonably well in predicting post-transplant in-hospital mortality in children undergoing heart re-transplant. This model may be a useful alternative method for assessing a child’s re-transplant candidacy independent of time since transplant. 3( 19) Prevalence of BK Polyomavirus Infection and Association with Renal Function in Pediatric Heart Transplant Recipients A.L. Ducharme-Smith ,1 A.E. Bobrowski,2 B.Z. Katz,3 C.L. Backer,4 E. Pahl.5 1Northwestern Feinberg School of Medicine, Chicago, IL; 2Nephrology, Ann & Robert H. Lurie Children’s Hospital, Chicago, IL; 3Infectious Disease, Ann & Robert H. Lurie Children’s Hospital, Chicago, IL; 4Cardiovascular-Thoracic Surgery, Ann & Robert H. Lurie Children’s Hospital, Chicago, IL; 5Medical Director, Heart Transplant Program, Ann & Robert H. Lurie Children’s Hospital, Chicago, IL. Purpose: BK polyomavirus (BKV) infection and related nephropathy is a well-known cause of renal dysfunction in renal transplant recipients; however the impact of BKV in the native kidneys of pediatric heart
transplant (HTx) recipients is unknown. Our study assessed the prevalence of BKV infection and its association with renal dysfunction in pediatric HTx recipients. Methods: We conducted a single center retrospective cohort study on all pediatric HTx recipients (aged < 18) who received a HTx between May 1989 and July 2013 who are currently followed at our center and had BKV testing. Since April 2012, urine BKV loads have been checked in all patients at time of annual evaluation, and prior to that, in patients with chronic kidney disease or acute kidney dysfunction. Serum BK viremia was assayed in patients with positive BK viruria. Data collected included demographics, donor information, immunosuppression regimen, and history of viral illnesses. Descriptive statistics, Fisher’s exact analysis, and Student’s T-test were done to compare patients with and without BK viruria (controls). Results: Of 100 eligible HTx recipients, 51 have been screened to date. Seventeen (33%) of these had BK viruria, and 4 (8%) developed viremia. One viremic patient (2%) progressed to BKV nephropathy diagnosed by biopsy, and required a renal transplant for end stage renal disease. Increasing mean urine viral load was significantly associated with progression from BK viruria (2.1x10^8 copies/mL) to viremia (22.2x10^8 copies/mL) (p= 0.01). History of positive EBV serologies (p= 0.01), use of Sirolimus immunosuppression (p= 0.0006), and duration of time since HTx (6.42 years vs. 3.84 years; p= 0.04) were significantly associated with BK viruria. Renal function, in terms of Schwartz CKiD eGFR, was not significantly different between patients with BK viruria and controls (74.2 vs. 79.8 mL/min per 1.73 m^2, p= 0.41). Conclusion: Increasing mean urine BK viral load, time since HTx, evidence of past EBV infection, and use of Sirolimus were associated with BKV. A prospective study is planned to assess the incidence of BKV in HTx recipients. Routine screening of the urine BK viral load should be considered in this population. 3( 20) Risk Factors for Sudden Death in Children with Cardiac Allograft Vasculopathy B.J. Hong ,1 K. Sexson Tejtel,1 A. Jeewa,1 A.G. Cabrera,1 J.F. Price,1 J.S. Heinle,2 W.J. Dreyer,1 S.W. Denfield.1 1Pediatric Cardiology, Baylor College of Medicine/Texas Children’s Hospital, Houston, TX; 2Pediatric Cardiothoracic Surgery, Baylor College of Medicine/Texas Children’s Hospital, Houston, TX. Purpose: Cardiac allograft vasculopathy (CAV) is one of the leading causes of late mortality in pediatric heart transplant patients. Many do not survive to retransplantation, and a subset die suddenly. The purpose of this study is to determine risk factors associated with sudden death (SD) in pediatric patients with CAV. Methods: This is a single center retrospective review of all pediatric patients transplanted from 1984 to 2012 who died or were retransplanted following a diagnosis of CAV. The diagnosis of CAV was made by coronary angiography, explant pathology, or autopsy. Data including demographics, episodes of rejection, cardiac catheterization and echocardiographic data, time to CAV diagnosis, and cause of death were collected to compare SD patients to those who died of end-stage heart failure. Results: Of the 54 patients with CAV, 40 died or underwent retransplantation (RT) and 14 are alive. Three patients were excluded as their causes of death were unknown or noncardiac. Of the 37 patients who met inclusion criteria, 9 patients (24%) died suddenly. The other 28 patients died of heart failure (12/28 patients) or were retransplanted (16/28 patients). Comparison of the SD group to the heart failure death/RT group did not find any differences in age at transplant, episodes of cellular or antibody mediated rejection, or time to CAV diagnosis or death. Systolic function was significantly better in the SD group with a median ejection fraction of 62% (range 50-70%) compared to 50% (range 24-75%) in the heart failure death/RT group (p= 0.045). Hemodynamics also differed, with a median right ventricular end diastolic pressure of 8 mmHg (range 3-16 mmHg) in the SD group compared to a median of 14 mmHg (range 4-24 mmHg) in the heart failure death/RT group (p= 0.011) and a median pulmonary capillary wedge pressure of 9 mmHg (range 4-16 mmHg) in the SD group compared to a median of 14 mmHg (range 7-27 mmHg) in the heart failure death group/RT (p= 0.027). B-type natriuretic peptide (BNP) levels before death or retransplantation were lower in the SD group with a median of 260 pg/ml (range 81-953 pg/ml) compared
Abstracts S123 to the heart failure death/RT group with a median of 1081 pg/ml (range 2075258 pg/ml) (p= 0.013). Conclusion: Sudden death occurred in 24% of CAV associated patient or organ deaths. The SD patients were more likely to have normal hemodynamics and a lower BNP. Normal hemodynamics may not be reassuring in the setting of CAV. 3( 21) Antithymocyte Globulin But Not Basiliximab Is Beneficial After Infant Heart Transplantation - Analysis of the UNOS Database B. Coleman , A. Phillips, J. Mirocha, J. Patel, F. Arabia, J. Kobashigawa. Cedars- Sinai Heart Institute, Los Angeles, CA. Purpose: Disparities in pediatric heart transplant (HTx) outcomes comparing African American (AA) to Caucasian American (CA) recipients are known. The role of induction therapy in the AA infant population has not been established. Furthermore, it is not known whether all induction therapy medications confer the same post transplant outcomes. We explored the impact of Antithymocyte globulin (ATG), Basiliximab (Bas) and no induction on HTx outcomes in AA and CA infants, using the UNOS database. Methods: 979 (222 AA; 757 CA) infant HTx recipients (age 0 to 2 years) transplanted between 5/1999 to 3/2011 were included in this study. Three groups were analyzed and stratified by race; patients who received ATG (84 AA; 322 CA), Bas (22 AA; 49 CA) induction therapy or no induction therapy (116 AA; 386 CA). Cox proportional hazards models were used to assess factors related to 10-year survival, hazard ratios and 95% confidence intervals (CI). Ten-year survival was estimated by the Kaplan-Meier method. Survival was compared across induction types by the Log-Rank test. Results: AA infants who received ATG but not Bas had improved survival at 10 years compared to no induction (p = 0.010, HR 0.50 95% CI 0.30-0.86, Log-Rank). No survival benefit was found for CA infants who received ATG or Bas compared to no induction (overall Log-Rank P = 0.72). Conclusion: In infant HTx, AA recipients had improved 10-year survival with ATG compared with no induction therapy. CA infant recipients demonstrated no benefit from use of either ATG or Bas. Prospective randomized trials are needed to confirm these observations.
3( 22) C1q Testing in Pediatric Heart Transplant Recipients at Risk for Antibody Mediated Rejection E. Albers ,1 R. Boucek,1 M. Kemna,1 S. Law,1 P. Warner,2 Y. Law.1 1Pediatric Cardiology, Seattle Children’s Hospital, Seattle, WA; 2Puget Sound Blood Center, Seattle, WA. Purpose: Antibody mediated rejection (AMR) is an important cause of morbidity and mortality after pediatric heart transplant. Donor-specific antibodies (DSA) against human leukocyte antigens (HLA) have been associated with AMR. Not all DSA, however, result in clinical rejection. Testing for complement-fixing (C1q) DSA may help identify patients at higher risk for AMR. Methods: A single center retrospective review was conducted to identify patients with at least 1 DSA or history of AMR. Samples with the maximum single locus DSA MFI (if no history of AMR) or at diagnosis of AMR were retrospectively tested for C1q DSA. All DSA were considered positive if MFI > 5000. Comparisons were made with respect to AMR and graft survival. Results: Of 38 patients who met inclusion criteria, 17 (44.7%) had 21 episodes of AMR. Of 42 cases with either positive DSA or AMR, 38 samples were available for C1q testing. Of these, 20 had C1q DSA: 11 with AMR vs. 9 with no AMR (p = 0.321, positive predictive value [PPV] = 55%). Thirtyseven (88.1%) had DSA to Class II HLA (16 C1q), while only 11 (26.2%) had DSA to Class I HLA (5 C1q). AMR was associated with the presence of Class I DSA (p = 0.014, PPV 82%) and Class I C1q DSA (p= 0.016, PPV 100%). Twenty-one (50%) had DSA to > 1 HLA locus of either Class (6 C1q), of which 15 (5 C1q) had AMR (p = 0.005, PPV 71%; C1q: p = 0.075, PPV 83%). Over a median follow-up period of 42 months, 4 patients died and 1 required re-transplant (graft survival 92% at 5yrs, 86% at 10yrs). When considering either a history of AMR, C1q DSA, the presence of Class I DSA, or the presence of > 1 DSA locus, only the presence of > 1 DSA locus was associated with decreased graft survival (p = 0.044). Conclusion: AMR occurred in fewer than 50% of patients in this cohort with positive DSA. A positive C1q test alone was not predictive of AMR, but in certain cases increased the PPV of DSA testing. Most patients had DSA to Class II HLA, but only the presence of DSA to Class I HLA was associated with AMR. The presence of DSA to > 1 HLA locus was not only associated with AMR, it was also associated with decreased graft survival. 3( 23) How Does Donor Specific Antibody Relate to Biopsy-diagnosed Antibody-mediated Rejection after Pediatric Heart Transplantation? A. Ware ,1 G. Snow,2 E. Hammond,3 D.V. Miller,3 J. Stehlik,4 A.G. Kfoury,3 A. Eckhauser,4 D. Eckels,5 M. Everitt.4 1University of Utah, Salt Lake City, UT; 2Intermountain Medical Center, Salt Lake City, UT; 3Intermountain Medical Center/UTAH Cardiac Transplant Program, Salt Lake City, UT; 4University of Utah/UTAH Cardiac Transplant Program, Salt Lake City, UT; 5Pathology, University of Utah, Salt Lake City, UT. Purpose: Antibody-mediated rejection (AMR) is a major cause of mortality after heart transplant (HT). Both biopsy grading of pathologic AMR (pAMR) and assessment for circulating donor specific antibodies (DSA) are recommended for post HT monitoring. However, the relationship between pAMR grade and DSA has not been reported in children after HT. This is the aim of our analysis. Methods: The UTAH Cardiac Transplant database was queried for all children ≤ 21 yrs of age that had testing for DSA within 3 days of EMB. Solid phase immunoassay was used to determine the presence of DSA with positivity defined as antibody specificity to donor HLA at mean fluorescent intensity ≥ 2000. The relationship of DSA (class I, class II, or both) to pAMR grade was assessed using the Mantel-Haenzel chi-squared test. Results: Of 70 HT recipients followed between 2009 and 2013, 28 (40%) had ≥ 1 test positive for DSA. Those with detectable DSA vs. without any DSA were more likely to have a diagnosis of congenital heart disease (CHD) (75% vs. 43%, p= 0.01), more likely to be sensitized (non-donor HLA antibody) pre-HT (46% vs. 10%, p< 0.001), and more commonly received antilymphocyte induction (50% vs. 12%, p< 0.001). Of the 28 with DSA, 4 (14%) had pre-HT DSA with a positive crossmatch at HT. There were 258 EMB with a paired DSA test. Of 56 pAMR1 (h or i) episodes, 57% had DSA. For pAMR2, 27/28 (96%) had DSA. Of 5 pAMR3 episodes, all had DSA. Among 169 EMB negative for AMR, 62 (37%) had circulating DSA.
The Journal of Heart and Lung Transplantation, Vol 32, No 4S, April 2014
Conclusion: The proposed risk score appears to discriminate 1-yr survival in ACHD HTx recipients. If validated, this risk score may help in defining acceptable thresholds of risk among ACHD patients undergoing evaluation for HTx. Future research will focus on validating this risk score in an additional cohort to determine its predictive value.
3( 18) Evaluating Pediatric Heart Re-transplant Candidates: Using a Risk Prediction Model to Estimate Early Mortality after Re-Transplant S.L. Siehr ,1 S.A. Hollander,1 K. Gauvreau,2 D.N. Rosenthal,1 T.P. Singh,2 B. Kaufman,1 J. Yeh,1 C.S. Almond.2 1Pediatric Cardiology, Stanford University School of Medicine, Palo Alto, CA; 2Pediatric Cardiology, Harvard Medical School, Boston, MA. Purpose: Pediatric heart transplant (HT) centers may be reluctant to offer re-transplant to children within 6 months of primary HT because of studies suggesting graft survival is poor. The purpose of this study was to explore an alternate method for risk-stratifying re-transplant candidates by determining whether a previously validated pediatric post-transplant risk-prediction model can accurately predict early mortality in heart re-transplant candidates. Methods: All children listed for heart re-transplantation between 2004 and 2010 were identified using Organ Procurement and Transplant Network (OPTN) data. Using standard model discrimination and calibration statistics, the observed in-hospital mortality of the re-transplant cohort was compared to their predicted in-hospital mortality using a validated risk-prediction model originally developed in a cohort of primary HT candidates. Results: Of 137 children who underwent heart re-transplantation during the 6-year study period, the median age was 13 years (Interquartile range (IQR) 9, 15), the median weight was 41 kg (IQR 26, 54); 4% were supported on Extra-corporeal membrane oxygenation (ECMO) at transplant, 7% a ventilator, 34% were listed UNOS status 1A, 46% had an abnormal estimated creatinine clearance, and 13% had a bilirubin level ≥ 2 mg/dL. Overall, 9 of 137 patients (7%) died prior to hospital discharge. When the original risk prediction model was applied to the re-transplant cohort, the C-statistic (0.71) and Hosmer-Lemeshow goodness-of-fit (P= 0.37) suggested acceptable prediction of post-transplant in-hospital mortality. Conclusion: Overall unadjusted in-hospital mortality for children undergoing heart re-transplant is relatively similar to patients undergoing primary HT. A risk-prediction model validated previously in children undergoing primary HT performs reasonably well in predicting post-transplant in-hospital mortality in children undergoing heart re-transplant. This model may be a useful alternative method for assessing a child’s re-transplant candidacy independent of time since transplant. 3( 19) Prevalence of BK Polyomavirus Infection and Association with Renal Function in Pediatric Heart Transplant Recipients A.L. Ducharme-Smith ,1 A.E. Bobrowski,2 B.Z. Katz,3 C.L. Backer,4 E. Pahl.5 1Northwestern Feinberg School of Medicine, Chicago, IL; 2Nephrology, Ann & Robert H. Lurie Children’s Hospital, Chicago, IL; 3Infectious Disease, Ann & Robert H. Lurie Children’s Hospital, Chicago, IL; 4Cardiovascular-Thoracic Surgery, Ann & Robert H. Lurie Children’s Hospital, Chicago, IL; 5Medical Director, Heart Transplant Program, Ann & Robert H. Lurie Children’s Hospital, Chicago, IL. Purpose: BK polyomavirus (BKV) infection and related nephropathy is a well-known cause of renal dysfunction in renal transplant recipients; however the impact of BKV in the native kidneys of pediatric heart
transplant (HTx) recipients is unknown. Our study assessed the prevalence of BKV infection and its association with renal dysfunction in pediatric HTx recipients. Methods: We conducted a single center retrospective cohort study on all pediatric HTx recipients (aged < 18) who received a HTx between May 1989 and July 2013 who are currently followed at our center and had BKV testing. Since April 2012, urine BKV loads have been checked in all patients at time of annual evaluation, and prior to that, in patients with chronic kidney disease or acute kidney dysfunction. Serum BK viremia was assayed in patients with positive BK viruria. Data collected included demographics, donor information, immunosuppression regimen, and history of viral illnesses. Descriptive statistics, Fisher’s exact analysis, and Student’s T-test were done to compare patients with and without BK viruria (controls). Results: Of 100 eligible HTx recipients, 51 have been screened to date. Seventeen (33%) of these had BK viruria, and 4 (8%) developed viremia. One viremic patient (2%) progressed to BKV nephropathy diagnosed by biopsy, and required a renal transplant for end stage renal disease. Increasing mean urine viral load was significantly associated with progression from BK viruria (2.1x10^8 copies/mL) to viremia (22.2x10^8 copies/mL) (p= 0.01). History of positive EBV serologies (p= 0.01), use of Sirolimus immunosuppression (p= 0.0006), and duration of time since HTx (6.42 years vs. 3.84 years; p= 0.04) were significantly associated with BK viruria. Renal function, in terms of Schwartz CKiD eGFR, was not significantly different between patients with BK viruria and controls (74.2 vs. 79.8 mL/min per 1.73 m^2, p= 0.41). Conclusion: Increasing mean urine BK viral load, time since HTx, evidence of past EBV infection, and use of Sirolimus were associated with BKV. A prospective study is planned to assess the incidence of BKV in HTx recipients. Routine screening of the urine BK viral load should be considered in this population. 3( 20) Risk Factors for Sudden Death in Children with Cardiac Allograft Vasculopathy B.J. Hong ,1 K. Sexson Tejtel,1 A. Jeewa,1 A.G. Cabrera,1 J.F. Price,1 J.S. Heinle,2 W.J. Dreyer,1 S.W. Denfield.1 1Pediatric Cardiology, Baylor College of Medicine/Texas Children’s Hospital, Houston, TX; 2Pediatric Cardiothoracic Surgery, Baylor College of Medicine/Texas Children’s Hospital, Houston, TX. Purpose: Cardiac allograft vasculopathy (CAV) is one of the leading causes of late mortality in pediatric heart transplant patients. Many do not survive to retransplantation, and a subset die suddenly. The purpose of this study is to determine risk factors associated with sudden death (SD) in pediatric patients with CAV. Methods: This is a single center retrospective review of all pediatric patients transplanted from 1984 to 2012 who died or were retransplanted following a diagnosis of CAV. The diagnosis of CAV was made by coronary angiography, explant pathology, or autopsy. Data including demographics, episodes of rejection, cardiac catheterization and echocardiographic data, time to CAV diagnosis, and cause of death were collected to compare SD patients to those who died of end-stage heart failure. Results: Of the 54 patients with CAV, 40 died or underwent retransplantation (RT) and 14 are alive. Three patients were excluded as their causes of death were unknown or noncardiac. Of the 37 patients who met inclusion criteria, 9 patients (24%) died suddenly. The other 28 patients died of heart failure (12/28 patients) or were retransplanted (16/28 patients). Comparison of the SD group to the heart failure death/RT group did not find any differences in age at transplant, episodes of cellular or antibody mediated rejection, or time to CAV diagnosis or death. Systolic function was significantly better in the SD group with a median ejection fraction of 62% (range 50-70%) compared to 50% (range 24-75%) in the heart failure death/RT group (p= 0.045). Hemodynamics also differed, with a median right ventricular end diastolic pressure of 8 mmHg (range 3-16 mmHg) in the SD group compared to a median of 14 mmHg (range 4-24 mmHg) in the heart failure death/RT group (p= 0.011) and a median pulmonary capillary wedge pressure of 9 mmHg (range 4-16 mmHg) in the SD group compared to a median of 14 mmHg (range 7-27 mmHg) in the heart failure death group/RT (p= 0.027). B-type natriuretic peptide (BNP) levels before death or retransplantation were lower in the SD group with a median of 260 pg/ml (range 81-953 pg/ml) compared
Abstracts S123 to the heart failure death/RT group with a median of 1081 pg/ml (range 2075258 pg/ml) (p= 0.013). Conclusion: Sudden death occurred in 24% of CAV associated patient or organ deaths. The SD patients were more likely to have normal hemodynamics and a lower BNP. Normal hemodynamics may not be reassuring in the setting of CAV. 3( 21) Antithymocyte Globulin But Not Basiliximab Is Beneficial After Infant Heart Transplantation - Analysis of the UNOS Database B. Coleman , A. Phillips, J. Mirocha, J. Patel, F. Arabia, J. Kobashigawa. Cedars- Sinai Heart Institute, Los Angeles, CA. Purpose: Disparities in pediatric heart transplant (HTx) outcomes comparing African American (AA) to Caucasian American (CA) recipients are known. The role of induction therapy in the AA infant population has not been established. Furthermore, it is not known whether all induction therapy medications confer the same post transplant outcomes. We explored the impact of Antithymocyte globulin (ATG), Basiliximab (Bas) and no induction on HTx outcomes in AA and CA infants, using the UNOS database. Methods: 979 (222 AA; 757 CA) infant HTx recipients (age 0 to 2 years) transplanted between 5/1999 to 3/2011 were included in this study. Three groups were analyzed and stratified by race; patients who received ATG (84 AA; 322 CA), Bas (22 AA; 49 CA) induction therapy or no induction therapy (116 AA; 386 CA). Cox proportional hazards models were used to assess factors related to 10-year survival, hazard ratios and 95% confidence intervals (CI). Ten-year survival was estimated by the Kaplan-Meier method. Survival was compared across induction types by the Log-Rank test. Results: AA infants who received ATG but not Bas had improved survival at 10 years compared to no induction (p = 0.010, HR 0.50 95% CI 0.30-0.86, Log-Rank). No survival benefit was found for CA infants who received ATG or Bas compared to no induction (overall Log-Rank P = 0.72). Conclusion: In infant HTx, AA recipients had improved 10-year survival with ATG compared with no induction therapy. CA infant recipients demonstrated no benefit from use of either ATG or Bas. Prospective randomized trials are needed to confirm these observations.
3( 22) C1q Testing in Pediatric Heart Transplant Recipients at Risk for Antibody Mediated Rejection E. Albers ,1 R. Boucek,1 M. Kemna,1 S. Law,1 P. Warner,2 Y. Law.1 1Pediatric Cardiology, Seattle Children’s Hospital, Seattle, WA; 2Puget Sound Blood Center, Seattle, WA. Purpose: Antibody mediated rejection (AMR) is an important cause of morbidity and mortality after pediatric heart transplant. Donor-specific antibodies (DSA) against human leukocyte antigens (HLA) have been associated with AMR. Not all DSA, however, result in clinical rejection. Testing for complement-fixing (C1q) DSA may help identify patients at higher risk for AMR. Methods: A single center retrospective review was conducted to identify patients with at least 1 DSA or history of AMR. Samples with the maximum single locus DSA MFI (if no history of AMR) or at diagnosis of AMR were retrospectively tested for C1q DSA. All DSA were considered positive if MFI > 5000. Comparisons were made with respect to AMR and graft survival. Results: Of 38 patients who met inclusion criteria, 17 (44.7%) had 21 episodes of AMR. Of 42 cases with either positive DSA or AMR, 38 samples were available for C1q testing. Of these, 20 had C1q DSA: 11 with AMR vs. 9 with no AMR (p = 0.321, positive predictive value [PPV] = 55%). Thirtyseven (88.1%) had DSA to Class II HLA (16 C1q), while only 11 (26.2%) had DSA to Class I HLA (5 C1q). AMR was associated with the presence of Class I DSA (p = 0.014, PPV 82%) and Class I C1q DSA (p= 0.016, PPV 100%). Twenty-one (50%) had DSA to > 1 HLA locus of either Class (6 C1q), of which 15 (5 C1q) had AMR (p = 0.005, PPV 71%; C1q: p = 0.075, PPV 83%). Over a median follow-up period of 42 months, 4 patients died and 1 required re-transplant (graft survival 92% at 5yrs, 86% at 10yrs). When considering either a history of AMR, C1q DSA, the presence of Class I DSA, or the presence of > 1 DSA locus, only the presence of > 1 DSA locus was associated with decreased graft survival (p = 0.044). Conclusion: AMR occurred in fewer than 50% of patients in this cohort with positive DSA. A positive C1q test alone was not predictive of AMR, but in certain cases increased the PPV of DSA testing. Most patients had DSA to Class II HLA, but only the presence of DSA to Class I HLA was associated with AMR. The presence of DSA to > 1 HLA locus was not only associated with AMR, it was also associated with decreased graft survival. 3( 23) How Does Donor Specific Antibody Relate to Biopsy-diagnosed Antibody-mediated Rejection after Pediatric Heart Transplantation? A. Ware ,1 G. Snow,2 E. Hammond,3 D.V. Miller,3 J. Stehlik,4 A.G. Kfoury,3 A. Eckhauser,4 D. Eckels,5 M. Everitt.4 1University of Utah, Salt Lake City, UT; 2Intermountain Medical Center, Salt Lake City, UT; 3Intermountain Medical Center/UTAH Cardiac Transplant Program, Salt Lake City, UT; 4University of Utah/UTAH Cardiac Transplant Program, Salt Lake City, UT; 5Pathology, University of Utah, Salt Lake City, UT. Purpose: Antibody-mediated rejection (AMR) is a major cause of mortality after heart transplant (HT). Both biopsy grading of pathologic AMR (pAMR) and assessment for circulating donor specific antibodies (DSA) are recommended for post HT monitoring. However, the relationship between pAMR grade and DSA has not been reported in children after HT. This is the aim of our analysis. Methods: The UTAH Cardiac Transplant database was queried for all children ≤ 21 yrs of age that had testing for DSA within 3 days of EMB. Solid phase immunoassay was used to determine the presence of DSA with positivity defined as antibody specificity to donor HLA at mean fluorescent intensity ≥ 2000. The relationship of DSA (class I, class II, or both) to pAMR grade was assessed using the Mantel-Haenzel chi-squared test. Results: Of 70 HT recipients followed between 2009 and 2013, 28 (40%) had ≥ 1 test positive for DSA. Those with detectable DSA vs. without any DSA were more likely to have a diagnosis of congenital heart disease (CHD) (75% vs. 43%, p= 0.01), more likely to be sensitized (non-donor HLA antibody) pre-HT (46% vs. 10%, p< 0.001), and more commonly received antilymphocyte induction (50% vs. 12%, p< 0.001). Of the 28 with DSA, 4 (14%) had pre-HT DSA with a positive crossmatch at HT. There were 258 EMB with a paired DSA test. Of 56 pAMR1 (h or i) episodes, 57% had DSA. For pAMR2, 27/28 (96%) had DSA. Of 5 pAMR3 episodes, all had DSA. Among 169 EMB negative for AMR, 62 (37%) had circulating DSA.