- Email: [email protected]
Predicting Myocardial Recovery in Children with Dilated Cardiomyopathy
S240
The Journal of Heart and Lung Transplantation, Vol 32, No 4S, April 2013
one episode of hypoglycemia requiring hospitalization, but there was no need to discontinue medication. Conclusions: Mortality and transplant remain common outcomes for children with DCM, particularly in the first year following presentation. Carvedilol and ACE inhibitors are safely tolerated with long-term use, and at higher doses than previously reported. Hypoglycemia may be a serious side effect that can be avoided by taking carvedilol with food. Persistent NTproBNPZ1000 may indicate need for transplantation. 658 Atopy, Eosinophilia, Complete Blood Count (CBC) and the Risk of Rejection in Pediatric Heart Transplant Recipients K. Arbon,1 E. Albers,2 S. Law,2 M. Kemna,2 L. Permut,3 Y.M. Law.2 1 University of Washington School of Medicine, Seattle, WA; 2 Pediatrics, Seattle Children’s Hospital, University of Washington, Seattle, WA; 3Surgery, Seattle Children’s Hospital, University of Washington, Seattle, WA. Purpose: Further understanding of risk factors for rejection can allow clinicians to reduce immunosuppression. CD3 lymphocytes play a central role in adaptive immune function with the Th1 phenotype (pro-inflammatory) being a mediator and the Th2 (pro-atopic)possibly being suppressive of rejection. Children have less rejection and more atopic conditions compared to adults. Therefore, we ask whether an association exists between the atopic state and freedom from rejection. Methods and Materials: Single-center, observational study of recipients transplanted before 21yrs of age with Z12 mos FU. Pre-specified biannual CBCs plus clinical information were collected. Individual patient CBC values were grouped and then further combined for comparative analyses. Rejection is defined by need for rescue therapy. Results: Study period was 1994-2011 and 86 patients qualified. Median age at transplant was 14.5 mos with mean FU of 40.5 mos and 6.8 CBCs/patient. Atopic conditions necessitating intervention were common (56% of patients) and was associated with age at transplant o3 yrs (po0.001). Rejection occurred in 42 patients (49%): 38 (44%) experienced acute cellular (ACR) and 11 antibody mediated (AMR, 13%). Only female sex (p¼0.082) and low eosinophil count (p¼0.071) approached significance as risk factors for ACR. Sensitization pretransplant (po0.006), presence of HLA-I donor specific antibody (p¼0.014), low WBC (p¼0.004), low ALC (p¼0.012), and low eosinophil count (po0.001) were associated with AMR. In multivariable analysis, sex (p¼0.016) and eosinophil count (p¼0.052) remained associated with ACR; only sensitization to HLA-I (p¼0.051) and eosinophil count as continuous variable (p¼0.139) or ordinal variable (cutoff of 250/mm3, p¼0.068 ) approached significance with AMR. Conclusions: This is the first study to suggest an association between low eosinophil count and rejection. Eosinophilia may be a useful marker of low rejection risk. Future studies will examine its clinical relationship to Th1/Th2 phenotype balance. 659 Outcomes with High Pre-Transplant PRA in Pediatric Heart Transplantation at a Single Center D.A. Dodd,1 B. Mettler.2 1Pediatric Cardiology, Vanderbilt University, Nashville, TN; 2Pediatric CT Surgery, Vanderbilt University, Nashville, TN. Purpose: Acceptance and management of pediatric heart transplant (Tx) candidates with high pre-Tx PRA remains center dependent, largely due to lack of medium and longterm followup on outcomes. Some centers proceed only with a negative crossmatch, essentially guaranteeing no suitable donor in the worst cases. Other centers proceed across a positive crossmatch, feeling mortality is more likely waiting for a suitable donor, but with uncertain outcomes. We review outcomes after pediatric heart Tx with positive pre-Tx PRA (410%) at a center that has not used prospective crossmatch, and more recently has chosen to transplant across a positive virtual crossmatch for those with markedly elevated PRA.
Methods and Materials: This is a retrospective chart review of all children undergoing heart transplantation at our center. Results: We identified 19 recipients with pre-Tx PRA 410%: 11 class I, 2 class II, and 6 both class I and II. PRA class I mean was 43% (range 0-100) and class II mean was 27% (0-100). 11 of 18 tested had a positive retrospective crossmatch; 1 had no crossmatch. Only the 2 most recent recipients had specific intra-operative therapy to reduce antibody. Anti-thymocyte antibody induction is used. Post-Tx medications are often modified for better B cell coverage in this group. There were 5 deaths: rejection 2.3 y; rejection 3.2 y; PTLD 3.4 y; infection 7.0 y; and suicide 10.4 y. Both rejection deaths were linked to noncompliance. None of the high PRA recipients had documented coronary vasculopathy. Actuarial survival was 100% at 1 y; 79% at 5 y; 69% at 10y. 7 of 19 had rejection: 3 cellular, 2 AMR and 2 diagnosed clinically without biopsy. Time to first rejection was o3 mn in 4 and 41 y in 3. 3 recipients had 41 rejection episode. Positive crossmatch did not predict those likely to have rejection or death from rejection. Conclusions: Reasonable outcomes in pediatric heart Tx recipients with high PRA, with or without a positive crossmatch, support offering Tx across a positive virtual crossmatch for those unlikely to otherwise undergo Tx. 660 Predicting Myocardial Recovery in Children with Dilated Cardiomyopathy S.C. West,1 M. Seckeler,2 S. Hallowell,3 C.H. Saunders,3 K.A. Jayakumar,4 D.S. Schneider.3 1Pediatric Cardiology, Children’s Hospital of Pittsburgh, Pittsburgh, PA; 2Pediatric Cardiology, Cincinnati Children’s Hospital, Cincinnati, OH; 3Pediatrics, University of Virginia Children’s Hospital, Charlottesville, VA; 4Pediatrics, Sanger Heart and Vascular Institute, Charlotte, NC. Purpose: Dilated cardiomyopathy (DCM) is a common indication for heart transplantation (Tx) in children but not all progress to Tx. Standard 2D echocardiography (2DE) and Doppler techniques do not predict which patients will recover function. Myocardial function can be reliably determined using Velocity Vector Imaging (VVI), an angle independent method of evaluating myocardial mechanics using conventional 2DE images. We believe VVI provides a valid and reproducible measure of myocardial function in DCM patients with correlation to clinical outcomes. Methods and Materials: Medical records and 2DEs were retrospectively reviewed on patients with DCM. VVI analysis was performed offline using Siemens Syngo software. Using VVI on a 4 chamber image, longitudinal velocity (LVel), strain (S), strain rate (SR) were obtained. Ventricular functional parameters were compared to normal. Results: 22 patients were treated for DCM 8 patients recovered function, 4 patients underwent Tx, 3 patients were listed for Tx, 7 patients died without recovering or while awaiting Tx. Mortality was associated with mechanical, ventilatory support, and renal failure. The overall mortality rate was 36% (8/28). LVel, S, and SR were decreased compared to normal in all groups. LVel, S, and SR were statistically different in those who progressed to Tx and listed for Tx compared to those who did recover. S and SR did not return to normal even in the group who clinically recovered. Ejection fraction and 2DE dimensions correlated with VVI parameters. Conclusions: VVI derived myocardial functional parameters do not return to normal despite clinical recovery and return to normal of conventional 2DE parameters. VVI is an effective tool to predict degree of myocardial recovery and serves as an adjunct to conventional 2DE measures of systolic and diastolic function. 661 Does Surgeon Training or Hospital (Pediatric vs. Adult) Affect Survival after Heart Transplant in Adults with Congenital Heart Disease? D. Boucek,1,2 A.T. Yetman,2 K.D. Brunisholz,1,3 A.G. Kfoury,1,3 J. Stehlik,1,2 E.M. Gilbert,1,2 C.H. Selzman,1,2 A.K. Kaza,1,2 A. Eckhauser,1,2 R. Alharethi,1,3 D. Budge,1,3 J.N. Nativi,1,2 S.G. Drakos,1,2 K.M. Molina,1,2 M.D. Everitt.1,2 1UTAH Cardiac
The Journal of Heart and Lung Transplantation, Vol 32, No 4S, April 2013
one episode of hypoglycemia requiring hospitalization, but there was no need to discontinue medication. Conclusions: Mortality and transplant remain common outcomes for children with DCM, particularly in the first year following presentation. Carvedilol and ACE inhibitors are safely tolerated with long-term use, and at higher doses than previously reported. Hypoglycemia may be a serious side effect that can be avoided by taking carvedilol with food. Persistent NTproBNPZ1000 may indicate need for transplantation. 658 Atopy, Eosinophilia, Complete Blood Count (CBC) and the Risk of Rejection in Pediatric Heart Transplant Recipients K. Arbon,1 E. Albers,2 S. Law,2 M. Kemna,2 L. Permut,3 Y.M. Law.2 1 University of Washington School of Medicine, Seattle, WA; 2 Pediatrics, Seattle Children’s Hospital, University of Washington, Seattle, WA; 3Surgery, Seattle Children’s Hospital, University of Washington, Seattle, WA. Purpose: Further understanding of risk factors for rejection can allow clinicians to reduce immunosuppression. CD3 lymphocytes play a central role in adaptive immune function with the Th1 phenotype (pro-inflammatory) being a mediator and the Th2 (pro-atopic)possibly being suppressive of rejection. Children have less rejection and more atopic conditions compared to adults. Therefore, we ask whether an association exists between the atopic state and freedom from rejection. Methods and Materials: Single-center, observational study of recipients transplanted before 21yrs of age with Z12 mos FU. Pre-specified biannual CBCs plus clinical information were collected. Individual patient CBC values were grouped and then further combined for comparative analyses. Rejection is defined by need for rescue therapy. Results: Study period was 1994-2011 and 86 patients qualified. Median age at transplant was 14.5 mos with mean FU of 40.5 mos and 6.8 CBCs/patient. Atopic conditions necessitating intervention were common (56% of patients) and was associated with age at transplant o3 yrs (po0.001). Rejection occurred in 42 patients (49%): 38 (44%) experienced acute cellular (ACR) and 11 antibody mediated (AMR, 13%). Only female sex (p¼0.082) and low eosinophil count (p¼0.071) approached significance as risk factors for ACR. Sensitization pretransplant (po0.006), presence of HLA-I donor specific antibody (p¼0.014), low WBC (p¼0.004), low ALC (p¼0.012), and low eosinophil count (po0.001) were associated with AMR. In multivariable analysis, sex (p¼0.016) and eosinophil count (p¼0.052) remained associated with ACR; only sensitization to HLA-I (p¼0.051) and eosinophil count as continuous variable (p¼0.139) or ordinal variable (cutoff of 250/mm3, p¼0.068 ) approached significance with AMR. Conclusions: This is the first study to suggest an association between low eosinophil count and rejection. Eosinophilia may be a useful marker of low rejection risk. Future studies will examine its clinical relationship to Th1/Th2 phenotype balance. 659 Outcomes with High Pre-Transplant PRA in Pediatric Heart Transplantation at a Single Center D.A. Dodd,1 B. Mettler.2 1Pediatric Cardiology, Vanderbilt University, Nashville, TN; 2Pediatric CT Surgery, Vanderbilt University, Nashville, TN. Purpose: Acceptance and management of pediatric heart transplant (Tx) candidates with high pre-Tx PRA remains center dependent, largely due to lack of medium and longterm followup on outcomes. Some centers proceed only with a negative crossmatch, essentially guaranteeing no suitable donor in the worst cases. Other centers proceed across a positive crossmatch, feeling mortality is more likely waiting for a suitable donor, but with uncertain outcomes. We review outcomes after pediatric heart Tx with positive pre-Tx PRA (410%) at a center that has not used prospective crossmatch, and more recently has chosen to transplant across a positive virtual crossmatch for those with markedly elevated PRA.
Methods and Materials: This is a retrospective chart review of all children undergoing heart transplantation at our center. Results: We identified 19 recipients with pre-Tx PRA 410%: 11 class I, 2 class II, and 6 both class I and II. PRA class I mean was 43% (range 0-100) and class II mean was 27% (0-100). 11 of 18 tested had a positive retrospective crossmatch; 1 had no crossmatch. Only the 2 most recent recipients had specific intra-operative therapy to reduce antibody. Anti-thymocyte antibody induction is used. Post-Tx medications are often modified for better B cell coverage in this group. There were 5 deaths: rejection 2.3 y; rejection 3.2 y; PTLD 3.4 y; infection 7.0 y; and suicide 10.4 y. Both rejection deaths were linked to noncompliance. None of the high PRA recipients had documented coronary vasculopathy. Actuarial survival was 100% at 1 y; 79% at 5 y; 69% at 10y. 7 of 19 had rejection: 3 cellular, 2 AMR and 2 diagnosed clinically without biopsy. Time to first rejection was o3 mn in 4 and 41 y in 3. 3 recipients had 41 rejection episode. Positive crossmatch did not predict those likely to have rejection or death from rejection. Conclusions: Reasonable outcomes in pediatric heart Tx recipients with high PRA, with or without a positive crossmatch, support offering Tx across a positive virtual crossmatch for those unlikely to otherwise undergo Tx. 660 Predicting Myocardial Recovery in Children with Dilated Cardiomyopathy S.C. West,1 M. Seckeler,2 S. Hallowell,3 C.H. Saunders,3 K.A. Jayakumar,4 D.S. Schneider.3 1Pediatric Cardiology, Children’s Hospital of Pittsburgh, Pittsburgh, PA; 2Pediatric Cardiology, Cincinnati Children’s Hospital, Cincinnati, OH; 3Pediatrics, University of Virginia Children’s Hospital, Charlottesville, VA; 4Pediatrics, Sanger Heart and Vascular Institute, Charlotte, NC. Purpose: Dilated cardiomyopathy (DCM) is a common indication for heart transplantation (Tx) in children but not all progress to Tx. Standard 2D echocardiography (2DE) and Doppler techniques do not predict which patients will recover function. Myocardial function can be reliably determined using Velocity Vector Imaging (VVI), an angle independent method of evaluating myocardial mechanics using conventional 2DE images. We believe VVI provides a valid and reproducible measure of myocardial function in DCM patients with correlation to clinical outcomes. Methods and Materials: Medical records and 2DEs were retrospectively reviewed on patients with DCM. VVI analysis was performed offline using Siemens Syngo software. Using VVI on a 4 chamber image, longitudinal velocity (LVel), strain (S), strain rate (SR) were obtained. Ventricular functional parameters were compared to normal. Results: 22 patients were treated for DCM 8 patients recovered function, 4 patients underwent Tx, 3 patients were listed for Tx, 7 patients died without recovering or while awaiting Tx. Mortality was associated with mechanical, ventilatory support, and renal failure. The overall mortality rate was 36% (8/28). LVel, S, and SR were decreased compared to normal in all groups. LVel, S, and SR were statistically different in those who progressed to Tx and listed for Tx compared to those who did recover. S and SR did not return to normal even in the group who clinically recovered. Ejection fraction and 2DE dimensions correlated with VVI parameters. Conclusions: VVI derived myocardial functional parameters do not return to normal despite clinical recovery and return to normal of conventional 2DE parameters. VVI is an effective tool to predict degree of myocardial recovery and serves as an adjunct to conventional 2DE measures of systolic and diastolic function. 661 Does Surgeon Training or Hospital (Pediatric vs. Adult) Affect Survival after Heart Transplant in Adults with Congenital Heart Disease? D. Boucek,1,2 A.T. Yetman,2 K.D. Brunisholz,1,3 A.G. Kfoury,1,3 J. Stehlik,1,2 E.M. Gilbert,1,2 C.H. Selzman,1,2 A.K. Kaza,1,2 A. Eckhauser,1,2 R. Alharethi,1,3 D. Budge,1,3 J.N. Nativi,1,2 S.G. Drakos,1,2 K.M. Molina,1,2 M.D. Everitt.1,2 1UTAH Cardiac