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Outcomes of low-intensity biopsy surveillance for rejection in paediatric cardiac transplantation

Published online by Cambridge University Press:  17 June 2019

Patrick D. Evers Open the ORCID record for Patrick D. Evers [Opens in a new window] ,
Neal Jorgensen ,
Borah Hong ,
Erin Albers ,
Mariska Kemna ,
Josh Friedland-Little ,
Robert J. Boucek  and
Yuk Law
Patrick D. Evers
Affiliation:
The Heart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA
Neal Jorgensen
Affiliation:
Division of Cardiology, Department of Pediatrics, University of Washington School of Medicine and Seattle Children’s Hospital, Seattle, WA, USA
Borah Hong
Affiliation:
Division of Cardiology, Department of Pediatrics, University of Washington School of Medicine and Seattle Children’s Hospital, Seattle, WA, USA
Erin Albers
Affiliation:
Division of Cardiology, Department of Pediatrics, University of Washington School of Medicine and Seattle Children’s Hospital, Seattle, WA, USA
Mariska Kemna
Affiliation:
Division of Cardiology, Department of Pediatrics, University of Washington School of Medicine and Seattle Children’s Hospital, Seattle, WA, USA
Josh Friedland-Little
Affiliation:
Division of Cardiology, Department of Pediatrics, University of Washington School of Medicine and Seattle Children’s Hospital, Seattle, WA, USA
Robert J. Boucek
Affiliation:
Division of Cardiology, Department of Pediatrics, University of Washington School of Medicine and Seattle Children’s Hospital, Seattle, WA, USA
Yuk Law*
Affiliation:
Division of Cardiology, Department of Pediatrics, University of Washington School of Medicine and Seattle Children’s Hospital, Seattle, WA, USA
*
Author for correspondence: Yuk Law, MD, Division of Cardiology, Seattle Children’s Hospital, M/S RC.2.820, PO Box 5371, Seattle, WA 98105, USA. Tel: 206-987-1417; Fax: 206-987-3839. E-mail: yuk.law@seattlechildrens.org
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Abstract

Background:

Significant inter-centre variability in the intensity of endomyocardial biopsy surveillance for rejection following paediatric cardiac transplantation has been reported. Our aim was to determine if low-intensity biopsy surveillance with two scheduled biopsies in the first year would produce outcomes similar to published registry outcomes.

Methods:

A retrospective study of paediatric recipients transplanted between 2008 and 2014 using a low-intensity biopsy protocol consisting of two surveillance biopsies at 3 and 12–13 months in the first post-transplant year, then annually thereafter. Additional biopsies were performed based on echocardiographic and clinical surveillance. Excluded were recipients that were re-transplanted or multi-organ transplanted or were followed at another institution.

Results:

A total of 81 recipients in the first 13 months after transplant underwent an average of 2 (SD ± 1.3) biopsies, 24 ± 6.8 echocardiograms, and 17 ± 4.4 clinic visits per recipient. During the 13-month period, 19 recipients had 24 treated rejection episodes, with the first at an average of 2.8 months post-transplant. The 3-, 12-, 36-, and 60-month conditional on discharge graft survival were 100%, 98.8%, 98.8%, and 90.4%, respectively, comparable to reported figures in major paediatric registries. At a mean follow-up of 4.7 ± 2.1 years, four patients (4.9%) developed cardiac allograft vasculopathy, three (3.7%) developed a malignancy, and seven (8.6%) suffered graft loss.

Conclusion:

Rejection surveillance with a low-intensity biopsy protocol demonstrated similar intermediate-term outcomes and safety measures as international registries up to 5 years post-transplant.

Keywords

Organ transplantationechocardiographypaediatrics
Type
Original Article
Information
Cardiology in the Young , Volume 29 , Issue 7 , July 2019 , pp. 910 - 916
Copyright
© Cambridge University Press 2019 

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References

Rossano, JW, Dipchand, AI, Edwards, LB, et al. The registry of the International Society for Heart and Lung Transplantation: Nineteenth Pediatric Heart Transplantation Report-2016; focus theme: primary diagnostic indications for transplant. J Heart Lung Transplant 2016; 35: 1185–1195.CrossRefGoogle ScholarPubMed
Gossett, JG, Canter, CE, Zheng, J, et al. Decline in rejection in the first year after pediatric cardiac transplantation: a multi-institutional study. J Heart Lung Transplant 2010; 29: 625–632.CrossRefGoogle ScholarPubMed
Mills, RM, Naftel, DC, Kirklin, JK, et al. Heart transplant rejection with hemodynamic compromise: a multiinstitutional study of the role of endomyocardial cellular infiltrate. Cardiac Transplant Research Database. J Heart Lung Transplant 1997; 16: 813–821.Google ScholarPubMed
Kobashigawa, JA. The search for a gold standard to detect rejection in heart transplant patients: are we there yet? Circulation 2017; 135: 936–938.CrossRefGoogle Scholar
Costanzo, MR, Dipchand, A, Starling, R, et al. The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients. J Heart Lung Transplant 2010; 29: 914–956.CrossRefGoogle ScholarPubMed
Wagner, K, Oliver, MC, Boyle, GJ, et al. Endomyocardial biopsy in pediatric heart transplant recipients: a useful exercise? (Analysis of 1,169 biopsies). Pediatr Transplant 2000; 4: 186–192.CrossRefGoogle Scholar
Levi, DS, DeConde, AS, Fishbein, MC, Burch, C, Alejos, JC, Wetzel, GT. The yield of surveillance endomyocardial biopsies as a screen for cellular rejection in pediatric heart transplant patients. Pediatr Transplant 2004; 8: 22–28.CrossRefGoogle ScholarPubMed
Rosenthal, DN, Chin, C, Nishimura, K, et al. Identifying cardiac transplant rejection in children: diagnostic utility of echocardiography, right heart catheterization and endomyocardial biopsy data. J Heart Lung Transplant 2004; 23: 323–329.CrossRefGoogle ScholarPubMed
Godown, J, Harris, MT, Burger, J, Dodd, DA. Variation in the use of surveillance endomyocardial biopsy among pediatric heart transplant centers over time. Pediatr Transplant 2015; 19: 612–617.CrossRefGoogle ScholarPubMed
Bhat, G, Burwig, S, Walsh, R. Morbidity of endomyocardial biopsy in cardiac transplant recipients. Am Heart J 1993; 125: 1180–1181.CrossRefGoogle ScholarPubMed
Baraldi-Junkins, C, Levin, HR, Kasper, EK, Rayburn, BK, Herskowitz, A, Baughman, KL. Complications of endomyocardial biopsy in heart transplant patients. J Heart Lung Transplant 1993; 12: 63–67.Google ScholarPubMed
Pophal, SG, Sigfusson, G, Booth, KL, et al. Complications of endomyocardial biopsy in children. J Am Coll Cardiol 1999; 34: 2105–2110.CrossRefGoogle ScholarPubMed
Ye, XT, Parker, A, Brink, J, Weintraub, RG, Konstantinov, IE. Cost-effectiveness of the National Pediatric Heart Transplantation Program in Australia. J Thorac Cardiovasc Surg 2018.CrossRefGoogle Scholar
Dodd, DA, Brady, LD, Carden, KA, Frist, WH, Boucek, MM, Boucek, RJ Jr. Pattern of echocardiographic abnormalities with acute cardiac allograft rejection in adults: correlation with endomyocardial biopsy. J Heart Lung Transplant 1993; 12: 1009–1017.Google ScholarPubMed
Valantine, HA, Yeoh, TK, Gibbons, R, et al. Sensitivity and specificity of diastolic indexes for rejection surveillance: temporal correlation with endomyocardial biopsy. J Heart Lung Transplant 1991; 10: 757–765.Google ScholarPubMed
Moran, AM, Lipshultz, SE, Rifai, N, et al. Non-invasive assessment of rejection in pediatric transplant patients: serologic and echocardiographic prediction of biopsy-proven myocardial rejection. J Heart Lung Transplant 2000; 19: 756–764.CrossRefGoogle ScholarPubMed
Boucek, MM, Mathis, CM, Boucek, RJ Jr., et al. Prospective evaluation of echocardiography for primary rejection surveillance after infant heart transplantation: comparison with endomyocardial biopsy. J Heart Lung Transplant 1994; 13: 66–73.Google ScholarPubMed
Tantengco, MV, Dodd, D, Frist, WH, Boucek, MM, Boucek, RJ. Echocardiographic abnormalities with acute cardiac allograft rejection in children: correlation with endomyocardial biopsy. J Heart Lung Transplant 1993; 12: S203–210.Google ScholarPubMed
Boucek, RJ Jr., Boucek, MM, Asante-Korang, A. Advances in methods for surveillance of rejection. Cardiol Young 2004; 14 Suppl 1: 93–96.CrossRefGoogle ScholarPubMed
Asante-Korang, A, Fickey, M, Boucek, MM, Boucek, RJ Jr. Diastolic performance assessed by tissue Doppler after pediatric heart transplantation. J Heart Lung Transplant 2004; 23: 865–872.CrossRefGoogle ScholarPubMed
Pauliks, LB, Pietra, BA, DeGroff, CG, et al. Non-invasive detection of acute allograft rejection in children by tissue Doppler imaging: myocardial velocities and myocardial acceleration during isovolumic contraction. J Heart Lung Transplant 2005; 24: S239–S248.CrossRefGoogle ScholarPubMed
Putzer, GJ, Cooper, D, Keehn, C, Asante-Korang, A, Boucek, MM, Boucek, RJ Jr. An improved echocardiographic rejection-surveillance strategy following pediatric heart transplantation. J Heart Lung Transplant 2000; 19: 1166–1174.CrossRefGoogle ScholarPubMed
Stewart, S, Winters, GL, Fishbein, MC, et al. Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection. J Heart Lung Transplant 2005; 24: 1710–1720.CrossRefGoogle Scholar
Berry, GJ, Angelini, A, Burke, MM, et al. The ISHLT working formulation for pathologic diagnosis of antibody-mediated rejection in heart transplantation: evolution and current status (2005-2011). J Heart Lung Transplant 2011; 30: 601–611.CrossRefGoogle Scholar
Everitt, MD, Donaldson, AE, Casper, TC, et al. Effect of ABO-incompatible listing on infant heart transplant waitlist outcomes: analysis of the United Network for Organ Sharing (UNOS) database. J Heart Lung Transplant 2009; 28: 1254–1260.CrossRefGoogle ScholarPubMed
Zinn, MD, Wallendorf, MJ, Simpson, KE, Osborne, AD, Kirklin, JK, Canter, CE. Impact of routine surveillance biopsy intensity on the diagnosis of moderate to severe cellular rejection and survival after pediatric heart transplantation. Pediatr Transplant 2018; 22: e13131.CrossRefGoogle Scholar
Everitt, MD, Pahl, E, Schechtman, KB, et al. Rejection with hemodynamic compromise in the current era of pediatric heart transplantation: a multi-institutional study. J Heart Lung Transplant 2011; 30: 282–288.CrossRefGoogle ScholarPubMed
Zinn, MD, Wallendorf, MJ, Simpson, KE, Osborne, AD, Kirklin, JK, Canter, CE. Impact of age on incidence and prevalence of moderate-to-severe cellular rejection detected by routine surveillance biopsy in pediatric heart transplantation. J Heart Lung Transplant 2017; 36: 451–456.CrossRefGoogle ScholarPubMed
Dipchand, AI, Rossano, JW, Edwards, LB, et al. The registry of the International Society for Heart and Lung Transplantation: Eighteenth Official Pediatric Heart Transplantation Report-2015; Focus Theme: Early Graft Failure. J Heart Lung Transplant 2015; 34: 1233–1243.CrossRefGoogle ScholarPubMed
Weckbach, LT, Maurer, U, Schramm, R, et al. Lower frequency routine surveillance endomyocardial biopsies after heart transplantation. PLoS One 2017; 12: e0182880.CrossRefGoogle ScholarPubMed
Winters, GL, Loh, E, Schoen, FJ. Natural history of focal moderate cardiac allograft rejection. Is treatment warranted? Circulation 1995; 91: 1975–1980.CrossRefGoogle ScholarPubMed
Winters, GL, McManus, BM. Consistencies and controversies in the application of the International Society for Heart and Lung Transplantation working formulation for heart transplant biopsy specimens. Rapamycin Cardiac Rejection Treatment Trial Pathologists. J Heart Lung Transplant 1996; 15: 728–735.Google ScholarPubMed
Yang, HM, Lai, CK, Gjertson, DW, et al. Has the 2004 revision of the International Society of Heart and Lung Transplantation grading system improved the reproducibility of the diagnosis and grading of cardiac transplant rejection? Cardiovasc Pathol 2009; 18: 198–204.CrossRefGoogle ScholarPubMed
Brunner-La Rocca, HP, Sutsch, G, Schneider, J, Follath, F, Kiowski, W. Natural course of moderate cardiac allograft rejection (International Society for Heart Transplantation grade 2) early and late after transplantation. Circulation 1996; 94: 1334–1338.CrossRefGoogle ScholarPubMed
Sethi, GK, Kosaraju, S, Arabia, FA, Roasdo, LJ, McCarthy, MS, Copeland, JG. Is it necessary to perform surveillance endomyocardial biopsies in heart transplant recipients? J Heart Lung Transplant 1995; 14: 1047–1051.Google ScholarPubMed
Chin, C, Akhtar, MJ, Rosenthal, DN, Bernstein, D. Safety and utility of the routine surveillance biopsy in pediatric patients 2 years after heart transplantation. J Pediatr 2000; 136: 238–242.CrossRefGoogle ScholarPubMed
Zinn, M, Simpson, K, Wallendorf, M, Osborne, A, Kirklin, J, Canter, C. Impact of routine surveillance biopsy intensity on the diagnosis of moderate to severe cellular rejection and survival after pediatric heart transplant. J Heart Lung Transplant 2016; 35: S406.CrossRefGoogle Scholar
Alonzo, TA, Pepe, MS. Assessing the accuracy of a new diagnostic test when a gold standard does not exist. UW Biostatistics Working Paper Series. 1998. https://biostats.bepress.com/uwbiostat/paper156Google Scholar
Auerbach, SR, Gralla, J, Campbell, DN, Miyamoto, SD, Pietra, BA. Steroid avoidance in pediatric heart transplantation results in excellent graft survival. Transplantation 2014; 97: 474–480.CrossRefGoogle ScholarPubMed
Singh, TP, Faber, C, Blume, ED, et al. Safety and early outcomes using a corticosteroid-avoidance immunosuppression protocol in pediatric heart transplant recipients. J Heart Lung Transplant 2010; 29: 517–522.CrossRefGoogle ScholarPubMed