Advertisement
The Journal of Heart and Lung Transplantation
International Society for Heart and Lung Transplantation.

Epidemiology, risk factors, and outcomes of lung retransplantation: An analysis of the International Society for Heart and Lung Transplantation Thoracic Transplant Registry

  • Michael O. Harhay
    Correspondence
    Reprint requests: Michael O. Harhay, PhD, Perelman School of Medicine, University of Pennsylvania, 304 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021. Telephone/Fax: 215-898-0861.
    Affiliations
    Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

    Palliative and Advanced Illness Research (PAIR) Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

    Pulmonary, Allergy and Critical Care Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

    International Society for Heart and Lung Transplantation - International Thoracic Organ Transplant Registry, Dallas, Texas
    Search for articles by this author
  • Wida S. Cherikh
    Affiliations
    International Society for Heart and Lung Transplantation - International Thoracic Organ Transplant Registry, Dallas, Texas

    United Network for Organ Sharing (UNOS), Richmond, Virginia
    Search for articles by this author
  • Alice E. Toll
    Affiliations
    United Network for Organ Sharing (UNOS), Richmond, Virginia
    Search for articles by this author
  • Jason D. Christie
    Affiliations
    Pulmonary, Allergy and Critical Care Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
    Search for articles by this author
  • Josef Stehlik
    Affiliations
    International Society for Heart and Lung Transplantation - International Thoracic Organ Transplant Registry, Dallas, Texas

    Division of Cardiovascular Medicine, University of Utah School of Medicine, Salt Lake City, Utah
    Search for articles by this author
  • Daniel Chambers
    Affiliations
    International Society for Heart and Lung Transplantation - International Thoracic Organ Transplant Registry, Dallas, Texas

    School of Clinical Medicine, The University of Queensland, Brisbane, Australia
    Search for articles by this author
  • Don Hayes Jr.
    Affiliations
    International Society for Heart and Lung Transplantation - International Thoracic Organ Transplant Registry, Dallas, Texas

    Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
    Search for articles by this author
  • Edward Cantu
    Affiliations
    Division of Cardiovascular Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
    Search for articles by this author

      Background

      Lung retransplantation is a complex surgical decision that represents the only potential treatment option for recipients suffering from lung allograft failure. We sought to describe the modern landscape of lung retransplantation and to compare the relative importance of selected clinical, donor, and recipient factors on mortality in the year following lung retransplantation.

      Methods

      We conducted a retrospective cohort study of first-time adult recipients of deceased donor lung retransplants reported to the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Transplant Registry from May 2005 through June 2017. In addition to describing the characteristics of lung retransplant recipients, we examined 1 year survival overall, and by initial transplant-retransplant procedure type, recipient age, retransplant indication, and time-to-lung retransplantation (i.e., inter-transplant interval). We used the Somers' Dxy rank correlation statistic for censored data to assess the relative importance of several potential prognostic risk factors for mortality in the year following lung retransplantation.

      Results

      Our cohort included 1,597 lung retransplant recipients. 2005 was the first year with more than 100 retransplants, and since 2007, 138 to 188 retransplants (approximately 4%-6% of all transplants) were reported annually to the ISHLT Registry. The median inter-transplant interval was 3.4 years (interquartile range: 1.6-6.2 years). Forty-three percent of the cohort had an obliterative bronchiolitis retransplant indication, whereas 17% had primary graft failure. One-third (32%) were retransplanted within 2 years of their primary transplant, and 64% received a double lung transplant both times, whereas 36% received consecutive single lung transplants. Six-month and 1 year survival (82% and 76%) were higher for double-double lung retransplant recipients than for single-single recipients (76% and 69%). The 3 strongest prognostic factors for 1 year mortality were the inter-transplant interval (decreasing hazard with longer intervals), donor age (increasing hazard with older age), and need for mechanical ventilation preceding lung retransplantation.

      Conclusions

      Retransplants comprise approximately 5% of annual lung transplants worldwide. The factor most strongly associated with 1 year mortality in this population was the duration of time since the primary lung transplant, with a persistent reduction in risk as more time elapses.

      KEYWORDS

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to The Journal of Heart and Lung Transplantation
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Vock DM
        • Durheim MT
        • Tsuang WM
        • et al.
        Survival benefit of lung transplantation in the modern era of lung allocation.
        Ann Am Thorac Soc. 2017; 14: 172-181
        • Seiler A
        • Klaghofer R
        • Ture M
        • Komossa K
        • Martin-Soelch C
        • Jenewein J
        A systematic review of health-related quality of life and psychological outcomes after lung transplantation.
        J Heart Lung Transplant. 2016; 35: 195-202
        • Rana A
        • Gruessner A
        • Agopian VG
        • et al.
        Survival benefit of solid-organ transplant in the United States.
        JAMA Surg. 2015; 150: 252-259
        • Verleden GM
        • Glanville AR
        • Lease ED
        • et al.
        Chronic lung allograft dysfunction: Definition, diagnostic criteria, and approaches to treatment-A consensus report from the Pulmonary Council of the ISHLT.
        J Heart Lung Transplant. 2019; 38: 493-503
        • Strueber M
        • Fischer S
        • Gottlieb J
        • et al.
        Long-term outcome after pulmonary retransplantation.
        J Thorac Cardiovasc Surg. 2006; 132: 407-412
        • Yusen RD
        • Edwards LB
        • Kucheryavaya AY
        • et al.
        The registry of the International Society for Heart and Lung Transplantation: thirty-first adult lung and heart-lung transplant report–2014; focus theme: retransplantation.
        J Heart Lung Transplant. 2014; 33: 1009-1024
        • Chambers DC
        • Cherikh WS
        • Harhay MO
        • et al.
        The international thoracic organ transplant registry of the international society for heart and lung transplantation: thirty-sixth adult lung and heart-lung transplantation report-2019; Focus theme: Donor and recipient size match.
        J Heart Lung Transplant. 2019; 38: 1042-1055
        • Hayes D
        • Cherikh WS
        • Chambers DC
        • et al.
        The international thoracic organ transplant registry of the international society for heart and lung transplantation: twenty-second pediatric lung and heart-lung transplantation report-2019; focus theme: donor and recipient size match.
        J Heart Lung Transplant. 2019; 38: 1015-1027
        • Khush KK
        • Cherikh WS
        • Chambers DC
        • et al.
        The international thoracic organ transplant registry of the international society for heart and lung transplantation: thirty-sixth adult heart transplantation report - 2019; focus theme: Donor and recipient size match.
        J Heart Lung Transplant. 2019; 38: 1056-1066
        • Rossano JW
        • Singh TP
        • Cherikh WS
        • et al.
        The international thoracic organ transplant registry of the international society for heart and lung transplantation: twenty-second pediatric heart transplantation report - 2019; Focus theme: Donor and recipient size match.
        J Heart Lung Transplant. 2019; 38: 1028-1041
        • Doyle S
        • Hayes Jr., D
        • Stewart WCL
        • Whitson BA
        • Tobias JD
        • Tumin D
        Predictive utility of lung allocation score for retransplantation outcomes.
        Ann Thorac Surg. 2018; 106: 1525-1532
        • Kon ZN
        • Bittle GJ
        • Pasrija C
        • Sanchez PG
        • Griffith BP
        • Pierson 3rd, RN
        The optimal procedure for retransplantation after single lung transplantation.
        Ann Thorac Surg. 2017; 104: 170-175
        • Kawut SM
        • Lederer DJ
        • Keshavjee S
        • et al.
        Outcomes after lung retransplantation in the modern era.
        Am J Respir Crit Care Med. 2008; 177: 114-120
        • Osho AA
        • Castleberry AW
        • Snyder LD
        • et al.
        Differential outcomes with early and late repeat transplantation in the era of the lung allocation score.
        Ann Thorac Surg. 2014; 98 (discussion 20-1): 1914-1920
        • Thomas M
        • Belli EV
        • Rawal B
        • Agnew RC
        • Landolfo KP
        Survival after lung retransplantation in the United States in the current era (2004 to 2013): better or worse?.
        Ann Thorac Surg. 2015; 100: 452-457
        • Schumer EM
        • Rice JD
        • Kistler AM
        • et al.
        Single versus double lung retransplantation does not affect survival based on previous transplant type.
        Ann Thorac Surg. 2017; 103: 236-240
        • Hall DJ
        • Belli EV
        • Gregg JA
        • et al.
        Two decades of lung retransplantation: a single-center experience.
        Ann Thorac Surg. 2017; 103: 1076-1083
        • Abdelnour-Berchtold E
        • Federici S
        • Wurlod DA
        • et al.
        Outcome after extracorporeal membrane oxygenation-bridged lung retransplants: a single-centre experience.
        Interact Cardiovasc Thorac Surg. 2019; 28: 922-928
        • Halloran K
        • Aversa M
        • Tinckam K
        • et al.
        Comprehensive outcomes after lung retransplantation: a single-center review.
        Clin Transplant. 2018; 32: e13281
        • Royston P
        • Altman DG
        • Sauerbrei W
        Dichotomizing continuous predictors in multiple regression: a bad idea.
        Stat Med. 2006; 25: 127-141
        • Greenland S
        Dose-response and trend analysis in epidemiology: alternatives to categorical analysis.
        Epidemiology. 1995; 6: 356-365
        • Dinero TE
        Seven reasons why you should not categorize continuous data.
        J Health Soc Policy. 1996; 8: 63-72
        • White IR
        • Royston P
        • Wood AM
        Multiple imputation using chained equations: Issues and guidance for practice.
        Stat Med. 2011; 30: 377-399
        • R Development Core Team
        R: A Language and Environment for Statistical Computing.
        R Foundation for Statistical Computing, Vienna, Austria2021 (Available at:)
      1. Harrell FE, Jr.: CRAN-Package Hmisc: Harrell Miscellaneous. R package verison 4.6. Available at: https://hbiostat.org/R/Hmisc/2021.

        • Sutradhar R
        • Austin PC
        Relative rates not relative risks: addressing a widespread misinterpretation of hazard ratios.
        Ann Epidemiol. 2018; 28: 54-57
        • Harrell Jr., FE
        Multivariable Modeling Strategies: With Applications to Linear Models, Logistic and Ordinal Regression, and Survival Analysis.
        (editor)Second Edition. Springer, Cham2015
        • Brentnall AR
        • Cuzick J
        Use of the concordance index for predictors of censored survival data.
        Stat Methods Med Res. 2018; 27: 2359-2373
        • Randhawa SK
        • Yang Z
        • Morkan DB
        • et al.
        One-year survival worse for lung retransplants relative to primary lung transplants.
        Ann Thorac Surg. 2022; 113: 1265-1273
        • Harhay MO
        • Porcher R
        • Thabut G
        • et al.
        Donor lung sequence number and survival after lung transplantation in the United States.
        Ann Am Thorac Soc. 2019; 16: 313-320
        • Thabut G
        • Christie JD
        • Kremers WK
        • Fournier M
        • Halpern SD
        Survival differences following lung transplantation among US transplant centers.
        JAMA. 2010; 304: 53-60

      Related Podcast

      JHLT: The Podcast Episode 22: October 2022

      For this month’s episode, JHLT The Podcast explores two impactful studies from the October issue of The Journal of Heart and Lung Transplantation. The episode is hosted by Daniel R. Goldstein, MD, Editor-in-Chief of JHLT, who is joined by the JHLT Digital Media Editors. Listen now to hear study authors discuss their work, their studies, and next steps for their research.

      We hear from Anne Dipchand, MD (pictured), Professor of Pediatrics and Pediatric Cardiologist at the Hospital for Sick Children in Toronto, Canada, who is senior author on the study, “Eplet matching in pediatric heart transplantation: The SickKids experience.” Dr. Goldstein and David Schibilsky, MD, discuss the study with Dr. Dipchand. This single-center retrospective study measured allograft survival in 77 patients while performing HLA typing, antigen mismatch, and eplet mismatch analysis, with the goal of comparing the molecular level HLA matching with antigen level HL matching in post-heart transplant outcomes in children.