Cardiac allograft vasculopathy and graft failure in pediatric heart transplant recipients after rejection with severe hemodynamic compromise

Jake A. Kleinmahon, Jane Gralla, Richard Kirk, Scott R. Auerbach, Heather T. Henderson, Gonzalo A. Wallis, Karthik Ramakrishnan, Rakesh K. Singh, Randall L. Caldwell, Andrew J. Savage, Melanie D. Everitt

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Rejection with severe hemodynamic compromise (RSHC) carries a mortality risk approaching 50%. We aimed to identify current risk factors for RSHC and predictors of graft failure after RSHC. METHODS: Data from 3,259 heart transplant (HT) recipients between January 2005 and December 2015 in the Pediatric Heart Transplant Study (PHTS) were analyzed. Predictors for RSHC and outcome after RSHC were sought. Time to RSHC was analyzed using the Cox proportional hazards regression model. Cardiac allograft vasculopathy (CAV) after HT and CAV after RSHC were analyzed as time-dependent covariates. Timing of RSHC was analyzed as occurring before and after 4 years after RSHC. RESULTS: There were 309 patients (9.5%) with ≥ 1 RSHC episodes. In 143 patients with RSHC, the first episode was within 1 year after HT. Independent risk factors for RSHC were age 1 to 5 years at HT (hazard ratio [HR], 1.51; 95% confidence interval [CI], 1.04–2.18), age > 10 years at HT (HR, 1.83; 95% CI, 1.29–2.60), black race (HR, 1.64; 95% CI, 1.25–2.15), prior cardiac surgery (HR, 1.55; 95% CI, 1.03–2.31), ventricular assist device support at HT (HR, 1.65; 95% CI, 1.18–2.29), maintenance steroids (HR, 1.39; 95% CI, 1.06–1.82), and recipient on inotropes, pressors, or thyroid hormones (HR, 1.45; 95% CI, 1.09–1.94). Graft survival at 5 years after RSHC was 45.7%. RSHC was a greater risk factor for earlier CAV (HR, 7.78; 95% CI, 5.82–10.40) than other rejection types (HR, 2.31; 95% CI, 1.79–3.00). Patients with late RSHC, after 1 year after RSHC had increased risk of graft loss 4 years after RSHC (HR, 7.12; 95% CI, 2.18–23.22). The 5-year graft survival after RSHC was 50.5% for early RSHC and 39.0% for late RSHC. CONCLUSIONS: Mortality after RSHC is high in the current treatment era. Many patient risk factors for RSHC cannot be modified, including age, race, prior cardiac surgery, and ventricular assist device support. After RSHC, CAV is the only predictor of graft failure. Patients who have late RSHC fare worse than those who have RSHC within the first year after HT.

LanguageEnglish (US)
JournalJournal of Heart and Lung Transplantation
DOIs
StateAccepted/In press - Jan 1 2019

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Allografts
Hemodynamics
Pediatrics
Transplants
Confidence Intervals
Transplant Recipients
Heart-Assist Devices
Graft Survival
Thoracic Surgery
Mortality

Keywords

  • cardiac allograft vasculopathy
  • graft failure
  • heart transplant
  • pediatric
  • rejection with severe hemodynamic compromise

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

Cite this

Cardiac allograft vasculopathy and graft failure in pediatric heart transplant recipients after rejection with severe hemodynamic compromise. / Kleinmahon, Jake A.; Gralla, Jane; Kirk, Richard; Auerbach, Scott R.; Henderson, Heather T.; Wallis, Gonzalo A.; Ramakrishnan, Karthik; Singh, Rakesh K.; Caldwell, Randall L.; Savage, Andrew J.; Everitt, Melanie D.

In: Journal of Heart and Lung Transplantation, 01.01.2019.

Research output: Contribution to journalArticle

Kleinmahon, Jake A. ; Gralla, Jane ; Kirk, Richard ; Auerbach, Scott R. ; Henderson, Heather T. ; Wallis, Gonzalo A. ; Ramakrishnan, Karthik ; Singh, Rakesh K. ; Caldwell, Randall L. ; Savage, Andrew J. ; Everitt, Melanie D. / Cardiac allograft vasculopathy and graft failure in pediatric heart transplant recipients after rejection with severe hemodynamic compromise. In: Journal of Heart and Lung Transplantation. 2019.
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title = "Cardiac allograft vasculopathy and graft failure in pediatric heart transplant recipients after rejection with severe hemodynamic compromise",
abstract = "BACKGROUND: Rejection with severe hemodynamic compromise (RSHC) carries a mortality risk approaching 50{\%}. We aimed to identify current risk factors for RSHC and predictors of graft failure after RSHC. METHODS: Data from 3,259 heart transplant (HT) recipients between January 2005 and December 2015 in the Pediatric Heart Transplant Study (PHTS) were analyzed. Predictors for RSHC and outcome after RSHC were sought. Time to RSHC was analyzed using the Cox proportional hazards regression model. Cardiac allograft vasculopathy (CAV) after HT and CAV after RSHC were analyzed as time-dependent covariates. Timing of RSHC was analyzed as occurring before and after 4 years after RSHC. RESULTS: There were 309 patients (9.5{\%}) with ≥ 1 RSHC episodes. In 143 patients with RSHC, the first episode was within 1 year after HT. Independent risk factors for RSHC were age 1 to 5 years at HT (hazard ratio [HR], 1.51; 95{\%} confidence interval [CI], 1.04–2.18), age > 10 years at HT (HR, 1.83; 95{\%} CI, 1.29–2.60), black race (HR, 1.64; 95{\%} CI, 1.25–2.15), prior cardiac surgery (HR, 1.55; 95{\%} CI, 1.03–2.31), ventricular assist device support at HT (HR, 1.65; 95{\%} CI, 1.18–2.29), maintenance steroids (HR, 1.39; 95{\%} CI, 1.06–1.82), and recipient on inotropes, pressors, or thyroid hormones (HR, 1.45; 95{\%} CI, 1.09–1.94). Graft survival at 5 years after RSHC was 45.7{\%}. RSHC was a greater risk factor for earlier CAV (HR, 7.78; 95{\%} CI, 5.82–10.40) than other rejection types (HR, 2.31; 95{\%} CI, 1.79–3.00). Patients with late RSHC, after 1 year after RSHC had increased risk of graft loss 4 years after RSHC (HR, 7.12; 95{\%} CI, 2.18–23.22). The 5-year graft survival after RSHC was 50.5{\%} for early RSHC and 39.0{\%} for late RSHC. CONCLUSIONS: Mortality after RSHC is high in the current treatment era. Many patient risk factors for RSHC cannot be modified, including age, race, prior cardiac surgery, and ventricular assist device support. After RSHC, CAV is the only predictor of graft failure. Patients who have late RSHC fare worse than those who have RSHC within the first year after HT.",
keywords = "cardiac allograft vasculopathy, graft failure, heart transplant, pediatric, rejection with severe hemodynamic compromise",
author = "Kleinmahon, {Jake A.} and Jane Gralla and Richard Kirk and Auerbach, {Scott R.} and Henderson, {Heather T.} and Wallis, {Gonzalo A.} and Karthik Ramakrishnan and Singh, {Rakesh K.} and Caldwell, {Randall L.} and Savage, {Andrew J.} and Everitt, {Melanie D.}",
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month = "1",
day = "1",
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language = "English (US)",
journal = "Journal of Heart and Lung Transplantation",
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TY - JOUR

T1 - Cardiac allograft vasculopathy and graft failure in pediatric heart transplant recipients after rejection with severe hemodynamic compromise

AU - Kleinmahon, Jake A.

AU - Gralla, Jane

AU - Kirk, Richard

AU - Auerbach, Scott R.

AU - Henderson, Heather T.

AU - Wallis, Gonzalo A.

AU - Ramakrishnan, Karthik

AU - Singh, Rakesh K.

AU - Caldwell, Randall L.

AU - Savage, Andrew J.

AU - Everitt, Melanie D.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - BACKGROUND: Rejection with severe hemodynamic compromise (RSHC) carries a mortality risk approaching 50%. We aimed to identify current risk factors for RSHC and predictors of graft failure after RSHC. METHODS: Data from 3,259 heart transplant (HT) recipients between January 2005 and December 2015 in the Pediatric Heart Transplant Study (PHTS) were analyzed. Predictors for RSHC and outcome after RSHC were sought. Time to RSHC was analyzed using the Cox proportional hazards regression model. Cardiac allograft vasculopathy (CAV) after HT and CAV after RSHC were analyzed as time-dependent covariates. Timing of RSHC was analyzed as occurring before and after 4 years after RSHC. RESULTS: There were 309 patients (9.5%) with ≥ 1 RSHC episodes. In 143 patients with RSHC, the first episode was within 1 year after HT. Independent risk factors for RSHC were age 1 to 5 years at HT (hazard ratio [HR], 1.51; 95% confidence interval [CI], 1.04–2.18), age > 10 years at HT (HR, 1.83; 95% CI, 1.29–2.60), black race (HR, 1.64; 95% CI, 1.25–2.15), prior cardiac surgery (HR, 1.55; 95% CI, 1.03–2.31), ventricular assist device support at HT (HR, 1.65; 95% CI, 1.18–2.29), maintenance steroids (HR, 1.39; 95% CI, 1.06–1.82), and recipient on inotropes, pressors, or thyroid hormones (HR, 1.45; 95% CI, 1.09–1.94). Graft survival at 5 years after RSHC was 45.7%. RSHC was a greater risk factor for earlier CAV (HR, 7.78; 95% CI, 5.82–10.40) than other rejection types (HR, 2.31; 95% CI, 1.79–3.00). Patients with late RSHC, after 1 year after RSHC had increased risk of graft loss 4 years after RSHC (HR, 7.12; 95% CI, 2.18–23.22). The 5-year graft survival after RSHC was 50.5% for early RSHC and 39.0% for late RSHC. CONCLUSIONS: Mortality after RSHC is high in the current treatment era. Many patient risk factors for RSHC cannot be modified, including age, race, prior cardiac surgery, and ventricular assist device support. After RSHC, CAV is the only predictor of graft failure. Patients who have late RSHC fare worse than those who have RSHC within the first year after HT.

AB - BACKGROUND: Rejection with severe hemodynamic compromise (RSHC) carries a mortality risk approaching 50%. We aimed to identify current risk factors for RSHC and predictors of graft failure after RSHC. METHODS: Data from 3,259 heart transplant (HT) recipients between January 2005 and December 2015 in the Pediatric Heart Transplant Study (PHTS) were analyzed. Predictors for RSHC and outcome after RSHC were sought. Time to RSHC was analyzed using the Cox proportional hazards regression model. Cardiac allograft vasculopathy (CAV) after HT and CAV after RSHC were analyzed as time-dependent covariates. Timing of RSHC was analyzed as occurring before and after 4 years after RSHC. RESULTS: There were 309 patients (9.5%) with ≥ 1 RSHC episodes. In 143 patients with RSHC, the first episode was within 1 year after HT. Independent risk factors for RSHC were age 1 to 5 years at HT (hazard ratio [HR], 1.51; 95% confidence interval [CI], 1.04–2.18), age > 10 years at HT (HR, 1.83; 95% CI, 1.29–2.60), black race (HR, 1.64; 95% CI, 1.25–2.15), prior cardiac surgery (HR, 1.55; 95% CI, 1.03–2.31), ventricular assist device support at HT (HR, 1.65; 95% CI, 1.18–2.29), maintenance steroids (HR, 1.39; 95% CI, 1.06–1.82), and recipient on inotropes, pressors, or thyroid hormones (HR, 1.45; 95% CI, 1.09–1.94). Graft survival at 5 years after RSHC was 45.7%. RSHC was a greater risk factor for earlier CAV (HR, 7.78; 95% CI, 5.82–10.40) than other rejection types (HR, 2.31; 95% CI, 1.79–3.00). Patients with late RSHC, after 1 year after RSHC had increased risk of graft loss 4 years after RSHC (HR, 7.12; 95% CI, 2.18–23.22). The 5-year graft survival after RSHC was 50.5% for early RSHC and 39.0% for late RSHC. CONCLUSIONS: Mortality after RSHC is high in the current treatment era. Many patient risk factors for RSHC cannot be modified, including age, race, prior cardiac surgery, and ventricular assist device support. After RSHC, CAV is the only predictor of graft failure. Patients who have late RSHC fare worse than those who have RSHC within the first year after HT.

KW - cardiac allograft vasculopathy

KW - graft failure

KW - heart transplant

KW - pediatric

KW - rejection with severe hemodynamic compromise

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JF - Journal of Heart and Lung Transplantation

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