Acute Cellular Rejection and the Subsequent Development of Allograft Vasculopathy After Cardiac Transplantation

Eugenia Raichlin, Brooks Sayre Edwards, Walter K Kremers, Alfredo L. Clavell, Richard J. Rodeheffer, Robert Frantz, Naveen Luke Pereira, Richard C. Daly, Christopher G. McGregor, Amir Lerman, Sudhir S. Kushwaha

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Abstract

Background: Cardiac allograft vasculopathy (CAV) is primarily immune-mediated. We investigated the role of cellular rejection in CAV development. Methods: The study comprised 252 cardiac transplant recipients (mean age, 49.02 ± 17.05 years; mean follow-up, 7.61 ± 4.49 years). Total rejection score (TRS) based on the 2004 International Society of Heart and Lung Transplantation R grading system (0R = 0, 1R = 1, 2R = 2, 3R = 3) and any rejection score (ARS; calculated as 0R = 0, 1R = 1, 2R = 1; 3R = 1, or the number of rejections of any grade) were normalized for the total number of biopsy specimens. CAV was defined as coronary stenosis of 40% or more and/or distal pruning of secondary side branches. Thirty-two patients had undergone 3-dimensional intravascular ultrasound (IVUS) at baseline and with virtual histology (VH) IVUS at 24 months. Results: In univariate analysis, 6-month TRS (hazard ratio [HR], 1.9; 95% confidence interval [CI], 0.99-3.90, p = 0.05) and ARS (HR, 2.22; 95% CI, 1.01-4.95; p = 0.047) were associated with increased risk of CAV. In multivariate analysis, 6-month TRS (HR, 2.84; 95% CI, 1.44-6.91, p = 0.02) was significantly associated with increased risk of CAV onset. The 12- and 24-month rejection scores were not risk factors for the onset of CAV. By Kaplan-Meier analysis, 6-month TRS exceeding 0.3 was associated with a significantly shorter time to CAV onset (p = 0.018). There was direct correlation (r = 0.44, p = 0.012) between TRS at 6 months and the percentage of necrotic core demonstrated by VH-IVUS at 24 months. Conclusion: Recurrent cellular rejection has a cumulative effect on the onset of CAV. The mechanism may be due to increased inflammation resulting in increased plaque burden suggesting a relationship between the immune basis of cellular rejection and CAV.

Original languageEnglish (US)
Pages (from-to)320-327
Number of pages8
JournalJournal of Heart and Lung Transplantation
Volume28
Issue number4
DOIs
StatePublished - Apr 2009

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Heart Transplantation
Allografts
Confidence Intervals
Histology
Heart-Lung Transplantation
Coronary Stenosis
Kaplan-Meier Estimate
Multivariate Analysis
Inflammation
Biopsy

ASJC Scopus subject areas

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

Cite this

Acute Cellular Rejection and the Subsequent Development of Allograft Vasculopathy After Cardiac Transplantation. / Raichlin, Eugenia; Edwards, Brooks Sayre; Kremers, Walter K; Clavell, Alfredo L.; Rodeheffer, Richard J.; Frantz, Robert; Pereira, Naveen Luke; Daly, Richard C.; McGregor, Christopher G.; Lerman, Amir; Kushwaha, Sudhir S.

In: Journal of Heart and Lung Transplantation, Vol. 28, No. 4, 04.2009, p. 320-327.

Research output: Contribution to journalArticle

Raichlin, Eugenia ; Edwards, Brooks Sayre ; Kremers, Walter K ; Clavell, Alfredo L. ; Rodeheffer, Richard J. ; Frantz, Robert ; Pereira, Naveen Luke ; Daly, Richard C. ; McGregor, Christopher G. ; Lerman, Amir ; Kushwaha, Sudhir S. / Acute Cellular Rejection and the Subsequent Development of Allograft Vasculopathy After Cardiac Transplantation. In: Journal of Heart and Lung Transplantation. 2009 ; Vol. 28, No. 4. pp. 320-327.
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abstract = "Background: Cardiac allograft vasculopathy (CAV) is primarily immune-mediated. We investigated the role of cellular rejection in CAV development. Methods: The study comprised 252 cardiac transplant recipients (mean age, 49.02 ± 17.05 years; mean follow-up, 7.61 ± 4.49 years). Total rejection score (TRS) based on the 2004 International Society of Heart and Lung Transplantation R grading system (0R = 0, 1R = 1, 2R = 2, 3R = 3) and any rejection score (ARS; calculated as 0R = 0, 1R = 1, 2R = 1; 3R = 1, or the number of rejections of any grade) were normalized for the total number of biopsy specimens. CAV was defined as coronary stenosis of 40{\%} or more and/or distal pruning of secondary side branches. Thirty-two patients had undergone 3-dimensional intravascular ultrasound (IVUS) at baseline and with virtual histology (VH) IVUS at 24 months. Results: In univariate analysis, 6-month TRS (hazard ratio [HR], 1.9; 95{\%} confidence interval [CI], 0.99-3.90, p = 0.05) and ARS (HR, 2.22; 95{\%} CI, 1.01-4.95; p = 0.047) were associated with increased risk of CAV. In multivariate analysis, 6-month TRS (HR, 2.84; 95{\%} CI, 1.44-6.91, p = 0.02) was significantly associated with increased risk of CAV onset. The 12- and 24-month rejection scores were not risk factors for the onset of CAV. By Kaplan-Meier analysis, 6-month TRS exceeding 0.3 was associated with a significantly shorter time to CAV onset (p = 0.018). There was direct correlation (r = 0.44, p = 0.012) between TRS at 6 months and the percentage of necrotic core demonstrated by VH-IVUS at 24 months. Conclusion: Recurrent cellular rejection has a cumulative effect on the onset of CAV. The mechanism may be due to increased inflammation resulting in increased plaque burden suggesting a relationship between the immune basis of cellular rejection and CAV.",
author = "Eugenia Raichlin and Edwards, {Brooks Sayre} and Kremers, {Walter K} and Clavell, {Alfredo L.} and Rodeheffer, {Richard J.} and Robert Frantz and Pereira, {Naveen Luke} and Daly, {Richard C.} and McGregor, {Christopher G.} and Amir Lerman and Kushwaha, {Sudhir S.}",
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T1 - Acute Cellular Rejection and the Subsequent Development of Allograft Vasculopathy After Cardiac Transplantation

AU - Raichlin, Eugenia

AU - Edwards, Brooks Sayre

AU - Kremers, Walter K

AU - Clavell, Alfredo L.

AU - Rodeheffer, Richard J.

AU - Frantz, Robert

AU - Pereira, Naveen Luke

AU - Daly, Richard C.

AU - McGregor, Christopher G.

AU - Lerman, Amir

AU - Kushwaha, Sudhir S.

PY - 2009/4

Y1 - 2009/4

N2 - Background: Cardiac allograft vasculopathy (CAV) is primarily immune-mediated. We investigated the role of cellular rejection in CAV development. Methods: The study comprised 252 cardiac transplant recipients (mean age, 49.02 ± 17.05 years; mean follow-up, 7.61 ± 4.49 years). Total rejection score (TRS) based on the 2004 International Society of Heart and Lung Transplantation R grading system (0R = 0, 1R = 1, 2R = 2, 3R = 3) and any rejection score (ARS; calculated as 0R = 0, 1R = 1, 2R = 1; 3R = 1, or the number of rejections of any grade) were normalized for the total number of biopsy specimens. CAV was defined as coronary stenosis of 40% or more and/or distal pruning of secondary side branches. Thirty-two patients had undergone 3-dimensional intravascular ultrasound (IVUS) at baseline and with virtual histology (VH) IVUS at 24 months. Results: In univariate analysis, 6-month TRS (hazard ratio [HR], 1.9; 95% confidence interval [CI], 0.99-3.90, p = 0.05) and ARS (HR, 2.22; 95% CI, 1.01-4.95; p = 0.047) were associated with increased risk of CAV. In multivariate analysis, 6-month TRS (HR, 2.84; 95% CI, 1.44-6.91, p = 0.02) was significantly associated with increased risk of CAV onset. The 12- and 24-month rejection scores were not risk factors for the onset of CAV. By Kaplan-Meier analysis, 6-month TRS exceeding 0.3 was associated with a significantly shorter time to CAV onset (p = 0.018). There was direct correlation (r = 0.44, p = 0.012) between TRS at 6 months and the percentage of necrotic core demonstrated by VH-IVUS at 24 months. Conclusion: Recurrent cellular rejection has a cumulative effect on the onset of CAV. The mechanism may be due to increased inflammation resulting in increased plaque burden suggesting a relationship between the immune basis of cellular rejection and CAV.

AB - Background: Cardiac allograft vasculopathy (CAV) is primarily immune-mediated. We investigated the role of cellular rejection in CAV development. Methods: The study comprised 252 cardiac transplant recipients (mean age, 49.02 ± 17.05 years; mean follow-up, 7.61 ± 4.49 years). Total rejection score (TRS) based on the 2004 International Society of Heart and Lung Transplantation R grading system (0R = 0, 1R = 1, 2R = 2, 3R = 3) and any rejection score (ARS; calculated as 0R = 0, 1R = 1, 2R = 1; 3R = 1, or the number of rejections of any grade) were normalized for the total number of biopsy specimens. CAV was defined as coronary stenosis of 40% or more and/or distal pruning of secondary side branches. Thirty-two patients had undergone 3-dimensional intravascular ultrasound (IVUS) at baseline and with virtual histology (VH) IVUS at 24 months. Results: In univariate analysis, 6-month TRS (hazard ratio [HR], 1.9; 95% confidence interval [CI], 0.99-3.90, p = 0.05) and ARS (HR, 2.22; 95% CI, 1.01-4.95; p = 0.047) were associated with increased risk of CAV. In multivariate analysis, 6-month TRS (HR, 2.84; 95% CI, 1.44-6.91, p = 0.02) was significantly associated with increased risk of CAV onset. The 12- and 24-month rejection scores were not risk factors for the onset of CAV. By Kaplan-Meier analysis, 6-month TRS exceeding 0.3 was associated with a significantly shorter time to CAV onset (p = 0.018). There was direct correlation (r = 0.44, p = 0.012) between TRS at 6 months and the percentage of necrotic core demonstrated by VH-IVUS at 24 months. Conclusion: Recurrent cellular rejection has a cumulative effect on the onset of CAV. The mechanism may be due to increased inflammation resulting in increased plaque burden suggesting a relationship between the immune basis of cellular rejection and CAV.

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