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

Eugenia Raichlin, Brooks S. Edwards, Walter K. Kremers, Alfredo L. Clavell, Richard J. Rodeheffer, Robert P. Frantz, Naveen L. 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 1 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

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

Cite this

Raichlin, E., Edwards, B. S., Kremers, W. K., Clavell, A. L., Rodeheffer, R. J., Frantz, R. P., ... Kushwaha, S. S. (2009). Acute Cellular Rejection and the Subsequent Development of Allograft Vasculopathy After Cardiac Transplantation. Journal of Heart and Lung Transplantation, 28(4), 320-327. https://doi.org/10.1016/j.healun.2009.01.006

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

In: Journal of Heart and Lung Transplantation, Vol. 28, No. 4, 01.04.2009, p. 320-327.

Research output: Contribution to journalArticle

Raichlin, E, Edwards, BS, Kremers, WK, Clavell, AL, Rodeheffer, RJ, Frantz, RP, Pereira, NL, Daly, RC, McGregor, CG, Lerman, A & Kushwaha, SS 2009, 'Acute Cellular Rejection and the Subsequent Development of Allograft Vasculopathy After Cardiac Transplantation', Journal of Heart and Lung Transplantation, vol. 28, no. 4, pp. 320-327. https://doi.org/10.1016/j.healun.2009.01.006
Raichlin, Eugenia ; Edwards, Brooks S. ; Kremers, Walter K. ; Clavell, Alfredo L. ; Rodeheffer, Richard J. ; Frantz, Robert P. ; Pereira, Naveen L. ; 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.",
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AU - Rodeheffer, Richard J.

AU - Frantz, Robert P.

AU - Pereira, Naveen L.

AU - Daly, Richard C.

AU - McGregor, Christopher G.

AU - Lerman, Amir

AU - Kushwaha, Sudhir S.

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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.

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