Attenuation of cardiac allograft vasculopathy by sirolimus

Relationship to time interval after heart transplantation

Yoshiki Matsuo, Andrew Cassar, Satoshi Yoshino, Andreas J. Flammer, Jing Li, Rajiv Gulati, Yan Topilsky, Eugenia Raichlin, Ryan J. Lennon, Lilach O. Lerman, Charanjit S. Rihal, Sudhir S. Kushwaha, Amir Lerman

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background The aim of the study was to assess temporal changes in plaque size and components after heart transplantation (HTx), and to evaluate the differences in treatment effects on plaque progression between sirolimus and calcineurin inhibitors (CNIs). Methods The study comprised 146 HTx recipients who were converted from CNIs to sirolimus as primary immunosuppressant (sirolimus group, n = 61) and those who were maintained on CNIs (CNI group, n = 85). A retrospective compositional analysis of serial virtual histology-intravascular ultrasound was performed. Results During a median follow-up of 2.8 years, there was a significant difference in plaque volume in favor of sirolimus between groups (p = 0.004). When subjects were sub-classified according to the time interval between HTx and study inclusion, those in the early group (≤2 years after HTx) had a greater increase in plaque volume (p = 0.006), characterized by a higher progression rate of fibrous plaque volume (p = 0.01). The treatment difference between groups in plaque volume was identified in the early group in favor of sirolimus with attenuating effects on the progression of fibrous plaque component (both p = 0.03 for interaction). By contrast, there were significant differences in necrotic core and dense calcium volume (both p < 0.05 for interaction) in favor of CNIs in the late group (≥6 years after HTx). Conclusions Compared with continued CNI therapy, sirolimus attenuated plaque progression in recipients with early conversion, but contributed to increases in necrotic core and dense calcium volume in those with late conversion. Our study supports the hypothesis that early initiation of sirolimus offers greater benefits in the treatment of CAV.

Original languageEnglish (US)
Pages (from-to)784-791
Number of pages8
JournalJournal of Heart and Lung Transplantation
Volume32
Issue number8
DOIs
StatePublished - Aug 1 2013

Fingerprint

Sirolimus
Heart Transplantation
Allografts
Calcium
Therapeutics
Immunosuppressive Agents
Calcineurin Inhibitors
Histology

Keywords

  • calcineurin inhibitors
  • cardiac allograft vasculopathy
  • intravascular ultrasound
  • plaque composition
  • plaque progression
  • sirolimus
  • virtual histology

ASJC Scopus subject areas

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

Cite this

Attenuation of cardiac allograft vasculopathy by sirolimus : Relationship to time interval after heart transplantation. / Matsuo, Yoshiki; Cassar, Andrew; Yoshino, Satoshi; Flammer, Andreas J.; Li, Jing; Gulati, Rajiv; Topilsky, Yan; Raichlin, Eugenia; Lennon, Ryan J.; Lerman, Lilach O.; Rihal, Charanjit S.; Kushwaha, Sudhir S.; Lerman, Amir.

In: Journal of Heart and Lung Transplantation, Vol. 32, No. 8, 01.08.2013, p. 784-791.

Research output: Contribution to journalArticle

Matsuo, Y, Cassar, A, Yoshino, S, Flammer, AJ, Li, J, Gulati, R, Topilsky, Y, Raichlin, E, Lennon, RJ, Lerman, LO, Rihal, CS, Kushwaha, SS & Lerman, A 2013, 'Attenuation of cardiac allograft vasculopathy by sirolimus: Relationship to time interval after heart transplantation', Journal of Heart and Lung Transplantation, vol. 32, no. 8, pp. 784-791. https://doi.org/10.1016/j.healun.2013.05.015
Matsuo, Yoshiki ; Cassar, Andrew ; Yoshino, Satoshi ; Flammer, Andreas J. ; Li, Jing ; Gulati, Rajiv ; Topilsky, Yan ; Raichlin, Eugenia ; Lennon, Ryan J. ; Lerman, Lilach O. ; Rihal, Charanjit S. ; Kushwaha, Sudhir S. ; Lerman, Amir. / Attenuation of cardiac allograft vasculopathy by sirolimus : Relationship to time interval after heart transplantation. In: Journal of Heart and Lung Transplantation. 2013 ; Vol. 32, No. 8. pp. 784-791.
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abstract = "Background The aim of the study was to assess temporal changes in plaque size and components after heart transplantation (HTx), and to evaluate the differences in treatment effects on plaque progression between sirolimus and calcineurin inhibitors (CNIs). Methods The study comprised 146 HTx recipients who were converted from CNIs to sirolimus as primary immunosuppressant (sirolimus group, n = 61) and those who were maintained on CNIs (CNI group, n = 85). A retrospective compositional analysis of serial virtual histology-intravascular ultrasound was performed. Results During a median follow-up of 2.8 years, there was a significant difference in plaque volume in favor of sirolimus between groups (p = 0.004). When subjects were sub-classified according to the time interval between HTx and study inclusion, those in the early group (≤2 years after HTx) had a greater increase in plaque volume (p = 0.006), characterized by a higher progression rate of fibrous plaque volume (p = 0.01). The treatment difference between groups in plaque volume was identified in the early group in favor of sirolimus with attenuating effects on the progression of fibrous plaque component (both p = 0.03 for interaction). By contrast, there were significant differences in necrotic core and dense calcium volume (both p < 0.05 for interaction) in favor of CNIs in the late group (≥6 years after HTx). Conclusions Compared with continued CNI therapy, sirolimus attenuated plaque progression in recipients with early conversion, but contributed to increases in necrotic core and dense calcium volume in those with late conversion. Our study supports the hypothesis that early initiation of sirolimus offers greater benefits in the treatment of CAV.",
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AU - Li, Jing

AU - Gulati, Rajiv

AU - Topilsky, Yan

AU - Raichlin, Eugenia

AU - Lennon, Ryan J.

AU - Lerman, Lilach O.

AU - Rihal, Charanjit S.

AU - Kushwaha, Sudhir S.

AU - Lerman, Amir

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