4.5 Article

Pathophysiological evaluations of initial plaque development after heart transplantation via serial multimodality imaging and cytokine assessments

Journal

JOURNAL OF HEART AND LUNG TRANSPLANTATION
Volume 41, Issue 7, Pages 877-885

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.healun.2022.03.007

Keywords

cardiac allograft vasculopathy; optical coherence tomography; intravascular ultrasound; interleukin-31; heart transplantation

Funding

  1. JSPS KAKENHI [17K16005]

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This study investigates the morphological characteristics and association with serum cytokine levels of de novo and donor-transmitted plaques in patients with coronary allograft vasculopathy within one year after heart transplantation. The results indicate that fibrous proliferation contributes to the progression of these plaques, and baseline serum interleukin-31 levels may contribute to intimal fibrous proliferation.
BACKGROUND: Detailed morphological characteristics of de novo and donor-transmitted plaques and the association of serum T-lymphocyte cytokine levels with plaque progression of coronary allograft vasculopathy within 1 year after heart transplantation are unknown. METHODS: In this retrospective analysis of data in a prospectively maintained database, 40 heart transplant recipients were included. We performed serial 3 vessel optical coherence tomography and intravascular ultrasound analyses, at the 8 week (baseline) and 12 month post-transplantation follow-ups, and serum cytokine measurements (n = 23). The correlation between serum cytokines and Delta plaque burden (between baseline and follow-up) was evaluated depending on plaque morphology. RESULTS: Thirteen de novo plaques (maximum intimal thickness >= 0.5 mm at the 12 month follow-up without plaques at baseline) were identified in 8 recipients, and 31 donor-transmitted plaques (maximum intimal thickness >= 0.5 mm at baseline) were detected in 17 recipients. Compared with donor-transmitted plaques, the Delta plaque burden in the de novo plaques, with mainly fibrous morphology, was high (38.8% [29.6%-41.2%] vs 8.7% [1.33%-13.6%], p < 0.001). Stratification of the morphology of donor-transmitted plaques revealed that the Delta plaque burden in fibrous plaques (10.6% [7.0%-18.0%]) was similar to that in fibroatheroma (10.3% [8.7%-23.8%]). Serum interleukin-31 levels at baseline correlated with fibrous plaque proliferation (r = 0.73, p = 0.007) even under immunosuppressive conditions, whereas other cytokines (interleukin-1 beta, interleukin-17, and interferon-gamma) were mostly undetectable. CONCLUSIONS: Intimal fibrous proliferation contributed to the progression of donor-transmitted and de novo plaques. Serum interleukin-31 levels at baseline may contribute to intimal fibrous proliferation within 1 year after heart transplantation. (C) 2022 The Author(s). Published by Elsevier Inc. on behalf of International Society for Heart and Lung Transplantation.

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