Serial evaluation of cardiac allograft vasculopathy after heart transplantation by dual-modality intravascular ultrasound and optical coherence tomography

Abstract

Abstract Background Cardiac allograft vasculopathy is a combination of the development of de novo plaque and the progression of donor-transmitted plaque. Purpose This study aimed to evaluate the development of de novo plaque and the progression of donor-transmitted plaque within 12-month after heart transplantation (HTx) using serial intravascular ultrasound (IVUS) and optical coherence tomography (OCT). The association between inflammatory cytokines and plaque progression was also examined. Methods We prospectively enrolled 40 recipients to conduct serial three-vessel IVUS and OCT analysis at 8-week and 12-month after HTx. De novo plaque was defined as having maximum intimal thickness (MIT) ≥0.5 mm at 12-month in the absence of donor-transmitted plaques (MIT ≥0.5 mm at 8-week). Serum cytokines were screened with a bead-based multiplex assay. Results A total of 13 de novo plaques (fibrous, n=10; fibroatheroma, n=3) were detected in eight recipients. Serum interleukin (IL)-31 at 8-week was associated with the development of de novo plaques (p=0.009). A total of 31 donor-transmitted plaques (fibrous, n=12; fibroatheroma, n=11; fibrocalcific, n=8) were detected in 17 recipients. Multiple regression analysis revealed that fibrous (p=0.026) and fibroatheroma (p=0.012) observed at 8-week were significantly associated with subsequent plaque progression within 12-month after HTx. ΔPlaque burden was significant higher in de novo plaque than donor-transmitted plaque (38.8% [29.6–41.2] versus 8.7% [1.3–13.6], p<0.001). The prevalence of macrophage accumulation was lower in de novo plaque than in donor-transmitted plaque (8% versus 52%, p=0.006). Serum IL-31 at 8-week was correlated with the progression of donor-transmitted plaque as well as de novo plaque (r=0.663, p=0.029) although other cytokines like IL-1β, IL-6, IL-17, and tissue necrotic factor alpha were not. Conclusions In de novo plaques, fibrous plaque was the most common and macrophage accumulation was rarely observed. In donor-transmitted plaque, fibrous and fibroatheroma were independent predictor for the subsequent plaque progression. Serum interleukin-31 surge at subacute phase may play pathogenic role in cardiac allograft vasculopathy. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Grants-in-Aid for Scientific Research (KAKENHI)