Abstract：
BACKGROUND: Long-term clinical outcomes of early intravascular ultrasound (IVUS) findings in a prospective cohort of heart transplantation (HTx) patients have not been evaluated.
METHODS: This study included patients from 20 centers across Europe and North and South America among the original cohort of the RAD B253 study. Among these patients, 91 had paired IVUS images at baseline and 1-year post-transplant: everolimus 1.5 mg group (n = 25), everolimus 1.5 mg group (n = 33), and azathioprine 3.0 group (n = 33). The primary outcome was a composite of cardiovascular death, retransplantation, myocardial infarction (MI), coronary revascularization, and cardiac allograft vasculopathy (CAV) within a 10-year follow-up period. The secondary outcome was all-cause death, cardiovascular death, retransplantation, MI, coronary revascularization, and CAV. Donor disease was defined as baseline maximal intimal thickness (MIT) >0.66 mm, and rapid progression was defined as a change in MIT > 0.59 mm at 1 year.
RESULTS: Donor disease (46 patients) was associated with a higher incidence of the primary outcome (hazard ratio (HR) 4.444, 95% confidence interval [CI] 1.946-10.146, p < 0.001). Rapid progression (44 patients) was associated with a significantly higher incidence of the primary outcome (HR 2.942, 95% CI 1.383-6.260, p = 0.005). Higher-risk features on IVUS (positive both donor disease and rapid progression) were independently associated with poor clinical outcomes (HR 4.800, 95% CI 1.816-12.684, p = 0.002).
CONCLUSIONS: An increase in baseline MIT and a change in first-year MIT in IVUS post HTx was associated with poor outcomes up to 10 years. Early IVUS findings can be considered as surrogate endpoints for evaluating long-term outcomes in HTx clinical trials.
METHODS: This study included patients from 20 centers across Europe and North and South America among the original cohort of the RAD B253 study. Among these patients, 91 had paired IVUS images at baseline and 1-year post-transplant: everolimus 1.5 mg group (n = 25), everolimus 1.5 mg group (n = 33), and azathioprine 3.0 group (n = 33). The primary outcome was a composite of cardiovascular death, retransplantation, myocardial infarction (MI), coronary revascularization, and cardiac allograft vasculopathy (CAV) within a 10-year follow-up period. The secondary outcome was all-cause death, cardiovascular death, retransplantation, MI, coronary revascularization, and CAV. Donor disease was defined as baseline maximal intimal thickness (MIT) >0.66 mm, and rapid progression was defined as a change in MIT > 0.59 mm at 1 year.
RESULTS: Donor disease (46 patients) was associated with a higher incidence of the primary outcome (hazard ratio (HR) 4.444, 95% confidence interval [CI] 1.946-10.146, p < 0.001). Rapid progression (44 patients) was associated with a significantly higher incidence of the primary outcome (HR 2.942, 95% CI 1.383-6.260, p = 0.005). Higher-risk features on IVUS (positive both donor disease and rapid progression) were independently associated with poor clinical outcomes (HR 4.800, 95% CI 1.816-12.684, p = 0.002).
CONCLUSIONS: An increase in baseline MIT and a change in first-year MIT in IVUS post HTx was associated with poor outcomes up to 10 years. Early IVUS findings can be considered as surrogate endpoints for evaluating long-term outcomes in HTx clinical trials.
摘要：
背景：在心脏移植（HTx）患者的前瞻性队列中，早期血管内超声（IVUS）发现的长期临床结果尚未得到评估。
方法：这项研究包括来自欧洲20个中心的患者，RADB253研究的原始队列中的北美和南美。在这些患者中,91人在基线和移植后1年有配对的IVUS图像，包括依维莫司1.5mg组的25，依维莫司3.0mg组33，和33在硫唑嘌呤组。主要结局是心血管死亡的复合结果，重新移植,心肌梗死（MI），冠状动脉血运重建,和心脏移植血管病变（CAV）在10年的随访期内。次要结果是全因死亡，心血管死亡,重新移植,MI,冠状动脉血运重建,和CAV。供体疾病定义为基线最大内膜厚度(MIT)>0.66mm,快速进展定义为在一年时MIT的变化>0.59mm。
结果：供者疾病（46例）与较高的主要结局发生率相关（HR4.444，95％CI1.946-10.146，p<0.001）。快速进展（44例）与主要结局的发生率明显较高相关（HR2.942，95％CI1.383-6.260，p=0.005）。IVUS的高风险特征（供体疾病和快速进展均为阳性）与不良临床结局独立相关（HR4.800，95％CI1.816-12.684，p=0.002）。
结论：HTx后IVUS测量的基线MIT>0.66mm的增加和第一年MIT>0.59mm的变化与长达10年的不良预后相关。早期IVUS发现可被视为HTx临床试验中评估长期结果的替代终点。
方法：这项研究包括来自欧洲20个中心的患者，RADB253研究的原始队列中的北美和南美。在这些患者中,91人在基线和移植后1年有配对的IVUS图像，包括依维莫司1.5mg组的25，依维莫司3.0mg组33，和33在硫唑嘌呤组。主要结局是心血管死亡的复合结果，重新移植,心肌梗死（MI），冠状动脉血运重建,和心脏移植血管病变（CAV）在10年的随访期内。次要结果是全因死亡，心血管死亡,重新移植,MI,冠状动脉血运重建,和CAV。供体疾病定义为基线最大内膜厚度(MIT)>0.66mm,快速进展定义为在一年时MIT的变化>0.59mm。
结果：供者疾病（46例）与较高的主要结局发生率相关（HR4.444，95％CI1.946-10.146，p<0.001）。快速进展（44例）与主要结局的发生率明显较高相关（HR2.942，95％CI1.383-6.260，p=0.005）。IVUS的高风险特征（供体疾病和快速进展均为阳性）与不良临床结局独立相关（HR4.800，95％CI1.816-12.684，p=0.002）。
结论：HTx后IVUS测量的基线MIT>0.66mm的增加和第一年MIT>0.59mm的变化与长达10年的不良预后相关。早期IVUS发现可被视为HTx临床试验中评估长期结果的替代终点。
