评估心脏移植受者右心压力的生物标志物：一项概念验证研究。
Biomarkers to Assess Right Heart Pressures in Recipients of a Heart Transplant: A Proof-of-Concept Study.
作者信息
Huang Qi-Fang, Trenson Sander, Zhang Zhen-Yu, Van Keer Jan, Van Aelst Lucas N L, Yang Wen-Yi, Nkuipou-Kenfack Esther, Thijs Lutgarde, Wei Fang-Fei, Mujaj Blerim, Ciarka Agnieszka, Droogné Walter, Vanhaecke Johan, Janssens Stefan, Van Cleemput Johan, Mischak Harald, Staessen Jan A
机构信息
Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
Center for Epidemiological Studies and Clinical Trials and Center for Vascular Evaluations, Shanghai Institute of Hypertension, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
出版信息
Transplant Direct. 2018 Apr 23;4(5):e346. doi: 10.1097/TXD.0000000000000783. eCollection 2018 May.
BACKGROUND
This proof-of-concept study investigated the feasibility of using biomarkers to monitor right heart pressures (RHP) in heart transplanted (HTx) patients.
METHODS
In 298 patients, we measured 7.6 years post-HTx mean pressures in the right atrium (mRAP) and pulmonary artery (mPAP) and capillaries (mPCWP) along with plasma high-sensitivity troponin T (hsTnT), a marker of cardiomyocyte injury, and the multidimensional urinary classifiers HF1 and HF2, mainly consisting of dysregulated collagen fragments.
RESULTS
In multivariable models, mRAP and mPAP increased with hsTnT (per 1-SD, +0.91 and +1.26 mm Hg; < 0.0001) and with HF2 (+0.42 and +0.62 mm Hg; ≤ 0.035), but not with HF1. mPCWP increased with hsTnT (+1.16 mm Hg; < 0.0001), but not with HF1 or HF2. The adjusted odds ratios for having elevated RHP (mRAP, mPAP or mPCWP ≥10, ≥24, ≥17 mm Hg, respectively) were 1.99 for hsTnT and 1.56 for HF2 ( ≤ 0.005). In detecting elevated RHPs, areas under the curve were similar for hsTnT and HF2 (0.63 vs 0.65; = 0.66). Adding hsTnT continuous or per threshold or HF2 continuous to a basic model including all covariables did not increase diagnostic accuracy ( ≥ 0.11), whereas adding HF2 per optimized threshold increased both the integrated discrimination (+1.92%; = 0.023) and net reclassification (+30.3%; = 0.010) improvement.
CONCLUSIONS
Correlating RHPs with noninvasive biomarkers in HTx patients is feasible. However, further refinement and validation of such biomarkers is required before their clinical application can be considered.
背景
这项概念验证研究探讨了使用生物标志物监测心脏移植（HTx）患者右心压力（RHP）的可行性。
方法
在298例患者中，我们测量了HTx术后7.6年的右心房平均压力（mRAP）、肺动脉平均压力（mPAP）和毛细血管楔压（mPCWP），以及血浆高敏肌钙蛋白T（hsTnT，一种心肌细胞损伤标志物）和多维尿分类指标HF1和HF2，后者主要由失调的胶原蛋白片段组成。
结果
在多变量模型中，mRAP和mPAP随hsTnT升高（每增加1个标准差，分别升高0.91和1.26 mmHg；P<0.0001），也随HF2升高（分别升高0.42和0.62 mmHg；P≤0.035），但不随HF1升高。mPCWP随hsTnT升高（升高1.16 mmHg；P<0.0001），但不随HF1或HF2升高。RHP升高（mRAP、mPAP或mPCWP分别≥10、≥24、≥17 mmHg）的校正比值比，hsTnT为1.99，HF2为1.56（P≤0.005）。在检测升高的RHP时，hsTnT和HF2的曲线下面积相似（分别为0.63和0.65；P=0.66）。将hsTnT连续变量或阈值变量或HF2连续变量添加到包含所有协变量的基础模型中，并未提高诊断准确性（P≥0.11），而添加优化阈值下的HF2则提高了综合辨别力（提高1.92%；P=0.023）和净重新分类改善率（提高30.3%；P=0.010）。
结论
在HTx患者中，将RHP与非侵入性生物标志物相关联是可行的。然而，在考虑将此类生物标志物应用于临床之前，需要进一步完善和验证。
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