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左心室辅助装置支持对心血管应激、纤维化、液体平衡、炎症和肾损伤的生物标志物的影响。

Effects of left ventricular assist device support on biomarkers of cardiovascular stress, fibrosis, fluid homeostasis, inflammation, and renal injury.

机构信息

Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.

Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.

出版信息

JACC Heart Fail. 2015 Jan;3(1):30-39. doi: 10.1016/j.jchf.2014.06.013. Epub 2014 Nov 12.

Abstract

OBJECTIVES

The purpose of this study was to examine changes in a broad panel of biomarkers following left ventricular assist device (LVAD) support in advanced heart failure (HF).

BACKGROUND

LVAD therapy mechanically unloads the failing heart and may result in reversal of certain aspects of the end-stage HF phenotype. Changes in markers of myocardial stress, fibrosis, inflammation, fluid homeostasis, and renal injury in this setting are unknown.

METHODS

Amino-terminal pro-B-type natriuretic peptide (NT-proBNP), galectin-3, ST2, copeptin, growth differentiation factor (GDF)-15, C-reactive protein (CRP), and neutrophil gelatinase associated lipocalin (NGAL) levels were measured in frozen plasma collected from 37 individuals prior to continuous flow LVAD implantation and a median of 136 (interquartile range: 94 to 180) days after implantation.

RESULTS

The median age of patients was 68 years old. LVAD therapy was associated with significant decreases in NT-proBNP (3,093 to 2,090 pg/ml; p = 0.02), ST2 (67.5 to 45.2 ng/ml, p <0.01), galectin-3 (24.7 to 22.0 ng/ml; p = 0.04), GDF-15 (3,232 to 2,613 ng/l;p <0.001), hs-CRP (22.4 to 11.9 mg/l; p = 0.01), and copeptin (103 to 94 pmol/l; p = 0.003) but not NGAL (132 to 135 ng/ml; p = 0.06). Despite improvement over time, absolute values of each biomarker remained extremely abnormal. Greater reductions in biomarkers were noted in individuals with >25% decrease in NT-proBNP concentrations but reached statistical significance only in the case of galectin-3 (p = 0.01).

CONCLUSIONS

The biomarker profile in patients after LVAD placement improves but nonetheless remains significantly abnormal. Our results suggest the need for targeted therapeutic interventions to mitigate such abnormalities and potentially increase rates of myocardial recovery.

摘要

目的

本研究旨在探讨左心室辅助装置(LVAD)支持治疗晚期心力衰竭(HF)后广泛生物标志物的变化。

背景

LVAD 治疗可减轻衰竭心脏的负荷,可能导致终末期 HF 表型的某些方面逆转。在此背景下,心肌应激、纤维化、炎症、液体平衡和肾损伤标志物的变化尚不清楚。

方法

在连续血流 LVAD 植入前和植入后中位数 136(四分位距:94 至 180)天,从 37 名个体的冷冻血浆中测量氨基末端脑钠肽前体(NT-proBNP)、半乳糖凝集素-3、ST2、 copeptin、生长分化因子(GDF)-15、C 反应蛋白(CRP)和中性粒细胞明胶酶相关脂质运载蛋白(NGAL)水平。

结果

患者的中位年龄为 68 岁。LVAD 治疗与 NT-proBNP(3093 至 2090pg/ml;p=0.02)、ST2(67.5 至 45.2ng/ml,p<0.01)、半乳糖凝集素-3(24.7 至 22.0ng/ml;p=0.04)、GDF-15(3232 至 2613ng/l;p<0.001)、hs-CRP(22.4 至 11.9mg/l;p=0.01)和 copeptin(103 至 94pmol/l;p=0.003)显著降低,但 NGAL(132 至 135ng/ml;p=0.06)无变化。尽管随着时间的推移有所改善,但每个生物标志物的绝对值仍极不正常。在 NT-proBNP 浓度降低>25%的个体中,生物标志物的降低更为明显,但仅在半乳糖凝集素-3 中达到统计学意义(p=0.01)。

结论

LVAD 放置后患者的生物标志物谱有所改善,但仍明显异常。我们的结果表明,需要有针对性的治疗干预措施来减轻这些异常,并可能提高心肌恢复的速度。

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