Behnes Michael, Brueckmann Martina, Lang Siegfried, Weiß Christel, Ahmad-Nejad Parviz, Neumaier Michael, Borggrefe Martin, Hoffmann Ursula
First Department of Medicine, University Medical Centre Mannheim (UMM), Faculty of Medicine Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany,
Clin Res Cardiol. 2014 Feb;103(2):107-16. doi: 10.1007/s00392-013-0626-6. Epub 2013 Oct 22.
As a mediator of ECM homeostasis, connective tissue growth factor (CTGF) appears to be involved in adverse structural remodeling processes in the heart. However, the diagnostic and prognostic value of CTGF levels in acute heart failure (AHF) in addition to natriuretic peptide testing has not yet been evaluated.
A total of 212 patients presenting with acute dyspnea and/or peripheral edema to the Emergency Department were evaluated. CTGF and NT-proBNP plasma levels were measured at the initial presentation. All patients were followed up to 1 and 5 years. The first endpoint tested was the diagnostic non-inferiority of combined CTGF plus NT-proBNP compared to NT-proBNP alone for AHF diagnosis. Afterwards, the additional diagnostic value of CTGF plus NT-proBNP was tested. CTGF levels were higher in NYHA class III/IV and AHA/ACC class C/D patients compared to lower class patients (p = 0.04). Patients with HFREF revealed highest CTGF levels (median 93.3 pg/ml, IQR 18.2-972 pg/ml, n = 48) compared to patients with a normal heart function (i.e., without HFREF and HFPEF) (median 25.9, IQR <1-82.2 pg/ml, n = 37) (p < 0.05), followed by patients with HFPEF (median 82.2 pg/ml, IQR 11.5-447 pg/ml, n = 32) as assessed by echocardiography. Finally, CTGF levels were higher in patients with AHF (median 77.3 pg/ml, IQR 22.5-1012 pg/ml, n = 66) compared to those without (p = 0.002). CTGF plus NT-proBNP was non-inferior to NT-proBNP testing alone for AHF diagnosis (AUC difference 0.01, p > 0.05). CTGF plus NT-proBNP improved the diagnostic capacity for AHF (accuracy 82 %, specificity 83 %, positive predictive value 66 %, net reclassification improvement +0.11) compared to NT-proBNP alone (p = 0.0001). CTGF levels were not able to differentiate prognostic outcomes after 1 and 5 years.
Additional CTGF measurements might lead to a better discrimination of higher functional and structural heart failure stages and might identify patients of an increased risk for an acute cardiac decompensation.
作为细胞外基质稳态的介质，结缔组织生长因子（CTGF）似乎参与了心脏不良结构重塑过程。然而，除利钠肽检测外，CTGF水平在急性心力衰竭（AHF）中的诊断和预后价值尚未得到评估。
对212例因急性呼吸困难和/或外周水肿就诊于急诊科的患者进行评估。在初次就诊时测量CTGF和NT-proBNP血浆水平。所有患者随访1年和5年。首先测试的终点是联合检测CTGF加NT-proBNP与单独检测NT-proBNP用于AHF诊断的非劣效性。之后，测试CTGF加NT-proBNP的额外诊断价值。与心功能分级较低的患者相比，纽约心脏协会（NYHA）III/IV级和美国心脏协会（AHA）/美国心脏病学会（ACC）C/D级患者的CTGF水平更高（p = 0.04）。与心功能正常（即无射血分数降低的心力衰竭（HFREF）和射血分数保留的心力衰竭（HFPEF））的患者相比，HFREF患者的CTGF水平最高（中位数93.3 pg/ml，四分位间距18.2 - 972 pg/ml，n = 48）（中位数25.9，四分位间距<1 - 82.2 pg/ml，n = 37）（p < 0.05），其次是HFPEF患者（中位数82.2 pg/ml，四分位间距11.5 - 447 pg/ml，n = 32），通过超声心动图评估。最后，与无AHF的患者相比，AHF患者的CTGF水平更高（中位数77.3 pg/ml，四分位间距22.5 - 1012 pg/ml，n = 66）（p = 0.002）。CTGF加NT-proBNP在AHF诊断方面不劣于单独检测NT-proBNP（曲线下面积差异0.01，p > 0.05）。与单独检测NT-proBNP相比，CTGF加NT-proBNP提高了AHF的诊断能力（准确率82%，特异性83%，阳性预测值66%，净重新分类改善+0.11）（p = 0.0001）。CTGF水平无法区分1年和5年后的预后结果。
额外检测CTGF可能有助于更好地区分较高的心功能和结构心力衰竭阶段，并可能识别急性心脏失代偿风险增加的患者。
