BACKGROUND As the population of adults with congenital heart disease (CHD) grows, cardiologists continue to encounter patients with complex anatomies that challenge the standard treatment of care. Single ventricle Fontan palliated patients are the most complex within CHD, with a high morbidity and mortality burden. Factors driving this early demise are largely unknown. METHODS AND RESULTS We analyzed biomarker expression in 44 stable Fontan outpatients (29.2 ± 10.7 years, 68.2% female) seen in the outpatient Emory Adult Congenital Heart Center and compared them to 32 age, gender and race matched controls. In comparison to controls, Fontan patients had elevated levels of multiple cytokines within the inflammatory pathway including Tumor Necrosis Factor-α (TNF-α) (p < 0.001), Interleukin-6 (IL-6) (p < 0.011), Growth Derived Factor-15 (GDF-15) (p < 0.0001), β2-macroglobulin, (p = 0.0006), stem cell mobilization: Stromal Derived Factor-1∝ (SDF-1α) (p = 0.006), extracellular matrix turnover: Collagen IV (p < 0.0001), neurohormonal activation: Renin (p < 0.0001), renal dysfunction: Cystatin C (p < 0.0001) and Urokinase Receptor (uPAR) (p = 0.022), cardiac injury: Troponin-I (p < 0.0004) and metabolism: Adiponectin (p = 0.0037). Within 1 year of enrollment 50% of Fontan patients had hospitalizations, arrhythmias or worsening hepatic function. GDF-15 was significantly increased in Fontan patients with clinical events (p < 0.0001). In addition, GDF-15 moderately correlated with longer duration of Fontan (r = 0.55, p = 0.01) and was elevated in atriopulmonary (AP) Fontan circulation. Finally, in a multivariate model, VEGF-D and Collagen IV levels were found to be associated with a change in MELDXI, a marker of liver dysfunction. CONCLUSION Multiple clinical and molecular biomarkers are upregulated in Fontan patients, suggesting a state of chronic systemic dysregulation.

中文翻译：

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稳定的Fontan患者的生物标志物谱。

背景技术随着患有先天性心脏病（CHD）的成人的增长，心脏病专家继续遇到具有复杂解剖结构的患者，这些患者挑战了标准治疗方法。单脑室Fontan苍白的患者是冠心病中最复杂的患者，具有较高的发病率和死亡率负担。导致这种早期死亡的因素在很大程度上尚不清楚。方法和结果我们分析了在门诊埃默里成人先天性心脏病中心就诊的44例稳定的Fontan门诊患者（29.2±10.7岁，女性68.2％）的生物标志物表达，并将其与32位年龄，性别和种族相匹配的对照组进行了比较。与对照组相比，Fontan患者的炎症途径中多种细胞因子水平升高，包括肿瘤坏死因子-α（TNF-α）（p <0.001），白细胞介素-6（IL-6）（p <0.011），生长衍生因子15（GDF-15）（p <0.0001），β2-巨球蛋白（p = 0.0006），干细胞动员：基质衍生因子-1∝（SDF-1α）（p = 0.006），细胞外基质更新：IV型胶原（p <0.0001），神经激素激活：肾素（p <0.0001），肾功能不全：胱抑素C（p <0.0001）和尿激酶受体（uPAR）（p = 0.022），心脏损伤：肌钙蛋白I（p < 0.0004）和新陈代谢：脂联素（p = 0.0037）。在入组的1年内，50％的Fontan患者住院，心律不齐或肝功能恶化。在发生临床事件的丰坦患者中，GDF-15显着升高（p <0.0001）。此外，GDF-15与更长的Fontan持续时间适度相关（r = 0.55，p = 0.01），并且在房肺（AP）Fontan循环中升高。最后，在多元模型中，发现VEGF-D和胶原IV水平与MELDXI的变化有关，MELDXI是肝功能障碍的标志。结论Fontan患者的多种临床和分子生物标志物均被上调，提示其处于慢性全身失调状态。