Viethen Thomas, Gerhardt Felix, Dumitrescu Daniel, Knoop-Busch Susanne, ten Freyhaus Henrik, Rudolph Tanja K, Baldus Stephan, Rosenkranz Stephan
Klinik III für Innere Medizin, Herzzentrum der Universität zu Köln, Germany.
Klinik III für Innere Medizin, Herzzentrum der Universität zu Köln, Germany.
Int J Cardiol. 2014 Aug 1;175(2):233-9. doi: 10.1016/j.ijcard.2014.04.233. Epub 2014 Apr 27.
Pulmonary arterial hypertension (PAH) is a progressive condition harboring a poor prognosis. Iron deficiency in PAH correlates with disease severity and mortality. While replacement therapy may be beneficial, dietary iron absorption is impaired in PAH patients by hepcidin, a key regulatory protein of iron homoeostasis. We therefore assessed the therapeutic potential and safety of intravenous iron supplementation in patients with PAH and iron deficiency.
20 patients with PAH and iron deficiency, who were on stable targeted PAH therapy, received a single infusion of ≤1000 mg ferric carboxymaltose. All patients were assessed at baseline and two months after iron treatment. Exercise capacity was evaluated based on the 6-minute-walking distance (6MWD), and quality of life (QoL) was assessed by the SF-36 questionnaire (100 point scale). The effects were compared to 20 matched patients with stable PAH without iron deficiency who did not receive ferric carboxymaltose.
In iron deficient patients, iron supplementation led to a marked improvement of iron status (serum iron 5.7±0.4 to 11.1±1.1 μmol/L, ferritin 29.3±6.3 to 145.2±25.4 μg/L, transferrin saturation 7.5±0.7 to 19.3±2.3%, all p≤0.001). Iron-deficient patients receiving ferric carboxymaltose showed a significant increase of the 6MWD from 346.5±28.3 to 374.0±25.5 m (p=0.007), whereas no significant changes were found in the control group not receiving iron supplementation (6MWD 389.9±25.3 to 379.6±26.2 m; n.s.), resulting in a net increase in the 6MWD of 37.8m (p=0.003). This was associated with an improvement in QoL (SF-36 score from 44.3±3.7 to 50.6±3.6; p=0.01). Only minimal side-effects were reported.
These data indicate that parenteral iron supplementation with ferric carboxymaltose significantly improves exercise capacity and QoL and is well tolerated in patients with PAH and iron deficiency, and when administered in addition to targeted PAH therapies. Our results provide proof of concept for further studies evaluating the potential of iron as an adjunct in PAH treatment on a larger scale.
肺动脉高压（PAH）是一种预后不良的进行性疾病。PAH患者的缺铁与疾病严重程度和死亡率相关。虽然替代疗法可能有益，但PAH患者的膳食铁吸收会受到铁稳态关键调节蛋白铁调素的损害。因此，我们评估了静脉补铁对PAH合并缺铁患者的治疗潜力和安全性。
20例PAH合并缺铁且接受稳定靶向PAH治疗的患者接受了单次输注≤1000mg羧基麦芽糖铁。所有患者在基线和铁治疗后两个月进行评估。基于6分钟步行距离（6MWD）评估运动能力，并通过SF-36问卷（100分制）评估生活质量（QoL）。将这些效果与20例匹配的无缺铁的稳定PAH患者进行比较，这些患者未接受羧基麦芽糖铁治疗。
在缺铁患者中，补铁导致铁状态显著改善（血清铁从5.7±0.4μmol/L升至11.1±1.1μmol/L，铁蛋白从29.3±6.3μg/L升至145.2±25.4μg/L，转铁蛋白饱和度从7.5±0.7%升至19.3±2.3%，所有p≤0.001）。接受羧基麦芽糖铁治疗的缺铁患者6MWD从346.5±28.3m显著增加至374.0±25.5m（p=0.007），而未接受补铁的对照组未发现显著变化（6MWD从389.9±25.3m降至379.6±26.2m；无统计学意义），导致6MWD净增加37.8m（p=0.003）。这与QoL的改善相关（SF-36评分从44.3±3.7升至50.6±3.6；p=0.01）。仅报告了轻微的副作用。
这些数据表明，羧基麦芽糖铁静脉补铁可显著改善PAH合并缺铁患者的运动能力和QoL，并且耐受性良好，可在靶向PAH治疗的基础上使用。我们的结果为进一步大规模评估铁作为PAH治疗辅助手段的潜力的研究提供了概念验证。
