Sierpinski Radoslaw, Josiak Krystian, Suchocki Tomasz, Wojtas-Polc Katarzyna, Mazur Grzegorz, Butrym Aleksandra, Rozentryt Piotr, van der Meer Peter, Comin-Colet Josep, von Haehling Stephan, Kosmala Wojciech, Przewlocka-Kosmala Monika, Banasiak Waldemar, Nowak Jolanta, Voors Adriaan A, Anker Stefan D, Cleland John G F, Ponikowski Piotr, Jankowska Ewa A
Medical Research Agency, Warsaw, Poland.
Collegium Medicum, Cardinal Wyszyński University in Warsaw, Warsaw, Poland.
Eur J Heart Fail. 2021 Jun;23(6):919-932. doi: 10.1002/ejhf.2036. Epub 2020 Dec 4.
Iron deficiency (ID) is frequent in heart failure (HF), linked with exercise intolerance and poor prognosis. Intravenous iron repletion improves clinical status in HF patients with left ventricular ejection fraction (LVEF) ≤45%. However, uncertainty exists about the accuracy of serum biomarkers in diagnosing ID. The aims of this study were (i) to identify the iron biomarker with the greatest accuracy for the diagnosis of ID in bone marrow in patients with ischaemic HF, and (ii) to establish the prevalence of ID using this biomarker and its prognostic value in HF patients.
Bone marrow was stained for iron in 30 patients with ischaemic HF with LVEF ≤45% and 10 healthy controls, and ID was diagnosed for 0-1 grades (Gale scale). A total of 791 patients with HF with LVEF ≤45% were prospectively followed up for 3 years. Serum ferritin, transferrin saturation, soluble transferrin receptor (sTfR) were assessed as iron biomarkers. Most patients with HF (n = 25, 83%) had ID in bone marrow, but none of the controls (P < 0.001). Serum sTfR had the best accuracy in predicting ID in bone marrow (area under the curve 0.920, 95% confidence interval 0.761-0.987, for cut-off 1.25 mg/L sensitivity 84%, specificity 100%). Serum sTfR was ≥1.25 mg/L in 47% of HF patients, in 56% and 46% of anaemics and non-anaemics, respectively (P < 0.05). The reclassification methods revealed that serum sTfR significantly added the prognostic value to the baseline prognostic model, and to the greater extent than plasma N-terminal pro B-type natriuretic peptide. Based on internal derivation and validation procedures, serum sTfR ≥1.41 mg/L was the optimal threshold for predicting 3-year mortality, independent of other established variables.
High serum sTfR accurately reflects depleted iron stores in bone marrow in patients with HF, and identifies those with a high 3-year mortality.
缺铁（ID）在心力衰竭（HF）中很常见，与运动耐量下降和预后不良有关。静脉补铁可改善左心室射血分数（LVEF）≤45%的HF患者的临床状况。然而，血清生物标志物在诊断ID方面的准确性尚不确定。本研究的目的是：（i）确定在缺血性HF患者中诊断骨髓ID最准确的铁生物标志物；（ii）使用该生物标志物确定HF患者中ID的患病率及其预后价值。
对30例LVEF≤45%的缺血性HF患者和10名健康对照者的骨髓进行铁染色，并根据0 - 1级（盖尔分级）诊断ID。对791例LVEF≤45%的HF患者进行了为期3年的前瞻性随访。评估血清铁蛋白、转铁蛋白饱和度、可溶性转铁蛋白受体（sTfR）作为铁生物标志物。大多数HF患者（n = 25，83%）骨髓中有ID，但对照者均无（P < 0.001）。血清sTfR在预测骨髓ID方面准确性最佳（曲线下面积0.920，95%置信区间0.761 - 0.987，截断值为1.25 mg/L时，敏感性84%，特异性100%）。47%的HF患者血清sTfR≥1.25 mg/L，贫血患者和非贫血患者中这一比例分别为56%和46%（P < 0.05）。重新分类方法显示，血清sTfR显著增加了基线预后模型的预后价值，且比血浆N末端B型利钠肽原增加的程度更大。基于内部推导和验证程序，血清sTfR≥1.41 mg/L是预测3年死亡率的最佳阈值，独立于其他既定变量。
高血清sTfR准确反映HF患者骨髓中铁储备减少，并识别出3年死亡率高的患者。
