De Biase Nicolò, Del Punta Lavinia, L'Hoyes Wouter, Pellicori Pierpaolo, Cleland John G F, Masini Gabriele, Gargani Luna, Moura-Ferreira Sara, Hoedemakers Sarah, Di Fiore Valerio, Herbots Lieven, Stassen Jan, Mengozzi Alessandro, Armenia Silvia, Taddei Stefano, Masi Stefano, Verwerft Jan, Pugliese Nicola Riccardo
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Department of Cardiology, Jessa Hospital, Hasselt, Belgium.
Eur J Heart Fail. 2025 May;27(5):889-900. doi: 10.1002/ejhf.3534. Epub 2024 Nov 28.
Uncertainty exists about defining true iron deficiency (ID) in heart failure (HF) patients. We assessed the relationship of different ID definitions with cardiac structure and function, congestion, exercise capacity, and prognosis in HF outpatients.
Iron deficiency was defined according to guidelines (G-ID: ferritin <100 ng/ml or ferritin 100-299 ng/ml with transferrin saturation [TSAT] <20%). Alternative ID definitions based on TSAT (<20%), iron (≤13 μmol/L), and ferritin (<100 or < 300 ng/ml) were explored. Relationships with rest/exercise measures of cardiac function and congestion using ultrasound, effort intolerance and adverse outcome (HF hospitalizations or all-cause mortality) were assessed. Of 1502 patients (72% with left ventricular ejection fraction [LVEF] ≥50%), 471 (31%) had TSAT <20%, while 728 (48%) had G-ID. Patients with TSAT <20% or G-ID had greater left atrial volume but similar LVEF. Lower TSAT, iron and haemoglobin, but not ferritin, were associated with more signs of congestion by ultrasound. After correcting for multiple clinical variables, including haemoglobin, TSAT was directly associated with peak oxygen uptake (standardized coefficient 0.069, p = 0.041), while ferritin was not. There was no interaction with HF phenotype (HF with preserved vs. reduced LVEF). During a median follow-up of 18 months, TSAT <20% and iron ≤13 μmol/L were associated with worse outcomes in models adjusted for clinical variables, including LVEF and N-terminal pro-B-type natriuretic peptide (hazard ratio 2.48, 95% confidence interval 1.88-3.17 and 1.93, 1.48-2.52, respectively), while G-ID or ferritin <100 or <300 ng/ml were not.
In HF outpatients, TSAT <20% is more consistently associated with congestion by ultrasound and poorer functional capacity than other ID definitions, irrespective of LVEF. TSAT <20% and iron ≤13 μmol/L, but not G-ID or ferritin-based ID, predict a worse prognosis in HF outpatients with preserved and reduced LVEF.
心力衰竭（HF）患者中真正缺铁（ID）的定义存在不确定性。我们评估了不同ID定义与HF门诊患者心脏结构和功能、充血、运动能力及预后之间的关系。
根据指南定义缺铁（G-ID：铁蛋白<100 ng/ml或铁蛋白100 - 299 ng/ml且转铁蛋白饱和度[TSAT]<20%）。探索了基于TSAT（<20%）、铁（≤13 μmol/L）和铁蛋白（<100或<300 ng/ml）的替代ID定义。评估了与使用超声测量的静息/运动时心脏功能和充血情况、运动不耐受及不良结局（HF住院或全因死亡）之间的关系。在1502例患者中（72%左心室射血分数[LVEF]≥50%），471例（31%）TSAT<20%，而728例（48%）有G-ID。TSAT<20%或G-ID的患者左心房容积更大，但LVEF相似。较低的TSAT、铁和血红蛋白水平（而非铁蛋白）与超声显示的更多充血体征相关。在校正包括血红蛋白在内的多个临床变量后，TSAT与峰值摄氧量直接相关（标准化系数0.069，p = 0.041），而铁蛋白则无此关联。与HF表型（LVEF保留型与降低型HF）无相互作用。在中位随访18个月期间，在校正包括LVEF和N末端B型脑钠肽前体等临床变量的模型中，TSAT<20%和铁≤13 μmol/L与更差的结局相关（风险比分别为2.48，95%置信区间1.88 - 3.17和1.93，1.48 - 2.52），而G-ID或铁蛋白<100或<300 ng/ml则不然。
在HF门诊患者中，无论LVEF如何，TSAT<20%与超声显示的充血及比其他ID定义更差的功能能力更一致相关。TSAT<20%和铁≤13 μmol/L，而非G-ID或基于铁蛋白的ID，可预测LVEF保留型和降低型HF门诊患者更差的预后。
