Iron deficiency (ID) is an emerging problem in patients with chronic heart failure (HF) and can be a potential therapeutic target. However, not much is known about the prevalence, predictors, and prognosis of ID in patients with chronic HF. In an international pooled cohort comprising 1,506 patients with chronic HF, we studied the clinical associates of ID and its prognostic consequences. Iron deficiency (defined as a ferritin level <100 μg/L or ferritin 100-299 μg/L with a transferrin saturation <20%) was present in 753 patients (50%). Anemic patients were more often iron deficient than nonanemic patients (61.2% vs 45.6%, P < .001). Other independent predictors of ID were higher New York Heart Association class, higher N-terminal pro-brain-type natriuretic peptide levels, lower mean corpuscular volume levels, and female sex (all P < .05). During follow-up (median 1.92 years, interquartile range 1.18-3.26 years), 440 patients died (29.2%). Kaplan-Meier survival analysis revealed ID as a strong predictor for mortality (log rank χ(2) 10.2, P = .001). In multivariable hazard models, ID (but not anemia) remained a strong and independent predictor of mortality (hazard ratio 1.42, 95% confidence interval 1.14-1.77, P = .002). Finally, the presence of ID significantly enhanced risk classification and integrated discrimination improvement when added to a prediction model with established risk factors. Iron deficiency is common in patients with chronic HF, relates to disease severity, and is a strong and independent predictor of outcome. In this study, ID appears to have greater predictive power than anemia.

Beyond erythropoiesis, iron is involved in numerous biological processes crucial for maintenance of homeostasis. Patients with chronic heart failure (CHF) are prone to develop iron deficiency (ID), and iron supplementation improves their functional status and quality of life. We sought to examine the relationship between ID and survival in patients with systolic CHF. In a prospective observational study, we evaluated 546 patients with stable systolic CHF [age: 55 ± 11 (mean ± standard deviation) years, males: 88%, left ventricular ejection fraction: 26 ± 7%, New York Heart Association (NYHA) class (I/II/III/IV): 57/221/226/42]. Iron deficiency was defined as: ferritin <100 µg/L, or 100–300 µg/L with transferrin saturation <20%. The prevalence of ID was 37 ± 4% [±95% confidence intervals (CI)] in the entire CHF population (32 ± 4 vs. 57 ± 10%—in subjects without vs. with anaemia defined as haemoglobin level <12 g/dL in women and <13 g/dL in men, P < 0.001). In a multiple logistic model, ID was more prevalent in women, those in the advanced NYHA class, with higher plasma N-terminal pro-type B natriuretic peptide and higher serum high-sensitivity C-reactive protein (all P < 0.05). At the end of follow-up (mean duration: 731 ± 350 days), there were 153 (28%) deaths and 30 (6%) heart transplantations (HTX). In multivariable models, ID (but not anaemia) was related to an increased risk of death or HTX (adjusted hazard ratio 1.58, 95% CI 1.14–2.17, P < 0.01). In patients with systolic CHF, ID is common and constitutes a strong, independent predictor of unfavourable outcome. Iron supplementation may be considered as a therapeutic approach in these patients to improve prognosis.