Objective: This study aims to investigate the prevalence and prognostic impact of anemia and iron deficiency in patients hospitalized with heart failure with mildly reduced ejection fraction (HFmrEF). 

Background: Limited data regarding the prognostic impact of anemia and iron deficiency in patients with HFmrEF is available.

Methods: A large retrospective registry was used including all consecutive hospitalized patients with HFmrEF (i.e., left ventricular ejection fraction (LVEF) 41 – 49%) from 2016 to 2022 according to current European guidelines. Anemia was defined as hemoglobin <12g/dl. Iron deficiency was defined by ferritin < 100 µg/l or ferritin 100 - 300 µg/l with transferrin saturation < 20%. The primary endpoint was the first heart-failure related re-hospitalization at 36 months. Secondary endpoints comprised all-cause mortality and cardiovascular re-hospitalization. Kaplan-Meier, uni- and multivariable Cox regression analyses were applied for statistics.

Results: 793 consecutive HFmrEF patients were included with a median hemoglobin level of 12.2 g/dl. The rate of anemia was 60%. Aminoterminal pro-brain natriuretic peptide (NT-pro BNP) levels were higher in anemic than in non-anemic HFmrEF patients (9813 vs. 3099ng/l, p=0.001). Anemics were associated with an increased risk of heart-failure related re-hospitalization compared to non-anemics (11% vs. 6%; p=0.009; HR=2.010; 95% CI 1.177 – 3.431; p=0.011) even after multivariable adjustment (HR=1.932; 95% CI 1.125 – 3.321; p=0.017). In contrast, the risk of cardiovascular re-hospitalization (21% vs. 17%; p=0.148; HR=1.280; 95% CI 0.915-1.791; p=0.149) and in-hospital mortality (4% vs 3%; p=0.225) was similar between anemic and non-anemic patients. The corresponding rates of iron deficiency were 55% in anemic patients and 47% in non-anemic patients. However, iron deficiency did not affect the risk of heart-failure related re-hospitalization both in anemic (log rank p = 0.915) and non-anemic (log rank p = 0.366) HFmrEF patients.

Conclusions: HFmrEF patients are associated with a relevant rate of comorbid anemia revealing higher NT-pro BNP levels and increased risk of heart failure related re-hospitalization, whereas concomitant iron deficiency did not affect outcomes.