Table 2.
Iron deficiency-associated outcome in patients with heart failure (HF)
| Study | Study population | ID definition / iron status | ID / iron status-associated outcome |
|---|---|---|---|
| Jankowska et al. (2011) [49] | ID and stable systolic CHF |
Serum ferritin < 100 μg/L or Serum ferritin 100–300 μg/L + TSAT < 20% |
• Exercise capacity: reduced peak oxygen consumption VO2 and increased ventilatory response to exercise VE-VCO2 slope |
| Klip et al. (2013) [8] | ID and CHF |
Serum ferritin < 100 μg/L or Serum ferritin 100–299 μg/L + TSAT < 20% |
• Higher NYHA class • Higher NT-proBNP levels • Lower mean corpuscular volume levels • Higher risk of morality |
| Comín-Colet et al. (2013) [50] | ID and/or IDA and CHF |
Serum ferritin < 100 µg/L or Serum ferritin < 800 µg/L + TSAT < 20% or sTfR ≥ 1.62 mg/L |
• Worse QoL (assessed with MLHFQ) |
| Núñez et al. (2016) [56] | ID and AHF |
AID: serum ferritin < 100 μg/L or FID: serum ferritin 100–299 μg/L + TSAT < 20% |
• Increased risk of early rehospitalization (only for AID) |
| Moliner et al. (2017) [52] | ID and CHF |
Serum ferritin < 100 µg/L and/or TSAT < 20% |
• Higher NT-proBNP levels* • Worse QoL* • Higher risk of all-cause mortality |
| Martens et al. (2018) [7] | ID, IDA and HF with HFrEF, HFmrEF and HFpEF |
Serum ferritin < 100 μg/L or Serum ferritin 100–300 μg/L + TSAT < 20% |
• Lower VO2max • Progression to IDA • Higher risk of HF hospitalization • Higher risk of all-cause mortality |
| Grote Beverborg et al. (2018) [24] | ID and HF | TSAT ≤ 19.8% + serum iron ≤ 13 μmol/L | • Higher risk of all-cause mortality |
| Grote Beverborg et al. (2019) [51] | ID and HF | Serum ferritin ≤ 128 µg/L + TSAT < 20% |
• Impaired 6MWT • Higher proportion of anemia • Poorer QoL • Higher risk of all-cause mortality • Higher risk of HF hospitalization |
| Serum ferritin > 128 µg/L + TSAT < 20% |
• Impaired 6MWT • Higher levels of inflammatory markers (CRP, IL-6) |
||
| Grammer et al. (2019) [54] | ID/IDA and undergoing coronary angiography | Hb, serum iron, TSAT, sTfR, serum ferritin# | • J-shaped associations with cardiovascular and total mortality (marginal for Hb) |
| Hepcidin# | • Inverse association with mortality | ||
| Alcaide-Aldeano et al. (2020) [53] | ID and CHF with HFpEF |
Serum ferritin < 100 µg/L and/or TSAT < 20% or sTfR n/a** |
• Worse functional capacity (measured by 6MWT) • Worse QoL (assessed with MLHFQ) |
| Ambrosy et al. (2020) [55] | Older adults (aged ≥ 65 years) with HF and IDA |
IDA: Hb < 13 g/dL men or < 12 g/dL women + TSAT < 20% |
• Higher risk of HF hospitalization • Higher risk of all-cause mortality |
| Campodonico et al. (2021) [58] | ID and HF |
AID: serum ferritin < 100 μg/L or FID: serum ferritin 100–300 μg/L + TSAT < 20% |
• Worse prognosis (survival rate) (only for TSAT < 20% or serum ferritin 100 – 300 μg/L + TSAT < 20%) |
| Fitzsimons et al. (2021) [57] |
ID and HF (HFpEF, HFrEF) over time (6 months) |
IDFerritin: serum ferritin < 100 μg/L or serum ferritin 100–300 μg/L + TSAT < 20% or IDTsat: TSAT < 20% |
• Persistent IDTSAT is strongly associated with mortality (only for HFrEF) • IDTsat is the superior definition of ID |
6MWT 6-min walking test, AID absolute iron deficiency, AHF acute heart failure, CHF chronic heart failure, CRP C-reactive protein, FID functional iron deficiency, Hb hemoglobin, HF heart failure, HFmrEF mid-range ejection-fraction, HFpEF preserved ejection-fraction, HFrEF reduced ejection-fraction, ID iron deficiency, IDA iron deficiency anemia, IL-6 interleukin 6, MLHFQ Minnesota Living with Heart Failure questionnaire, n/a not available, NT-proBNP N-terminal pro-brain-type natriuretic peptide, NYHA New York Heart Association, QoL Quality of Life, sTfR soluble transferrin receptor, TSAT transferrin saturation
* isolated TSAT < 20% had higher NT-proBNP levels and worse QoL compared with isolated serum ferritin < 100 µg/L
** sTfR presented the highest performance as a predictor of functional capacity and QoL
# Iron status (median): iron(μg/dL), 94 men and 81 women; TSAT(%), 27.3 men and 23.4 women; ferritin(ng/mL) 177 men and 99 women; sTfR(mg/L), 1.28 men and 1.23 women; sTfR-F, 0.57 men and 0.66 women; Hb(g/dL), 14.4 men and 13.0 women; hepcidin(ng/mL), 6.6 men and 5.7 women