In HFpEF patients with TSAT >20%, low serum iron (<13 µmol/L) was associated with significantly worse combined outcomes compared to normal serum iron (HR 1.71; 95% CI 1.13-2.61; P=0.011).
Cohort (n=3,643)
Does iron deficiency worsen all-cause mortality and heart failure hospitalization in patients with heart failure across the LVEF spectrum?
Iron deficiency is common across all HF phenotypes and reduces quality of life, but while TSAT <20% predicts mortality in LVEF <50%, serum iron ≤13 μmol/L is a better prognostic marker in HFpEF.
Hazard Ratio: 1.71 (95% CI 1.13–2.61)
p-value: p=0.011
Abstract Background/purpose Iron deficiency (ID) is common in heart failure (HF) and associated with worse clinical outcomes in patients with a left ventricular ejection fraction (LVEF) 50% (HFrEF 20% or a serum iron ≤13 μmol/L. Results ID, according to both TSAT or serum iron respectively, was observed in 2130 (58%) or 2580 (71%) patients and followed a U-shaped distribution across the LVEF spectrum, with the highest prevalence in those with LVEF 20% and HFpEF. Among patients with TSAT 20%, those with serum iron ≤13 µmol/L exhibited worse clinical characteristics when compared to those with iron13 µmol/L. ID defined by either definitions was associated with lower quality of life and reduced physical activity as reflected by KCCQ overall summary score and physical limitation score across all groups (p 0.01). Independent predictors of ID included female sex, higher heart rate, proton pump inhibitor use, low hemoglobin and albumin levels, elevated white blood cells, fluid retention, and impaired kidney function, none of which were modified by LVEF (all interaction p 0.1). In multivariable survival analyses, ID was associated with increased all-cause mortality (HR: 1.38 95% CI: 1.17–1.63, p 0.001) and HF hospitalization (HR: 1.29 95% CI: 1.10–1.51, p = 0.002) in LVEF50% irrespective of the definition. However, in HFpEF, ID defined by TSAT was not associated with increased all-cause mortality (HR: 1.02 95% CI: 0.73–1.42, p = 0.899) or combined endpoints (HR: 0.97 95% CI: 0.75-1.26, p = 0.877). By contrast, when ID was defined using serum iron, the association with all-cause mortality and combined endpoints appeared stronger, though it did not reach statistical significance. Interaction analyses between the two definitions revealed that HFpEF patients with TSAT 20%, but serum iron 13 µmol/L had significantly worse combined outcomes (HR: 1.71 95% CI: 1.13-2.61, p = 0.011) compared to those with serum iron ≥13 µmol/L and TSAT20% (interaction p = 0.018). Conclusion ID is common across the HF spectrum and is associated with reduced quality of life and exercise capacity regardless of LVEF. While ID, defined by TSAT 20%, is linked to worse prognosis in LVEF50%, it was not predictive of outcomes in HFpEF. However, serum iron appears to better identify patients at risk for adverse outcomes, suggesting it may be a more clinically relevant marker of impaired iron availability that is not fully captured by TSAT alone particularly in HFpEF.Table1:Baseline characteristics Figure1:Clinical outcomes
Alnuwaysir et al. (Sat,) conducted a cohort in Heart failure (n=3,643). Low serum iron (<13 µmol/L) despite normal TSAT (>20%) vs. Normal serum iron (≥13 µmol/L) and normal TSAT (>20%) was evaluated on Combined outcomes (HR 1.71, 95% CI 1.13-2.61, p=0.011). In HFpEF patients with TSAT >20%, low serum iron (<13 µmol/L) was associated with significantly worse combined outcomes compared to normal serum iron (HR 1.71; 95% CI 1.13-2.61; P=0.011).