Low transferrin saturation predicts mortality in HFrEF across anemia strata: a registry-based IPTW analysis
H Nahoui, H Schirmer, K Berge, T Oevrebotten, P L MyhreAbstract
Background
Iron deficiency is common in heart failure (HF) and is associated with worse outcomes. We aimed to assess the prognostic impact of low transferrin saturation (TSAT) across anemia strata, and its links to symptoms and functional status in routine care of patients with HF and reduced ejection fraction (HFrEF).
Methods
Patients with HF and EF≤45% from the Norwegian Heart Failure Registry were included at outpatient HF-clinics with planned follow-up visits. Iron deficiency defined as TSAT <20% (vs ≥20%). Baseline associations with NT-proBNP, 6-minute walk distance (6MWD), and Minnesota Living with Heart Failure Questionnaire (MLHFQ) were tested using multivariable linear regression. Mortality was analyzed using IPTW-weighted Cox regression, including an interaction between TSAT and anemia (Hb<13 and 12 g/L for men and women, respectively). Change analyses used ΔTSAT and modeled follow-up outcomes adjusted for baseline levels and covariates.
Results
12,523 patients (mean age 69 years; 74% men), Table 1. TSAT <20% was associated with worse baseline HF-status: higher log-NT-proBNP (β=0.33; 95% CI 0.29–0.36; p<0.001), shorter 6MWT (β=−27.0 m; 95% CI −32.8 to −21.3; p<0.001), and higher MLHFQ (β=2.70; 95% CI 1.93–3.47; p<0.001). In IPTW Cox models, TSAT <20% predicted higher mortality overall (HR 1.54; 95% CI 1.39–1.70; p<0.001). The association was stronger without anemia (HR 1.63; 95% CI 1.43–1.87; p<0.001) than with anemia (HR 1.19; 95% CI 1.02–1.38; p=0.029), with evidence of interaction (p=0.007), Figure 1. TSAT improvement was independently associated with lower follow-up log NT-proBNP (β=−0.0060 per 1% TSAT; 95% CI −0.0081 to −0.0039), longer 6MWT (β=+0.476 m per 1%; 95% CI 0.284–0.667), and lower MLHFQ (β=−0.095 points per 1%; 95% CI −0.133 to −0.057).
Conclusion
In a real-world HFrEF cohort, TSAT <20% was linked to worse HF severity, poorer functional status. Association with mortality was strongest among patients without anemia. Future trials should investigate the effect of iron supplementation in HF patients with normal hemoglobin levels.For image description, please refer to the figure legend and surrounding text.Figure 1For image description, please refer to the figure legend and surrounding text.