Association of elevated levels of soluble transferrin receptor with left ventricular remodeling and mortality in patients with heart failure: Evidence from observational and genetic investigations.

Background: Iron deficiency (ID) is prevalent in heart failure (HF) patients and correlates with adverse outcomes. Serum soluble transferrin receptor (sTfR) levels reflect bone marrow and myocardial iron stores, potentially impacting HF prognosis. However, the specific role of sTfR in the progression of HF remains unclear.

Methods: In a retrospective cohort of 391 patients with HF and left ventricular ejection fraction (LVEF) < 50 %, multivariate logistic regression and Cox proportional hazard regression identified mortality-associated factors. The receiver operating characteristic (ROC) curve determined sTfR cut-off value based on the area under the curve. Kaplan-Meier curves were used to compare the cumulative survival rates. Spearman's rank correlation assessed sTfR's relation to left ventricular (LV) parameters. Mendelian randomization (MR) analysis explored causal associations.

Results: High sTfR levels (≥1.96 mg/L) predicted worse survival and were associated with increased LV volume and lower LVEF. sTfR correlated significantly with LV end-diastolic volume (LVEDV) (r = 0.09, P = 0.0152), LV end-systolic volume (LVESV) (r = 0.16, P = 0.0018), body surface area-indexed LVEDV (LVEDVI) (r = 0.12, P = 0.0140), body surface area-indexed LVESV (LVESVI) (r = 0.14, P = 0.0058), and negatively with LVEF (r = -0.20, P = 0.0001). MR analysis showed a causal link between elevated sTfR and increased LVEDV (β = 0.092; 95 % CI: 1.031-1.162; P = 0.0056) and LVESV (β = 0.089; 95 % CI: 1.027-1.058; P = 0.0079).

Conclusions: Elevated sTfR levels identify HF patients at higher risk of mortality and are linked to detrimental LV structural and functional changes, particularly enlargement of LVEDV and LVESV.