Changes in Cardiac Function and Exercise Capacity Following Ferric Carboxymaltose Administration in HFrEF Patients with Iron Deficiency

Abstract

Background/Objectives: Iron deficiency (ID) is a common and prognostically relevant comorbidity in heart failure with reduced ejection fraction (HFrEF). It contributes to reduced functional status, exercise capacity, and survival. Intravenous ferric carboxymaltose (FCM) improves symptoms, but its effect on cardiac structure and function remains incompletely understood. The aim of this study was to assess the impact of intravenous FCM on echocardiographic indices of left ventricular (LV), left atrial (LA), and right ventricular (RV) morphology and function in HFrEF patients with ID and determine whether these changes correlate with improvements in exercise capacity. Methods: This sub-analysis of the RESAFE-HF registry (NCT04974021) included 86 HFrEF patients with ID (median age 71.8 years, 83% male). Transthoracic echocardiography was performed at baseline and 12 months post-FCM. Parameters assessed included LV ejection fraction (LVEF), LV global longitudinal strain (GLS), LV diastolic function grade, LAVi, LA strain, TAPSE, and RV free wall strain (FWS). Peak VO₂ was measured to assess exercise capacity. Results: LVEF improved from 29.3 ± 7.8% to 32.5 ± 10.6% (p < 0.001), LV GLS from -7.89% to -8.62%, and the LV diastolic dysfunction grade improved (p < 0.001). LAVi, peak LA strain, TAPSE, and RV FWS also showed significant improvement. Peak VO₂ increased from 11.3 ± 3.2 to 12.1 ± 4.1 mL/min/kg (p < 0.001). Improvements in LVEF, RV FWS, and LV GLS were independent predictors of VO₂ increase (p < 0.001, p < 0.001, and p = 0.01, respectively), explaining 42% of the variance. Conclusions: FCM therapy improves biventricular and atrial function, with echocardiographic gains correlating with an enhanced exercise capacity in HFrEF patients with ID.

Keywords: HFrEF; diastolic dysfunction; exercise capacity; ferric carboxymaltose; iron deficiency; strain imaging.

Figure 1

Flow diagram for study participants.

Figure 2

Diastolic dysfunction grades of patients at baseline and after 12 months of iron supplementation.

Figure 3

The relative contribution of left ventricular ejection fraction (LVEF), left ventricular global longitudinal strain (LV GLS), and right ventricular free wall strain to the improvement of peak VO₂. The proportion of unaccounted variance was based on R² values; the relative contribution of explained variance was based on each parameter’s Pratt index.