Exercise performance in patients with heart failure and impaired iron transport: a single-centre retrospective study

Objectives Iron deficiency (ID) is frequent in heart failure (HF). Among patients with HF and ID, those with impaired iron transport (IIT) (transferrin saturation (TSAT) <20%) have the worst ID phenotype. In HF, exercise limitation is mainly related to abnormality in oxygen delivery (VO 2 ) and utilisation and/or to ventilation inefficiency. We evaluated whether it is possible to identify the leading cause of exercise limitation in patients with HF and IIT. Design Observational study. Setting Retrospective study. Participants We analysed 1043 consecutive hospitalised patients with HF (66±14 years, 49.8% females) who underwent cardiopulmonary exercise test (CPET). Outcome measures Associations between CPET parameters and TSAT were explored using general linear models adjusted for potential confounders (haemoglobin, left ventricle ejection fraction, age, gender, C reactive protein, serum creatinine). Results We observed that: (a) 413 patients with HF and IIT had worse functional capacity compared with non-IIT cases: peak VO 2 (15±3 vs 16±6 mL/min/kg, p<0.0001) and ventilation/carbon dioxide relationship (VE/VCO 2 ) slope (38±9 vs 33±8, p<0.0001); (b) VE/VCO 2 values remained significantly different between IIT and non-IIT cases after adjusting for confounding variables including peak VO 2 ; differently, peak VO 2 after adjusting also for VE/VCO 2 slope, resulted not different in IIT compared with non-IIT HF cases; (c) patients with both low peak VO 2 (<14 mL/min/kg) and high VE/VCO 2 (≥34) had a higher B-type natriuretic peptide (BNP), lower TSAT and higher MECKI (Metabolic Exercise combined with Cardiac and Kidney Index) score compared with patients with high peak VO 2 and low VE/VCO 2 (BNP 951±1041 vs 413±623 pg/mL (p<0.0001); TSAT 19.5%±10.5% vs 26.9%±10.2% (p<0.0001); MECKI score 14.8%±1.4% vs 1.2%±2.3% (p<0.0001). Conclusions High VE/VCO 2 slope is directly associated with IIT, independent of peak VO 2 , suggesting a pivotal role for ventilation inefficiency in exercise impairment in patients with IIT and HF. In patients with HF, the worst exercise performance is associated with low TSAT, high BNP and the highest MECKI score.

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Journal
BMJ Open
Published
2026-07-01
DOI
https://doi.org/10.1136/bmjopen-2025-104344
Primary Topic
Erythropoietin and Anemia Treatment
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article
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article

Exercise performance in patients with heart failure and impaired iron transport: a single-centre retrospective study

Jeness Campodonico, Carlo Vignati, Beatrice Lorenzon, Piergiuseppe Agostoni et al.
BMJ Open
Erythropoietin and Anemia Treatment
article

Exercise performance in patients with heart failure and impaired iron transport: a single-centre retrospective study

Jeness Campodonico, Carlo Vignati, Beatrice Lorenzon, Piergiuseppe Agostoni, Beatrice Pezzuto, Irene Mattavelli, Alice Bonomi, E Salvioni, Alp Ayali, Massimo Mapelli, Alessandro Acquistapace
article en

Abstract

Objectives Iron deficiency (ID) is frequent in heart failure (HF). Among patients with HF and ID, those with impaired iron transport (IIT) (transferrin saturation (TSAT) <20%) have the worst ID phenotype. In HF, exercise limitation is mainly related to abnormality in oxygen delivery (VO 2 ) and utilisation and/or to ventilation inefficiency. We evaluated whether it is possible to identify the leading cause of exercise limitation in patients with HF and IIT. Design Observational study. Setting Retrospective study. Participants We analysed 1043 consecutive hospitalised patients with HF (66±14 years, 49.8% females) who underwent cardiopulmonary exercise test (CPET). Outcome measures Associations between CPET parameters and TSAT were explored using general linear models adjusted for potential confounders (haemoglobin, left ventricle ejection fraction, age, gender, C reactive protein, serum creatinine). Results We observed that: (a) 413 patients with HF and IIT had worse functional capacity compared with non-IIT cases: peak VO 2 (15±3 vs 16±6 mL/min/kg, p<0.0001) and ventilation/carbon dioxide relationship (VE/VCO 2 ) slope (38±9 vs 33±8, p<0.0001); (b) VE/VCO 2 values remained significantly different between IIT and non-IIT cases after adjusting for confounding variables including peak VO 2 ; differently, peak VO 2 after adjusting also for VE/VCO 2 slope, resulted not different in IIT compared with non-IIT HF cases; (c) patients with both low peak VO 2 (<14 mL/min/kg) and high VE/VCO 2 (≥34) had a higher B-type natriuretic peptide (BNP), lower TSAT and higher MECKI (Metabolic Exercise combined with Cardiac and Kidney Index) score compared with patients with high peak VO 2 and low VE/VCO 2 (BNP 951±1041 vs 413±623 pg/mL (p<0.0001); TSAT 19.5%±10.5% vs 26.9%±10.2% (p<0.0001); MECKI score 14.8%±1.4% vs 1.2%±2.3% (p<0.0001). Conclusions High VE/VCO 2 slope is directly associated with IIT, independent of peak VO 2 , suggesting a pivotal role for ventilation inefficiency in exercise impairment in patients with IIT and HF. In patients with HF, the worst exercise performance is associated with low TSAT, high BNP and the highest MECKI score.

BMJ OpenVol. 16(7)
University of Milan (IT), Centro Cardiologico Monzino (IT)
Ministero della Salute
Good health and well-being
Openalex Percentile: Top 8%
Erythropoietin and Anemia Treatment
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