Empagliflozin effects on iron metabolism as a possible mechanism for improved clinical outcomes in non-diabetic patients with systolic heart failure

Christiane E. Angermann, Carlos G. Santos-Gallego, Juan Antonio Requena-Ibanez, Susanne Sehner, Tanja Zeller, Louisa M.S. Gerhardt, Christoph Maack, Javier Sanz, Stefan Frantz, Valentin Fuster, Georg Ertl, Juan J. Badimon

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Sodium-glucose co-transporter-2 (SGLT2) inhibitors improve clinical outcomes in patients with heart failure (HF), but mechanisms of action are incompletely understood. In the EMPA-TROPISM trial, empagliflozin reversed cardiac remodeling and increased physical capacity in stable non-diabetic patients with systolic HF. Here we explore, post hoc, whether treatment effects in this cohort, comprising patients who had a high prevalence of iron deficiency, were related to iron metabolism. Myocardial iron content estimated by cardiac magnetic resonance T2* quantification increased after initiation of empagliflozin but not placebo (treatment effect: P = 0.01). T2* changes significantly correlated with changes in left ventricular volumes, mass and ejection fraction, peak oxygen consumption and 6-minute walking distance; concomitant changes in red blood cell indices were consistent with augmented hematopoiesis. Exploratory causal mediation analysis findings indicated that changes in myocardial iron content after treatment with empagliflozin may be an important mechanism to explain its beneficial clinical effects in patients with HF. ClinicalTrials.gov: NCT03485222 .

Original languageEnglish
Pages (from-to)1032-1043
Number of pages12
JournalNature Cardiovascular Research
Volume2
Issue number11
DOIs
StatePublished - Nov 2023

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