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Empagliflozin effects on iron metabolism as a possible mechanism for improved clinical outcomes in non-diabetic patients with systolic heart failure
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Empagliflozin effects on iron metabolism as a possible mechanism for improved clinical outcomes in non-diabetic patients with systolic heart failure
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Journal Article
Empagliflozin effects on iron metabolism as a possible mechanism for improved clinical outcomes in non-diabetic patients with systolic heart failure
2023
Overview
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 .
Publisher
Nature Publishing Group,Nature Publishing Group UK
Subject
/ Benzhydryl Compounds - pharmacology
/ Benzhydryl Compounds - therapeutic use
/ Exercise Tolerance - drug effects
/ Female
/ Glucosides - therapeutic use
/ Heart Failure, Systolic - drug therapy
/ Heart Failure, Systolic - metabolism
/ Humans
/ Iron
/ Ischemia
/ Male
/ Patients
/ Recovery of Function - drug effects
/ Sodium-Glucose Transporter 2 Inhibitors - pharmacology
/ Sodium-Glucose Transporter 2 Inhibitors - therapeutic use
