Comprehensive Heart Failure Center, Würzburg University and University Hospital Würzburg, and Department of Medicine 1, University Hospital Würzburg, Würzburg, Germany.
Atherothrombosis Research Unit, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Nat Cardiovasc Res. 2023 Nov;2(11):1032-1043. doi: 10.1038/s44161-023-00352-5. Epub 2023 Oct 26.
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 .
钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂可改善心力衰竭（HF）患者的临床结局，但作用机制尚不完全清楚。在 EMPA-TROPISM 试验中，恩格列净可逆转稳定的非糖尿病收缩性 HF 患者的心脏重构并增加体力。在这里，我们事后探讨了该队列（其中缺铁的患病率较高）的治疗效果是否与铁代谢有关。心脏磁共振 T2定量估计的心肌铁含量在开始使用恩格列净后增加，但安慰剂组没有增加（治疗效果：P=0.01）。T2的变化与左心室容积、质量和射血分数、峰值耗氧量和 6 分钟步行距离的变化显著相关；同时红细胞指数的变化与增强的造血作用一致。探索性因果中介分析结果表明，恩格列净治疗后心肌铁含量的变化可能是其解释 HF 患者临床获益的重要机制。临床试验.gov：NCT03485222。
