Modulation of inflammatory response after myocardial infarction: one explanation for the cardiovascular benefit of empagliflozin in the EMMY trial?

Abstract

We read with great interest the clinical research article entitled 'Empagliflozin in acute myocardial infarction: the EMMY trial' by von Lewinski et al..1 In this trial, the authors investigated the effects of empagliflozin in patients hospitalized with acute large myocardial infarction (MI). Empagliflozin treatment was associated with a significant reduction of B-type natriuretic peptide levels compared to placebo after 26 weeks. Additionally, improvement in left ventricular systolic and diastolic function assessed by echocardiography was observed in the empagliflozin group. Left ventricle (LV) end-systolic and end-diastolic volumes, surrogate markers of post-MI adverse remodelling, were less impacted in the empagliflozin arm. On top of several hypotheses raised by the authors to explain the beneficial effects of empagliflozin, we would like to shed light on the major role of post-MI inflammatory response and its potential modulation by empagliflozin. Adverse LV remodelling after MI is the first step leading to ischaemic heart failure (HF), due to dynamic changes in LV geometry, structure, and function. The magnitude of myocardial dysfunction and LV remodelling is mainly determined by the infarct size and the efficacy of post-MI reparative mechanisms including inflammatory response, matrix remodelling, neovascularization, and wound healing. The early inflammatory response triggered by hypoxia and danger-associated molecular patterns released by jeopardized cardiomyocytes is the first stage of cardiac repair. It involves myocardial infiltration of inflammatory cells and upregulation of several proinflammatory cytokines.2 Timely resolution of inflammation may help prevent HF development and progression. Neurohormonal activation, including the renin-angiotensin system, is another pathway promoting adverse LV remodelling.