Kwon JM, et al. Korean Circ J. 2018 Aug;49:e56. https://doi.org/10.4070/kcj.2018.0446

Background: The immune and inflammatory responses play a considerable role in left ventricular remodeling after myocardial infarction (MI). Binding of AhR (aryl hydrocarbon receptor) to its ligands modulates immune and inflammatory responses; however, the effects of AhR in the context of MI are unknown. Therefore, we evaluated the potential association between AhR and MI by treating mice with a nontoxic endogenous AhR ligand, ITE (2‐[1’H‐indole‐3’‐carbonyl]‐thiazole‐4‐carboxylic acid methyl ester). We hypothesized that activation of AhR by ITE in MI mice would boost regulatory T‐cell differentiation, modulate macrophage activity, and facilitate infarct healing. Methods and Results: Acute MI was induced in C57BL/6 mice by ligation of the left anterior descending coronary artery. Then, the mice were randomized to daily intraperitoneal injection of ITE (200 µg/mouse, n=19) or vehicle (n=16) to examine the therapeutic effects of ITE during the postinfarct healing process. Echocardiographic and histopathological analyses revealed that ITE‐treated mice exhibited significantly improved systolic function ( P <0.001) and reduced infarct size compared with control mice ( P <0.001). In addition, we found that ITE increased regulatory T cells in the mediastinal lymph node, spleen, and infarcted myocardium, and shifted the M1/M2 macrophage balance toward the M2 phenotype in vivo, which plays vital roles in the induction and resolution of inflammation after acute MI. In vitro, ITE expanded the Foxp3 ⁺ (forkhead box protein P3‐positive) regulatory T cells and tolerogenic dendritic cell populations. Conclusions: Activation of AhR by a nontoxic endogenous ligand, ITE, improves cardiac function after MI. Post‐MI mice treated with ITE have a significantly lower risk of developing advanced left ventricular systolic dysfunction than nontreated mice. Thus, the results imply that ITE has a potential as a stimulator of cardiac repair after MI to prevent heart failure.

Korean Circulation Journal 대한심장학회지 순환기 Chang K, et al. Korean Circ J. 2021 Apr;51(4):289-307. https://doi.org/10.4070/kcj.2021.0043

Background: Little is known about the characteristics and long‐term clinical outcomes of patients with heart failure with improved ejection fraction (HFimpEF) after acute myocardial infarction. Methods and Results: From a multicenter, consecutive cohort of patients with acute myocardial infarction undergoing percutaneous coronary intervention, patients with an initial echocardiogram with left ventricular ejection fraction ≤40% and at least 1 follow‐up echocardiogram after 14 days and within 2 years of the initial event were considered for analyses. HFimpEF was defined as an initial left ventricular ejection fraction ≤40% and serial left ventricular ejection fraction >40% with an increase of ≥10% from baseline at follow‐up. Independent factors predicting HFimpEF were identified, and clinical outcomes of patients with HFimpEF were compared with those without improvement. From an initial cohort of 10 719 patients with acute myocardial infarction, 191 patients with HFimpEF and 256 patients with non‐HFimpEF who had initial and follow‐up echocardiographic data were analyzed. The median follow‐up duration was 4.5 (interquartile range, 2.9–5.0) years. The factors predicting HFimpEF were lower peak creatine kinase myocardial band, smaller left ventricular dimensions, lower ratio between early mitral inflow velocity and mitral annular early diastolic velocity ′, and the use of β blockers or renin–angiotensin system blockers at discharge. HFimpEF was associated with a significantly decreased risk of all‐cause death compared with non‐HFimpEF (hazard ratio, 0.377 [95% CI, 0.234–0.609]; P <0.001). In 2‐year landmark analysis, these findings were consistent not only before but also after the landmark point. Similar findings were true for cardiovascular death and admission for heart failure. Conclusions: Patients with HFimpEF after acute myocardial infarction showed distinct clinical and echocardiographic characteristics and were associated with better long‐term clinical outcomes. Registration: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT02806102.