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Background: Acute decompensated heart failure (ADHF) is a life-threatening condition with a high mortality rate. Levosimendan is an effective inotropic agent used to maintain cardiac output and a long-lasting effect. However, only few studies have compared the clinical outcomes, after levosimendan therapy, among etiologies of ADHF. Methods: Between July 2014 and December 2019, 184 patients received levosimendan therapy for ADHF at our hospital. A total of 143 patients had ischemic cardiomyopathy (ICM), and 41 patients had non-ICM (NICM). Data on comorbidities, echocardiographic findings, laboratory findings, use of mechanical devices, consumption of other inotropic or vasopressor agents, frequency of HF hospitalization, cardiovascular (CV) mortality, and all-cause mortality were compared between the ICM and NICM groups. Results: Patients with ICM were older with higher prevalence of diabetes mellitus when compared to patients with NICM. Patients with NICM had a poorer left ventricular ejection fraction (LVEF) and higher left ventricular end-systolic volume when compared to patients with ICM. At the 30 day follow-up period, a lower CV mortality (ICM vs. NICM: 20.9% vs. 5.1%; log-rank p = 0.033) and lower all-cause mortality (ICM vs. NICM: 28.7% vs. 9.8%; log-rank p = 0.018) was observed in the NICM patients. A significantly lower all-cause mortality was noted at 180 day (ICM vs. NICM: 39.2% vs. 22.0%; log-rank p = 0.043) and 1 year (ICM vs. NICM: 41.3% vs. 24.4%; log-rank p = 0.046) follow up in the NICM subgroup. NICM (hazard ratio (HR): 0.303, 95% confidence interval (CI): 0.108–0.845; p = 0.023) and ECMO use (HR: 2.550, 95% CI: 1.385–4.693; p = 0.003) were significant predictors of 30 day all-cause mortality. Conclusions: In our study on levosimendan use for ADHF patients, better clinical outcomes were noted in the NICM population when compared to the ICM population. In the patients with cardiogenic shock or ventilator use, significantly lower incidence of 30 day mortality presented in the NICM population when compared with the ICM population. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea syndrome (OSAS) is a significant risk factor for left atrial (LA) remodeling. Intermittent hypoxemia occurs during the sleep cycle in patients with OSAS and plays a crucial role in cardiovascular pathologies such as stroke, arrhythmia, and coronary artery disease. However, there is very little information about the role of intermittent hypoxemia in LA remodeling in patients with OSAS. In total, 154 patients with sleep-related breathing disorders (SRBD) were prospectively recruited for this study. All enrolled SRBD patients underwent polysomnography and echocardiography. Significant OSAS was defined as an oxygen desaturation index (ODI) of ≥10 per hour. Intermittent hypoxia/reoxygenation (IHR) stimulation was used to test the effect of hypoxia on the viability, reactive oxygen species, apoptosis, and inflammation-associated cytokine expression in the HL-1 cell line. To investigate the effect of patients' exosomes on HIF-1 and inflammation-associated cytokine expression, as well as the relationship between ODI and their expression, exosomes were purified from the plasma of 95 patients with SRBD and incubated in HL-1 cells. The LA size was larger in patients with significant OSAS than in those without. There was a significant association between ODI, lowest SpO2, mean SpO2, and LA size (all p < 0.05) but not between the apnea–hypopnea index and LA size. IHR condition caused increased LDH activity, reactive oxygen species (ROS) levels, and apoptosis in HL-1 cells and decreased cellular viability (all p < 0.05). The expression of HIF-1α, TNF-α, IL-6, and TGF-β increased in the IHR condition compared with the control (all p < 0.05). The expression of HIF-1α, IL-1β, and IL-6 increased in the HL-1 cells incubated with exosomes from those patients with significant OSAS than those without (all p < 0.05). There was a significantly positive correlation between ODI and the expression of HIF-1α, TNF-α, IL-1β, IL-6, and TGF-β; a significantly negative correlation between mean SpO2 and IL-6 and TGF-β; and a significantly negative correlation between the lowest SpO2 and HIF-1α (all p < 0.05). In conclusion, intermittent hypoxemia was strongly associated with LA remodeling, which might be through increased ROS levels, LDH activity, apoptosis, and the expression of HIF-1α and inflammation-associated cytokines. [ABSTRACT FROM AUTHOR]

Hyperglycaemia causes endothelial dysfunction, which is the initial process in the development of diabetic vascular complications. Upon injury, endothelial cells undergo an endothelial-to-mesenchymal transition (EndMT), lose their specific marker, and gain mesenchymal phenotypes. This study investigated the effect of liraglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, on EndMT inhibition and neointima formation in diabetic mice induced by streptozotocin. The diabetic mice with a wire-induced vascular injury in the right carotid artery were treated with or without liraglutide for four weeks. The degree of neointima formation and re-endothelialisation was evaluated by histological assessments. Endothelial fate tracing revealed that endothelium-derived cells contribute to neointima formation through EndMT in vivo. In the diabetic mouse model, liraglutide attenuated wire injury-induced neointima formation and accelerated re-endothelialisation. In vitro, a high glucose condition (30 mmol/L) triggered morphological changes and mesenchymal marker expression in human umbilical vein endothelial cells (HUVECs), which were attenuated by liraglutide or Activin receptor-like 5 (ALK5) inhibitor SB431542. The inhibition of AMP-activated protein kinase (AMPK) signaling by Compound C diminished the liraglutide-mediated inhibitory effect on EndMT. Collectively, liraglutide was found to attenuate neointima formation in diabetic mice partially through EndMT inhibition, extending the potential therapeutic role of liraglutide. [ABSTRACT FROM AUTHOR]