Effect of levosimendan on plasma intestinal barrier factors in heart failure patients with reduced ejection fraction.

OBJECTIVES: In addition to dyspnea and edema, gastrointestinal discomfort is common among patients with heart failure (HF). Reduced cardiac output can lead to inadequate perfusion of the intestinal mucosa and subsequent impairment of the intestinal barrier. Levosimendan, a novel inotropic agent, binds to cardiac troponin C to enhance calcium sensitivity, activates ATP-dependent potassium channels in cardiomyocytes and vascular smooth muscle cells, exerts positive inotropic and vasodilatory effects, and reduces free radical generation, thereby improving systemic hemodynamics including intestinal circulation. However, clinical evidence regarding its protective effects on the intestinal barrier in HF patients remains limited, and the underlying mechanisms require further clarification. This study aims to investigate whether levosimendan confers protective effects on the intestinal barrier in HF patients and to explore its potential mechanisms. METHODS: =31). The conventional treatment group received standard anti-HF therapy, while the levosimendan treatment group received levosimendan in addition to standard therapy. Enzyme-linked immunosorbent assays were used to measure plasma levels and changes in the intestinal-barrier proteins zonulin, intestinal fatty acid binding protein (I-FABP), proinflammatory cytokines [interleukin (IL)-17, IL-6, and tumor necrosis factor (TNF)-α], anti-inflammatory cytokine IL-10, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Improvements in cardiac function and gastrointestinal symptoms were evaluated using the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Gastrointestinal Symptom Rating Scale (GSRS). RESULTS: >0.05). CONCLUSIONS: Levosimendan not only improves HF and gastrointestinal symptoms in hospitalized patients with acute exacerbation of HFrEF but also reduces plasma intestinal barrier factor levels. These effects may be associated with decreased plasma proinflammatory cytokines and increased anti-inflammatory cytokines after treatment, potentially involving IL-17 and TNF signaling pathways.