ArticleACS pharmacology & translational science2026
Cross-Sectional Plasma Proteomic Phenotypes Associated with Prolonged Intermittent Levosimendan Exposure in Advanced Heart Failure.
Article in ACS pharmacology & translational science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Levosimendan is intermittently administered in selected patients with advanced heart failure, but data on prolonged exposure and associated circulating molecular profiles remain limited. We conducted a retrospective observational study of 41 patients with heart failure with reduced ejection fraction, including eight patients exposed to ≥22 intermittent levosimendan infusions and 33 nonexposed controls followed in the same specialist heart failure setting. Baseline clinical characteristics, follow-up outcomes, and plasma proteomic profiles were assessed using label-free data-independent acquisition mass spectrometry. Patients exposed to prolonged intermittent levosimendan were older and had more advanced heart failure at baseline, including lower left ventricular ejection fraction and higher NT-proBNP concentrations. During clinical follow-up from the first specialist cardiology observation to plasma sampling, cardiovascular hospitalization occurred in 3/8 levosimendan-exposed patients and 1/33 controls, while cardiovascular death occurred in 2/8 and 0/33, respectively; these outcomes are reported descriptively because of baseline imbalance, retrospective treatment allocation, and the small exposed-group size. These outcomes are reported descriptively because of baseline imbalance and the small exposed-group size. Plasma proteomic analysis identified cross-sectional differences between groups. Control patients showed higher representation of immune and inflammatory proteins, whereas levosimendan-exposed patients showed higher abundance of proteins related to antioxidant defense, redox regulation, coagulation/hemostasis, and metabolic adaptation, including GPX3, SELENOP, PROS1, F2, AHSG, and ALDOA. These findings define an exploratory plasma proteomic phenotype associated with prolonged intermittent levosimendan exposure in real-world advanced heart failure. Prospective controlled studies with baseline and serial proteomic sampling are required to determine whether these molecular differences reflect treatment-associated adaptation or underlying clinical differences.
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