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Objectives and questions: Polytrauma (PT) is frequently complicated by myocardial damage. The right ventricle (RV) is particularly vulnerable due to its anterior position in the thorax, thin wall, and high sensitivity to afterload. However, biomarkers of RV impairment after PT remain poorly defined. The aim of the present study was to identify circulating biomarkers associated with RV impairment after PT and to explore the functional relevance of the most promising miRNA candidate in vitro.

Material and methods: A total of 45 PT patients (ISS ≥16) and 7 healthy controls were included in the analysis. Plasma samples collected in the emergency room (ER) were assessed for the protein biomarker Fibroblast growth factor 23 (FGF-23) and candidate miRNA biomarkers (miR-20a-5p, miR-486-5p, miR-122-5p, miR-494-3p, and miR-212-3p) using ELISA and RT-qPCR, respectively. Candidate biomarker expression was first compared between PT patients and healthy controls, and subsequently within the PT cohort according to cardiac injury(troponin T and NT-proBNP) and injury pattern (presence or absence of thoracic trauma). Echocardiographic analyses included group-wise comparisons based on tricuspid regurgitation (TR) and central venous pressure (CVP), as well as Spearman correlation analyses with parameters of the ventricular function (TAPSE, RVEDD, EF%, and LVEDD). To evaluate the functional relevance of the most promising miRNA candidate, miR-20a-5p, human cardiomyocytes (HCMs) were transfected with its mimic and subsequently exposed to a polytrauma cocktail (PTC) to model trauma-induced cellular stress. Cell metabolic activity and apoptosis were measured using alamarBlue and Caspase-3/7 activity assays, respectively.

Results: FGF-23 levels were significantly elevated in PT patients with cardiac injury (increased NT-proBNP or TnT) and were also higher in PT patients with TR and abnormal CVP. MiR-20a-5p showed a trend toward higher expression in PT patients with thoracic trauma (p = 0.05), was increased in PT patients with TR, and was positively correlated with TAPSE and negatively correlated with RVEDD. MiR-494-3p and miR-122-5p were upregulated in PT patients compared with healthy controls and further elevated in PT patients with thoracic trauma. MiR-486-5p expression was higher in PT patients with TR and in those with abnormal CVP. MiR-212-3p was elevated in PT patients and was associated with left ventricular function. In vitro, transfection with a miR-20a-5p mimic partially rescued PTC-induced injury by preserving cell metabolic activity and reducing caspase-3/7 activation.

Discussion and conclusions: Following PT, circulating FGF-23 is strongly associated with cardiac injury and RV load, while miR-20a-5p is linked to RV systolic function and shows functional relevance in post-traumatic cardiac damage in vitro.