Abstract
Introduction: Not only are mechanisms involved in tricuspid regurgitation (TR) incompletely understood, there is no established means of risk stratification for patients undergoing tricuspid valve interventions. A better understanding of underlying biological mechanisms allows for identification of therapeutic targets as well as biomarkers for disease staging, monitoring, and prediction following intervention. Methods: Preoperatively, 276 patients undergoing tricuspid annuloplasty, divided into training and validation cohorts, were assessed and followed-up for adverse events defined as death or heart failure requiring hospitalisation. Preoperative plasma samples were analysed for levels of cardiac troponin-T, NTproBNP, as well as 91 other markers (Olink multiplex assay). Correlated network analysis was used for clustering plasma markers. The relations of clusters to echocardiographic parameters and adverse outcomes were assessed by linear and Cox regression respectively. Pathway overrepresentation analysis was conducted to ascertain biological mechanisms overrepresented in relevant clusters by enrichment with reference to existing knowledge. Results: Over a median follow-up period of 3.7 years, 83 adverse events occurred. Two clusters of biomarkers in the training cohort significantly correlate with right chamber and tricuspid annular dilatation, regurgitant jet area, effective regurgitant orifice area and/or adverse outcomes following tricuspid annuloplasty (P<0.05). The two clusters are represented by hub proteins TNF Receptor Superfamily Member 10A and TRAIL receptor 2. Overrepresented biological pathways in the two clusters include immunological responses, cytokine production regulation, and responses to lipids. Both clusters are conserved in the validation cohort. Conclusion: Immunoinflammatory pathways may be implicated in tricuspid regurgitation, and markers related to such pathways show prognostic significance.
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