Platelet bioenergetic profiling and metabolic reprogramming as a novel biomarker in Ebstein anomaly
F Klauco, Z Sumbalova, T Hlavata, A Reptova, T Valkovicova, A Gvozdjakova, I SimkovaAbstract
Background
Chronic right ventricular (RV) volume overload due to primary tricuspid regurgitation in Ebstein anomaly (EA) drives progressive dilatation and pathological myocardial remodeling. Identifying the optimal timing for surgical intervention before irreversible myocardial damage occurs remains challenging. Since platelets reflect systemic metabolic shifts, this study investigates whether platelet mitochondrial bioenergetics can serve as a translational biomarker for disease severity and RV dysfunction in EA patients.
Methods
Analysed were isolated platelets from 14 EA patients and 18 healthy controls. The patient cohort was stratified based on the 2020 ESC guidelines into two groups: EA-0 (no current indication for surgery) and EA-1 (meeting Class Ia or IIb indications for surgical intervention). High-resolution respirometry was utilized to evaluate oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO), and electron transport capacity. Additionally, endogenous antioxidant levels (CoQ10 and γ-tocopherol) were quantified.
Results
Complex I (CI)-linked respiration and FAO-linked OXPHOS were moderately elevated in the EA-0 cohort (120% and 122% of controls, respectively) but exhibited a marked, significant hyperactivation in the EA-1 cohort (CI: 259%; FAO: 197%). This increased oxygen consumption in EA-1 was accompanied by severe depletion of endogenous antioxidants, specifically CoQ10 (59% of controls) and γ-tocopherol (23% of controls).
Conclusion
Mitochondrial bioenergetics revealed compensatory metabolic reprogramming that strongly correlated with clinical severity. The pronounced hyperactivation of CI-linked respiration, combined with severe CoQ10 deficiency in platelets, reflects a systemic maladaptive response and reductive stress driven by chronic RV overload. This accessible bioenergetic profile provides a promising novel biomarker for personalized risk stratification, offering valuable mechanistic insights to guide the optimal timing of surgical intervention in EA.Platelet respiration & FAO in EAP-L coupling efficiency of FAO-linked OXPHOS