Coagulation–fibrinolysis biomarkers and hemodynamic response during balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension
T Kostelidou, I E Iliopoulou Eugenia, M H Habibi Martha, H P Habibis Pavlos, P A Pouleres Alexandros, K P Karyofyllis PanagiotisAbstract
Background
Balloon pulmonary angioplasty (BPA) improves hemodynamics and functional status in chronic thromboembolic pulmonary hypertension (CTEPH). Whether these changes are accompanied by measurable shifts in coagulation–fibrinolysis biomarkers during the BPA treatment course remains incompletely defined.
Purpose
To assess paired changes in hemodynamic/clinical parameters and coagulation–fibrinolysis biomarkers during the BPA course in CTEPH, and to explore whether selected biomarker changes relate to hemodynamic response.
Methods
Sixteen CTEPH patients with paired data were analyzed between protocol entry and interim reassessment during treatment. Hemodynamics included right atrial pressure (RAP), mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), and cardiac index (CI); clinical assessment included WHO functional class, SaO2, and NT-proBNP. Biomarkers included TFPI, TAFI antigen, α2-antiplasmin (plasmin inhibitor; PI), and other coagulation/fibrinolysis parameters. Baseline represented the first available protocol assessment and not necessarily a true pre-treatment state, as some patients had already undergone BPA sessions before enrollment. The second timepoint was the nearest available clinically stable interim reassessment.
Results
Significant improvements were observed in mPAP [48 (41–55) to 30 (26–41), adjusted p<0.001], PVR [9.4 (6.6–11) to 4.0 (3.2–6.9), adjusted p=0.004], SaO2 [92% (88–94) to 97% (93–98), adjusted p=0.013], and WHO functional class (adjusted p=0.012). In parallel, α2-antiplasmin (PI)decreased [88 (83–101) to 75 (63–88), adjusted p=0.012], TFPI increased [9.4 (6.1–14) to 25 (22–37), adjusted p=0.004], with a shift toward normal categorical distribution, and TAFI antigen increased markedly [6993 (5305–10391) to 35455 (20423–41088) ng/mL, adjusted p=0.001]. Exploratory analysis showed an inverse correlation between %ΔPI and %ΔmPAP (rs=−0.54, p=0.029). Patients with >4 BPA sessions before study entry showed a greater % increase in TAFI than those with ≤4 sessions (p=0.037).
Conclusions
In this paired pre–interim CTEPH analysis, improvement in hemodynamic and clinical status during the BPA course was accompanied by significant changes in coagulation–fibrinolysis and endothelial-related biomarkers. The association between PI change and mPAP response suggests that selected biomarker shifts may reflect treatment-related biological adaptation, while TAFI dynamics may vary according to prior BPA exposure. These findings support the concept that response to BPA extends beyond hemodynamic improvement alone.