Abstract 10323: Tadalafil Therapy Improves Endothelial Thrombomodulin in Hypoxemic Patients With Pulmonary Arterial Hypertension Associated With the Eisenmenger Syndrome
Introduction: Thrombomodulin (TM) is a plasma membrane chondroitin sulfate proteoglycan acting as a natural endothelial anticoagulant and anti-thrombotic factor. Binding of TM to thrombin leads to protein C activation with subsequent cleavage of activated coagulation factors V and VIII. In pulmonary arterial hypertension (PAH), particularly in hypoxemic patients with Eisenmenger syndrome, endothelial dysfunction is associated with heightened circulating levels of von Willebrand factor antigen (VWF:Ag) and tissue plasminogen activator (t-PA), but decreased TM reflecting diminished endothelial production.
Hypothesis: Plasma TM, t-PA, VWF:Ag and functional parameters may be improved in patients with Eisenmenger syndrome subjected to chronic treatment with tadalafil.
Methods: Fifteen patients aged 12 to 51 years (median 30 years) were evaluated at baseline, and 90 and 180 days of treatment with oral tadalafil (single daily dose of 40 mg). The functional capacity was accessed using the six-minute walk test and endothelial markers were analyzed by enzyme-linked immunoassays.
Results: At baseline, levels of all three endothelial markers were altered in patients compared to controls (respectively, 8.62±3.50 ng/mL vs. 5.13±1.69 ng/mL for t-PA, 121±21 U/dL vs. 94±23 U/dL for VWF:Ag and 1.92±0.49 ng/mL vs. 3.41±0.50 ng/mL for TM. Tadalafil treatment resulted in improvement of exercise capacity (six-minute walked distance, 6MWD) and peripheral oxygen saturation (O2 Sat), with decreased hematocrit (Htc). Plasma TM increased mildly but significantly, while t-PA level decreased (Table).
Conclusion: In the Eisenmenger syndrome, PAH therapy with tadalafil improves not only the physical capacity, O2 Sat and Htc, but also endothelial markers. The modest increase in circulating TM may reflect improved endothelial TM production and protection against in situ thrombosis, a largely known complication of this syndrome.
Author Disclosures: M.M. Clavé: None. N.Y. Maeda: None. A.M. Thomaz: None. S.M. Mesquita: None. S.P. Bydlowski: None. A.A. Lopes: None.
- © 2015 by American Heart Association, Inc.