Abstract 18330: Asymmetric Dimethylarginine, a Biomarker for the Effects of Drug Therapy in Pulmonary Hypertension
Rationale: Pulmonary hypertension (PH) is characterized by high morbidity and mortality, requiring aggressive treatment. Asymmetric dimethylarginine (ADMA), a potent endogenous nitric oxide synthase inhibitor, is increased in PH, and associated with unfavorable outcome. We hypothesized that ADMA may serve as a biomarker to monitor disease progression under pulmonary arterial hypertension (PAH)-specific treatment.
Methods: ADMA plasma levels were measured at baseline and at least after 24 weeks of treatment in consecutive patients (pts) under PAH-targeted treatments (endothelin receptor antagonists (bosentan, ambrisentan), phosophodiesterase-V inhibitors (sildenafil), high dose calcium channel blockers (diltiazem) and prostanoids (subcutaneous treprostinil)). Therapy “responders” were defined by decrease of pulmonary vascular resistance (PVR) of at least 200dynes.cm-1.s-5, 6-minute walking distance >380m, and improvement of WHO by one class and were compared with “non-responders”.
Results: 51 consecutive patients (44 pts with PAH; 23 pts with idiopathic PAH, 8 pts with PAH associated (APAH) with congenital heart disease (CHD), 2 APAH pts with HIV, 4 APAH pts with connective tissue diseases (CTD), 5 pts with portopulmonary hypertension, 2 PAH patient with hepatitis C) and 7 patients with PH due to lung disease/hypoxia) were enrolled in this study. According to our definition; there were 16 non-responders, and 23 responders to treatments. 11 patients showed no change. ADMA plasma levels did not change significantly under treatment in the whole group. However, there was a significant drop of ADMA in responder group (p<0.0001), Furthermore, ADMA change in “responders” and “non-responders” was significantly different (p=0.003). The decrease of ADMA correlated with the decrease of PVR (r=0.56, p<0.0001), and with the decrease of mean pulmonary arterial pressure (r=0.44, p=0.001). Furthermore, the difference of ADMA correlated with the increase of cardiac index (r=-0.38, p=0.005) and mixed venous saturation (r=-0.3, p=0.03).
Conclusions: ADMA parallels the hemodynamic benefit of PAH-specific treatment in patients with PH of various etiologies. ADMA can serve as a biomarker for the effect of PAH-specific treatments.
- © 2012 by American Heart Association, Inc.