Endothelial nitric oxide synthase genetic variations-786CT and 84GT were common but irrelevant to severity and outcome of patients with submassive ulmonary embolism treated in a andomied trial of inhaled nitric oxide

Introduction: rior work has shown that two endothelial nitric oxide synthase (eNOS) genetic sequence variations (-786CT and 84GT) increase risk for pulmonary embolism (E) and severity of multiple vascular diseases. Hypothesis: atients with these genotypes would associate with more severe E and greater clinical response to inhaled NO Methods: hase II, (NCT193931), randomied, double blind, placebo-controlled trial. atients had CT-proven acute E, were normotensive, and had V dysfunction using explicit criteria. Subjects were randomied to either 50 ppm NOO2 (treatment) or O2 only (placebo), delivered by nasal cannula and identical equipment for 24 h with blood sampling before and after treatment to assess high sensitivity troponin T (hsTnT), brain natriuretic peptide (BN). Severe E was defined as patients with both hsTnT and BN 3 quartile. All patients had post treatment echocardiography. Results: We enrolled 76 patients per protocol with 38 randomied to each treatment. Genetic variations in eNOS were common: 54 had -786CT, 5 had 84GT, and 77 had either. resence of either variation was not associated with E severity: 5/6 (83) with severe E vs. 53/6 (77) without severe E had either variation (0., Fishers exact). Likewise, presence of either eNOS variation was not associated with increased probability of a normal hsTnT (14 pg/mL), or normal BN (0 pg/mL) or normal echocardiogram after 24 hours of NO treatment. lasma nitrate concentrations (M) increased significantly in NO treated but not placebo, indicating successful NO delivery. Conclusions: Two eNOS polymorphisms thought to reduce endogenous NO synthesis were present in the majority of patients with E, but had no association with severity or clinical response to NO treatment. These data do not support a personalied medicine approach to NO-based E treatment based upon eNOS genotype.