Relationship between effects of riociguat and levels of methemoglobin in patients with chronic thromboembolic pulmonary hypertension

Abstract Background Soluble guanyl cyclase (sGC) is a receptor for nitric oxide (NO) and plays an important role in vascular tonus. sGC stimulant is a therapeutic agent for pulmonary hypertension and an advantage of sGC stimulant over phosphodiesterase (PDE)-5 inhibitors is that sGC stimulant exerts its effect even when NO production is reduced. NO derived from vascular endothelial cells is immediately absorbed by hemoglobin (Hb), which leads to the production of methemoglobin (Met-Hb) when oxidized. Previous report has shown that the therapeutic effect of PDE-5 inhibitors was associated with levels of Met-Hb. Purpose In this study, we examined the relationship between the effect of riociguat and levels of Met-Hb in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Methods The study population comprised 18 patients with CTEPH. Mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) were assessed before and after administration of riociguat, and changes in mPAP and PVR were defined as ΔmPAP and ΔPVR, respectively. Since the level of Met-Hb was obtained as the percentage of Hb (FMet-Hb), the amount of Met-Hb was calculated by following formula: Met-Hb (mg/dL) = Hb (g/dL) × FMet-Hb (%) × 10. Results The amount of Met-Hb value before administration of riociguat was significantly correlated with the degree of improvement in mPAP and PVR after administration of riocigat (R=−0.502, P