Post-capillary pulmonary hypertension (pc-PH) is defined as mean pulmonary arterial pressure≥25 mmHg and mean pulmonary capillary wedge pressure>15 mmHg, and is classified into 2 types depending on the status of pulmonary vascular resistance (PVR) or trans-pulmonary pressure gradient (TPG) : reactive pc-PH with elevated PVR (>2. 5WU) and/or TPG (>12 mmHg), and passive pc-PH with normal PVR (≤2.5WU) and TPG (≤12 mmHg). The pathogenesis of passive pc-PH is a simple backward transmission of elevated left atrial pressure, whereas reactive pc-PH is caused by functional and/or structural changes of pulmonary arteries as a result of chronic elevation of pulmonary venous pressure. Indeed, a high prevalence of pc-PH has been reported in patients with advanced systolic heart failure, diastolic heart failure, valvular heart diseases including mitral valve disease, and advanced heart failure referred for heart transplantation. Especially, reactive pc-PH is a significant prognostic factor regardless of heart failure etiology (ischemic vs. non-ischemic) and left ventricular ejection fraction (reduced vs. preserved).
Future studies are required to clarify this issue and to develop a new therapeutic target for pc-PH. Riociguat is a novel, first-in-class oral drug that directly stimulates soluble guanylate cyclase, both independent of the endogenous vasodilator NO and synergistic with NO. Phase III clinical trials of riociguat evaluating the long-term safety and clinical effectiveness of the agent in pc-PH are on-going, which may demonstrate that riociguat is effective in patients with pc-PH. (Jpn J Clin Pharmacol Ther 2012; 43(5): 311-315)