Is inflammation a potential therapeutic target in chronic thromboembolic pulmonary hypertension?

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but notoriously underdiagnosed complication of pulmonary embolism, which carries a poor prognosis if left untreated. CTEPH results from the obstruction of the pulmonary vascular bed by fibro-thrombotic material, which may completely occlude the lumen. Although massive or recurrent pulmonary embolism is thought to be the initiating event, a significant proportion of patients have no history of symptomatic pulmonary embolism and only a few patients with acute pulmonary embolism develop CTEPH [1]. As a consequence, the true prevalence and incidence of CTEPH remain unknown [2]. Current data, retrieved from registries, suggest that the incidence of CTEPH averages between three and 30 per million in the general population [3], and that the proportion of patients developing CTEPH after acute pulmonary embolism may vary between 0.1% and 9.1% [4]. The standard and potentially curative treatment for CTEPH is a surgical procedure, known as pulmonary endarterectomy (PEA) [5], which involves removing organised thrombi, neointima and media inner layers obstructing the pulmonary arteries (fig. 1b) [6]. PEA, when performed in experienced centres and on selected patients, shows low perioperative mortality, and provides major improvements in haemodynamics, symptoms and survival [7]. Moreover, CTEPH is a “dual” pulmonary vascular disorder combining major vessel obstruction and small vessel arteriopathy, which is histologically indistinguishable from idiopathic pulmonary arterial hypertension (PAH) in the non-occluded lung areas [8]. As a consequence, PAH-targeted therapy, including prostacyclin analogues, endothelin-1 receptor antagonists and phosphodiesterase-5 inhibitors, has been largely used in CTEPH [9] and should be considered for inoperable patients or patients with persistent pulmonary hypertension after PEA [10]. More recently, riociguat, a stimulator of soluble guanylate cyclase, has been approved for the treatment of …