The efficacy and safety of combining bosentan, an orally active dual endothelin receptor antagonist and epoprostenol, a continuously infused prostaglandin, in the treatment of pulmonary arterial hypertension (PAH) was investigated.In this double-blind, placebo-controlled prospective study, 33 patients with PAH started epoprostenol treatment (2 ng?kg -1 min -1 starting dose, up to 14 ¡ 2 ng?kg -1 min -1 at week 16) and were randomised for 16 weeks in a 2:1 ratio to bosentan (62.5 mg b.i.d for 4 weeks then 125 mg b.i.d) or placebo. Haemodynamics, exercise capacity and functional class improved in both groups at week 16. In the combination treatment group, there was a trend for a greater (although nonsignificant) improvement in all measured haemodynamic parameters. There were four withdrawals in the bosentan/epoprostenol group (two deaths due to cardiopulmonary failure, one clinical worsening, and one adverse event) and one withdrawal in the placebo/epoprostenol group (adverse event).This study showed a trend but no statistical significance towards haemodynamics or clinical improvement due to the combination of bosentan and epoprostenol therapy in patients with pulmonary arterial hypertension. Several cases of early and late major complications were reported. Additional information is needed to evaluate the risk/benefit ratio of combined bosentan-epoprostenol therapy in pulmonary arterial hypertension. Pulmonary arterial hypertension (PAH) is an uncommon disease characterised by a progressive increase in pulmonary vascular resistance leading to right ventricular failure and death [1]. PAH can be idiopathic (referred to as primary pulmonary hypertension-PPH), or occur as a complication of various conditions, including scleroderma [2] or systemic lupus erythematosus [3]. The pathogenesis of PAH involves multiple and complex mechanisms triggered by endothelial dysfunction in the pulmonary bed, resulting in pulmonary vasoconstriction and vascular remodelling. An imbalance between vasoconstrictor/vasodilator activities in favour of vasoconstriction could be responsible for altered pulmonary vascular tone and structure [4]. In PAH patients, relaxing factors such as prostacyclin [5] are decreased and nitric oxide synthesis is impaired [6], whereas constricting factors including thromboxane [7], serotonin [8], and endothelin [9] are increased. Restoration of this imbalance by targeted therapies such as prostacyclin and endothelin receptor antagonists should further improve treatment options for the management of PAH.Prostacyclin (epoprostenol), a potent pulmonary vasodilator, decreases pulmonary vascular resistance and improves the survival of patients with severe PAH [10][11][12][13][14][15]. Despite major improvements in prognosis, mortality in patients with severe PAH treated with epoprostenol is still high, emphasising the need for novel therapeutic approaches in this patient population. In addition, epoprostenol is associated with dose-related side-effects (e.g. diarrhoea, flushing, headache, jaw pain, hypot...

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New and innovative tools have emerged for the treatment of massive and submassive pulmonary embolism (PE). These novel treatments, when considered alongside existing therapy, such as anticoagulation, systemic intravenous thrombolysis, and open surgical pulmonary embolectomy, have the potential to improve patient outcomes. However, data comparing different treatment modalities are sparse, and guidelines provide only general advice for their use. Treatment decisions rest on clinician expertise and institutional resources. Because various medical and surgical specialties offer different perspectives and expertise, a multidisciplinary approach to patients with massive and submassive PE is required. To address this need, we created a novel multidisciplinary program - the Massachusetts General Hospital (MGH) Pulmonary Embolism Response Team (PERT) - which brings together multiple specialists to rapidly evaluate intermediate- and high-risk patients with PE, formulate a treatment plan, and mobilize the necessary resources to provide the highest level of care. Development of a clinical, educational, and research infrastructure, as well as the creation of a national PERT consortium, will make our experience available to other institutions and serve as a platform for future studies to improve the care of complex patients with massive and submassive PE.

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