Our approach to the management of pulmonary arterial hypertension due to pulmonary veno-occlusive disease

PAH: pulmonary arterial hypertension; PVOD: pulmonary veno-occlusive disease; WHO: World Health Organization; ECMO: extracorporeal membrane oxygenation.

* Similar to patients who have class I PAH (eg, idiopathic), patients with PVOD should exercise as tolerated, receive routine vaccinations, be counselled against smoking and pregnancy, and be treated with supportive measures including oxygen and diuretics, when indicated. The administration of anticoagulant therapy is controversial due to a potentially higher risk of alveolar hemorrhage (refer to UpToDate text for details). We favor limited trials of immunomodulatory medications (eg, corticosteroids, antimetabolites) in patients with PVOD who also have prominent autoimmune features. This preference is based upon anecdotal responses that have occurred with these agents, particularly in the context of limited treatment options.

¶ Advanced therapy is therapy that is directed at the pulmonary hypertension itself. Compared with patients who have class I PAH (eg, idiopathic), advanced therapy in this population has an increased risk of adverse effects including pulmonary edema, respiratory failure, and cardiac arrest. While some experts prefer to avoid advanced therapy, we administer cautious trials of advanced therapy as a bridge to transplant. When this approach is chosen, we initiate low doses of agent together with close monitoring and rapidly available treatment of pulmonary edema with oxygen and high dose diuretics; therapy can then be slowly escalated every 1 to 2 weeks to the maximum tolerated dose.

Δ Single agent and combined oral therapy (double therapy) increase the risk of adverse effects and may not be tolerated in this population. When using combined therapy, agents from 2 different classes should be used and only 1 agent should be added each time. Agent selection is individualized and varies according to the institution, patient preference, and cost. Among the available oral agents, an endothelin receptor antagonist (eg, ambrisentan, macitentan, bosentan) or a phosphodiesterase inhibitor (eg, sildenafil) may be appropriate. Some experts administer a third oral agent or a single agent intravenous epoprostenol for patients who have WHO functional class III and have rapidly progressive disease. Refer to UpToDate text for further details.

◊ Combined therapy increases the risk of adverse effects and may not be tolerated in this population. Some experts combine intravenous agents with 1 or 2 oral agents (double or triple therapy, respectively). Agents from different classes should be used and only added sequentially.

§ Up to 2 oral agents can be combined with intravenous prostanoid therapy. Agents from 2 different classes should be used and only 1 agent should be added each time. Due to the increased risk of adverse effects, agent selection is individualized and varies according to the institution, patient preference, and cost. Among the available oral agents, an endothelin receptor antagonist (eg, ambrisentan, macitentan, bosentan) or a phosphodiesterase inhibitor (eg, sildenafil) may be appropriate. Refer to UpToDate text for further details.