Update on pulmonary hypertension

The hemodynamic definition of pulmonary hypertension including a mean pulmonary arterial pressure > 20 mmHg is evidence based, but the threshold of 15 mmHg for the pulmonary arterial wedge pressure, deciding between pre-and postcapillary PH, is not. Indeed, based on the most recent literature, the normal PAWP is ≤ 13.0 mmHg, raising some interesting questions. The TASK Force on treatment of pulmonary arterial hypertension (PAH) at the latest world symposium for pulmonary hypertension published a new therapeutic algorithm for PAH that looks simpler than the previous algorithm. However, this algorithm exclusively refers to high-quality evidence from pivotal studies. Sildenafil appears to be safe and effective up to 80 mg TID, combination pills including macitentan and tadalafil are available. The activin signaling inhibitor sotatercept has changed our way of thinking about PAH therapy due to unprecedented efficacy. It is highly efficacious not only in WHO FC 2–3 but also in WHO FC 4 PAH. However, according to the recent literature, the long-term effects include systemic and pulmonary microvascular malformations. The serotonin-, tyrosine kinase-, estrogen, and carboanhydrase pathways have successfully been targeted in several PH models and showed excellent safety profiles in early clinical development. However, the approval-oriented clinical studies, published in high-ranking journals, have only met their primary endpoint in case of inhaled seralutinib and inhaled MK5475. Group 3 PH comprises patients which pulmonary hypertension associated to chronic lung diseases or chronic hypoxia. However, there is an overlap between idiopathic PAH with a “lung phenotype” and Group 3 PH. In Europe, PAH targeted therapies have not been approved for group 3 PH. Treatment for COPD PH appears to be more challenging than treatment of ILD PH. However, according to a large retrospective study, sildenafil might provide beneficial effects for COPD PH patients, particularly in those with a strongly elevated PVR and a relatively well-preserved FEV1. For chronic thromboembolic pulmonary disease, pulmonary endarterectomy is therapy of choice. If this is not feasible, balloon pulmonary angioplasty is superior to medical therapy with riociguat. However, among medical therapies, riociguat still appears to be the most reliable medication that is globally approved for CTEPH.