Shifting Paradigms in the Management of Pulmonary Hypertension

Abstract

Pulmonary arterial hypertension (PAH) is a long-term condition characterised by increased resistance to blood flow in the pulmonary circulation. The disease has a progressive course and is associated with a poor prognosis. Without treatment, PAH is associated with mortality in <3 years. Over the past decade, many advances have been made in revising the haemodynamic definition, clinical classification, risk calculation score, treatment options etc. Suggestions from the Sixth World Symposium on Pulmonary Hypertension were incorporated into a literature review that was included in the European Society of Cardiology/European Respiratory Society (ESC/ERS)’s most recent iteration of their guidelines in 2022. The traditional cut-off for pulmonary hypertension (PH), i.e., mean pulmonary artery pressure (mPAP) >25 mm Hg, has been challenged by observational cohort studies, which have shown poor outcomes for values of 21–24 mmHg; the new consensus is that PH is defined at mPAP >20 mm Hg. Although the gold standard for diagnosis and the major source of therapy guidance continues to be right cardiac catheterisation, echocardiography remains the initial test of choice. A multidisciplinary approach is highly recommended when treating PH patients and careful evaluation of patients will aid in proper diagnosis and prognosis. Pharmacotherapy for PAH has seen a paradigm shift with the successful use of newer agents in more extensive, longer and more inclusive trials driven by hard endpoints. Macitentan, selexipag and riociguat are three oral agents that have shown astounding success in PAH randomised studies in the past decade. Upfront combination therapy with two agents is now becoming the norm (following the AMBITION, OPTIMA and ITALY trials) and the momentum is shifting towards triple therapy as for essential hypertension. More recently, inhaled treprostinil was shown to improve exercise capacity in PH associated with interstitial lung disease in the phase III INCREASE study and has been granted regulatory approval for World Health Organization group 3 PH. A new class of drug, sotatercept (a tumour growth factor-β signalling inhibitor), has also been recently approved by the Food and Drugs Administration for management of PAH based on positive results from the phase III STELLAR study. Pulmonary artery denervation and balloon pulmonary angioplasty have emerged as viable alternatives in PH that are resistant to drug therapy. This article aims to summarise the key changes and recent advances in diagnosis and managing PH in general, with an emphasis on certain subgroups.