This review covers the full clinical picture of pulmonary arterial hypertension (PAH) — from its pathophysiology and diagnosis through to current and emerging treatments.
Understanding the Disease Pulmonary arterial hypertension is driven by progressive structural remodelling of the pulmonary arteries, creating a vicious cycle of vasoconstriction, inflammation, and uncontrolled cell growth that ultimately leads to right heart failure. Three key molecular pathways — endothelin-1, nitric oxide, and prostacyclin — are central to this process and remain the main targets of current therapies.
Diagnosis Diagnosis remains challenging, as early symptoms are non-specific. Echocardiography is the standard screening tool, but right heart catheterisation is the gold standard for confirmation. Risk stratification using multiparametric tools — combining walk distance, World Health Organisation (WHO) functional class, and biomarkers — is essential for guiding treatment decisions.
Treatment The days of monotherapy are over. Current guidelines recommend upfront combination therapy, with dual therapy (ERA + PDE5 inhibitor) for low-to-intermediate risk patients and triple therapy including intravenous prostacyclin for high-risk patients. Sotatercept represents a breakthrough, targeting the activin signalling pathway to potentially modify rather than merely manage the disease. For patients failing maximal therapy, lung transplantation remains an option.
Looking Ahead Several promising treatments are in the pipeline, including tyrosine kinase inhibitors and new agents targeting established pathways. Pulmonary arterial hypertension remains incurable, but the therapeutic landscape is advancing rapidly — and for the first time, disease modification rather than symptom management appears within reach.
Supplementary material to this article includes a list of current clinical trials on pulmonary arterial hypertension.
Read more at this link on the US Cardiology Review
Citation
Apoorva Gangavelli, Ronaldo C Fabiano, Mariam Riad, Gurleen Kaur, Devesh Rai, Mardi Gomberg-Maitland, The Pathophysiology, Mechanism, Diagnosis, and Management of Pulmonary Arterial Hypertension: A Comprehensive Literature Review, US Cardiology Review 2026;20:e01. https://doi.org/10.15420/usc.2025.05