Abstract
Pulmonary arterial hypertension (PAH) is the most serious complication of congenital heart disease (CHD), constituting a heterogeneous clinical entity classified within Group 1 of the Clinical Classification of Pulmonary Hypertension (PH). PAH associated with congenital heart disease (PAH-CHD) affects approximately 3-10% of patients with CHD and accounts for up to one-third of all PAH cases in the adult population. This review provides an educational and up-to-date perspective on the epidemiology, pathophysiology, diagnosis, and management of PAH-CHD. The updated haemodynamic definitions of the 2022 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines (mean pulmonary artery pressure (PAP) ≥20 mmHg) and the importance of contemporary registries (COMPERA-CHD, HOPE) in defining prognosis are discussed. The pathophysiology is explored in depth, from initial shear stress to the imbalance in the three canonical pathways that regulate pulmonary vascular functions (endothelin, nitric oxide, prostacyclin), the role of inflammation and metabolism, and the central importance of the TGF-β/BMPR2 genetic pathway, which has led to new disease-modifying therapies. Moreover, this review addresses the crucial clinical distinction between paediatric management, constrained by limited evidence, and adult management (ACHD), with a focus on the multisystem disorder of Eisenmenger syndrome (ES) and the challenges of care transition. The gold-standard diagnostic (right heart catheterisation), the 'treat and repair' strategy in the haemodynamic 'grey zone', and the complex risk stratification in this population are also analysed. Additionally, the evidence from key trials (BREATHE-5, MAESTRO, REPLACE) and the paradigm shift towards initial combination therapy (AMBITION) are reviewed from a therapeutic perspective. Finally, the most significant advance is highlighted: Sotatercept, a vascular remodelling reversal agent (STELLAR study), concluding with a review of chronic complications and prospects in the field.