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Risk stratification has gained an increasing role in predicting outcomes and guiding the treatment of patients with pulmonary arterial hypertension (PAH). The most predictive prognostic factors are three noninvasive parameters (World Health Organization functional class, 6-min walk distance and natriuretic peptides) that are included in all currently validated risk stratification tools. However, suffering from limitations mainly related to reduced specificity of PAH severity, these variables may not always be adequate in isolation for guiding individualised treatment decisions. Moreover, with effective combination treatment regimens and emerging PAH therapies, markers associated with pulmonary vascular remodelling are expected to become of increasing relevance in guiding the treatment of patients with PAH. While reaching a low mortality risk, assessed with a validated risk tool, remains an important treatment goal, preliminary data suggest that invasive haemodynamics and cardiac imaging may add incremental value in guiding treatment decisions., Competing Interests: Conflict of interest: F. Dardi reports consultancy fees from Janssen and Chiesi Farmaceutici, and payment or honoraria for lectures, presentations, manuscript writing or educational events from Janssen. A. Boucly reports grants from Acceleron, Janssen and MSD, payment or honoraria for lectures, presentations, manuscript writing or educational events from Janssen, Merck, AOP Orphan, Ferrer and AstraZeneca, and support for attending meetings from Janssen, MSD, Ferrer and AOP Orphan. R. Benza reports consultancy fees from Cereno, Gossamer and United Therapeutics, and participation on a data safety monitoring board or advisory board with Altavant. R. Frantz reports grants from NHLBI and Gossamer Bio, royalties or licences from UpToDate, consultancy fees from Gossamer Bio, Insmed, Merck and Liquidia, participation on a data safety monitoring board or advisory board with Aerovate Pharmaceuticals, leadership role with Pulmonary Hypertension Association Scientific Leadership Council, and stock (or stock options) with Merck. V. Mercurio reports consultancy fees from MSD, payment or honoraria for lectures, presentations, manuscript writing or educational events from Janssen, and support for attending meetings from Janssen and MSD. H. Olschewski reports consultancy fees from Actelion, AstraZeneca, Bayer, Boehringer, Janssen, MSD, Chiesi, GSK, Inventiva, Ferrer, Menarini and Sanofi, payment or honoraria for lectures, presentations, manuscript writing or educational events from Springer, Medupdate and Mondial, support for attending meetings from Boehringer, Menarini and MSD, participation on a data safety monitoring board or advisory board with Aerovate, Bayer, Pfizer and IQVIA, receipt of equipment, materials, drugs, medical writing, gifts or other services from Boehringer, and the following financial (or non-financial) interests: Deputy Director, Ludwig Boltzmann Institute for Lung Vascular Research, Graz. G. Rådegran reports grants from Nordic Infucare, payment or honoraria for lectures, presentations, manuscript writing or educational events from Janssen, MSD, Nodic Infucare and Orpha Care/AOP Health, and participation on a data safety monitoring board or advisory board with Janssen, MSD and Orpha Care/AOP Health. L.J. Rubin reports consultancy fees from Gossamer and SoniVie, payment for expert testimony from Sandoz, and is a member of the Organizing and Founders Committees, WSPH. M.M. Hoeper reports consultancy fees from Acceleron, Actelion, AOP Health, Bayer, Ferrer, Gossamer Bio, Janssen, Keros and MSD, and payment or honoraria for lectures, presentations, manuscript writing or educational events from Actelion, AOP Health, Bayer, Ferrer, Janssen and MSD., (Copyright ©The authors 2024.)

Pulmonary arterial hypertension (PAH) is a rare dyspnoea-fatigue syndrome caused by a progressive increase in pulmonary vascular resistance and eventual right ventricular (RV) failure. In spite of extensive pulmonary vascular remodelling, lung function in PAH is generally well preserved, with hyperventilation and increased physiological dead space, but minimal changes in lung mechanics and only mild to moderate hypoxaemia and hypocapnia. Hypoxaemia is mainly caused by a low mixed venous oxygen tension from a decreased cardiac output. Hypocapnia is mainly caused by an increased chemosensitivity. Exercise limitation in PAH is cardiovascular rather than ventilatory or muscular. The extent of pulmonary vascular disease in PAH is defined by multipoint pulmonary vascular pressure-flow relationships with a correction for haematocrit. Pulsatile pulmonary vascular pressure-flow relationships in PAH allow for the assessment of RV hydraulic load. This analysis is possible either in the frequency domain or in the time domain. The RV in PAH adapts to increased afterload by an increased contractility to preserve its coupling to the pulmonary circulation. When this homeometric mechanism is exhausted, the RV dilates to preserve flow output by an additional heterometric mechanism. Right heart failure is then diagnosed by imaging of increased right heart dimensions and clinical systemic congestion signs and symptoms. The coupling of the RV to the pulmonary circulation is assessed by the ratio of end-systolic to arterial elastances, but these measurements are difficult. Simplified estimates of RV-pulmonary artery coupling can be obtained by magnetic resonance or echocardiographic imaging of ejection fraction., Competing Interests: Conflicts of interest: R. Naeije reports relationships including consultancies, speaker fees and membership of advisory boards with AOP Orphan Pharmaceuticals, Johnson & Johnson, Lung Biotechnology Corporation and United Therapeutics. Conflicts of interest: M.J. Richter has received funding from the German Research Foundation (DFG, 413584448) and from the Collaborative Research Center (SFB) 1213 – Pulmonary Hypertension and Cor Pulmonale (grant number SFB1213/1, project B08; German Research Foundation, Bonn, Germany). Conflicts of interest: L.J. Rubin reports consultancies with Actelion, SoniVie, Gossamer Bio and Bellerophon., (Copyright ©The authors 2022.)