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Review
. 2024 Oct 31;64(4):2401323.
doi: 10.1183/13993003.01323-2024. Print 2024 Oct.

Risk stratification and treatment goals in pulmonary arterial hypertension

Fabio Dardi  1 , Athénaïs Boucly  2 , Raymond Benza  3 , Robert Frantz  4 , Valentina Mercurio  5 , Horst Olschewski  6 , Göran Rådegran  7 , Lewis J Rubin  8 , Marius M Hoeper  9
Affiliations
Review

Risk stratification and treatment goals in pulmonary arterial hypertension

Fabio Dardi et al. Eur Respir J. .

Abstract

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.

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Conflict of interest statement

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.

Figures

None
Multidimensional strategy for risk stratification and treatment decisions in pulmonary arterial hypertension (PAH). ESC: European Society of Cardiology; ERS: European Respiratory Society; PVR: pulmonary vascular resistance; mPAP: mean pulmonary artery pressure; PAC: pulmonary arterial compliance; RAP: right atrial pressure; CI: cardiac index; SVI: stroke volume index; SvO2: mixed venous oxygen saturation; WHO-FC: World Health Organization functional class; 6MWD: 6-min walk distance; BNP: brain natriuretic peptide; NT-proBNP: N-terminal pro-BNP; cMRI: cardiac magnetic resonance imaging; RV: right ventricle; FAC: fractional area change; RVFWS: RV free wall strain; TAPSE: tricuspid annular plane systolic excursion; sPAP: systolic pulmonary artery pressure; IVC: inferior vena cava; TR: tricuspid regurgitation; RA: right atrium; PE: pericardial effusion; IVS: interventricular septum.
FIGURE 1
FIGURE 1
Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) risk tools. WHO: World Health Organization; eGFR: estimated glomerular filtration rate; BP: blood pressure; WHO-FC: WHO functional class; 6MWD: 6-min walk distance; BNP: brain natriuretic peptide; NT-proBNP: N-terminal pro-BNP; PE: pericardial effusion; DLCO: diffusing capacity of the lung for carbon monoxide; RAP: right atrial pressure; PVR: pulmonary vascular resistance; WU: Wood Units; CTD: connective tissue disease; PoPH: portopulmonary hypertension.
FIGURE 2
FIGURE 2
European Society of Cardiology (ESC)/European Respiratory Society (ERS) risk tools. RHC: right heart catheterisation; HF: heart failure; WHO-FC: World Health Organization functional class; 6MWD: 6-min walk distance; CPET: cardiopulmonary exercise testing; V′O2: oxygen uptake; V′E: minute ventilation; V′CO2: carbon dioxide production; BNP: brain natriuretic peptide; NT-proBNP: N-terminal pro-BNP; RA: right atrium; TAPSE: tricuspid annular plane systolic excursion; sPAP: systolic pulmonary artery pressure; PE: pericardial effusion; cMRI: cardiac magnetic resonance imaging; RVEF: right ventricular ejection fraction; SVI: stroke volume index; RVESVI: right ventricular end-systolic volume index; RAP: right atrial pressure; CI: cardiac index; SvO2: mixed venous oxygen saturation; SPAHR: Swedish Pulmonary Arterial Hypertension Registry; COMPERA: Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension; FPHR: French Pulmonary Hypertension Registry.
FIGURE 3
FIGURE 3
Comprehensive treatment goals in pulmonary arterial hypertension (PAH). RV: right ventricle; 6MWD: 6-min walk distance; WHO-FC: World Health Organization functional class; BNP: brain natriuretic peptide; NT-proBNP: N-terminal pro-BNP; RA: right atrium; TR: tricuspid regurgitation; TAPSE/sPAP: tricuspid annular plane systolic excursion/systolic pulmonary artery pressure ratio (estimated by echocardiography); RAP: right atrial pressure; CI: cardiac index; SVI: stroke volume index; SvO2: mixed venous oxygen saturation; PVR: pulmonary vascular resistance; WU: Wood Units; mPAP: mean pulmonary artery pressure; PAC: pulmonary arterial compliance; ESC: European Society of Cardiology; ERS: European Respiratory Society.
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