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The right ventricle and its stress response is perhaps the most important arbiter of survival in patients with pulmonary hypertension of many causes. The physiology of the cardiopulmonary unit and definition of right heart failure proposed in the 2018 World Symposium on Pulmonary Hypertension have proven useful constructs in subsequent years. Here, we review updated knowledge of basic mechanisms that drive right ventricular function in health and disease, and which may be useful for therapeutic intervention in the future. We further contextualise new knowledge on assessment of right ventricular function with a focus on metrics readily available to clinicians and updated understanding of the roles of the right atrium and tricuspid regurgitation. Typical right ventricular phenotypes in relevant forms of pulmonary vascular disease are reviewed and recent studies of pharmacological interventions on chronic right ventricular failure are discussed. Finally, unanswered questions and future directions are proposed., Competing Interests: Conflict of interest: A.R. Hemnes reports grants from NIH/NHLBI, consultancy fees from Bayer, Gossamer Bio, Merck, Janssen, United Therapeutics and Tenax, participation on a data safety monitoring board or advisory board with NIH/NHLBI, leadership roles with Nashville Ballet and Pulmonary Vascular Research Institute, and stock (or stock options) with Tenax Therapeutics. D.S. Celermajer has no potential conflicts of interest to disclose. M. D'Alto reports consultancy fees and payment or honoraria for lectures, presentations, manuscript writing or educational events from Merck Sharp and Dhome, Dompé, AOP and Janssen, and support for attending meetings from Dompé, AOP and Janssen. F. Haddad reports grants from Johnson & Johnson, and consultancy fees from Merck. P.M. Hassoun reports grants from NIH/NHLBI (R01 R01HL114910), and participation on a data safety monitoring board or advisory board with MSD and ARIA-CV. K.W. Prins reports grants from NHLBI (R01 HL158795 and 162927) and Bayer (PHAB grant), and consultancy fees from Edwards. R. Naeije reports consultancy fees from AOP Orphan Pharma, Johnson & Johnson, United Therapeutics and Lung Biotechnology, payment or honoraria for lectures, presentations, manuscript writing or educational events from AOP Orphan Pharma, support for attending meetings from AOP Orphan Pharma, and participation on a data safety monitoring board or advisory board with Johnson & Johnson, AOP Orphan Pharma and United Therapeutics. A. Vonk Noordegraaf reports payment or honoraria for lectures, presentations, manuscript writing or educational events from Actelion and Johnson & Johnson., (Copyright ©The authors 2024.)

Background: According to current guidelines, the diagnosis of pulmonary hypertension (PH) relies on echocardiographic probability followed by right heart catheterisation (RHC). How echocardiography predicts PH recently redefined by mean pulmonary arterial pressure (mPAP) >20 mmHg instead of ≥25 mmHg and pulmonary vascular disease defined by pulmonary vascular resistance (PVR) ≥3 or >2 WU has not been established., Methods: A total of 278 patients referred for PH underwent comprehensive echocardiography followed by RHC. 15 patients (5.4%) were excluded because of insufficient quality echocardiography., Results: With PH defined by mPAP >20 mmHg, 23 patients had no PH, 146 had pre-capillary PH and 94 had post-capillary PH. At univariate analysis, maximum tricuspid regurgitation velocity (TRV) 2.9-3.4 m·s -1 , left ventricle (LV) eccentricity index >1.1, right ventricle outflow tract acceleration time (RVOT-AT) <105 ms or notching, RV/LV basal diameter >1 and pulmonary artery diameter predicted PH, whereas inferior vena cava diameter and right atrial area did not. At multivariable analysis, only TRV ≥2.9 m·s -1 independently predicted PH. Additional independent prediction of PVR ≥3 WU was offered by LV eccentricity index >1.1, and RVOT-AT <105 ms and/or notching, but with no improvement of optimal combination of specificity and sensitivity or positive prediction., Conclusions: Echocardiography as recommended in current guidelines can be used to assess the probability of redefined PH in a referral centre. However, the added value of indirect signs is modest and sufficient quality echocardiographic signals may not be recovered in some patients., Competing Interests: Conflict of interest: M. D'Alto reports participation on a monitoring board for Actelion-Janssen, MSD, Dompè and Ferrer, outside the submitted work. R. Naeije reports lecture honoraria from AOP Pharmaceuticals; participation on a monitoring board for Johnson & Johnson, Actelion, Lung Biotechnology Corp and United Therapeutics, outside the submitted work. All other authors have nothing to disclose., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

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.)

Cardiopulmonary exercise testing (CPET) is an important tool for assessing functional capacity and prognosis in pulmonary arterial hypertension (PAH). However, the associations of CPET parameters with the adaptation of right ventricular (RV) function to afterload remain incompletely understood.In this study, 37 patients with PAH (idiopathic in 31 cases) underwent single-beat pressure-volume loop measurements of RV end-systolic elastance (Ees), arterial elastance (Ea) and diastolic elastance (Eed). Pulmonary arterial stiffness was assessed by magnetic resonance imaging. The results were correlated to CPET variables. The predictive relevance of RV function parameters for clinically relevant ventilatory inefficiency, defined as minute ventilation/carbon dioxide production ( V' E / V' CO 2 ) slope >48, was evaluated using logistic regression analysis.The median (interquartile range) of the V' E / V' CO 2 slope was 42 (32-52) and the V' E / V' CO 2 nadir was 40 (31-44). The mean±sd of peak end-tidal carbon dioxide tension ( P ETCO 2 ) was 23±8 mmHg. Ea, Eed and parameters reflecting pulmonary arterial stiffness (capacitance and distensibility) correlated with the V' E / V' CO 2 slope, V' E / V' CO 2 nadir, P ETCO 2 and peak oxygen pulse. RV Ees and RV-arterial coupling as assessed by the Ees/Ea ratio showed no correlations with CPET parameters. Ea (univariate OR 7.28, 95% CI 1.20-44.04) and Eed (univariate OR 2.21, 95% CI 0.93-5.26) were significantly associated with ventilatory inefficiency (p<0.10).Our data suggest that impaired RV lusitropy and increased afterload are associated with ventilatory inefficiency in PAH., Competing Interests: Conflict of interest: K. Tello reports that this work was funded by the Excellence Cluster Cardio-Pulmonary System (ECCPS) and the Collaborative Research Center (SFB) 1213 - Pulmonary Hypertension and Cor Pulmonale, grant number SFB1213/1, project B08 (grant from German Research Foundation, Bonn, Germany) and editorial support was funded by University of Giessen, during the conduct of the study; and personal fees for lectures from Actelion and Bayer, outside the submitted work. Conflict of interest: A. Dalmer has nothing to disclose. Conflict of interest: R. Vanderpool has nothing to disclose. Conflict of interest: H.A. Ghofrani reports that this work was funded by the ECCPS and the Collaborative Research Center (SFB) 1213 - Pulmonary Hypertension and Cor Pulmonale, grant number SFB1213/1, project B08 (grant from German Research Foundation, Bonn, Germany) and editorial support was funded by University of Giessen, during the conduct of the study; and personal fees for consultancy and advisory board work from Bayer and Pfizer, personal fees for consultancy, lectures and advisory board work from Actelion and GSK, personal fees for consultancy from Merck, grants and personal fees for consultancy from Novartis, grants and personal fees for lectures from Bayer HealthCare and Encysive/Pfizer, grants from Aires, German Research Foundation, Excellence Cluster Cardiopulmonary Research and German Ministry for Education and Research, and personal fees for advisory board work from Takeda, outside the submitted work. Conflict of interest: R. Naeije reports grants and personal fees for consultancy and advisory board work from AOP Orphan Pharmaceuticals, Actelion, Bayer, Reata, Lung Biotechnology Corporation and United Therapeutics, outside the submitted work. Conflict of interest: F. Roller has nothing to disclose. Conflict of interest: W. Seeger reports that this work was funded by the ECCPS and the Collaborative Research Center (SFB) 1213 - Pulmonary Hypertension and Cor Pulmonale, grant number SFB1213/1, project B08 (grant from German Research Foundation, Bonn, Germany) and editorial support was funded by University of Giessen, during the conduct of the study; and personal fees for consultancy and lectures from Pfizer and Bayer Pharma AG, outside the submitted work. Conflict of interest: D. Dumitrescu reports personal fees and advisory board membership from Actelion and Novartis, and personal fees from Bayer Healthcare, GSK, MSD and Servier, outside the submitted work. Conflict of interest: N. Sommer reports personal fees from Actelion, outside the submitted work. Conflict of interest: A. Brunst has nothing to disclose. Conflict of interest: H. Gall reports that this work was funded by the ECCPS and the Collaborative Research Center (SFB) 1213 - Pulmonary Hypertension and Cor Pulmonale, grant number SFB1213/1, project B08 (grant from German Research Foundation, Bonn, Germany) and editorial support was funded by University of Giessen, during the conduct of the study; and personal fees from Actelion, AstraZeneca, Bayer, BMS, GSK, Janssen-Cilag, Lilly, MSD, Novartis, OMT, Pfizer and United Therapeutics, outside the submitted work. Conflict of interest: M.J. Richter reports that this work was funded by the ECCPS and the Collaborative Research Center (SFB) 1213 - Pulmonary Hypertension and Cor Pulmonale, grant number SFB1213/1, project B08 (grant from German Research Foundation, Bonn, Germany) and editorial support was funded by University of Giessen, during the conduct of the study; and grants from United Therapeutics, grants and personal fees for consultancy and lectures from Bayer, and personal fees for lectures from Actelion, Mundipharma, Roche and OMT, outside the submitted work., (Copyright ©ERS 2019.)