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Background: Haemodynamic variables are prognostic factors in pulmonary arterial hypertension (PAH). However, right heart catheterisation (RHC) is not systematically recommended to assess the risk status during follow-up. This study aimed to assess the added value of haemodynamic variables in prevalent patients to predict the risk of death or lung transplantation according to their risk status assessed by the non-invasive four-strata model as recommended by the European guidelines., Methods: We evaluated incident patients with PAH enrolled in the French pulmonary hypertension registry between 2009 and 2020 who had a first follow-up RHC. Cox regression identified, in each follow-up risk status, haemodynamic variables significantly associated with transplant-free survival. Optimal thresholds were determined by time-dependent receiver operating characteristics. Several multivariable Cox regression models were performed to identify the haemodynamic variables improving the non-invasive risk stratification model., Results: We analysed 1240 incident patients reassessed within 1 year by RHC. None of the haemodynamic variables were significantly associated with transplant-free survival among low-risk (n=386) or high-risk (n=71) patients. Among patients at intermediate (intermediate-low, n=483 and intermediate-high, n=300) risk at first follow-up, multivariable models including either stroke volume index (SVI) or mixed venous oxygen saturation ( S vO 2 ) were the best. The prognostic performance of a refined six-strata risk stratification model including the non-invasive four-strata model and SVI >37 mL·m -2 and/or S vO 2 >65% for patients at intermediate risk (area under the curve (AUC) 0.81; c-index 0.74) was better than that of the four-strata model (AUC 0.79, p=0.009; c-index 0.72)., Conclusion: Cardiopulmonary haemodynamics may improve risk stratification at follow-up in patients at intermediate risk., Competing Interests: Conflict of interest: A. Boucly reports grants from Acceleron, Janssen and MSD, and lecture honoraria and travel support from Janssen, Merck, AOP Orphan and Ferrer, outside the submitted work. S. Turquier reports consulting fees from Ferrer, lecture honoraria from MSD, and travel support from Ferrer, MSD and Janssen, outside the submitted work. P. de Groote reports consulting fees from Boehringer Ingelheim, Servier, Bayer and MSD, and lecture honoraria from BMS, Novartis, Vifor and Pfizer, outside the submitted work. A. Chaouat reports travel support from MSD and Janssen, outside the submitted work. C. Cheron reports travel support from MSD, outside the submitted work. X. Jaïs reports grants from Acceleron, Janssen, MSD and Bayer HealthCare, and lecture honoraria from Janssen and MSD, outside the submitted work. F. Picard reports lecture honoraria from Bayer, Boehringer Ingelheim/Lilly, Novartis, MSD, AstraZeneca and Novo Nordisk, and travel support from Bayer and Novartis, outside the submitted work. G. Prévot reports lecture honoraria and travel support from Janssen and MSD, outside the submitted work. V. Cottin reports consulting fees from Ferrer/United Therapeutics and Liquidia, and lecture honoraria from Ferrer/United Therapeutics, outside the submitted work. D. Montani reports grants from Acceleron, Merck MSD and Janssen, consulting fees from Acceleron, Merck MSD, Janssen and Ferrer; and lecture honoraria from Bayer, Janssen, Boehringer, Chiesi, GSK, Ferrer and Merck MSD, outside the submitted work. M. Humbert reports grants from Acceleron, AOP Orphan, Janssen, Merck and Shou Ti, consulting fees from 35 Pharma, Aerovate, AOP Orphan, Bayer, Chiesi, Ferrer, Janssen, Keros, Merck, MorphogenIX, Shou Ti and United Therapeutics, lecture honoraria from Janssen and Merck, and advisory board participation with Acceleron, Altavant, Janssen, Merck and United Therapeutics, outside the submitted work. L. Savale reports lecture honoraria and travel support from MSD and Janssen and Janssen, outside the submitted work. O. Sitbon reports grants from Aerovate, AOP Orphan, Ferrer, Janssen and MSD, consulting fees from Altavant/Enzyvant, AOP Orphan, Ferrer, Gossamer Bio, Janssen, Liquidia, MSD and Respira Therapeutics, lecture honoraria from AOP Orphan, Janssen, Ferrer and MSD, and advisory board participation with Altavant/Enzyvant, Gossamer Bio and Janssen, outside the submitted work. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024.)

The prognostic importance of follow-up haemodynamics and the validity of multidimensional risk assessment are not well established for systemic sclerosis (SSc)-associated pulmonary arterial hypertension (PAH).We assessed incident SSc-PAH patients to determine the association between clinical and haemodynamic variables at baseline and first follow-up right heart catheterisation (RHC) with transplant-free survival. RHC variables included cardiac index, stroke volume index (SVI), pulmonary arterial compliance and pulmonary vascular resistance. Risk assessment was performed according to the number of low-risk criteria: functional class I or II, 6-min walking distance (6MWD) >440 m, right atrial pressure <8 mmHg and cardiac index ≥2.5 L·min -1 ·m -2 Transplant-free survival from diagnosis (n=513) was 87%, 55% and 35% at 1, 3 and 5 years, respectively. At baseline, 6MWD was the only independent predictor. A follow-up RHC was available for 353 patients (median interval 4.6 months, interquartile range 3.9-6.4 months). The 6MWD, functional class, cardiac index, SVI, pulmonary arterial compliance and pulmonary vascular resistance were independently associated with transplant-free survival at follow-up, with SVI performing better than other haemodynamic variables. 1-year outcomes were better with increasing number of low-risk criteria at baseline (area under the curve (AUC) 0.63, 95% CI 0.56-0.69) and at first follow-up (AUC 0.71, 95% CI 0.64-0.78).Follow-up haemodynamics and multidimensional risk assessment had greater prognostic significance than at baseline in SSc-PAH., Competing Interests: Conflict of interest: J. Weatherald reports grants from the European Respiratory Society and the Canadian Thoracic Society, during the conduct of the study; personal fees and non-financial support from Actelion Pharmaceuticals and Bayer, personal fees from Novartis, grants from Canadian Vascular Network, outside the submitted work. Conflict of interest: A. Boucly reports non-financial support from GSK, Bayer and MSD, and personal fees and non-financial support from Actelion, outside the submitted work. Conflict of interest: D. Launay reports grants from Pfizer, during the conduct of the study; and personal fees from Actelion, grants and personal fees from GSK, outside the submitted work. Conflict of interest: V. Cottin reports personal fees for consultancy, lecturing and travel to medical meetings from Actelion and Roche, personal fees for development of educational presentations, consultancy, lecturing and travel to medical meetings from Boehringer Ingelheim, personal fees for consultancy from Bayer and GSK, personal fees for adjudication committee work from Gilead, personal fees consultancy and travel to medical meetings from MSD, personal fees for consultancy and lecturing from Novartis and Sanofi, institutional grants from Boehringer Ingelheim and Roche, personal fees for chairing a DSMB from Promedior amd Celgene, and personal fees for consultancy and chairing a DSMB from Galapagos, outside the submitted work. Conflict of interest: G. Prévôt reports personal fees for consultancy, lecturing, development of educational presentations and travel to medical meetings from Actelion, Bayer, Boehringer Ingelheim, GSK and Roche, outside the submitted work. Conflict of interest: D. Bourlier reports personal fees from Novartis, outside the submitted work. Conflict of interest: C. Dauphin has nothing to disclose. Conflict of interest: A. Chaouat reports grants from Direction Générale de l'Offre de Soins (DGOS), during the conduct of the study, personal fees and non-financial support from Actelion Pharmaceuticals, Bayer and MSD, and non-financial support from GSK, outside the submitted work. Conflict of interest: L. Savale reports grants, personal fees and non-financial support from Actelion Pharmaceuticals, Bayer, GlaxoSmithKline and MSD and grants and personal fees from Pfizer, outside the submitted work. Conflict of interest: X. Jaïs reports personal fees and non-financial support from Actelion Pharmaceuticals, grants and personal fees from Bayer, and grants, personal fees and non-financial support from MSD and GSK, outside the submitted work. Conflict of interest: M. Jevnikar has nothing to disclose. Conflict of interest: J. Traclet reports personal fees from Actelion Pharmaceuticals, Boehringer Ingelheim and Roche, outside the submitted work. Conflict of interest: P. De Groote has nothing to disclose. Conflict of interest: G. Simonneau reports grants, personal fees and non-financial support from Actelion Pharmaceuticals, Bayer, GlaxoSmithKline and MSD and grants and personal fees from Pfizer, outside the submitted work. Conflict of interest: E. Hachulla has nothing to disclose. Conflict of interest: L. Mouthon has nothing to disclose. Conflict of interest: D. Montani reports grants and personal fees from Actelion and Bayer, and personal fees from BMS, GSK, MSD and Pfizer, outside the submitted work. Conflict of interest: M. Humbert has relationships with drug companies including Actelion, Bayer, GSK, Novartis and Pfizer. In addition to being investigator in trials involving these companies, relationships include consultancy service and membership of scientific advisory boards. Conflict of interest: O. Sitbon reports grants, personal fees and non-financial support from Actelion Pharmaceuticals, Bayer, GlaxoSmithKline and MSD, and grants and personal fees from Pfizer, outside the submitted work., (Copyright ©ERS 2018.)

Pre-capillary pulmonary hypertension (PH) in systemic sclerosis (SSc) is a heterogeneous condition with an overall bad prognosis. The objective of this study was to identify and characterize homogeneous phenotypes by a cluster analysis in SSc patients with PH. Patients were identified from two prospective cohorts from the US and France. Clinical, pulmonary function, high-resolution chest tomography, hemodynamic and survival data were extracted. We performed cluster analysis using the k-means method and compared survival between clusters using Cox regression analysis. Cluster analysis of 200 patients identified four homogenous phenotypes. Cluster C1 included patients with mild to moderate risk pulmonary arterial hypertension (PAH) with limited or no interstitial lung disease (ILD) and low DLCO with a 3-year survival of 81.5% (95% CI: 71.4-88.2). C2 had pre-capillary PH due to extensive ILD and worse 3-year survival compared to C1 (adjusted hazard ratio [HR] 3.14; 95% CI 1.66-5.94; p = 0.0004). C3 had severe PAH and a trend towards worse survival (HR 2.53; 95% CI 0.99-6.49; p = 0.052). Cluster C4 and C1 were similar with no difference in survival (HR 0.65; 95% CI 0.19-2.27, p = 0.507) but with a higher DLCO in C4. PH in SSc can be characterized into distinct clusters that differ in prognosis.

A resting mean pulmonary artery pressure (mPAP) of 21-24 mmHg is above the upper limit of normal but does not reach criteria for the diagnosis of pulmonary hypertension (PH). We sought to determine whether an mPAP of 21-24 mmHg is associated with an increased risk of developing an abnormal pulmonary vascular response during exercise.Consecutive patients (n=290) with resting mPAP <25 mmHg who underwent invasive exercise haemodynamics were analysed. Risk factors for pulmonary vascular disease or left heart disease were present in 63.4% and 43.8% of subjects. An abnormal pulmonary vascular response (or exercise PH) was defined by mPAP >30 mmHg and total pulmonary vascular resistance >3 WU at maximal exercise.Exercise PH occurred in 74 (86.0%) out of 86 versus 96 (47.1%) out of 204 in the mPAP of 21-24 mmHg and mPAP <21 mmHg groups, respectively (OR 6.9, 95% CI: 3.6-13.6; p<0.0001). Patients with mPAP of 21-24 mmHg had lower 6-min walk distance (p=0.002) and higher New York Heart Association functional class status (p=0.03). Decreasing levels of mPAP were associated with a lower prevalence of exercise PH, which occurred in 60.3%, 38.7% and 7.7% of patients with mPAP of 17-20, 13-16 and <13 mmHg, respectively.In an at-risk population, a resting mPAP between 21-24 mmHg is closely associated with exercise PH together with worse functional capacity., (Copyright ©ERS 2016.)

The previous definition of exercise pulmonary hypertension (PH) with a mean pulmonary artery pressure (mPAP) >30 mmHg was abandoned because healthy individuals can exceed this threshold at high cardiac output (CO). We hypothesised that incorporating assessment of the pressure-flow relationship using the mPAP/CO ratio, i.e. total pulmonary resistance (TPR), might enhance the accuracy of diagnosing an abnormal exercise haemodynamic response.Exercise haemodynamics were evaluated in 169 consecutive subjects with normal resting mPAP ≤20 mmHg. Subjects were classified into controls without heart or lung disease (n=68) versus patients with pulmonary vascular disease (PVD) (n=49) and left heart disease (LHD) (n=52).TPR and mPAP at maximal exercise produced diagnostic accuracy with area under the receiver operating curve of 0.99 and 0.95, respectively, for discriminating controls versus patients with PVD and LHD. The old criterion of mPAP >30 mmHg had sensitivity of 0.98 but specificity of 0.77. Combining maximal mPAP >30 mmHg and TPR >3 mmHg·min·L(-1) retained sensitivity at 0.93 but improved specificity to 1.0. The accuracy of the combined criteria was high across different age groups, sex, body mass index and diagnosis (PVD or LHD).Combining mPAP >30 mmHg and TPR >3 mmHg·min·L(-1) is superior to mPAP >30 mmHg alone for defining a pathological haemodynamic response of the pulmonary circulation during exercise., (Copyright ©ERS 2015.)

Pulmonary veno-occlusive disease (PVOD) is an uncommon form of pulmonary hypertension (PH) characterized by progressive obstruction of small pulmonary veins and a dismal prognosis. Limited case series have reported a possible association between different chemotherapeutic agents and PVOD. We evaluated the relationship between chemotherapeutic agents and PVOD. Cases of chemotherapy-induced PVOD from the French PH network and literature were reviewed. Consequences of chemotherapy exposure on the pulmonary vasculature and hemodynamics were investigated in three different animal models (mouse, rat, and rabbit). Thirty-seven cases of chemotherapy-associated PVOD were identified in the French PH network and systematic literature analysis. Exposure to alkylating agents was observed in 83.8% of cases, mostly represented by cyclophosphamide (43.2%). In three different animal models, cyclophosphamide was able to induce PH on the basis of hemodynamic, morphological, and biological parameters. In these models, histopathological assessment confirmed significant pulmonary venous involvement highly suggestive of PVOD. Together, clinical data and animal models demonstrated a plausible cause-effect relationship between alkylating agents and PVOD. Clinicians should be aware of this uncommon, but severe, pulmonary vascular complication of alkylating agents., (Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Introduction et objectifs: L’impact des traitements actuels de l’infection VIH (HAART) et des traitements spécifiques de l’hypertension artérielle pulmonaire (HTAP) sur la sévérité et le pronostic de l’HTAP associée à l’infection VIH (HTAP-VIH) est mal connu. Les objectifs de cette étude étaient de déterminer les facteurs pronostiques au cours l’HTAP-VIH à l’heure des traitements modernes. Matériels et méthodes: Analyse rétrospective des données de tous les patients consécutifs ayant une HTAP-VIH sans autre facteur de risque pour l’HTAP vus dans le Centre National de Référence de l’HTAP entre 10/2000 et 1/2008. Résultats: 77 patients (58 % hommes, âge moyen 41 ans, ancienneté de l’infection VIH 11,1 ans, toxicomanie 36 %). Lors du diagnostic d’HTAP, 81 % des patients recevaient HAART, 79 % avaient des CD4+ >200/mm3 et 49 % une charge virale indétectable. La classe NYHA était : II (22 %), III (69 %) et IV (9 %). La distance de marche médiane au test de marche de 6 minutes (DM6’) était de 375m, et les résistances vasculaires pulmonaires médianes de 689 d.s.cm−5. Tous les patients ont été traités par HAART (quel que soit leur statut VIH) et 50 ont reçu un traitement spécifique de l’HTAP, conduisant à une amélioration de la DM6’ et de l’hémodynamique. Chez les patients ayant reçu HAART sans traitement spécifique de l’HTAP, la DM6’ s’est améliorée mais l’hémodynamique ne s’est pas modifiée. La survie globale était 88 % à 1 an et de 72 % à 3 ans. En analyse multivariée, un index cardiaque > 2,8L/min/m2 et untaux de CD4+ > 200/mm3 étaient des facteurs pronostiques indépendants de survie. Conclusion: Chez les patients HTAP-VIH, un traitement antirétroviral seul (HAART) ne permet pas d’amélioration hémodynamique. Le pronostic des patients HTAP-VIH est essentiellement lié aux taux de CD4+ et à la fonction cardiaque. [Copyright &y& Elsevier]