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Objective Pulmonary venoocclusive disease (PVOD) is an uncommon form of pulmonary hypertension (PH) characterized by obstruction of small pulmonary veins. Pulmonary venous involvement has been reported in pathologic assessment of patients with systemic sclerosis (SSc) presenting with precapillary PH. High-resolution computed tomography (HRCT) of the chest is a noninvasive diagnostic tool used to screen for PVOD. No HRCT data are available on SSc patients with precapillary PH. We undertook this study to evaluate the frequency and effect on prognosis of HRCT signs of PVOD in SSc patients with precapillary PH. Methods We reviewed chest HRCT data from 26 SSc patients with precapillary PH and 28 SSc patients without pulmonary arterial hypertension (PAH) or interstitial lung disease (ILD). Results The radiographic triad of HRCT signs of PVOD (lymph node enlargement [57.7% versus 3.6%], centrilobular ground-glass opacities [46.2% versus 10.7%], and septal lines [88.5% versus 7.1%]) was significantly more frequent in SSc patients with precapillary PH than in SSc patients without PAH or ILD (all P < 0.005). Indeed, 61.5% of SSc patients with precapillary PH had ≥2 of these signs. Cardiomegaly ( P < 0.0001), pulmonary artery enlargement ( P < 0.0001), and pericardial effusion ( P < 0.0005) were also significantly more frequent in SSc patients with precapillary PH. Pulmonary venous involvement was histologically confirmed in 2 patients with radiographic signs of PVOD. The presence of ≥2 radiographic signs of PVOD was associated with the occurrence of pulmonary edema after initiation of PAH-specific therapy (in 8 of 16 patients) and with more rapid progression from diagnosis of PH to death. Conclusion HRCT signs of PVOD are frequently observed in SSc patients with precapillary PH, correlated with histologic assessment, and were associated with a high risk of pulmonary edema. [ABSTRACT FROM AUTHOR]

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.)

Background: Pulmonary arterial hypertension (PAH) has been described in patients treated with proteasome inhibitors (PIs). Our objective was to evaluate the association between PIs and PAH., Methods: Characteristics of incident PAH cases previously treated with carfilzomib or bortezomib were analysed from the French pulmonary hypertension registry and the VIGIAPATH programme from 2004 to 2023, concurrently with a pharmacovigilance disproportionality analysis using the World Health Organization (WHO) global database (VigiBase) and a meta-analysis of randomised controlled trials., Results: 11 incident cases of PI-associated PAH were identified (six with carfilzomib and five with bortezomib) with a female:male ratio of 2.7:1, a median age of 61 years, and a median delay between PI first exposure and PAH of 6 months. Four patients died (two from right heart failure, one from respiratory distress and one from an unknown cause). At diagnosis, six were in New York Heart Association Functional Class III/IV with severe haemodynamic impairment (median mean pulmonary arterial pressure 39 mmHg, cardiac index 2.45 L·min -1 ·m -2 and pulmonary vascular resistance 7.2 WU). In the WHO pharmacovigilance database, 169 cases of PH associated with PI were reported since 2013 with significant signals of disproportionate reporting (SDR) for carfilzomib, regardless of the definition of cases or control group. However, SDR for bortezomib were inconsistent. The systematic review identified 17 clinical trials, and carfilzomib was associated with a significantly higher risk of dyspnoea, severe dyspnoea and PH compared with bortezomib., Conclusion: PIs may induce PAH in patients undergoing treatment, with carfilzomib emitting a stronger signal than bortezomib, and these patients should be monitored closely., Competing Interests: Conflict of interest: X. Jaïs reports grants from Acceleron, Janssen, MSD and Bayer HealthCare, lecture honoraria from Janssen and MSD, and travel support from MSD, outside the submitted work. L. Savale reports grants from Acceleron, AOP Orphan, Janssen, Merck and Shou Ti, consulting fees from Acceleron, Bayer, Janssen and Merck, and lecture honoraria from Janssen and Merck, outside the submitted work. M. Jevnikar reports consulting fees from Janssen, and travel support from MSD and Janssen, outside the submitted work. 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. G. Simonneau reports consulting fees and lecture honoraria from Actelion, Jansen, Bayer and MSD, travel support from Janssen, and advisory board participation with Acceleron, outside the submitted work. O. Sitbon reports grants from Acceleron (now MSD), AOP Orphan, Janssen (formerly Actelion) and MSD, consulting fees from Acceleron (now MSD), Altavant (now Enzyvant), AOP Orphan, Ferrer, Gossamer Bio, Janssen (formerly Actelion) and MSD, lecture honoraria from AOP Orphan, Janssen (formerly Actelion), Ferrer and MSD, and advisory board participation with Altavant (now Enzyvant), Gossamer Bio, Janssen (formerly Actelion) and MSD, outside the submitted work. M. Humbert reports grants from Acceleron, AOP Orphan, Janssen, Merck and Shou Ti, consulting fees from Acceleron, Aerovate, Altavant, AOP Orphan, Bayer, Chiesi, Ferrer, Janssen, Merck, Morphogen-IX, 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. D. Montani reports grants from Acceleron, Janssen and Merck MSD, 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. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Rationale: The relationship between the initial treatment strategy and survival in pulmonary arterial hypertension (PAH) remains uncertain. Objectives: To evaluate the long-term survival of patients with PAH categorized according to the initial treatment strategy. Methods: A retrospective analysis of incident patients with idiopathic, heritable, or anorexigen-induced PAH enrolled in the French Pulmonary Hypertension Registry (January 2006 to December 2018) was conducted. Survival was assessed according to the initial strategy: monotherapy, dual therapy, or triple-combination therapy (two oral medications and a parenteral prostacyclin). Measurements and Main Results: Among 1,611 enrolled patients, 984 were initiated on monotherapy, 551 were initiated on dual therapy, and 76 were initiated on triple therapy. The triple-combination group was younger and had fewer comorbidities but had a higher mortality risk. The survival rate was higher with the use of triple therapy (91% at 5 yr) as compared with dual therapy or monotherapy (both 61% at 5 yr) ( P  < 0.001). Propensity score matching of age, sex, and pulmonary vascular resistance also showed significant differences between triple therapy and dual therapy (10-yr survival, 85% vs. 65%). In high-risk patients ( n  = 243), the survival rate was higher with triple therapy than with monotherapy or dual therapy, whereas there was no difference between monotherapy and double therapy. In intermediate-risk patients ( n  = 1,134), survival improved with an increasing number of therapies. In multivariable Cox regression, triple therapy was independently associated with a lower risk of death (hazard ratio, 0.29; 95% confidence interval, 0.11-0.80; P  = 0.017). Among the 148 patients initiated on a parenteral prostacyclin, those on triple therapy had a higher survival rate than those on monotherapy or dual therapy. Conclusions: Initial triple-combination therapy that includes parenteral prostacyclin seems to be associated with a higher survival rate in PAH, particularly in the youngest high-risk patients.

Purpose: Common variable immunodeficiency (CVID) is known to cause infectious, inflammatory, and autoimmune manifestations. Pulmonary hypertension (PH) is an unusual complication of CVID with largely unknown characteristics and mechanisms., Methods: We report the clinical, functional, hemodynamics, radiologic and histologic characteristics, and outcomes of CVID-associated PH patients from the French PH Network., Results: Ten patients were identified. The median (range) age at CVID diagnosis was 36.5 (4-49) years and the median delay between CVID and PH diagnosis was 12 (0-30) years. CVID-associated PH affected predominantly women (female-to-male ratio 9:1). Most patients were New York Heart Association functional class III with a severe hemodynamic profile and frequent portal hypertension (n = 6). Pulmonary function tests were almost normal in 70% of patients and showed a mild restrictive syndrome in 30% of patients while the diffusing capacity for carbon monoxide was decreased in all but one patient. High-resolution computed tomography found enlarged mediastinal nodes, mild interstitial infiltration with reticulations and nodules. Two patients had a CIVD-interstitial lung disease, and one presented with bronchiectasis. Pathologic assessment of lymph nodes performed in 5 patients revealed the presence of granulomas (n = 5) and follicular lymphoid hyperplasia (n = 3). At last follow-up (median 24.5 months), 9 patients were alive, and one patient died of Hodgkin disease., Conclusion: PH is a possible complication of CVID whose pathophysiological mechanisms, while still unclear, would be due to the inflammatory nature of CVID. CVID-associated PH presents as precapillary PH with multiple possible causes, acting in concert in some patients: a portal hypertension, a pulmonary vascular remodeling, sometimes a pulmonary parenchymal involvement and occasionally an extrinsic compression by mediastinal lymphadenopathies, which would be consistent with its classification in group 5 of the current PH classification., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Pulmonary venoocclusive disease (PVOD) is an uncommon form of pulmonary hypertension (PH) predominantly characterized by pulmonary vein and capillary involvement. An association between chemotherapy, in particular mitomycin C (MMC), and PVOD has been reported., Research Question: What are the characteristics of MMC-induced PVOD, and what is the prognosis for patients with MMC-induced PVOD?, Study Design and Methods: We report the clinical, functional, radiologic, and hemodynamic characteristics at diagnosis and outcomes of patients with PVOD from the French PH Registry after exposure to MMC. The results are expressed as the median (minimum-maximum)., Results: From June 2011 to December 2018, 17 incident cases of MMC-induced PVOD were identified. At diagnosis, these patients had severe clinical and functional impairment, with 12 patients having a New York Heart Association (NYHA) functional class of III or IV and a 6-min walk distance of 220 (0-465) m. Right heart catheterization confirmed severe precapillary PH with a mean pulmonary artery pressure of 38 (30-52) mm Hg, a cardiac index of 2.2 (1.5-4) L/(min × m 2 ), and pulmonary vascular resistance of 8.3 (5.1-14.5) Wood units. The diffusing capacity of the lungs for carbon monoxide was markedly decreased at 31% (20%-51%) of the theoretical values associated with severe hypoxemia. MMC was withdrawn for all patients, and 14 patients received specific pulmonary arterial hypertension (PAH) therapies. Among these patients, mild but statistically insignificant improvements were observed in NYHA functional class (P = .10), 6-min walk distance (P = .09), and pulmonary vascular resistance (-4.7 Wood units; P = .052) at reassessment (median delay of 4.8 months). Three patients experienced pulmonary edema requiring the cessation or reduction of PAH treatment. The median overall survival was 20 months, and the 6-, 12-, and 24-month survival rates were 76%, 58%, and 18%, respectively., Interpretation: PVOD after MMC treatment is a rare but life-threatening complication associated with a poor prognosis despite MMC withdrawal and PAH-specific therapy., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Viral respiratory infections are the main causes of asthma exacerbation. The susceptibility of patients with asthma to develop an exacerbation when they present with severe pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is unknown. The objective of this study was to investigate the characteristics and outcomes of asthmatic patients with coronavirus disease 2019 (COVID-19) pneumonia who required hospitalisation during the spring 2020 outbreak in Paris, France., Methods: A prospective cohort follow-up was carried out from 15 March to 15 April 2020 in Bicêtre Hospital, University Paris-Saclay, France. All hospitalised patients with a SARS-CoV-2 infection who reported a history of asthma were included., Results: Among 768 hospitalised patients, 37 (4.8%) reported a history of asthma, which had been previously confirmed by a pulmonologist in 85% of cases. These asthmatic patients were mainly female (70%) and nonsmokers (85%), with a median age of 54 years (interquartile range (IQR) 42-67 years). None of them presented with an asthma exacerbation. 22 (59%) had major comorbidities and 31 (84%) had a body mass index ≥25 kg·m -2 . The most common comorbidities were obesity (36%), hypertension (27%) and diabetes (19%). All patients had a confirmed diagnosis of COVID-19 pneumonia on computed tomography of the chest. Eosinopenia was a typical biological feature with a median count of 0 cells·mm -3 (IQR 0-0 cells·mm -3 ). 11 patients (30%) were admitted into the intensive care unit, with three deaths (8.1%) occurring in the context of comorbidities., Conclusion: Asthma patients were not overrepresented among those with severe pneumonia due to SARS-CoV-2 infection who required hospitalisation. The worst outcomes were observed mainly in patients with major comorbidities., Competing Interests: Conflict of interest: A. Beurnier has nothing to disclose. Conflict of interest: E-M. Jutant has nothing to disclose. Conflict of interest: M. Jevnikar has nothing to disclose. Conflict of interest: A. Boucly has nothing to disclose. Conflict of interest: J. Pichon has nothing to disclose. Conflict of interest: M. Preda has nothing to disclose. Conflict of interest: M. Frank has nothing to disclose. Conflict of interest: J. Laurent has nothing to disclose. Conflict of interest: C. Richard has nothing to disclose. Conflict of interest: X. Monnet has nothing to disclose. Conflict of interest: J. Duranteau has nothing to disclose. Conflict of interest: A. Harrois has nothing to disclose. Conflict of interest: M-C. Chaumais has nothing to disclose. Conflict of interest: M-F. Bellin has nothing to disclose. Conflict of interest: N. Noël has nothing to disclose. Conflict of interest: S. Bulifon has nothing to disclose. Conflict of interest: X. Jaïs has nothing to disclose. Conflict of interest: F. Parent has nothing to disclose. Conflict of interest: A. Seferian has nothing to disclose. Conflict of interest: L. Savale has nothing to disclose. Conflict of interest: O. Sitbon reports grants, personal fees and non-financial support from Actelion Pharmaceuticals and MSD, personal fees from Acceleron Pharmaceuticals, Gossamer Bio and Ferrer, grants and personal fees from Bayer, grants from GlaxoSmithKline, outside the submitted work. Conflict of interest: D. Montani has nothing to disclose. Conflict of interest: M. Humbert reports grants, personal fees and non-financial support from GlaxoSmithKline, personal fees from AstraZeneca, Novartis, Roche, Sanofi and Teva, outside the submitted work., (Copyright ©ERS 2020.)

Rationale: Pulmonary hypertension (PH) associated with neurofibromatosis type 1 (NF1) is a rare and largely unknown complication of NF1. Objectives: To describe characteristics and outcomes of PH-NF1. Methods: We reported the clinical, functional, radiologic, histologic, and hemodynamic characteristics, response to pulmonary arterial hypertension (PAH)-approved drugs, and transplant-free survival of patients with PH-NF1 from the French PH registry. Measurements and Main Results: We identified 49 PH-NF1 cases, characterized by a female/male ratio of 3.9 and a median (minimum-maximum) age at diagnosis of 62 (18-82) years. At diagnosis, 92% were in New York Heart Association functional class III or IV. The 6-minute-walk distance was 211 (0-460) m. Pulmonary function tests showed low Dl CO (30% [12-79%]) and severe hypoxemia (Pa O 2 56 [38-99] mm Hg). Right heart catheterization showed severe precapillary PH with a mean pulmonary artery pressure of 45 (10) mm Hg and a pulmonary vascular resistance of 10.7 (4.2) Wood units. High-resolution computed tomography images revealed cysts (76%), ground-glass opacities (73%), emphysema (49%), and reticulations (39%). Forty patients received PAH-approved drugs with a significant improvement in functional class and hemodynamic parameters. Transplant-free survival at 1, 3, and 5 years was 87%, 54%, and 42%, respectively, and four patients were transplanted. Pathologic assessment showed nonspecific interstitial pneumonia and major pulmonary vascular remodeling. Conclusions: PH-NF1 is characterized by a female predominance, a low Dl CO , and severe functional and hemodynamic impairment. Despite a potential benefit of PAH treatment, prognosis remains poor, and double-lung transplantation is an option for eligible patients.

Background & Aims: Long-term outcomes in portopulmonary hypertension (PoPH) are poorly studied in the current era of pulmonary hypertension management. We analysed the effect of pulmonary arterial hypertension (PAH)-targeted therapies, survival and predictors of death in a large contemporary cohort of patients with PoPH., Methods: Data from patients with PoPH consecutively enrolled in the French Pulmonary Hypertension Registry between 2007 and 2017 were collected. The effect of initial treatment strategies on functional class, exercise capacity and cardiopulmonary haemodynamics were analysed. Survival and its association with PAH- and hepatic-related characteristics were also examined., Results: Six hundred and thirty-seven patients (mean age 55 ± 10 years; 58% male) were included. Fifty-seven percent had mild cirrhosis, i.e. Child-Pugh stage A. The median model for end-stage liver disease (MELD) score was 11 (IQR 9-15). Most patients (n = 474; 74%) were initiated on monotherapy, either with a phosphodiesterase-5 inhibitor (n = 336) or with an endothelin-receptor antagonist (n = 128); 95 (15%) were initiated on double oral combination therapy and 5 (1%) on triple therapy. After a median treatment time of 4.5 months, there were significant improvements in functional class (p <0.001), 6-minute walk distance (6MWD) (p <0.0001) and pulmonary vascular resistance (p <0.0001). Overall survival rates were 84%, 69% and 51% at 1, 3 and 5 years, respectively. Baseline 6MWD, sex, age and MELD score or Child-Pugh stage were identified as independent prognostic factors. Survival from PoPH diagnosis was significantly better in the subgroup of patients who underwent liver transplantation (92%, 83% and 81% at 1, 3 and 5 years, respectively)., Conclusion: Survival of patients with PoPH is strongly associated with the severity of liver disease. Patients who underwent liver transplantation had the best long-term outcomes., Lay Summary: Portopulmonary hypertension is defined by the presence of pulmonary arterial hypertension in the context of chronic liver disease and is characterized by progressive shortness of breath and exercise limitation. The presence of severe pulmonary arterial hypertension in liver transplant candidates represents a contraindication for such a surgery; however, treatments targeting pulmonary arterial hypertension are efficacious, allowing for safe transplantation and conferring good survival outcomes in those who undergo liver transplantation., Competing Interests: Conflict of interest LS reports grants and personal fees from Actelion, grants and personal fees from MSD, grants and personal fees from GSK, outside the submitted work. MH reports grants and personal fees from Actelion, grants and personal fees from Bayer, grants from GSK, grants and personal fees from MSD, personal fees from Ferrer, personal fees from Acceleron, outside the submitted work. GS reports grants and personal fees from Actelion, grants and personal fees from Bayer, grants from GSK, grants and personal fees from MSD, outside the submitted work. OS reports grants and personal fees from Actelion, grants and personal fees from Bayer, grants from GSK, grants and personal fees from MSD, personal fees from Ferrer, personal fees from Gossamer Bio, personal fees from Acceleron, outside the submitted work. DM reports grants and personal fees from Actelion, grants and personal fees from Bayer, grants and personal fees from GSK, personal fees from MSD, outside the submitted work. PDG reports personal fees from Actelion, MSD, Bayer, outside the submitted work. XJ reports grants and personal fees from Actelion, grants and personal fees from Bayer, grants and personal fees from GSK, personal fees from Merck, outside the submitted work. DS reports personal fees from Intercept, personal fees from Biotest, personal fees from Abbvie , personal fees from Gilead sciences, outside the submitted work. PDG reports personal fees and non-financial support from ACTELION, personal fees and non-financial support from BAYER - MSD, personal fees and non-financial support from NOVARTIS, personal fees and non-financial support from VIFOR, personal fees from ABBOTT, personal fees and non-financial support from SERVIER, personal fees from ASTRA-ZENECA, non-financial support from AMGEN, outside the submitted work. NL reports personal fees and other from MSD, personal fees from AMICUS THERAPEUTICS, other from BMS, personal fees from NOVARTIS, personal fees from ASTRA-ZENECA, personal fees from BAYER, personal fees from AKCEA, outside the submitted work. MG, NE, MF, MJ, SR, DHL, CT, CC, GP, AC, PM, EAM, BD, RT, CB, HB, ACS, MR, NF, SP, DB, PM, VC, EB, AC, FD, CF, PH, JCDV have nothing to disclose. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Introduction: TBX4 mutation causes small patella syndrome (SPS) and/or pulmonary arterial hypertension (PAH). The characteristics and outcomes of PAH associated with TBX4 mutations are largely unknown., Methods: We report the clinical, functional, radiologic, histologic and haemodynamic characteristics and outcomes of heritable PAH patients carrying a TBX4 mutation from the French pulmonary hypertension (PH) network., Results: 20 patients were identified in 17 families. They were characterised by a median age at diagnosis of 29 years (0-76 years) and a female to male ratio of three. Most of the patients (70%) were in New York Heart Association (NYHA) functional class III or IV with a severe haemodynamic impairment (median pulmonary vascular resistance (PVR) of 13.6 (6.2-41.8) Wood units). Skeletal signs of SPS were present in 80% of cases. Half of the patients had mild restrictive or obstructive limitation and diffusing capacity of the lung for carbon monoxide ( D LCO ) was decreased in all patients. High-resolution computed tomography (HRCT) showed bronchial abnormalities, peri-bronchial cysts, mosaic distribution and mediastinal lymphadenopathies. PAH therapy was associated with significant clinical improvement. At follow-up (median 76 months), two patients had died and two had undergone lung transplantation. One-year, three-year and five-year event-free survival rates were 100%, 94% and 83%, respectively. Histologic examination of explanted lungs revealed alveolar growth abnormalities, major pulmonary vascular remodelling similar to that observed in idiopathic pulmonary arterial hypertension (IPAH) and accumulation of cholesterol crystals within the lung parenchyma., Conclusion: PAH due to TBX4 mutations may occur with or without skeletal abnormalities across a broad age range from birth to late adulthood. PAH is usually severe and associated with bronchial and parenchymal abnormalities., Competing Interests: Conflict of interest: P. Thoré has nothing to disclose. Conflict of interest: B. Girerd has nothing to disclose. Conflict of interest: X. Jaïs reports grants and personal fees from Actelion and MSD, and grants from Bayer, outside the submitted work. Conflict of interest: L. Savale reports grants, personal fees and non-financial support from Actelion, grants and personal fees from MSD, and non-financial support from GSK, outside the submitted work. Conflict of interest: M-R. Ghigna has nothing to disclose. Conflict of interest: M. Eyries has nothing to disclose. Conflict of interest: M. Levy has nothing to disclose. Conflict of interest: C. Ovaert has nothing to disclose. Conflict of interest: A. Servettaz has nothing to disclose. Conflict of interest: A. Guillaumot has nothing to disclose. Conflict of interest: C. Dauphin has nothing to disclose. Conflict of interest: C. Chabanne has nothing to disclose. Conflict of interest: E. Boiffard has nothing to disclose. Conflict of interest: V. Cottin reports personal fees for advisory board work and non-financial (travel) support from Actelion, grants and personal fees for advisory board work, lectures and steering committee work, as well as non-financial (travel) support from Boehringer Ingelheim, personal fees for advisory board work and data monitoring committee work from Bayer/MSD and Galapagos, personal fees for advisory board work from Gilead and Novartis, personal fees for advisory board work, lectures and steering committee work, as well as non-financial (travel) support from Roche SAS, personal fees for lectures and non-financial (travel) support from Sanofi, personal fees for steering committee work and data monitoring committee work from Promedior, and personal fees for data monitoring committee work from Celgene and Galecto, outside the submitted work. Conflict of interest: F.Perros has nothing to disclose. Conflict of interest: G. Simonneau reports grants, personal fees and non-financial support from Actelion, Bayer, GSK and Merck, outside the submitted work. Conflict of interest: O. Sitbon reports grants, personal fees and non-financial support from Actelion Pharmaceuticals, Bayer HealthCare and MSD, personal fees from Acceleron Pharmaceuticals, Ferrer, Gossamer Bio and United Therapeutics, and grants from GlaxoSmithKline, outside the submitted work. Conflict of interest: F. Soubrier has nothing to disclose. Conflict of interest: D. Bonnet reports personal fees for advisory board work and steering committee work from Actelion Pharmaceuticals, Eli Lilly and Novartis, outside the submitted work. Conflict of interest: M. Remy-Jardin has nothing to disclose. Conflict of interest: A. Chaouat has nothing to disclose. Conflict of interest: M. Humbert reports personal fees from Acceleron, Actelion, MSD and United Therapeutics, and grants and personal fees from Bayer and GSK, outside the submitted work. Conflict of interest: D. Montani reports grants and personal fees from Actelion and Bayer, and personal fees from GSK, Pfizer, MSD and Chiesi, outside the submitted work., (Copyright ©ERS 2020.)

Aims: To evaluate safety and efficacy of balloon pulmonary angioplasty (BPA) in a large cohort of patients with chronic thromboembolic pulmonary hypertension (CTEPH)., Methods: From 2014 to 2017, 184 inoperable CTEPH patients underwent 1006 BPA sessions. Safety and efficacy during the first 21 months (initial period) were compared with those of the last 21 months (recent period). A total of 154 patients had a full evaluation after a median duration of 6.1 months., Results: Overall, there was a significant improvement in New York Heart Association functional class, 6-min walk distance (mean change +45 m), and a significant decrease in mean pulmonary artery pressure (PAP) and in pulmonary vascular resistance (PVR) by 26% and 43%, respectively. The percentage decreases of mean PAP and PVR were 22% and 37% in the initial period versus 30% and 49% in the recent period, respectively (p<0.05). The main complications included lung injury, which occurred in 9.1% of 1006 sessions (13.3% in the initial period versus 5.9% in the recent period; p<0.001). Per-patient multivariate analysis revealed that baseline mean PAP and the period during which BPA procedure was performed (recent versus initial period) were the strongest factors related to the occurrence of lung injury. 3-year survival was 95.1%., Conclusion: This study confirms that a refined BPA strategy improves short-term symptoms, exercise capacity and haemodynamics in inoperable CTEPH patients with an acceptable risk-benefit ratio. Safety and efficacy improve over time, underscoring the unavoidable learning curve for this procedure., Competing Interests: Conflict of interest: P. Brenot has nothing to disclose. Conflict of interest: X. Jaïs reports grants and personal fees from Actelion, GSK, Bayer and MSD, outside the submitted work. Conflict of interest: Y. Taniguchi has nothing to disclose. Conflict of interest: C. Garcia Alonso has nothing to disclose. Conflict of interest: B. Gerardin has nothing to disclose. Conflict of interest: S. Mussot has nothing to disclose. Conflict of interest: O. Mercier has nothing to disclose. Conflict of interest: D. Fabre has nothing to disclose. Conflict of interest: F. Parent has nothing to disclose. Conflict of interest: M. Jevnikar has nothing to disclose. Conflict of interest: D. Montani reports grants and personal fees from Actelion and Bayer, personal fees from GSK, Pfizer, BMS and MSD, outside the submitted work. Conflict of interest: L. Savale reports grants, personal fees and non-financial support from Actelion and GSK, personal fees and non-financial support from MSD, outside the submitted work. Conflict of interest: O. Sitbon reports grants, personal fees and non-financial support from Actelion Pharmaceuticals and GlaxoSmithKline, grants and personal fees from Bayer HealthCare, grants and non-financial support from Merck, personal fees from Arena Pharmaceuticals, outside the submitted work. Conflict of interest: E. Fadel has nothing to disclose. Conflict of interest: M. Humbert reports grants and personal fees from Actelion, Bayer, GSK and from MSD, personal fees from Johnson & Johnson and United Therapeutics, outside the submitted work. Conflict of interest: G. Simonneau reports grants, personal fees and non-financial support from Actelion Pharmaceuticals, Bayer Healthcare, Merck and GlaxoSmithKline, outside the submitted work., (Copyright ©ERS 2019.)

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.)

Background: An obesity paradox, wherein patients who are obese have lower mortality, has been described in cardiopulmonary diseases, including pulmonary arterial hypertension (PAH). Our objective was to determine whether obesity and BMI are associated with mortality in patients with PAH., Methods: We assessed incident patients with idiopathic, drug-induced, and heritable PAH from the French Pulmonary Hypertension Network registry. Cox regression and Kaplan-Meier analysis were used to assess the association between BMI and obesity with all-cause mortality., Results: Of 1,255 patients included, 30% were obese. A higher proportion of women (65.1% vs 53.4%, P < .01), drug-induced PAH (28.9% vs 9.2%, P < .01), systemic hypertension, diabetes, and hypothyroidism were present in the obese group. More obese patients were in New York Heart Association class III (66.4% vs 57.1%), fewer were class IV (11.8% vs 16.9%, P < .01), and 6-min walk distance was lower (276 ± 121 vs 324 ± 146, P < .01). Right atrial pressure, pulmonary wedge pressure, and cardiac index were higher, whereas pulmonary vascular resistance was lower in patients who were obese. Neither BMI (hazard ratio [HR], 0.99; 95% CI, 0.97-1.01; P = .41) nor obesity (HR, 1.0; 95% CI, 0.99-1.01; P = .46) were associated with mortality in multivariable analyses. There was a significant interaction between age and obesity such that mortality increased among patients < 65 years of age who were morbidly obese (HR, 3.01; 95% CI, 1.56-5.79; P = .001)., Conclusions: Obesity was not associated with mortality in the overall population, but there was an age-obesity interaction with increased mortality among young patients who were morbidly obese. These results have implications for active weight management in younger patients who are morbidly obese who are otherwise candidates for lung transplantation., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Hemodynamic variables such as cardiac index and right atrial pressure have consistently been associated with survival in pulmonary arterial hypertension (PAH) at the time of diagnosis. Recent studies have suggested that pulmonary arterial compliance may also predict prognosis in PAH. The prognostic importance of hemodynamic values achieved after treatment initiation is less well established., Methods: Our objective was to evaluate the prognostic importance of clinical and hemodynamic variables during follow-up, including pulmonary arterial compliance, after initial management in PAH. We evaluated incident patients with idiopathic, drug- and toxin-induced, or heritable PAH enrolled in the French pulmonary hypertension registry between 2006 and 2016 who had a follow-up right-sided heart catheterization (RHC). The primary outcome was death or lung transplantation. We used stepwise Cox regression and the Kaplan-Meier method to assess variables obtained at baseline and at first follow-up RHC., Results: Of 981 patients, a primary outcome occurred in 331 patients (33.7%) over a median follow-up duration of 2.8 years (interquartile range, 1.1-4.6 years). In a multivariable model considering only baseline variables, no hemodynamic variables independently predicted prognosis. Median time to first follow-up RHC was 4.6 months (interquartile range, 3.7-7.8 months). At first follow-up RHC (n=763), New York Heart Association functional class, 6-minute walk distance, stroke volume index (SVI), and right atrial pressure were independently associated with death or lung transplantation, adjusted for age, sex, and type of PAH. Pulmonary arterial compliance did not independently predict outcomes at baseline or during follow-up. The adjusted hazard ratio for SVI was 1.28 (95% confidence interval, 1.11-1.49; P <0.01) per 10-mL/m 2 decrease and for right atrial pressure was 1.05 (95% confidence interval, 1.02-1.09; P <0.01) per 1-mm Hg increase. Among patients who had 2 (n=355) or 3 (n=193) low-risk prognostic features at follow-up, including a cardiac index ≥2.5 L·min -1 ·m -2 , 6-minute walk distance >440 m, and New York Heart Association class I or II functional class, lower SVI was still associated with higher rates of death or lung transplantation ( P <0.01)., Conclusions: SVI and right atrial pressure were the hemodynamic variables that were independently associated with death or lung transplantation at first follow-up RHC after initial PAH treatment. These findings suggest that the SVI could be a more appropriate treatment target than cardiac index in PAH., (© 2017 American Heart Association, Inc.)

Studies reporting the effects of modern strategies with pulmonary arterial hypertension (PAH)-targeted therapies in sarcoidosis-associated pulmonary hypertension (S-APH) are limited.Clinical and haemodynamic data from newly diagnosed patients with severe S-APH (mean pulmonary artery pressure (mPAP) >35 mmHg or mPAP 25-35 mmHg with cardiac index <2.5 L·min -1 ·m -2 ) were collected from the French Pulmonary Hypertension Registry between 2004 and 2015.Data from 126 patients with severe S-APH were analysed (mean±sd age 57.5±11.6 years, 74% radiological stage IV). 97 patients (77%) received PAH-targeted therapy and immunosuppressive therapy was initiated or escalated in 33 patients at the time of pulmonary hypertension diagnosis. Four months after PAH-targeted therapy initiation, mean±sd pulmonary vascular resistance decreased from 9.7±4.4 to 6.9±3.0 Wood units (p<0.001), without significant improvement in exercise capacity. Among the 11 patients treated only with immunosuppressive therapy, a haemodynamic improvement was observed in four patients, including two with compressive lymph nodes. After a median follow-up of 28 months, 39 patients needed PAH-targeted therapy escalation, nine underwent lung transplantation and 42 had died. Survival at 1, 3 and 5 years was 93%, 74% and 55%, respectively.PAH-targeted therapy improved short-term pulmonary haemodynamics in severe S-APH without change in exercise capacity. Immunosuppressive therapy improved haemodynamics in selected patients. Pulmonary hypertension in sarcoidosis remains associated with a poor prognosis., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2017.)

Genetic causes of pulmonary arterial hypertension (PAH) and pulmonary veno-occlusive disease (PVOD) have been identified, leading to a growing need for genetic counselling.Between 2003 and 2014, genetic counselling was offered to 529 PAH and 100 PVOD patients at the French Referral Centre for Pulmonary Hypertension.Mutations in PAH-predisposing genes were identified in 72 patients presenting as sporadic PAH (17% of cases; 62 mutations in BMPR2, nine in ACVRL1 (ALK1) and one in ENG) and in 94 patients with a PAH family history (89% of cases; 89 mutations in BMPR2, three in ACVRL1 (ALK1) and two in KCNK3). Bi-allelic mutations in EIF2AK4 were identified in all patients with a family history of PVOD (n=19) and in seven patients (8.6%) presenting as sporadic PVOD. Pre-symptomatic genetic diagnosis was offered to 272 relatives of heritable PAH patients, identifying mutations in 36.4% of them. A screening programme is now offered to asymptomatic mutation carriers to detect PAH in an early phase and to identify predictors of outcomes in asymptomatic BMPR2 mutation carriers. BMPR2 screening allowed us to offer pre-implantation diagnosis to two couples with a BMPR2 mutation.Genetic counselling can be implemented in pulmonary hypertension centres., (Copyright ©ERS 2016.)

Isolated cases of pulmonary arterial hypertension (PAH) in patients treated with interferon (IFN) α or β have been reported in the literature. The aim of this study was to describe all consecutive cases of PAH patients with a history of IFN exposure identified in the French reference centre for severe pulmonary hypertension between 1998 and 2012. A total of 53 patients with PAH and a history of IFN therapy were identified. 48 patients had been treated with IFNα for chronic hepatitis C. Most of them had portal hypertension (85%) and 56% had HIV co-infection. Five additional patients had been treated with IFNβ for multiple sclerosis. The diagnosis of PAH was made within 3 years after IFN therapy in 66% of patients. Repeated haemodynamic assessment was available in 13 out of 16 patients exposed to IFN after the diagnosis of PAH. Increased pulmonary vascular resistance >20% was observed in 11 out of 13 cases (median 43% increase; IQR 32-67%). In five of these patients, IFN withdrawal resulted in spontaneous haemodynamic improvement. This retrospective analysis suggests that IFN therapy may trigger PAH. However, most of these patients had other risk factors for PAH. A prospective case-control study is necessary to definitively establish a link between IFN exposure and PAH., (©ERS 2014.)

Rationale: Activin A receptor type II-like kinase-1 (ACVRL1, also known as ALK1) mutation is a cause of hereditary hemorrhagic telangiectasia (HHT) and/or heritable pulmonary arterial hypertension (PAH)., Objectives: To describe the characteristics of patients with PAH carrying an ACVRL1 mutation., Methods: We reviewed clinical, functional, and hemodynamic characteristics of 32 patients with PAH carrying an ACVRL1 mutation, corresponding to 9 patients from the French PAH Network and 23 from literature analysis. These cases were compared with 370 patients from the French PAH Network (93 with a bone morphogenetic protein receptor type 2 [BMPR2] mutation and 277 considered as idiopathic cases without identified mutation). Distribution of mutations in the ACVRL1 gene in patients with PAH was compared with the HHT Mutation Database., Measurements and Main Results: At diagnosis, ACVRL1 mutation carriers were significantly younger (21.8 +/- 16.7 yr) than BMPR2 mutation carriers and noncarriers (35.7 +/- 14.9 and 47.6 +/- 16.3 yr, respectively; P < 0.0001). In seven of the nine patients from the French PAH Network, PAH diagnosis preceded manifestations of HHT. ACVRL1 mutation carriers had better hemodynamic status at diagnosis, but none responded to acute vasodilator challenge and they had shorter survival when compared with other patients with PAH despite similar use of specific therapies. ACVRL1 mutations in exon 10 were more frequently observed in patients with PAH, as compared with what was observed in the HHT Mutation Database (33.3 vs. 5%; P < 0.0001)., Conclusions: ACVRL1 mutation carriers were characterized by a younger age at PAH diagnosis. Despite less severe initial hemodynamics and similar management, these patients had worse prognosis compared with other patients with PAH, suggesting more rapid disease progression.

Objectives: To examine baseline characteristics and outcome, and to determine variables affecting survival in patients with pulmonary arterial hypertension (PAH) associated with HIV infection (PAH-HIV) in the modern era of highly-active antiretroviral therapy (HAART) and specific PAH therapy., Design: Retrospective review of data from PAH-HIV patients without other associated risk factors for PAH, and comparison with previous series., Methods: Data were reviewed for 77 consecutive patients treated at the French Reference Centre for Pulmonary Hypertension between October 2000 and January 2008. Results were expressed as median [1st-3rd quartile] values., Results: At diagnosis of PAH, 81% patients were on HAART, 79% had a CD4+ count more than 200 cells/microl and 49% had undetectable HIV load. New York Heart Association functional class assessment was II (22%), III (69%), and IV (9%). Six-minute walk distance (6MWD) was 375 [288-421] m, and pulmonary vascular resistance was 689 [524-852] dyn s/cm(5). All patients received HAART irrespective of HIV disease stage. Specific PAH therapy was started in 50 patients and led to improvements in 6MWD and haemodynamic parameters. In patients who did not receive specific PAH therapy, 6MWD improved but haemodynamics did not change. Overall survival rate was 88% at 1 year and 72% at 3 years. On multivariate analysis, cardiac index more than 2.8 l/min per m(2) and CD4+ lymphocyte count more than 200 cells/microl were independent predictors of survival., Conclusion: In patients with PAH-HIV, HAART seems unable to improve haemodynamic parameters. Prognosis in PAH-HIV is mainly related to CD4+ lymphocyte count and cardiac function.

In France, pulmonary arterial hypertension associated with various diseases (connective-tissue diseases, congenital heart diseases, portal hypertension, HIV infection, consumption of anorectic agents) account for approximately 50% of cases of pulmonary arterial hypertension. As it is shown in idiopathic or familial pulmonary arterial hypertension, these forms of pulmonary arterial hypertension are characterized by pulmonary endothelial dysfunction and intense smooth muscle cell proliferation. Their clinical presentation and therapeutic management are similar to those of idiopathic and familial pulmonary arterial hypertension. However, their prognosis differs greatly: it is poor in scleroderma, and much better in congenital heart diseases.

Rationale: Portopulmonary hypertension (PoPH) can be defined as elevation of pulmonary arterial pressure and pulmonary vascular resistance in the setting of portal hypertension. Survival results in PoPH are contrasting, and prognostic factors need to be identified., Objectives: To analyze long-term survival in a large cohort of patients with PoPH with the aim of determining the independent variables affecting survival., Methods: We retrospectively analyzed charts of all patients referred to the French Referral Center for pulmonary arterial hypertension with the diagnosis of PoPH between 1984 and 2004., Measurements and Main Results: The study population comprised 154 patients; 57% male. Mean age at diagnosis was 49 +/- 11 years, 60% of patients were in New York Heart Association functional class III-IV, and mean 6-minute walk distance was 326 +/- 116 m. Hemodynamic measurements showed a mean pulmonary arterial pressure of 53 +/- 13 mm Hg, cardiac index of 2.9 +/- 0.9 L/min/m(2), and pulmonary vascular resistance of 752 +/- 377 dyn/s/cm(5). Portal hypertension was related to cirrhosis in 136 patients, with a severity assessed as follows: Child-Pugh class A 51%, Child-Pugh class B 38%, Child-Pugh class C 11%. Overall survival rates at 1, 3, and 5 yr were 88, 75, and 68%, respectively. Multivariate regression analysis individualized the presence and severity of cirrhosis and cardiac index as major independent prognostic factors., Conclusions: Prognosis in PoPH is mainly related to the presence and severity of cirrhosis and to cardiac function. The place of pulmonary arterial hypertension-specific therapies remains to be determined in the setting of PoPH.

The aim of the present study was to describe a large cohort of fenfluramine-associated pulmonary arterial hypertension (fen-PAH) and its possible prognostic markers. The records of all patients with a diagnosis of fen-PAH evaluated at the present authors' centre from 1986-2004 were retrospectively studied. Baseline clinical and haemodynamic data were collected, as well as survival times. The median duration of fenfluramine exposure was 6 months, with a median of 4.5 yrs between exposure and onset of symptoms. Nine (22.5%) out of 40 patients evaluated resulted positive for the presence of germline bone morphogenetic protein receptor (BMPR) type 2 mutations. In these patients, the duration of exposure to fenfluramine was significantly lower than in patients without mutation. The median survival was 6.4 yrs, without significant difference between fen-PAH and a control group of idiopathic and familial pulmonary arterial hypertension patients referred to the present authors' centre during the same time frame and treated identically. Duration of fenfluramine exposure showed no relation to survival, while cardiac index was the only independent predictor of multivariate analysis. Fenfluramine-associated pulmonary arterial hypertension shares clinical, functional, haemodynamic and genetic features with idiopathic pulmonary arterial hypertension, as well as overall survival rates. Therefore, the present authors conclude that fenfluramine exposure characterises a potent trigger for pulmonary arterial hypertension without influencing its clinical course.