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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.

Background Recent literature reports a strong thrombotic tendency in patients hospitalized for a coronavirus disease 2019 (COVID-19) infection. This characteristic is unusual and seems specific to COVID-19 infections, especially in their severe form. Viral infections can trigger acquired thrombophilia, which can then lead to thrombotic complications. We investigate for the presence of acquired thrombophilia, which could participate in this phenomenon, and report its prevalence. We also wonder if these thrombophilias participate in the bad prognosis of severe COVID-19 infections. Methods and Results In 89 consecutive patients hospitalized for COVID-19 infection, we found a 20% prevalence of PS (protein S) deficiency and a high (ie, 72%) prevalence of antiphospholipid antibodies: mainly lupus anticoagulant. The presence of PS deficiency or antiphospholipid antibodies was not linked with a prolonged activated partial thromboplastin time nor with D-dimer, fibrinogen, or CRP (C-reactive protein) concentrations. These coagulation abnormalities are also not linked with thrombotic clinical events occurring during hospitalization nor with mortality. Conclusions We assess a high prevalence of positive tests detecting thrombophilia in COVID-19 infections. However, in our series, these acquired thrombophilias are not correlated with the severity of the disease nor with the occurrence of thrombotic events. Albeit the strong thrombotic tendency in COVID-19 infections, the presence of frequent acquired thrombophilia may be part of the inflammation storm of COVID-19 and should not systematically modify our strategy on prophylactic anticoagulant treatment, which is already revised upwards in this pathological condition. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT04335162.

Congenital heart diseases (CHDs) are the most common congenital malformations. The objective of our study was to evaluate the prenatal screening accuracy of congenital heart disease (CHD) in Southern France and to evaluate the impact of a prenatal diagnosis on pregnancies outcomes and neonatal outcomes. We performed a bicentric, retrospective observational study in the southern region over 4 years was conducted between 1 January 2014 and 31 December 2017. All foetuses and children under one year of age with CHD monitored in the UTHs (University Teaching Hospitals) in Marseille and Nice were included. CHD cases were divided into 3 groups: group 1, those with no possible options for anatomical repair; group 2, those with anatomical repair possibilities but that may require neonatal cardiologic management; and group 3, those with anatomical repair possibilities that do not require an emergency neonatal procedure. Among the 249070 deliveries during the study period, 677 CHD cases were included in the study. The overall prenatal screening rate was 71.5%. The screening rates were 97.8%, 63.6%, and 65.9% for groups 1, 2 and 3, respectively. Among group 2 CHD cases, 80% of the transpositions of the great arteries, 56% of the aortic coarctations, and 20% of the total anomalous pulmonary venous returns were detected during the prenatal period. A genetic anomaly was found in 16% of CHD cases. The overall mortality rate was 11.3% with a higher death rate in cases of prenatal screening (17.2% versus 2.1%; p < 0.001). However, when focusing only on children who died of CHD, prenatal screening did not create an impact (56.6% versus 100%, p = 0,140). Our data showed that the prenatal screening rate of CHD appears satisfactory in Southern France. Nevertheless, it could be improved for some CHD. This study did not find any benefit in terms of mortality from prenatal screening for CHD., Competing Interests: The authors have declared that no competing interests exist.

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.)

Background: Most diseases encountered in the intensive care unit are associated with major stress that can potentially trigger Takotsubo syndrome. Many severe cardiovascular complications are associated with Takotsubo syndrome, yet little is known about Takotsubo syndrome in the intensive care unit., Aims: We sought to determine the incidence of Takotsubo syndrome, and to describe its clinical features and outcome in an intensive care unit., Methods: This prospective single-centre study included all patients admitted consecutively over a 12-month period who had transthoracic echocardiography, electrocardiography and a troponin I assay performed on admission, at 24 and 48hours after admission, and at discharge and in the case of clinical worsening., Results: The incidence of Takotsubo syndrome was 4.6% (13/280 patients) and female sex predominated (69.2%). The median age of the subgroup with Takotsubo syndrome was 64 (56-72) years. Pulmonary disease and sepsis were the most frequent triggers (46.2% and 38.5%, respectively). Median left ventricular ejection fraction was 29.0% (20.0-37.0). Patients with Takotsubo syndrome presented with shock and arrhythmias and needed ventilation more frequently than patients without Takotsubo syndrome (69.2% vs. 36.3%, P=0.035; 46.2% vs. 13.5%, P=0.006; and 92.3% vs. 60.7%, P=0.021), but mortality rates were similar. The median delay to cardiac index recovery, when impaired, was 2.0 (1.0-2.75) days, and that of left ventricular ejection fraction was 12.5 (7-14.75) days., Conclusion: Takotsubo syndrome in the intensive care unit is not uncommon and is associated with substantial haemodynamic and respiratory instability. New-onset arrhythmias and respiratory and haemodynamic worsening could arouse suspicion of and prompt screening for Takotsubo syndrome in the intensive care unit., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Aims: Survival in pulmonary hypertension (PH) relates to right ventricular (RV) function. However, the RV unique anatomy and structure limit 2D analysis and its regional 3D function has not been studied yet. The aim of this study was to assess the implications of global and regional 3D RV deformation on clinical condition and survival in adults with PH and healthy controls., Methods and Results: We collected a prospective longitudinal cohort of 104 consecutive PH patients and 34 healthy controls between September 2014 and December 2015. Acquired 3D transthoracic RV echocardiographic sequences were analysed by semi-automatic software (TomTec 4D RV-Function 2.0). Output meshes were post-processed to extract regional motion and deformation. Global and regional statistics provided deformation patterns for each subgroup of subjects. RV lateral and inferior regions showed the highest deformation. In PH patients, RV global and regional motion and deformation [both circumferential, longitudinal, and area strain (AS)] were affected in all segments (P < 0.001 against healthy controls). Deformation patterns gradually worsened with the clinical condition. Over 6.7 [5.8-7.2] months follow-up, 16 (15.4%) patients died from cardio-pulmonary causes. Right atrial pressure, global RV AS, tricuspid annular plane systolic excursion, 3D RV ejection fraction, and end-diastolic volume were independent predictors of survival. Global RV AS  > -18% was the most powerful RV function parameter, identifying patients with a 48%-increased risk of death (AUC 0.83 [0.74-0.90], P < 0.001)., Conclusion: Right ventricular strain patterns gradually worsen in PH patients and provide independent prognostic information in this population.

Background: Troponin I (TnI) is an important prognostic marker and risk-stratification tool in patients with pulmonary embolism (PE). However, the best timing for this biomarker measurement is still unclear., Objective: To analyse the kinetics of TnI in patients hospitalised for PE in order to better ascertain the evolution of the biomarker in this disease. In particular, we attempted to determine which measurement is the most appropriate to assess the PE risk according to this biomarker's status. DESIGN, SETTING, PATIENTS AND MAIN OUTCOME MEASURES: This was a prospective, single center, cohort study. TnI (Beckman Access method) was measured on admission, then every 8 h for 72 h in 200 stable patients hospitalised for PE in our cardiology department. Patients were classified into two groups: TnI-(negative) or TnI +., Results: Mean TnI peak occurred at H8: 0.67±0.55 ng/ml. TnI values then decreased quickly, but remained positive (>0.06 ng/ml) beyond the 72-h surveillance period. The TnI biological profile varied widely after admission. Of the patients TnI- on the first assessment, 15% were positive at the second measurement. Among patients hospitalised less than 24 h after the onset of symptoms, 30% were misclassified on admission. In all cases, the second assessment, eight hours after admission, gave the biomarker's true status., Conclusion: Our study clarifies the kinetics of TnI in PE and highlights the situations in which an early TnI can be false negative. Many misclassifications could be avoided by taking into account the value of this biomarker obtained at H8.