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Background: Right ventricular function predicts outcome in patients with pulmonary hypertension (PH). Therefore accurate assessment of right ventricular function is essential to graduate severity, assess follow-up, and response to therapy. Purpose: To evaluate whether PH severity could be assessed using electrocardiography-gated CT (ECG-gated CT) functional parameters. A further objective was to evaluate cardiac output (CO) using two ECG-gated CT methods: the reference Simpson technique and the fully automatic technique generated by commercially available cardiac software. Material and Methods: Our institutional review board approved this study; patient consent was not required. Twenty-seven patients who had undergone ECG-gated CT and right heart catheterization (RHC) were included. Two independent observers measured pulmonary artery (PA) diameter, PA distensibility, aorta diameter, right ventricular cardiac output (CT-RVCO) and right ventricular ejection fraction (CT-RVEF) with automatic and Simpson techniques on ECG-gated CT. RHC-CO and mean pulmonary arterial pressure (mPAP) were measured on RHC. Relationship between ECG-gated CT and RHC measurements was tested with linear regression analysis. Results: Inter-observer agreement was good for all measurements (r > 0.7) except for CT-RVCO calculated with Simpson's technique (r = 0.63). Pulmonary artery (PA) distensibility was significantly correlated to mPAP (r = -0.426, P = 0.027). CT-RVEF was correlated with mPAP only when issued from Simpson technique (r = -0.417, P = 0.034). CT-RVEF was not significantly correlated to RHC-CO (P > 0.2). CT-RVCO measured with Simpson technique (r = 0.487, P = 0.010) and automatic segmentation (r = 0.549, P = 0.005) correlated equally with RHC-CO. Conclusion: CT-RVEF and CT-RVCO measured on ECG-gated CT are significantly correlated, respectively, to mPAP and RHC-CO in this population with severe reduction of the right ventricular ejection fraction and could be useful for evaluating and following patients with PH. [ABSTRACT FROM AUTHOR]

Abstract A 24-year-old patient was admitted for dyspnoea and syncope. He had a previous history of complete atrio-ventricular septal defect and trisomy 21. At the age of 6 months, in 1984, cardiac catheterization revealed a quasi-systemic pulmonary arterial hypertension with a bidirectional shunt corresponding to an Eisenmenger syndrome. Corrective cardiac surgery was not performed at this time because surgical risk was considered too high. Until the age of 20 years old, he showed few symptoms while under medical treatment. But since 2006, his functional status became worse with an increased dyspnoea, syncopes, and severe cyanosis. In these conditions, haemodynamic parameters have been re-evaluated in 2006 and 2008. They highlighted a late and progressive development of a valvular and infundibular pulmonary stenosis leading to a normalisation of pulmonary arterial pressures. At the age of 24 , the patient underwent corrective cardiac surgery which was successful. Late development of both infundibular and valvular pulmonary stenosis have not been described before in non operated congenital ventricular septal defects, but development of one or the other abnormality would be found in 8% of patients. The physiopathological mechanism of this obstruction is unclear. Nevertheless, in unoperated congenital cardiac shunt lesions, reversibility of severe pulmonary arterial hypertension should be reconidered and re-assessed during follow up.

Background and Aims: Based on retrospective studies, the 2022 European guidelines changed the definition of post-capillary pulmonary hypertension (pcPH) in heart failure (HF) by lowering the level of mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR). However, the impact of this definition and its prognostic value has never been evaluated prospectively., Methods: Stable left HF patients with the need for right heart catheterization were enrolled from 2010 to 2018 and prospectively followed up in this multicentre study. The impact of the successive pcPH definitions on pcPH prevalence and subgroup [i.e. isolated (IpcPH) vs. combined pcPH (CpcPH)] was evaluated. Multivariable Cox regression analysis was used to assess the prognostic value of mPAP and PVR on all-cause death or hospitalization for HF (primary outcome)., Results: Included were 662 HF patients were (median age 63 years, 60% male). Lowering mPAP from 25 to 20 mmHg resulted in +10% increase in pcPH prevalence, whereas lowering PVR from 3 to 2 resulted in +60% increase in CpcPH prevalence (with significant net reclassification improvement for the primary outcome). In multivariable analysis, both mPAP and PVR remained associated with the primary outcome [hazard ratio (HR) 1.02, 95% confidence interval (CI) 1.00-1.03, P = .01; HR 1.07, 95% CI 1.00-1.14, P = .03]. The best PVR threshold associated with the primary outcome was around 2.2 WU. Using the 2022 definition, pcPH patients had worse survival compared with HF patients without pcPH (log-rank, P = .02) as well as CpcPH compared with IpcPH (log-rank, P = .003)., Conclusions: This study is the first emphasizing the impact of the new pcPH definition on CpcPH prevalence and validating the prognostic value of mPAP > 20 mmHg and PVR > 2 WU among HF patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction: Pulmonary arterial hypertension (PAH) is a rare and severe disease for which most of the evidence about prognostic factors, evolution and treatment efficacy comes from cohorts, registries and clinical trials. We therefore aimed to develop and validate a new PAH identification algorithm that can be used in the French healthcare database "Système National des Données de Santé (SNDS)"., Methods: We developed and validated the algorithm using the Grenoble Alpes University Hospital medical charts. We first identified PAH patients following a previously validated algorithm, using in-hospital ICD-10 (10th revision of the International Statistical Classification of Diseases) codes, right heart catheterisation procedure and PAH-specific treatment dispensing. Then, we refined the latter with the exclusion of chronic thromboembolic pulmonary hypertension procedures and treatment, the main misclassification factor. Second, we validated this algorithm using a gold standard review of in-hospital medical charts and calculated sensitivity, specificity, positive and negative predictive value (PPV and NPV) and accuracy. Finally, we applied this algorithm in the French healthcare database and described the characteristics of the identified patients., Results: In the Grenoble University Hospital, we identified 252 unique patients meeting all the algorithm's criteria between 1 January 2010 and 30 June 2022, and reviewed all medical records. The sensitivity, specificity, PPV, NPV and accuracy were 91.0%, 74.3%, 67.9%, 93.3% and 80.6%, respectively. Application of this algorithm to the SNDS yielded the identification of 9931 patients with consistent characteristics compared to PAH registries., Conclusion: Overall, we propose a new PAH identification algorithm developed and adapted to the French specificities that can be used in future studies using the French healthcare database., Competing Interests: Conflict of interest: H. Bouvaist reports payment for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Merck, outside the submitted work. Conflict of interest: M. Humbert reports grants or contracts from Acceleron, AOP Orphan, Janssen, Merck and Shou Ti, outside the submitted work; consulting fees from 35 Pharma, Aerovate, AOP Orphan, Bayer, Chiesi, Ferrer, Janssen, Keros, Merck, MorphogenIX, Shou Ti and United Therapeutics, outside the submitted work; payment for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Janssen and Merck, outside the submitted work; and participation on a data safety monitoring or advisory board for Acceleron, Altavant, Janssen, Merck and United Therapeutics, outside the submitted work. Conflict of interest: D. Montani reports grants or contracts from Acceleron, Janssen and Merck MSD, outside the submitted work; consulting fees from Acceleron, Merck MSD, Janssen and Ferrer, outside the submitted work; payment or honoraria for speakers' bureaus from Bayer, Janssen, Boerhinger, Chiesi, GSK, Ferrer and Merck MSD, outside the submitted work. Conflict of interest: The remaining authors have nothing to disclose., (Copyright ©The authors 2024.)

Background and Aims: Cardiopulmonary fitness in congenital heart disease (CHD) decreases faster than in the general population resulting in impaired health-related quality of life (HRQoL). As the standard of care seems insufficient to encourage and maintain fitness, an early hybrid cardiac rehabilitation programme could improve HRQoL in CHD., Methods: The QUALIREHAB multicentre, randomized, controlled trial evaluated and implemented a 12-week centre- and home-based hybrid cardiac rehabilitation programme, including multidisciplinary care and physical activity sessions. Adolescent and young adult CHD patients with impaired cardiopulmonary fitness were randomly assigned to either the intervention (i.e. cardiac rehabilitation) or the standard of care. The primary outcome was the change in HRQoL from baseline to 12-month follow-up in an intention-to-treat analysis. The secondary outcomes were the change in cardiovascular parameters, cardiopulmonary fitness, and mental health., Results: The expected number of 142 patients was enroled in the study (mean age 17.4 ± 3.4 years, 52% female). Patients assigned to the intervention had a significant positive change in HRQoL total score [mean difference 3.8; 95% confidence interval (CI) 0.2; 7.3; P = .038; effect size 0.34], body mass index [mean difference -0.7 kg/m2 (95% CI -1.3; -0.1); P = .022; effect size 0.41], level of physical activity [mean difference 2.5 (95% CI 0.1; 5); P = .044; effect size 0.39], and disease knowledge [mean difference 2.7 (95% CI 0.8; 4.6); P = .007; effect size 0.51]. The per-protocol analysis confirmed these results with a higher magnitude of differences. Acceptability, safety, and short-time effect of the intervention were good to excellent., Conclusions: This early hybrid cardiac rehabilitation programme improved HRQoL, body mass index, physical activity, and disease knowledge, in youth with CHD, opening up the possibility for the QUALIREHAB programme to be rolled out to the adult population of CHD and non-congenital cardiac disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Transcatheter closure of a patent foramen ovale (PFO) is performed in cryptogenic stroke and other conditions. Information is lacking for some devices. Methods: We aimed to evaluate the Figulla Flex II PFO Occluder (FFP) and Figulla Flex UNI Occluder (FFU) through a retrospective multi-center registry. Results : 527 patients were included. Mean age was 48.9 (±13.8) years. The procedure was under transthoracic, transesophageal or intracardiac echocardiography in 185 (35.1%), 193 (36.6%) and 149 (28.3%) cases, respectively, and under general anesthesia in 191 patients (36.2%). The FFP and FFU were used in 408 (77.4%) and 119 (22.6%) cases, respectively. The success rate was 99.1%. Median follow-up was 1.1 (0.5-2.5) years. A new atrial fibrillation/flutter within six months occurred in 14 (2.7%) cases, with no difference between devices. One device embolization in the pulmonary artery was identified two years post-procedure. Residual shunts occurred in 18 (6.9%) cases at 1 year, with TIA in three (16.6%) patients. Out of 437 patients with stroke/TIA, 260 (59%) were followed more than one year after closure. Median follow-up was 2.1 (1.17-3.1) years, with four recurrent strokes/TIA. Conclusions: The FFP and FFU devices are safe and effective for PFO closure, with very few atrial fibrillation/flutter and neurologic events, except in cases with a residual shunt., Competing Interests: Alain Fraisse and Francois Godart are both consultants and proctors for Occlutech Inc and Abbott Inc. Other authors have no conflicts of interest.

In patients with very severe CTEPH eligible for BPA, it is possible to achieve major haemodynamic improvement with upfront triple PH therapy including epoprostenol and then to perform angioplasties https://bit.ly/3vZZvib., Competing Interests: Conflict of interest: The authors have nothing to disclose., (Copyright ©The authors 2024.)

Background and Aims: Transcatheter pulmonary valve implantation (TPVI) is indicated to treat right-ventricular outflow tract (RVOT) dysfunction related to congenital heart disease (CHD). Outcomes of TPVI with the SAPIEN 3 valve that are insufficiently documented were investigated in the EUROPULMS3 registry of SAPIEN 3-TPVI., Methods: Patient-related, procedural, and follow-up outcome data were retrospectively assessed in this observational cohort from 35 centres in 15 countries., Results: Data for 840 consecutive patients treated in 2014-2021 at a median age of 29.2 (19.0-41.6) years were obtained. The most common diagnosis was conotruncal defect (70.5%), with a native or patched RVOT in 50.7% of all patients. Valve sizes were 20, 23, 26, and 29 mm in 0.4%, 25.5%, 32.1%, and 42.0% of patients, respectively. Valve implantation was successful in 98.5% [95% confidence interval (CI), 97.4%-99.2%] of patients. Median follow-up was 20.3 (7.1-38.4) months. Eight patients experienced infective endocarditis; 11 required pulmonary valve replacement, with a lower incidence for larger valves (P = .009), and four experienced pulmonary valve thrombosis, including one who died and three who recovered with anticoagulation. Cumulative incidences (95%CI) 1, 3, and 6 years after TPVI were as follows: infective endocarditis, 0.5% (0.0%-1.0%), 0.9% (0.2%-1.6%), and 3.8% (0.0%-8.4%); pulmonary valve replacement, 0.4% (0.0%-0.8%), 1.3% (0.2%-2.4%), and 8.0% (1.2%-14.8%); and pulmonary valve thrombosis, 0.4% (0.0%-0.9%), 0.7% (0.0%-1.3%), and 0.7% (0.0%-1.3%), respectively., Conclusions: Outcomes of SAPIEN 3 TPVI were favourable in patients with CHD, half of whom had native or patched RVOTs., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Right ventricular (RV) function plays a critical role in the pathophysiology and acute prognosis of pulmonary embolism (PE). We analyzed the temporal changes of RV function in the cohort of a prospective multicentre study investigating if an early switch to oral anticoagulation in patients with intermediate-risk PE is effective and safe., Methods: Echocardiographic and laboratory examinations were performed at baseline (PE diagnosis), 6 days and 6 months. Echocardiographic parameters were classified into categories representing RV size, RV free wall/tricuspid annulus motion, RV pressure overload and right atrial (RA)/central venous pressure., Results: RV dysfunction based on any abnormal echocardiographic parameter was present in 84% of patients at baseline. RV dilatation was the most frequently abnormal finding (40.6%), followed by increased RA/central venous pressure (34.6%), RV pressure overload (32.1%), and reduced RV free wall/tricuspid annulus motion (20.9%). As early as day 6, RV size remained normal or improved in 260 patients (64.7%), RV free wall/tricuspid annulus motion in 301 (74.9%), RV pressure overload in 297 (73.9%), and RA/central venous pressure in 254 (63.2%). At day 180, the frequencies slightly increased. The median NT-proBNP level decreased from 1448 pg/ml at baseline to 256.5 on day 6 and 127 on day 180., Conclusion: In the majority of patients with acute intermediate-risk PE switched early to a direct oral anticoagulant, echocardiographic parameters of RV function normalised within 6 days and remained normal throughout the first 6 months. Almost one in four patients, however, continued to have evidence of RV dysfunction over the long term., (© 2022. The Author(s).)

Purpose: Patients with pulmonary hypertension (PH) have long been advised to avoid exercise in fear of deterioration in right-sided heart function. Since the 2009 European Society of Cardiology guidelines, rehabilitation in expert centers is considered to have a specific role in care of patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). We report routine rehabilitation effects in patients with PH as a component of real-life multimodal treatment., Methods: Patients with PAH or CTEPH were recommended for either in- or outpatient rehabilitation in addition to their usual care, unless there were practical problems or the patient declined. Assessment was conducted according to New York Heart Association classes, adverse events, 6 min-walk test, hemodynamics, and risk stratification after rehabilitation., Results: Forty-one patients, 61% female, age 60 ±18 yr were included between March 2010 and May 2019. No major adverse events or deaths related to progression of right-sided heart failure were reported. Nevertheless, 22% of participants suffered adverse events in most cases not linked with physical activity. Rehabilitation as add-on to medical therapy and/or arterial deobstruction improved New York Heart Association class: mean difference, -0.39 (95% CI, -0.68 to -0.10), 6-min walk test: mean difference, 80 m (95% CI, 46-114), and was associated with improved right-sided heart hemodynamics. The risk assessment grade improved by -0.25 points (95% CI, -0.44 to -0.06) after rehabilitation., Conclusions: For patients with PAH or CTEPH, supervised rehabilitation as add-on to medical therapy and/or arterial deobstruction is safe and effective in improving patient and clinically related outcomes., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The current treatment algorithm for chronic thromboembolic pulmonary hypertension (CTEPH) as depicted in the 2022 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines on the diagnosis and treatment of pulmonary hypertension (PH) includes a multimodal approach of combinations of pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA) and medical therapies to target major vessel pulmonary vascular lesions, and microvasculopathy. Today, BPA of >1700 patients has been reported in the literature from centers in Asia, the US, and also Europe; many more patients have been treated outside literature reports. As BPA becomes part of routine care of patients with CTEPH, benchmarks for safe and effective care delivery become increasingly important. In light of this development, the ESC Working Group on Pulmonary Circulation and Right Ventricular Function has decided to publish a document that helps standardize BPA to meet the need of uniformity in patient selection, procedural planning, technical approach, materials and devices, treatment goals, complications including their management, and patient follow-up, thus complementing the guidelines. Delphi methodology was utilized for statements that were not evidence based. First, an anatomical nomenclature and a description of vascular lesions are provided. Second, treatment goals and definitions of complete BPA are outlined. Third, definitions of complications are presented which may be the basis for a standardized reporting in studies involving BPA. The document is intended to serve as a companion to the official ESC/ERS guidelines., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Pediatric patients with congenital heart disease (CHD) often undergo low dose ionizing radiation (LDIR) from cardiac catheterization (CC) for the diagnosis and/or treatment of their disease. Although radiation doses from a single CC are usually low, less is known about the long-term radiation associated cancer risks. We aimed to assess the risk of lympho-hematopoietic malignancies in pediatric CHD patients diagnosed or treated with CC. A French cohort of 17,104 children free of cancer who had undergone a first CC from 01/01/2000 to 31/12/2013, before the age of 16 was set up. The follow-up started at the date of the first recorded CC until the exit date, i.e., the date of death, the date of first cancer diagnosis, the date of the 18th birthday, or the 31/12/2015, whichever occurred first. Poisson regression was used to estimate the LDIR associated cancer risk. The median follow-up was 5.9 years, with 110,335 person-years. There were 22,227 CC procedures, yielding an individual active bone marrow (ABM) mean cumulative dose of 3.0 milligray (mGy). Thirty-eight incident lympho-hematopoietic malignancies were observed. When adjusting for attained age, gender and predisposing factors to cancer status, no increased risk was observed for lympho-hematopoietic malignancies RR /mGy = 1.00 (95% CI: 0.88; 1.10). In summary, the risk of lympho-hematopoietic malignancies and lymphoma was not associated to LDIR in pediatric patients with CHD who undergo CC. Further epidemiological studies with greater statistical power are needed to improve the assessment of the dose-risk relationship., (© 2023. Springer Nature B.V.)

Objective: To determine whether changes in pulmonary vascular resistance (PVR) and changes in pulmonary artery compliance ( C pa ) are associated with changes in exercise capacity assessed either by changes in peak oxygen consumption ( V ' O 2 ) or by changes in 6-min walk distance (6MWD) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing balloon pulmonary angioplasty (BPA)., Methods: Invasive haemodynamic parameters, peak V ' O 2 and 6MWD were measured within 24 h, before and after BPA (interval 3.1±2.4 months) in 34 CTEPH patients without significant cardiac and/or pulmonary comorbidities, of whom 24 received at least one pulmonary hypertension-specific treatment. C pa was calculated according to the pulse pressure method: C pa =((SV/PP)/1.76+0.1), where SV is the stroke volume and PP is the pulse pressure. The resistance-compliance (RC)-time of the pulmonary circulation was calculated as the PVR and C pa product., Results: After BPA, PVR decreased (562±234 versus 290±106 dyn·s·cm -5 ; p<0.001); C pa increased (0.90±0.36 versus 1.63±0.65 mL·mmHg -1 ; p<0.001); but RC-time did not change (0.325±0.069 versus 0.321±0.083 s; p=0.75). There were improvements in peak V ' O 2 (1.11±0.35 versus 1.30±0.33 L·min -1 ; p<0.001) and in 6MWD (393±119 versus 432±100 m; p<0.001). After adjustment for age, height, weight and gender, changes in exercise capacity, assessed either by peak V ' O 2 or 6MWD, were significantly associated with changes in PVR, but not with changes in C pa ., Conclusions: Contrary to what has been reported in CTEPH patients undergoing pulmonary endarterectomy, in CTEPH patients undergoing BPA, changes in exercise capacity were not associated with changes in C pa ., Competing Interests: Conflict of interest: The authors do not have any conflict of interest to declare relative to the present study. The results of the present study are presented clearly, honestly, and without fabrication, falsification or inappropriate data manipulation., (Copyright ©The authors 2023.)

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: Transcatheter closure of a symptomatic prosthetic paravalvular leak (PVL) is feasible, but there is presently no conclusive evidence to show consistent efficacy. We aimed to identify predictors of clinical success after transcatheter PVL closure., Methods: Consecutive patients referred to 24 European centers for transcatheter PVL closure in 2017 to 2019 were included in a prospective registry ( Fermeture de Fuite ParaProthétique , FFPP). Clinical success was absence of any of the following within 1 month: re-admission for heart failure, blood transfusion, open-heart valvular surgery, and death., Results: We included 216 symptomatic patients, who underwent 238 percutaneous PVL closure procedures on the mitral (64.3%), aortic (34.0%), or tricuspid (1.7%) valve. Symptoms were heart failure, hemolytic anemia, or both in 48.9%, 7.8%, and 43.3% of patients, respectively. One, 2, and 3 leaks were treated during the same procedure in 69.6%, 26.6%, and 3.8% of patients, respectively. The PVL was pinpoint or involved 1/8 or 1/4 of the valve circumference in 18.6%, 52.4%, and 28.1% of cases, respectively. The most frequently used devices were the Vascular Plug 3, Ventricular Septal Defect Occluder, Vascular Plug 2, and Paravalvular Leak Device (45.0%, 16.6%, 14.2%, and 13.6% of cases, respectively). Successful device(s) implantation with leak reduction to ≤grade 2 was obtained in 85.0% of mitral and 91.4% of aortic procedures, respectively ( P =0.164); with major periprocedural adverse event rates of 3.3% and 1.2%, respectively ( P =0.371); and clinical success rates of 70.3% and 88.0%, respectively ( P =0.004). By multivariate analysis, technical failure, mechanical valve, and hemolytic anemia were independently associated with absence of clinical success (odds ratios [95% CIs], 7.7 [2.0-25.0]; P= 0.002; 3.6 [1.1-11.1]; P =0.036; and 3.7 [1.2-11.9]; P =0.025; respectively)., Conclusions: Transcatheter PVL closure is efficient and safe in symptomatic patients but is associated with a lower clinical success rate in patients with hemolysis and/or a mechanical valve., Registration: URL: https://www., Clinicaltrials: gov; Unique identifiers: NCT05089136.

Background: Riociguat and balloon pulmonary angioplasty (BPA) are treatment options for inoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, randomised controlled trials comparing these treatments are lacking. We aimed to evaluate the efficacy and safety of BPA versus riociguat in patients with inoperable CTEPH., Methods: In this phase 3, multicentre, open-label, parallel-group, randomised controlled trial done in 23 French centres of expertise for pulmonary hypertension, we enrolled treatment-naive patients aged 18-80 years with newly diagnosed, inoperable CTEPH and pulmonary vascular resistance of more than 320 dyn·s/cm 5 . Patients were randomly assigned (1:1) to BPA or riociguat via a web-based randomisation system, with block randomisation (block sizes of two or four patients) without stratification. The primary endpoint was change in pulmonary vascular resistance at week 26, expressed as percentage of baseline pulmonary vascular resistance in the intention-to-treat population. Safety analyses were done in all patients who received at least one dose of riociguat or had at least one BPA session. Patients who completed the RACE trial continued into an ancillary 26-week follow-up during which symptomatic patients with pulmonary vascular resistance of more than 320 dyn·s/cm 5 benefited from add-on riociguat after BPA or add-on BPA after riociguat. This trial is registered at ClinicalTrials.gov, NCT02634203, and is completed., Findings: Between Jan 19, 2016, and Jan 18, 2019, 105 patients were randomly assigned to riociguat (n=53) or BPA (n=52). At week 26, the geometric mean pulmonary vascular resistance decreased to 39·9% (95% CI 36·2-44·0) of baseline pulmonary vascular resistance in the BPA group and 66·7% (60·5-73·5) of baseline pulmonary vascular resistance in the riociguat group (ratio of geometric means 0·60, 95% CI 0·52-0·69; p<0·0001). Treatment-related serious adverse events occurred in 22 (42%) of 52 patients in the BPA group and five (9%) of 53 patients in the riociguat group. The most frequent treatment-related serious adverse events were lung injury (18 [35%] of 52 patients) in the BPA group and severe hypotension with syncope (two [4%] of 53 patients) in the riociguat group. There were no treatment-related deaths. At week 52, a similar reduction in pulmonary vascular resistance was observed in patients treated with first-line riociguat or first-line BPA (ratio of geometric means 0·91, 95% CI 0·79-1·04). The incidence of BPA-related serious adverse events was lower in patients who were pretreated with riociguat (five [14%] of 36 patients vs 22 [42%] of 52 patients)., Interpretation: At week 26, pulmonary vascular resistance reduction was more pronounced with BPA than with riociguat, but treatment-related serious adverse events were more common with BPA. The finding of fewer BPA-related serious adverse events among patients who were pretreated with riociguat in the follow-up study compared with those who received BPA as first-line treatment points to the potential benefits of a multimodality approach to treatment in patients with inoperable CTEPH. Further studies are needed to explore the effects of sequential treatment combining one or two medications and BPA in patients with inoperable CTEPH., Funding: Programme Hospitalier de Recherche Clinique of the French Ministry of Health and Bayer HealthCare., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests XJ, PB, HB, MJ, LS, OS, FP, CP, LG, EF, DM, MH, and GS report grants from the French Ministry of Health and Bayer HealthCare, during the conduct of the study. XJ reports grants from Acceleron, Janssen, and Merck Sharp & Dohme (MSD); personal fees from Janssen and MSD; and non-financial support from Janssen, outside of this study. MC reports personal fees from Menarini, and non-financial support from France Oxygène and Actelion, outside of this study. AC reports grants from Actelion and GlaxoSmithKline; personal fees from MSD, Chiesi, and GlaxoSmithKline; and non-financial support from Asten Santé, Johnson & Johnson, Chiesi, and Boehringer Ingelheim, outside of this study. VC reports grants from Boehringer Ingelheim; personal fees from Boehringer Ingelheim, Roche, Galapagos, Galecto, Shionogi, Fibrogen, RedX, Promedior, Celgene, Bristol Myers Squibb, and PureTech; and non-financial support from Boehringer Ingelheim and Roche, outside of this study. PDG reports personal fees from Bayer HealthCare and MSD, outside of this study. LS reports grants from Janssen, MSD, and GlaxoSmithKline; personal fees from Janssen and MSD; and non-financial support from Janssen, outside of this study. OS reports grants from GlaxoSmithKline, Acceleron, Janssen, and MSD; and personal fees from Gossamer Bio, Janssen, AOP Orphan, Ferrer, Acceleron, and MSD, outside of this study. FP reports grants from Acceleron, MSD, and Janssen; personal fees from MSD and Bayer HealthCare; and non-financial support from Bayer HealthCare, outside of this study. CT reports personal fees from Bayer HealthCare, Janssen, and GlaxoSmithKline; and non-financial support from Orkyn and Bayer HealthCare, outside of this study. EF reports personal fees from MSD, outside of this study. DM reports grants from Acceleron, Janssen, and MSD; and personal fees from Acceleron, Bayer HealthCare, Janssen, and MSD, outside of this study. MH reports grants from the French National Research Agency, Acceleron, Janssen, and MSD; and personal fees from Acceleron, Janssen, MSD, and United Therapeutics, outside of this study. GS reports personal fees from Acceleron, Janssen, MSD, and Bayer HealthCare, outside of this study. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Rationale: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with pulmonary endothelial dysfunction. There are limited data available on the outcomes of coronavirus disease (COVID-19) in patients with pulmonary hypertension (PH), a disease characterized by pulmonary endothelial dysfunction. Objectives: To describe characteristics and outcomes of patients with precapillary PH and COVID-19. Methods: We prospectively collected characteristics, management, and outcomes of adult patients with precapillary PH in the French PH network who had COVID-19 between February 1, 2020, and April 30, 2021. Clinical, functional, and hemodynamic characteristics of PH before COVID-19 were collected from the French PH registry. Measurements and Main Results: A total of 211 patients with PH (including 123 with pulmonary arterial hypertension, 47 with chronic thromboembolic PH, and 41 with other types of PH) experienced COVID-19, and 40.3% of them were outpatients, 32.2% were hospitalized in a conventional ward, and 27.5% were in an ICU. Among hospitalized patients ( n  = 126), 54.0% received corticosteroids, 37.3% high-flow oxygen, and 11.1% invasive ventilation. Right ventricular and acute renal failure occurred in 30.2% and 19.8% of patients, respectively. Fifty-two patients (all hospitalized) died from COVID-19. Overall mortality was 24.6% (95% CI [confidence interval], 18.8-30.5) and in-hospital mortality 41.3% (95% CI, 32.7-49.9). Nonsurvivors were significantly older, more frequently male and suffering comorbidities (diabetes, chronic respiratory diseases, systemic hypertension, chronic cardiac diseases, and/or chronic renal failure), and had more severe PH at their most recent evaluation preceding COVID-19 diagnosis (in terms of functional class and 6-minute-walk distance; all P  < 0.05). Use of pulmonary arterial hypertension therapy was similar between survivors and nonsurvivors. Conclusions: COVID-19 in patients with precapillary PH was associated with a high in-hospital mortality. The typical risk factors for severe COVID-19 and severity of PH were associated with mortality in this population.

Coronary microvascular dysfunction (CMVD) is common and associated with poorer outcomes in patients with ST Segment Elevation Myocardial Infarction (STEMI). The index of microcirculatory resistance (IMR) and the index of hyperemic microvascular resistance (HMR) are both invasive indexes of microvascular resistance proposed for the diagnosis of severe CMVD after primary percutaneous coronary intervention (pPCI). However, these indexes are not routinely assessed in STEMI patients. Our main objective was to clarify the association between IMR or HMR and long-term major adverse cardiovascular events (MACE), through a systematic review and meta-analysis of observational studies. We searched Medline, PubMed, and Google Scholar for studies published in English until December 2020. The primary outcome was a composite of cardiovascular death, non-cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and rehospitalization for heart failure occurring after at least 6 months following CMVD assessment. We identified 6 studies, reporting outcomes in 1094 patients (mean age 59.7 ± 11.4 years; 18.2% of patients were women) followed-up from 6 months to 7 years. Severe CMVD, defined as IMR > 40 mmHg or HMR > 3mmHg/cm/sec was associated with MACE with a pooled HR of 3.42 [2.45; 4.79]. Severe CMVD is associated with an increased risk of long-term adverse cardiovascular events in patients with STEMI. Our results suggest that IMR and HMR are useful for the early identification of severe CMVD in patients with STEMI after PCI, and represent powerful prognostic assessments as well as new therapeutic targets for clinical intervention., Competing Interests: The authors have declared that no competing interests exist.

Excessive ventilation (V̇E) during exercise, ascribed to heightened neural ventilatory drive and/or to increased "wasted" ventilation, is a feature of chronic thromboembolic pulmonary hypertension (CTEPH). In selected CTEPH patients, balloon pulmonary angioplasty (BPA) allows near-normalization of resting haemodynamic parameters but does not allow excess exercise hyperventilation to normalize. Neural ventilatory drive can be estimated by studying how arterial PCO 2 (PaCO 2 ), end-tidal PCO 2 (PETCO 2 ), V̇E and CO 2 output (V̇CO 2 ) change across the exercise-to-recovery transition during a cardiopulmonary exercise test. Increased "wasted" ventilation can be quantified by the physiological dead space fraction of tidal volume (VD/VT) calculated with the Enghoff simplification of the Bohr equation. These measurements were made before and after BPA in 22 CTEPH patients without significant cardiac and/or pulmonary comorbidities. Our observations suggest that before BPA, excessive hyperventilation was secondary to both heightened neural ventilatory drive and increased "wasted" ventilation; after BPA, measurements made across the exercise-to-recovery transition suggest that heightened neural ventilatory drive was no longer present., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: In patients undergoing balloon pulmonary angioplasty (BPA) for inoperable chronic thromboembolic pulmonary hypertension (CTEPH), single-centre series from expert centres have recognized a learning curve for the magnitude of haemodynamic benefits., Objective: To report our 7-year experience with BPA, focusing on haemodynamic effects, complication rates and radiation exposure over time., Methods: Patients with CTEPH who were treated with BPA between May 2013 and February 2020 were analysed during the 'initial period' versus the 'recent period' (split date: March 2017)., Results: Among 192 patients who underwent at least one BPA procedure, 156 were included in the safety/radiation analysis and 119 were included in the efficacy analysis. During the 'recent period' versus the 'initial period', the median [interquartile range] number of procedures per patient was higher (4.5 [4.0-6.0] vs. 4.0 [3.0-4.0]; P=0.03), as was the number of dilated vessels per procedure (4.0 [3.5-5.0] vs. 3.5 [3.0-4.0]; P=0.002). Changes in haemodynamic parameters were also greater (mean pulmonary artery pressure: -22% [-31% to -14%] vs. -37% [-44% to -29%]; P=0.001; pulmonary vascular resistance: -38% [-51% to -8%] vs. -53% [-69% to -33%]; P=0.002); complication rates were similar (5.7% vs. 9.3% of procedures; P=0.38); and radiation exposure was lower (effective dose per patient: 43.9 [31.6-66.5] vs. 67.8 [47.9-101.9] mSv; P<0.001)., Conclusion: Our analysis is consistent with a learning curve for the magnitude of haemodynamic improvements. The complication rate was low and did not change over time, but radiation exposure decreased., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Coronary physiological assessment is now widely used to assess epicardial coronary lesions in cath lab. Based on clinical evidence, fractional flow reserve (FFR) is the gold standard method to select whether epicardial coronary lesions need revascularization. While additional epicardial indexes, such as instantaneous wave-free ratio (iFR), are also used for revascularization decision-making, several indexes are now also available to explore the coronary microcirculation. Therefore, coronary physiological assessment now allows to explore the entire coronary tree and offer the potential of precision medicine for patients affected by coronary artery disease (CAD). This paper will provide review of the epicardial and microvascular indexes available for the assessment of coronary physiology. More specifically, the already demonstrated contributions of these indexes in the management of CAD and the role they could play in precision medicine will be reviewed with special emphasis on chronic coronary syndrome., Competing Interests: Gilles Barone-Rochette has received research grants from Merck Sharp and Dohme, and consulting fees from Bayer, Abbott vascular, Novo Nordisk, Sanofi, and AMGEN. The others authors declare no conflict of interest., (Copyright: © 2022 The Author(s). Published by IMR Press.)

Background: Transcatheter closure of a patent ductus arteriosus in children is widely performed to reduce symptoms and decrease the risk of endocarditis. Most arterial ducts are closed successfully with dedicated devices. However, in a tubular or "type C" patent ductus arteriosus with congestive heart failure, the occlusion is more challenging with these devices, with a higher risk of complications, such as aortic or left pulmonary stenosis and device embolization., Aim: To report our experience with muscular ventricular septal defect devices for patent ductus arteriosus occlusion in small children., Methods: Retrospective observational series of patients weighing<10kg, with a tubular patent ductus arteriosus (typeC) and congestive heart failure, who underwent transcatheter closure with a muscular ventricular septal defect device between 2017 and 2019., Results: Eight patients were included. The mean age and weight at closure were 6.3 months (range 1-18 months) and 5.3kg (range 2.4-8.2kg), respectively. All patent ductus arteriosus were occluded successfully using Occlutech® (N=3) or Amplatzer® (N=5) muscular ventricular septal defect devices. In four cases, the muscular ventricular septal defect device was used after failure to close the patent ductus arteriosus with a dedicated patent ductus arteriosus device. Two patients had mild left pulmonary artery stenosis, with a maximum velocity on continuous Doppler of 3m/s and 2.7m/s, respectively. After a mean follow-up of 28 months (range 14-41 months), all patients were asymptomatic with excellent results. The mild pulmonary stenosis improved, with a maximum velocity of 2.3m/s in both patients., Conclusions: Closure of tubular patent ductus arteriosus in small children with congestive heart failure using a muscular ventricular septal defect device is safe in this preliminary experience. Further studies with more patients are warranted., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Objectives: The aim of this study was to assess the diagnostic performances of 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET)/computed tomography (CT) in congenital heart disease (CHD) patients with pulmonary prosthetic valve or conduit endocarditis (PPVE) suspicion., Background: PPVE is a major issue in the growing CHD population. Diagnosis is challenging, and usual imaging tools are not always efficient or validated in this specific population. Particularly, the diagnostic yield of 18 F-FDG PET/CT remains poorly studied in PPVE., Methods: A retrospective multicenter study was conducted in 8 French tertiary centers. Children and adult CHD patients who underwent 18 F-FDG PET/CT in the setting of PPVE suspicion between January 2010 and May 2020 were included. The cases were initially classified as definite, possible, or rejected PPVE regarding the modified Duke criteria and finally by the Endocarditis Team consensus. The result of 18 F-FDG PET/CT had been compared with final diagnosis consensus used as gold-standard in our study., Results: A total of 66 cases of PPVE suspicion involving 59 patients (median age 23 years, 73% men) were included. Sensitivity, specificity, positive predictive value, and negative predictive value of 18 F-FDG PET/CT in PPVE suspicion were respectively: 79.1% (95% CI: 68.4%-91.4%), 72.7% (95% CI: 60.4%-85.0%), 91.9% (95% CI: 79.6%-100.0%), and 47.1% (95% CI: 34.8%-59.4%). 18 F-FDG PET/CT findings would help to correctly reclassify 57% (4 of 7) of possible PPVE to definite PPVE., Conclusions: Using 18 F-FDG PET/CT improves the diagnostic accuracy of the Duke criteria in CHD patients with suspected PPVE. Its high positive predictive value could be helpful in routine to shorten diagnosis and treatment delays and improve clinical outcomes., Competing Interests: Funding Support and Author Disclosures Drs Venet, Jalal, and Thambo were supported by the French Government as part of the “Investments of the future” program managed by the National Research Agency (grant reference ANR-10-IAHU-04). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Highly thrombotic coronary lesions continue to be a serious and clinically significant problem that is not effectively and completely addressed by current technology., Objectives: We aimed to investigate whether a micro-net mesh (MNM) technology covering stent could preserve the index of microcirculatory resistance (IMR) after percutaneous coronary intervention (PCI) in patients with high thrombus burden., Methods and Results: Fifty-two patients with non-ST elevation myocardial infarction or ST Elevation Myocardial Infarction and high thrombus burden (TIMI thrombus grade ≥ 3) were randomized into two groups, PCI with a MNM covering stent (MNM group, n = 25) and PCI with any commercially available stent (DES group, n = 27). As the primary endpoint, IMR was measured immediately after PCI using a pressure-temperature sensor-tipped coronary wire. The secondary endpoint was left ventricular ejection fraction (LVEF) at 6 months of follow-up. The IMR in the MNM group was significantly lower in comparison to the DES group (33.2 [21.3, 48.9] vs. 57.2 [39.9, 98.0], p = 0.005). No significant differences were observed in baseline LVEF (54.5 ± 10.2% vs. 53.1 ± 6.87%, p = .57), while LVEF was significantly improved at follow-up in the MNM group (61.1 ± 7.1% vs. 53.9 ± 6.35%, p = .0001)., Conclusion: MNM technology significantly improved coronary microvascular dysfunction after PCI in patient with acute coronary syndrome and appears as a useful technological option for thrombus management., (© 2021 Wiley Periodicals LLC.)

Aims: The role of diuretics in patients with intermediate-risk pulmonary embolism (PE) is controversial. In this multicentre, double-blind trial, we randomly assigned normotensive patients with intermediate-risk PE to receive either a single 80 mg bolus of furosemide or a placebo., Methods and Results: Eligible patients had at least a simplified PE Severity Index (sPESI) ≥1 with right ventricular dysfunction. The primary efficacy endpoint assessed 24 h after randomization included (i) absence of oligo-anuria and (ii) normalization of all sPESI items. Safety outcomes were worsening renal function and major adverse outcomes at 48 hours defined by death, cardiac arrest, mechanical ventilation, or need of catecholamine. A total of 276 patients underwent randomization; 135 were assigned to receive the diuretic, and 141 to receive the placebo. The primary outcome occurred in 68/132 patients (51.5%) in the diuretic and in 49/132 (37.1%) in the placebo group (relative risk = 1.30, 95% confidence interval 1.04-1.61; P = 0.021). Major adverse outcome at 48 h occurred in 1 (0.8%) patients in the diuretic group and 4 patients (2.9%) in the placebo group (P = 0.19). Increase in serum creatinine level was greater in diuretic than placebo group [+4 µM/L (-2; 14) vs. -1 µM/L (-11; 6), P < 0.001]., Conclusion: In normotensive patients with intermediate-risk PE, a single bolus of furosemide improved the primary efficacy outcome at 24 h and maintained stable renal function. In the furosemide group, urine output increased, without a demonstrable improvement in heart rate, systolic blood pressure, or arterial oxygenation.ClinicalTrials.gov identifier NCT02268903., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background: Excessive ventilation (V̇E) and abnormal gas exchange during exercise are features of chronic thromboembolic pulmonary hypertension (CTEPH). In selected CTEPH patients, balloon pulmonary angioplasty (BPA) improves symptoms and exercise capacity. How BPA affects exercise hyperventilation and gas exchange is poorly understood., Methods: In this longitudinal observational study, symptom-limited cardiopulmonary exercise tests and carbon monoxide lung diffusion (DLCO) were performed before and after BPA (interval, mean (SD): 3.1 (2.4) months) in 36 CTEPH patients without significant cardiac and/or pulmonary comorbidities., Results: Peak work rate improved by 20% after BPA whilst V̇E at peak did not change despite improved ventilatory efficiency (lower V̇E with respect to CO 2 output [V̇CO 2 ]). At the highest identical work rate pre- and post-BPA (75 (30) watts), V̇E and alveolar-arterial oxygen gradient (P(Ai-a)O 2 ) decreased by 17% and 19% after BPA, respectively. The physiological dead space fraction of tidal volume (VD/VT), calculated from measurements of arterial and mixed expired CO 2 , decreased by 20%. In the meantime, DLCO did not change. The best correlates of P(Ai-a)O 2 measured at peak exercise were physiological VD/VT before BPA and DLCO after BPA., Conclusions: Ventilatory efficiency, physiological VD/VT, and pulmonary gas exchange improved after BPA. The fact that DLCO did not change suggests that the pulmonary capillary blood volume and probably the true alveolar dead space were unaffected by BPA. The correlation between DLCO measured before BPA and P(Ai-a)O 2 measured after BPA suggests that DLCO may provide an easily accessible marker to predict the response to BPA in terms of pulmonary gas exchange., Competing Interests: Disclosure statement MBN, NP, AG, SD, MS, FT, CA, HB report no disclosures. CP reports personal fees from Boehringer Ingelheim, Glaxo Smith Kline, Astra Zeneca and Sanofi outside submitted work. BA reports honoraria and consulting fees grant funding from Boehringer Ingelheim, Glaxo Smith Kline, Menarini, Chiesi, Astra Zeneca and Sanofi unrelated to the submitted work. BD reports grant funding from Novartis and honoraria and consulting fees from Boehringer Ingelheim, Nuvaira, Menarini, Chiesi, Glaxo Smith Kline, Astra Zeneca and Sanofi unrelated to the submitted work., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Introduction: Since 2014, Balloon Pulmonary Angioplasty (BPA) has become an emerging and complementary strategy for chronic thromboembolic hypertension (CTEPH) patients who are not suitable for pulmonary endarterectomy (PEA) or who have recurrent symptoms after the PEA procedure., Objective: To assess the hospital cost of BPA sessions and management in CTEPH patients., Methods: An observational retrospective cohort study of CTEPH-adults hospitalized for a BPA between January 1st, 2014 and June 30th, 2016 was conducted in the 2 centres performing BPA in France (Paris Sud and Grenoble) using the French national hospital discharge database (PMSI-MCO). Patients were followed until 6 months or death, whichever occurred first. Follow-up stays were classified as stays with BPA sessions, for BPA management or for CTEPH management based on a pre-defined algorithm and a medical review using type of diagnosis (ICD-10), delay from last BPA procedure stay and length of stay. Hospital costs (including medical transports) were estimated from National Health Insurance perspective using published official French tariffs from 2014 to 2016 and expressed in 2017 Euros., Results: A total of 191 patients were analysed; mainly male (53%), with a mean age of 64,3 years. The first BPA session was performed 1.1 years in median (IQR 0.3-2.92) after the first PH hospitalisation. A mean of 3 stays with BPA sessions per patient were reported with a mean length of stay of 8 days for the first stay and 6 days for successive stays. The total hospital cost attributable to BPA was € 4,057,825 corresponding to €8,764±3,435 per stay and €21,245±12,843 per patient. Results were sensitive to age classes, density of commune of residence and some comorbidities., Conclusions: The study generated robust real-world data to assess the hospital cost of BPA sessions and management in CTEPH patients within its first years of implementation in France., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Experts: VC, JD, HB and PB are independent experts who received fees for participating in the scientific committee of the study. Outside the submitted work, VC reports personal fees and non-financial support from Actelion, grants, personal fees and non-financial support from Boehringer Ingelheim, personal fees from Bayer / MSD, personal fees from Novartis, personal fees and non-financial support from Roche / Promedior, personal fees from Sanofi, 2 personal fees from Celgene / BMS, personal fees from Galapagos, personal fees from Galecto, personal fees from Shionogi, personal fees from Astra Zeneca, personal fees from Fibrogen, personal fees from RedX, personal fees from PureTech. Outside the submitted work, HB has received personal fees and/or non-financial support from MSD, Actelion, GSK. Outside the submitted work, PB and JD have no competing interest in relation with this topic to declare. MSD employees: LB, AH and LLB are employees of MSD, the company which financed the study. HEVA employees: AV is one of the co-founders of the CRO HEVA; FR and GC are employees of HEVA, a company who received funding from the study sponsor for the conduct of this study and for the analysis of the data. These commercial affiliations does not alter adherence to all PLOS ONE policies on sharing data and materials.

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: Current guidelines recommend a risk-adjusted treatment strategy for the management of acute pulmonary embolism. This is a particular patient category for whom optimal treatment (anticoagulant treatment, reperfusion strategies, and duration of hospitalisation) is currently unknown. We investigated whether treatment of acute intermediate-risk pulmonary embolism with parenteral anticoagulation for a short period of 72 h, followed by a switch to a direct oral anticoagulant (dabigatran), is effective and safe., Methods: We did a multinational, multicentre, single-arm, phase 4 trial at 42 hospitals in Austria, Belgium, France, Germany, Italy, Netherlands, Romania, Slovenia, and Spain. Adult patients (aged ≥18 years) with symptomatic intermediate-risk pulmonary embolism, with or without deep-vein thrombosis, were enrolled. Patients received parenteral low-molecular-weight or unfractionated heparin for 72 h after diagnosis of pulmonary embolism before switching to oral dabigatran 150 mg twice per day following a standard clinical assessment. The primary outcome was recurrent symptomatic venous thromboembolism or pulmonary embolism-related death within 6 months. The primary and safety outcomes were assessed in the intention-to-treat population. The study was terminated early, as advised by the data safety and monitoring board, following sample size adaptation after the predefined interim analysis on Dec 18, 2018. This trial is registered with the EU Clinical Trials Register (EudraCT 2015-001830-12) and ClinicalTrials.gov (NCT02596555)., Findings: Between Jan 1, 2016, and July 31, 2019, 1418 patients with pulmonary embolism were screened, of whom 402 were enrolled and were included in the intention-to-treat analysis (median age was 69·5 years [IQR 60·0-78·0); 192 [48%] were women and 210 [52%] were men). Median follow-up was 217 days (IQR 210-224) and 370 (92%) patients adhered to the protocol. The primary outcome occurred in seven (2% [upper bound of right-sided 95% CI 3]; p<0·0001 for rejecting the null hypothesis) patients, with all events occurring in those with intermediate-high-risk pulmonary embolism (seven [3%; upper bound of right-sided 95% CI 5] of 283). At 6 months, 11 (3% [95% CI 1-5]) of 402 patients had at least one major bleeding event and 16 (4% [2-6]) had at least one clinically relevant non-major bleeding event; the only fatal haemorrhage occurred in one (<1%) patient before the switch to dabigatran., Interpretation: A strategy of early switch from heparin to dabigatran following standard clinical assessment was effective and safe in patients with intermediate-risk pulmonary embolism. Our results can help to refine guideline recommendations for the initial treatment of acute intermediate-risk pulmonary embolism, optimising the use of resources and avoiding extended hospitalisation., Funding: German Federal Ministry of Education and Research, University Medical Center Mainz, and Boehringer Ingelheim., Competing Interests: Declaration of interests FAK reports research grants from Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Merck Sharpe & Dohme, the Netherlands Organisation for Health Research and Development, Actelion, the Dutch Heart foundation, and the Dutch Thrombosis Association, all outside the submitted work. SB reports congress and travel payments from Daiichi Sankyo and Bayer; honoraria from BTG Pharmaceuticals, Boston Scientific, Bayer HealthCare, and LeoPharma; and institutional grants from Sanofi, all outside the submitted work. WA reports research support from Bayer, and participating in advisory boards for Bayer, Boehringer Ingelheim, Daiichi Sankyo, Portola, Janssen, Aspen, and Sanofi all outside the submitted work. MB reports consulting and speaker fees from Bayer Healthcare, Daiichi Sankyo, and Sanofi Aventis outside the submitted work. FC reports research grant support from Bristol-Myers Squibb-Pfizer Alliance; fees for board memberships or symposia from Bayer, Bristol-Myers Squibb-Pfizer Alliance, and Astra Zeneca; and travel support from Bayer, Bristol-Myers Squibb-Pfizer Alliance, Leo Pharma, and Actelion all outside the submitted work. KD reports unrestricted research support and speaker or consultant fees from Janssen outside the submitted work. DD reports speaker's honoraria from Bayer Vital, Daiichi Sankyo, and Bristol-Myers Squibb-Pfizer Alliance; and consulting fees from Bayer Vital and Daiichi Sankyo all outside the submitted work. KE reports lecture fees from AstraZeneca, Bayer Vital, Berlin Chemie, Boehringer Ingelheim, and Novartis; and consulting fees from Bayer Vital, Boehringer Ingelheim, Novartis, and Novo Nordisk all outside the submitted work. GG reports personal fees or research grants, or both, from Bayer, Boehringer Ingelheim, Leo, Merck Sharpe & Dohme, and Pfizer outside the submitted work. MVH reports grants from the ZonMW Dutch Healthcare Fund; and grants and personal fees to the Leiden University Medical Center from Boehringer Ingelheim, Bristol-Myers Squibb-Pfizer Alliance, Bayer Health Care, Aspen, and Daiichi Sankyo, all outside the submitted work. DJ reports serving as an advisor or consultant for Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Leo Pharma, Pfizer, ROVI, and Sanofi; serving as a speaker or a member of a speakers' bureau for Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Leo Pharma, ROVI, and Sanofi; and receiving grants for clinical research from Daiichi Sankyo, Sanofi, and ROVI all outside the submitted work. MK reports speaker fees from Pfizer, Boehringer Ingelheim, and Bayer outside the submitted work. IML reports receiving consulting fees and research grants from, and being a member of scientific advisory boards for AOPOrphan Pharmaceuticals, Actelion-Janssen, Merck Sharpe & Dohme, United Therapeutics, Medtronic, Neutrolis, and Ferrer, in addition to being an investigator in trials involving these companies. ML reports consultant and speaker fees from Actelion, Bayer, Thermo Fisher Scientific, Daiichi Sankyo, Merck Sharpe & Dohme, and Bristol-Myers Squibb-Pfizer Alliance; and project funding from Thermo Fisher Scientific all outside the submitted work. NM reports consulting fees, speaker fees, and project funding from Bayer and Bristol-Myers Squibb-Pfizer Alliance; speaker fees from AstraZeneca and Boehringer Ingelheim; and consulting fees from Abbott and Terumo all outside the submitted work. AOP reports speaker fees from SC Pfizer Romania, Servier Pharma, Novartis Pharma Services Romania, Bayer, and SC Sanience outside the submitted work. AS reports consulting fees from Pfizer outside the submitted work. SS reports consulting fees and speaker fees from Aspen and Boehringer Ingelheim; speaker fees from Bayer and Daiichi Sankyo; and project funding and speaker fees from Bristol-Myers Squibb-Pfizer Alliance all outside the submitted work. K-HS reports speaker and consulting fees from Merck Sharpe & Dohme, Janssen-Cilag, and Abbott outside the submitted work. FV reports research grants from Daiichi Sanyo, Boehringer-Ingelheim, Radiometer, and Biomerieux, outside the submitted work. SVK reports institutional research grants and personal consultancy or speaker fees from Actelion/Janssen, Bayer, Daiichi Sankyo, and Boston Scientific; institutional research grants from Boehringer Ingelheim and Servier; and personal consultancy or speaker fees from Bristol-Myers Squibb-Pfizer Alliance and Novartis all outside the submitted work. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Severe pulmonary edema, secondary to left ventricular afterload increment, is a common problem occurring in patients receiving venoarterial extracorporeal membrane oxygenation. No consensus is currently available for its management, but several devices/procedures have been described, including an Impella device (Abiomed), balloon atrial septostomy, intraaortic balloon counterpulsation, or an additional venous cannula, as possible adjuncts. We report the feasibility and efficacy of the atrial flow regulator device (Occlutech) for left ventricular unloading in a 58-year-old patient receiving extracorporeal membrane oxygenation. However, the benefits of this device relative to simple balloon atrial septostomy need to be further investigated., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: The folded valve is a manual shortening of the Melody device, which has been validated as a valuable therapeutic option for the management of dysfunctional right ventricular outflow tracts needing a short valved stent. In this article, we aimed to evaluate, in a multicenter cohort, the mid-term outcomes of patients in whom a percutaneous pulmonary valve implantation was performed using the folded valve technique., Methods: A 2012 to 2018 retrospective multicenter study was performed in 7 European institutions. All patients who benefit from percutaneous pulmonary valve implantation with a folded Melody valve were included., Results: A total of 49 patients (median age, 19 years [range 4–56], 63% male) were included. The primary percutaneous pulmonary valve implantation indication was right ventricular outflow tract stenosis (n=19; 39%), patched native right ventricular outflow tracts were the most common substrate (n=15; 31%). The folded technique was mostly used in short right ventricular outflow tracts (n=28; 57%). Procedural success was 100%. After a median follow-up of 28 months (range, 4–80), folded Melody valve function was comparable to the immediate postimplantation period (mean transvalvular peak velocity=2.6±0.6 versus 2.4±0.6 m/s, P>0.1; only 2 patients had mild pulmonary regurgitation). Incidence rate of valve-related reinterventions was 2.1% per person per year (95% CI, 0.1%–3.9%). The probability of survival without valve-related reinterventions at 36 months was 90% (95% CI, 76%–100%)., Conclusions: The folded Melody valve is a safe technique with favorable mid-term outcomes up to 6.5 years after implantation, comparable with the usual Melody valve implantation procedure. Complications and reinterventions rates were low, making this technique relevant in selected patients.

We present an exceptional case of a quadricuspid aortic valve associated with a left atrial myxoma. Both are rare conditions, and this association has not been reported yet. These conditions can be silent but may lead to several complications. This case highlights importance of a careful echocardiographic evaluation for early management. ( Level of Difficulty: Beginner. )., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2021 The Authors.)

Acute pulmonary embolism is a frequent cardiovascular emergency with an increasing incidence. The prognosis of patients with high-risk and intermediate-high-risk pulmonary embolism has not improved over the last decade. The current treatment strategies are mainly based on anticoagulation to prevent recurrence and reduce pulmonary vasculature obstruction. However, the slow rate of thrombus lysis under anticoagulation is unable to acutely decrease right ventricle overload and pulmonary vasculature resistance in patients with severe obstruction and right ventricle dysfunction. Therefore, patients with high-risk and intermediate-high-risk pulmonary embolism remain a therapeutic challenge. Reperfusion therapies may be discussed for these patients, and include systemic thrombolysis, catheter-directed therapies and surgical thrombectomy. High-risk patients require systemic thrombolysis, but may have contraindications as a result of the high risk of bleeding. In addition, intermediate-high-risk patients should not receive systemic thrombolysis, despite its high efficacy, because of prohibitive bleeding complications. Recently, percutaneous reperfusion techniques have been developed to acutely decrease pulmonary vascular obstruction with lower-dose or no thrombolytic agents and, thus, potentially higher safety than systemic thrombolysis. Some of these techniques improve key haemodynamic variables. Cardiac surgical techniques and venoarterial extracorporeal membrane oxygenation as temporary circulatory support may be useful in selected cases. The development of pulmonary embolism centres with multidisciplinary pulmonary embolism teams is mandatory to enable adequate use of reperfusion and improve outcomes. We aim to present the state of the art regarding reperfusion therapies in pulmonary embolism, but also to provide guidance on their indications and patient selection., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Objective: We aimed to compare baseline characteristics, coronary angiogram findings, and in-hospital outcomes between female and male patients with ST-segment elevation myocardial infarction (STEMI) under the age of 45 years., Background: Although sex differences in risk factor profile have been documented for young patients with STEMI, limited data exist on the prevalence of spontaneous coronary artery dissection in these patients., Methods: As part of an ongoing hospital-based registry of suspected STEMI, we analyzed the original data for 51 women under the age of 45 years matched with 93 men of similar age who underwent coronary angiography at two percutaneous coronary intervention centers, between January 2003 and December 2012. Two interventional cardiologists independently reviewed coronary angiograms for all patients., Results: The mean age for all patients was 39 years (range, 24-44) and the overall prevalence of cigarette smoking, dyslipidemia, hypertension, and diabetes mellitus were 70, 32, 13, and 4%, respectively. Young women were more likely to present with spontaneous coronary artery dissection (22 vs. 3%, p = .003) and more of them experienced reinfarction during the hospital course (15 vs. 1%, p = .01). The in-hospital mortality rate was 2% for both sexes., Conclusions: Spontaneous coronary artery dissection is an important cause of myocardial infarction in young female adults, accounting for 22% (95% confidence interval, 11-35%) of women with STEMI under the age of 45 years. The true prevalence of spontaneous coronary artery dissection might even be underestimated, because of the limited availability of advanced imaging techniques at the time of our study., (© 2019 Wiley Periodicals, Inc.)

Aims: Patent ductus arteriosus (PDA) is common in preterm infants and can contribute to morbidity and mortality. We aimed to compare results and outcome of transcatheter closure using the Amplatzer Piccolo Occluder versus surgical closure in 2 matched groups of preterm infants weighing <3000 g., Methods and Results: A total of 147 babies from three tertiary centres were retrospectively analysed. Sixty-four babies undergoing catheter closure were compared with 83 matched surgical cases. Patent ductus arteriosus closure was successful in all cases. During neonatal unit course, mortality was 6.3% (n = 4) after catheterization and 12% (n = 10) after surgery (p = 0.24). Median duration of mechanical ventilation was shorter after catheterisation than after surgery (3 vs 5 days, p = 0.035). Before 4 weeks of age the difference between transcatheter and surgical closure for mechanical ventilation was even more pronounced (3 vs 9 days, p = 0.022). Additionally, when catheterisation was performed before 4 weeks, babies were discharged home earlier as compared to those who underwent closure later in life (39 +1 vs. 42 +1 weeks, p = 0.021). Such difference was not found in the surgical group., Conclusions: Transcatheter closure of patent ductus arteriosus is safe, effective and is associated with shorter mechanical ventilation than after surgery. Hospital stay might be shorter when performed earlier in life., Competing Interests: Declaration of competing interest Alain Fraisse is consultant and proctor for Abbott and for Occlutech. Alban-Elouen Baruteau is consultant and proctor for Abbott., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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.)

Competing Interests: Competing interests: None declared.