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Chronic thromboembolic pulmonary hypertension occurs in a proportion of patients with prior acute pulmonary embolism and is characterised by breathlessness, persistently raised pulmonary pressures and right heart failure. Surgical pulmonary endarterectomy (PEA) offers significant prognostic and symptomatic benefits for patients with proximal disease distribution. For those with inoperable disease, management options include balloon pulmonary angioplasty (BPA) and medical therapy. Current clinical practice relies on the evaluation of pulmonary haemodynamics to assess disease severity, timing of and response to treatment. However, pulmonary haemodynamics correlate poorly with patient symptoms, which are influenced by right ventricular tolerance of the increased afterload. How best to manage symptomatic patients with chronic thromboembolic pulmonary disease (CTEPD) in the absence of pulmonary hypertension is not resolved.Right ventricular–pulmonary artery coupling (RV-PAC) describes the energy transfer within the whole cardiopulmonary unit. Thus, it can identify the earliest signs of decompensation even before pulmonary hypertension is overt. Invasive measurement of coupling using pressure volume loop technology is well established in research settings. The development of efficient and less invasive measurement methods has revived interest in coupling as a viable clinical tool. Significant improvement in RV-PAC has been demonstrated after both PEA and BPA. Further studies are required to understand its clinical utility and prognostic value, in particular, its potential to guide management in patients with CTEPD. Finally, given the reported differences in coupling between sexes in pulmonary arterial hypertension, further work is required to understand the applicability of proposed thresholds for decoupling in therapeutic decision making.

BACKGROUND: We describe baseline characteristics, disease progression and mortality in chronic thromboembolic pulmonary disease patients as a function of mean pulmonary artery pressure (mPAP) according to new and previous definitions of pulmonary hypertension. METHODS: All patients diagnosed with chronic thromboembolic pulmonary disease between January, 2015 and December, 2019 were dichotomized according to initial mPAP: ≤ 20 mmHg ('normal') vs 21-24 mmHg ('mildly-elevated'). Baseline features were compared between the groups, and pairwise analysis performed to determine changes in clinical endpoints at 1-year, excluding those who underwent pulmonary endarterectomy or did not attend follow-up. Mortality was assessed for the whole cohort over the entire study period. RESULTS: One hundred thirteen patients were included; 57 had mPAP ≤ 20 mmHg and 56 had mPAP 21-24 mmHg. Normal mPAP patients had lower pulmonary vascular resistance (1.6 vs 2.5WU, p < 0.01) and right ventricular end-diastolic pressure (5.9 vs 7.8 mmHg, p < 0.01) at presentation. At 3 years, no major deterioration was seen in either group. No patients were treated with pulmonary artery vasodilators. Eight had undergone pulmonary endarterectomy. Over 37 months median follow-up, mortality was 7.0% in the normal mPAP group and 8.9% in the mildly-elevated mPAP group. Cause of death was malignancy in 62.5% of cases. CONCLUSIONS: Chronic thromboembolic pulmonary disease patients with mild pulmonary hypertension have statistically higher right ventricular end-diastolic pressure and pulmonary vascular resistance than those with mPAP ≤ 20 mmHg. Baseline characteristics were otherwise similar. Neither group displayed disease progression on non-invasive tests up to 3 years. Mortality over 37 months follow-up is 8%, and mainly attributable to malignancy. Further prospective study is required to validate these findings.

AIMS: To develop a suite of quality indicators (QIs) for the evaluation of the care and outcomes for adults with pulmonary arterial hypertension (PAH). METHODS AND RESULTS: We followed the European Society of Cardiology (ESC) methodology for the development of QIs. This included (i) the identification of key domains of care for the management of PAH, (ii) the proposal of candidate QIs following systematic review of the literature, and (iii) the selection of a set of QIs using a modified Delphi method. The process was undertaken in parallel with the writing of the 2022 ESC/European Respiratory Society (ERS) guidelines for the diagnosis and treatment of pulmonary hypertension and involved the Task Force chairs, experts in PAH, Heart Failure Association (HFA) members and patient representatives. We identified five domains of care for patients with PAH: structural framework, diagnosis and risk stratification, initial treatment, follow-up, and outcomes. In total, 23 main and one secondary QIs for PAH were selected. CONCLUSION: This document presents the ESC QIs for PAH, describes their development process and offers scientific rationale for their selection. The indicators may be used to quantify and improve adherence to guideline-recommended clinical practice and improve patient outcomes. ispartof: EUROPEAN JOURNAL OF HEART FAILURE vol:25 issue:4 pages:469-477 ispartof: location:England status: published

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism. It is caused by persistent obstruction of pulmonary arteries by chronic organised fibrotic clots, despite adequate anticoagulation. The pulmonary hypertension is also caused by concomitant microvasculopathy which may progress without timely treatment. Timely and accurate diagnosis requires the combination of imaging and haemodynamic assessment. Optimal therapy should be individualised to each case and determined by an experienced multidisciplinary CTEPH team with the ability to offer all current treatment modalities. This report summarises current knowledge and presents key messages from the International CTEPH Conference, Bad Nauheim, Germany, 2021. Sessions were dedicated to 1) disease definition; 2) pathophysiology, including the impact of the hypertrophied bronchial circulation, right ventricle (dys)function, genetics and inflammation; 3) diagnosis, early after acute pulmonary embolism, using computed tomography and perfusion techniques, and supporting the selection of appropriate therapies; 4) surgical treatment, pulmonary endarterectomy for proximal and distal disease, and peri-operative management; 5) percutaneous approach or balloon pulmonary angioplasty, techniques and complications; and 6) medical treatment, including anticoagulation and pulmonary hypertension drugs, and in combination with interventional treatments. Chronic thromboembolic pulmonary disease without pulmonary hypertension is also discussed in terms of its diagnostic and therapeutic aspects. ispartof: EUROPEAN RESPIRATORY REVIEW vol:32 issue:167 ispartof: location:England status: published

INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) is an underdiagnosed disease of uncertain etiology. Altered endothelial homeostasis, defective angiogenesis and inflammation are implicated. Angiopoietin 2 (Ang2) impairs acute thrombus resolution and is associated with vasculopathy in idiopathic pulmonary arterial hypertension. METHODS: We assessed circulating proteins associated with these processes in serum from patients with CTEPH (n = 71) before and after pulmonary endarterectomy (PEA), chronic thromboembolic pulmonary disease without pulmonary hypertension (CTEPD, n = 9) and healthy controls (n = 20) using Luminex multiplex arrays. Comparisons between groups were made using multivariable rank regression models. Ang2 and high-sensitivity C-reactive protein (hsCRP) were measured in a larger validation dataset (CTEPH = 277, CTEPD = 26). Cox proportional hazards models were used to identify markers predictive of survival. RESULTS: In CTEPH patients, Ang2, interleukin (IL) 8, tumor necrosis factor α, and hsCRP were elevated compared to controls, while vascular endothelial growth factor (VEGF) c was lower (p < 0.05). Ang2 fell post-PEA (p < 0.05) and was associated with both pre- and post-PEA pulmonary hemodynamic variables and functional assessments (p < 0.05). In the validation dataset, Ang2 was significantly higher in CTEPH compared to CTEPD. Pre-operative hsCRP was an independent predictor of mortality. CONCLUSIONS: We hypothesize that CTEPH patients have significant distal micro-vasculopathy and consequently high circulating Ang2. Patients with CTEPD without pulmonary hypertension have no discernible distal micro-vasculopathy and therefore have low circulating Ang2. This suggests Ang2 may be critical to CTEPH disease pathogenesis (impaired thrombus organization and disease severity).

Rationale: Iron deficiency, in the absence of anemia, is common in patients with idiopathic and heritable pulmonary arterial hypertension (PAH) and is associated with a worse clinical outcome. Oral iron absorption may be impeded by elevated circulating hepcidin concentrations. The safety and benefit of parenteral iron replacement in this patient population is unclear. Objectives: To evaluate the safety and efficacy of parenteral iron replacement in PAH. Methods: In two randomized, double-blind, placebo-controlled 12-week crossover studies, 39 patients in Europe received a single infusion of ferric carboxymaltose (Ferinject) (1,000 mg or 15 mg/kg if weight

According to the US Centers for Disease Control and Prevention (CDC), patients with underlying health conditions, including all types of lung and cardiovascular diseases, have an increased risk of developing serious disease when infected by SARS-CoV-2 [1]. Based on prior publications on the effects of acute right heart failure superimposed on systemic infection [2–5], Ryan et al. [6] suggested that right heart failure and concomitant COVID-19 infection may result in increased mortality in pulmonary arterial hypertension (PAH) patients. Surprisingly, the number of hospitalised PAH-COVID-19 patients remained rather low in Italy and the USA so far [7]. In late March 2020, experts from over 32 US PH expert centres answered a query endorsed by the US Pulmonary Hypertension Association. COVID-19 infection was reported in 13 PAH patients, among whom three required intubation and one died. This is consequently raising the question whether and why PAH patients appear to be at lower risk of developing severe COVID-19 [7]., This international survey highlights that a limited number of PAH and CTEPH patients suffered from severe #COVID19 infection https://bit.ly/3jGuBQq

Background: Autoimmunity may play a role in idiopathic pulmonary arterial hypertension (IPAH). It is not clear if this is causative, or as a bystander of disease and if it carries any prognostic or treatment significance. Methods: Comprehensive immune phenotyping was performed in IPAH patients, utilising patient samples from the UK National cohort study of Idiopathic and Heritable PAH. Standardised flow cytometric analysis of peripheral blood mononuclear cell types was assessed in IPAH patients and healthy controls. Serum autoantibody biomarkers were assayed using a Protoplex™ autoimmune panel in 473 type I PAH patients and 946 matched controls. Finally, a GST-fusion human proteomic screen was undertaken to identify novel circulating autoantibodies in PAH, and 350 PAH sera samples ELISA assayed for a putative antibody to BMPR2. Findings: Flow cytometric immune profiling demonstrates IPAH is associated with a signature consistent with altered humoral immune response. Increased autoantibody positivity was detected in PAH and patient subgroups associated with worse haemodynamic parameters but better overall survival. We identify a small subset of PAH patients who demonstrate immunoglobulin reactivity to the extracellular domain of the TGFbeta superfamily receptor, BMPR2, a protein which is strongly associated with hereditary causes of the disease. Interpretation: This evidence strongly suggests a proportion of patients with IPAH have an autoimmune component to the disease and that the BMPR2 pathway may be a target. Future trials targeting inflammation need to consider biomarker stratification. Funding Information: NIHR BRC, The Dinosaur Trust, MRC (MC_UU_00002/4) and the Wellcome Trust [WT107881]. Declarations of Interest: Gerry Coghlan reports grants and personal fees for conference attendance from Johnson & Johnson, personal fees for lectures from GlaxoSmithKline, Bayer and MSD, outside the submitted work. Paul Corris reports grants and personal fees for lectures and consultations from Actelion and Bayer, and personal fees for lectures and consultations from MSD, outside the submitted work. Luke Howard reports grants, personal fees for lectures, steering committee and advisory board work, and non-financial support for meeting attendance from Actelion, personal fees for lectures and advisory board work from Bayer and MSD, personal fees for advisory board work from GSK, outside the submitted work. Martin Johnson reports grants and personal fees for meeting attendance, lectures, and advisory board work from Actelion and MSD, outside the submitted work. David Kiely reports grants, personal fees, and other support from Actelion, Bayer and GSK, and personal fees and other support from MSD, outside the submitted work. Allan Lawrie reports grants from British Heart Foundation and Medical Research Council, grants, personal fees, and travel support from Actelion Pharmaceuticals Ltd, grants and personal fees from GlaxoSmithKline, outside the submitted work. James Lordan has received modest honoraria from Actelion and modest support to attend conference from Merck Sharp & Dohme, outside the submitted work. Joanna Pepke Zaba received fees for research grant, support to travel to meetings and honoraria from Actelion, Bayer, GlaxoSmithKline and Merck Sharp & Dohme, outside the submitted work. S.John Wort has received modest honoraria from GlaxoSmithKline, Actelion and Bayer and has received significant research grants from Actelion and Bayer, outside the submitted work. Nicholas Morrell reports personal fees from GSK and Johnson & Johnson/Actelion, outside the submitted work. Mark Toshner reports personal fees from GSK, grants and personal fees from J&J/Actelion, grants from Merck and Bayer, outside the submitted work. All other authors have nothing to disclose Ethics Approval Statement: Ethical approval was obtained, and informed written consent was given. For collection and processing of samples for autoantibody analysis, including controls ethical approval was obtained (An integrated approach to dissect the determinants, risk factors and pathways of ageing in the immune system 15/EE/0327, IRAS # 188383 and Genetics and epidemiology of aging-associated conditions in the Sardinian population, ProgeNIA PROT 2171/CE).

BackgroundInflammation and dysregulated immunity are important in the development of pulmonary arterial hypertension (PAH). Compelling preclinical data supports the therapeutic blockade of interleukin-6 (IL-6) signalling.MethodsWe conducted a phase 2 open-label study of intravenous tocilizumab (8 mg·kg−1) over 6 months in patients with group 1 PAH. Co-primary end-points were safety, defined by incidence and severity of adverse events, and change in pulmonary vascular resistance. Separately, a mendelian randomisation study was undertaken on 11 744 individuals with European ancestry including 2085 patients with idiopathic/heritable disease for the IL-6 receptor (IL6R) variant (rs7529229), known to associate with circulating IL-6R levels.ResultsWe recruited 29 patients (male/female 10/19; mean±sd age 54.9±11.4 years). Of these, 19 had heritable/idiopathic PAH and 10 had connective tissue disease-associated PAH. Six were withdrawn prior to drug administration; 23 patients received at least one dose of tocilizumab. Tocilizumab was discontinued in four patients owing to serious adverse events. There were no deaths. Despite evidence of target engagement in plasma IL-6 and C-reactive protein levels, both intention-to-treat and modified intention-to-treat analyses demonstrated no change in pulmonary vascular resistance. Inflammatory markers did not predict treatment response. Mendelian randomisation did not support an effect of the lead IL6R variant on risk of PAH (OR 0.99, p=0.88).ConclusionAdverse events were consistent with the known safety profile of tocilizumab. Tocilizumab did not show any consistent treatment effect.

ISHLT members have recognized the importance of a consensus statement on the evaluation and management of patients with chronic thromboembolic pulmonary hypertension. The creation of this document required multiple steps, including the engagement of the ISHLT councils, approval by the Standards and Guidelines Committee, identification and selection of experts in the field, and the development of 6 working groups. Each working group provided a separate section based on an extensive literature search. These sections were then coalesced into a single document that was circulated to all members of the working groups. Key points were summarized at the end of each section. Due to the limited number of comparative trials in this field, the document was written as a literature review with expert opinion rather than based on level of evidence. (C) 2021 International Society for Heart and Lung Transplantation. All rights reserved.

EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study in patients with pulmonary hypertension treated with riociguat. Patients were followed for 1-4 years, and the primary outcomes were adverse events (AEs) and serious AEs (SAEs), including embolic/thrombotic and hemorrhagic events. Here we report data on patients with chronic thromboembolic pulmonary hypertension (CTEPH) receiving a vitamin K antagonist (VKA; n = 683) or a non-vitamin K antagonist oral anticoagulant (NOAC; n = 198) at baseline. AEs and SAEs were reported in 438 patients (64.1%) and 257 patients (37.6%), respectively, in the VKA group, and in 135 patients (68.2%) and 74 patients (37.4%) in the NOAC group. Exposure-adjusted hemorrhagic event rates were similar in the two groups, while exposure-adjusted embolic and/or thrombotic event rates were higher in the NOAC group, although the numbers of events were small. Further studies are required to determine the long-term effects of anticoagulation strategies in CTEPH. ispartof: JOURNAL OF HEART AND LUNG TRANSPLANTATION vol:41 issue:6 pages:716-721 ispartof: location:United States status: published

Anatomical and physiological changes in the right heart as a direct consequence of the upstream pressure overload characteristic of idiopathic pulmonary hypertension (IPAH) are likely to lead to conduction disease in these patients. However, the prevalence and clinical implications of atrioventricular conduction disease in IPAH patients are not well-characterized. In this observational cohort study, we show that conduction disease is far more prevalent in a cohort of 175 IPAH patients than a group of matched comparators (37.1% vs 10.8%), and is associated with older age, male sex and more severe right heart dilatation. However, conduction disease is independently associated with worse functionality and higher mortality in this patient group. Prospective study is required to substantiate this, and whether intervention such as prophylactic pacing could restore prognosis.

Background Although bradycardia-related sudden death is common in patients with idiopathic pulmonary arterial hypertension (IPAH), the prevalence and prognostic significance of atrioventricular (AV) conduction disease in this patient group is not well-established. Objectives – Determine the prevalence of AV conduction disorders in patients with IPAH – Investigate the relationship between AV block and functional outcomes and mortality. Method 12-lead electrocardiograms (ECGs) of patients with IPAH were analysed. Patients were categorised according to the presence or absence of AV block. Demographic, pulmonary haemodynamic, cardiac structural characteristics and expression of genes associated with cardiac conduction were compared and functional and mortality outcomes analysed between groups. Student's t-tests and χ2 tests were used to compare data. Survival was estimated using Kaplan-Meier analyses. Initial exploratory covariates were included in a univariate analysis and those terms with P-value of Results 135 IPAH patients (mean age 55±16 years, 28.1% male) were eligible for analysis. Median follow up was 9 years (interquartile range 4–14 years). AV block was seen in 34.8% of patients with IPAH compared to 10.8% of matched comparators (p IPAH patients with conduction disease were more likely to be older (59±16 vs 53±17 years, p=0.038). AV block was associated with more severe right ventricular (RV) basal dilatation (5.1±1.0 vs 4.3±0.7cm, p=0.013) and worse RV function (fractional area change 26±9% vs 31±9%, p=0.14). Pulmonary haemodynamics, right atrial size and resting and exertional oxygen saturations were not significantly different. Expression of HCN1, HCN2, SCN1B, SCN5A, CAV1, and KCN2 genes in peripheral blood from a subcohort was similar between those with and without AV block. Lower 6 minute walk distances (344±153 vs 408±140m, p=0.035) and worse CAMPHOR scores across all 3 domains were seen in those with AV block (figure 1), and mortality was significantly higher (36.2 vs 13.6%, p=0.002) (figure 2). On multivariate analysis the presence of bundle branch block (BBB) was independently associated with a 2.1-fold increased risk of death (95% CI 1.89–4.85, p=0.045). Conclusions AV conduction disorders are more prevalent in IPAH than the general population, and are associated with worse prognosis and functional status. Prospective study is required to validate this finding. In our cohort AV block could not be explained by hypoxia, differences in pulmonary haemodynamics nor, in a small subgroup, by differential expression of specific transmembrane ion channels implicated in cardiac conduction. More detailed investigation into causal mechanisms of AV block in IPAH could establish whether improved prognosis could be achieved by treatment of AV block. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

BACKGROUND Chronic thromboembolic pulmonary hypertension (CTEPH) is an uncommon complication of acute pulmonary emboli necessitating lifelong anticoagulation. Despite this, few data exist on the safety and efficacy of vitamin K antagonists (VKAs) in CTEPH and none for direct oral anticoagulants (DOACs). OBJECTIVES To evaluate outcomes and complication rates in CTEPH following pulmonary endarterectomy (PEA) for individuals receiving VKAs or DOACs. METHODS Consecutive CTEPH patients undergoing PEA between 2007 and 2018 were included in a retrospective analysis. Postoperative outcomes, recurrent venous thromboembolism (VTE), and bleeding events were obtained from patient medical records. RESULTS Seven hundred ninety-four individuals were treated with VKAs and 206 with DOACs following PEA. Mean observation period was 612 (standard deviation: 702) days. Significant improvements in hemodynamics and functional status were observed in both groups following PEA (P

Background Pulmonary endarterectomy (PEA), pulmonary arterial hypertension (PAH) therapy and balloon pulmonary angioplasty (BPA) are currently accepted therapies for chronic thromboembolic pulmonary hypertension (CTEPH). This international CTEPH Registry identifies clinical characteristics of patients, diagnostic algorithms and treatment decisions in a global context. Methods 1010 newly diagnosed consecutive patients were included in the registry between February 2015 and September 2016. Diagnosis was confirmed by right heart catheterisation, ventilation–perfusion lung scan, computerised pulmonary angiography and/or invasive pulmonary angiography after at least 3 months on anticoagulation. Results Overall, 649 patients (64.3%) were considered for PEA, 193 (19.1%) for BPA, 20 (2.0%) for both PEA and BPA, and 148 (14.7%) for PAH therapy only. Reasons for PEA inoperability were technical inaccessibility (n=235), comorbidities (n=63) and patient refusal (n=44). In Europe and America and other countries (AAO), 72% of patients were deemed suitable for PEA, whereas in Japan, 70% of patients were offered BPA as first choice. Sex was evenly balanced, except in Japan where 75% of patients were female. A history of acute pulmonary embolism was reported for 65.6% of patients. At least one PAH therapy was initiated in 35.8% of patients (26.2% of PEA candidates, 54.5% of BPA candidates and 54.1% of those not eligible for either PEA or BPA). At the time of analysis, 39 patients (3.9%) had died of pulmonary hypertension-related causes (3.5% after PEA and 1.8% after BPA). Conclusions The registry revealed noticeable differences in patient characteristics (rates of pulmonary embolism and sex) and therapeutic approaches in Japan compared with Europe and AAO., There are distinct regional differences in the management of CTEPH patients but globally, the proportion of patients managed by PEA remains stable, independently of the new established treatment options of PAH therapies and BPA https://bit.ly/3zEXxkv

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism, either symptomatic or not. The occlusion of proximal pulmonary arteries by fibrotic intravascular material, in combination with a secondary microvasculopathy of vessels

BackgroundPulmonary arterial hypertension (PAH) covers a range of life-limiting illnesses characterized by increased pulmonary arterial pressures leading to right heart failure and death, if untreated. 15-25% of patients have genetic mutations, the most common affecting bone morphogenetic protein receptor type 2 (BMPR2). The aim was to define an inflammatory cytokine profile in BMPR2-mutation positive patients and analyze their influence on survival.MethodsLevels of cytokines were measured in plasma samples from BMPR2-mutation positive patients (BMPR2mut, n=54), patients without any driving mutations (n=54), and healthy controls (n=56) recruited from the United Kingdom cohort.FindingsBMPR2-mutation positive patients and patients without mutations had high levels of interleukin-6, interleukin-8, tumor necrosis factor-α, and vascular endothelial growth factor-A compared to controls. Only BMPR2-mutation carrying patients had higher G-CSF levels compared to controls. VEGF-A levels were substantially higher in patients without mutations compared to the BMPR2mut group. Interleukin-6 was a significant discriminator for mortality in the BMPR2mut cohort (cumulative survival with interleukin-6≥1.6pg/ml at 3 years was 65% compared to 96% with interleukin-6P=0·0013). N-Terminal pro-B-Type natriuretic peptide levels did not discriminate for survival in our BMPR2mut cohort (cumulative survival for patients with an NT-proBNP>130ng/ml at 3 years was 76% compared to 84% for patients with an NT-proBNP≤130ng/ml, P=0·37). NT-proBNP outperformed interleukin-6 in PAH without mutations.InterpretationBMPR2-mutation positivity has a direct impact not only on inflammatory profiles but also on effectiveness of prognostic biomarkers. In our BMPR2-mutation positive cohort IL-6 was the strongest prognostic biomarker and NT-proBNP failed to discriminate for survival.Key messagesWhat is the key question?Do pulmonary arterial hypertension patients who are BMPR2-mutation positive have a different cytokine signature than PAH patients without mutations?What is the bottom line?BMPR2-mutation positive and PAH patients without mutations display different patterns of cytokine elevation and these cytokines differ in the way they influence transplant-free survival.Why read on?In our cohort of BMPR2-mutation positive patients, IL-6 is the best prognostic biomarker while NT-proBNP failed to discriminate for survival – this implies that prognostic biomarkers and by inference treatments could be genotype-specific.Graphical AbstractTAKE HOME MESSAGEBMPR2-mutation positive patients have different inflammatory and growth factor profiles compared to PAH patients without mutations. Interleukin-6 is an effective biomarker for transplant-free survival in our cohort of BMPR2-mutation positive patients while NT-proBNP is ineffective. Conversely, NT-proBNP appears to be a more effective biomarker for pulmonary arterial patients without any mutations.

Background During the COVID-19 pandemic, most of the health care systems suspended their non-urgent activities. This included the cancellation of consultations for patients with rare diseases, such as severe pulmonary hypertension (PH), resulting in potential medication shortage and loss of follow-up. Thus, the aim of the study was to evaluate PH patient health status evolution, access to health care and mental health experience during the early phase of the pandemic. Methods We conducted an online patient survey, available in 16 languages, between 22/05/2020 and 28/06/2020. The survey included questions corresponding to demographic, COVID-19 and PH related information. Results 1073 patients (or relatives, 27%) from 52 countries all over the world participated in the survey. Seventy-seven percent (77%) of responders reported a diagnosis of pulmonary arterial hypertension and 15% of chronic thromboembolic PH. The COVID-19 related events were few: only 1% of all responders reported a diagnosis of COVID-19. However, 8% of patients reported health deterioration possibly related to PH, and 4% hospitalization for PH. Besides, 11% of the patients reported difficulties to access their PH expert centre, and 3% interruption of treatment due to shortage of medication. Anxiety or depression was reported by 67% of the participants. Conclusion Although COVID-19 incidence in PH patients was low, PH related problems occurred frequently as the pandemic progressed, including difficulties to have access to specialized care. The importance of primary health care was emphasized. Further studies are needed to evaluate the long-term consequences of COVID-related PH care disruption.

BACKGROUND Balloon pulmonary angioplasty (BPA) is delivered as a series of treatments for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) however, there is little published data on the procedural determinants of outcome. METHODS Pre- and post-BPA clinical and hemodynamic data, as well as serial hemodynamic and procedural data at each BPA session were evaluated to determine patient and procedure-related factors that influence hemodynamic response. RESULTS Per procedure data from 210 procedures in 84 patients and per patient data from 182 procedures in 63 patients with completed treatment and 3-month follow-up were analyzed. A median of 3 (range 1-6) BPA procedures treating a median of 2 segments per procedure (range 1-3) were performed per patient with a median interval between procedures of 42 (range 5-491) days. Clinical outcome correlated with hemodynamic change (pulmonary vascular resistance [ΔPVR] vs Cambridge Pulmonary Hypertension Outcome Review [CAMPHOR] symptom score: p < 0.001, Pearson's r = 0.48, n = 49). Responders to BPA had more severe disease at baseline and 37.5 % of non-responders were post-PEA. There was a dose-response relationship between per procedure and total number of segments treated and hemodynamic improvement (ΔPVR: 1 segment: -0.9%, 2: -14.5%, 3 or more: -16.1%, p < 0.001). Treating totally occluded vessels had a greater hemodynamic effect (mean pulmonary artery pressure [ΔmPAP]: sessions with occlusion: -8.0%, without occlusion treated: -3.2%, p < 0.05) without an increased complication rate. CONCLUSIONS The magnitude of clinical benefit is related to the hemodynamic effect of BPA which in turn is related to the number of segments treated and lesion severity. Patients who were post-PEA were less likely to respond to BPA.

Health-related quality of life (HRQoL) scores assess symptom burden in pulmonary arterial hypertension (PAH) but data regarding their role in prognostication and risk stratification are limited. We assessed these relationships using the emPHasis-10 HRQoL measure. 1745 patients with idiopathic or connective tissue disease-associated PAH who had completed emPHasis-10 questionnaires between 2014-17 at 6 UK referral centres were identified. Correlations with exercise capacity and WHO functional class (FC) were assessed, and exploratory risk stratification thresholds were tested. Moderate correlations were seen between emPHasis-10 scores and 6-minute walk distance (r=-0.546), incremental shuttle walking distance (r=-0.504) and WHO FC (r=0.497; p all