Challenges and advances in the heterologous expression of cellulolytic enzymes: a review

Second generation biofuel development is increasingly reliant on the recombinant expression of cellulases. Designing or identifying successful expression systems is thus of preeminent importance to industrial progress in the field. Recombinant production of cellulases has been performed using a wide range of expression systems in bacteria, yeasts and plants. In a number of these systems, particularly when using bacteria and plants, significant challenges have been experienced in expressing full-length proteins or proteins at high yield. Further difficulties have been encountered in designing recombinant systems for surface-display of cellulases and for use in consolidated bioprocessing in bacteria and yeast. For establishing cellulase expression in plants, various strategies are utilized to overcome problems, such as the auto-hydrolysis of developing plant cell walls. In this review, we investigate the major challenges, as well as the major advances made to date in the recombinant expression of cellulases across the commonly used bacterial, plant and yeast systems. We review some of the critical aspects to be considered for industrial-scale cellulase production

Trends in COVID-19-associated mortality in patients with pulmonary hypertension: a COMPERA analysis

In patients with pulmonary hypertension, the mortality rate associated with COVID-19 has declined sharply with the emergence of the Omicron variants https://bit.ly/42OMsf

Pulmonary Hypertension in Patients With COPD : Results From the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA)

Funding Information: FUNDING/SUPPORT: This work was supported by the German Center of Lung Research (DZL). COMPERA is funded by unrestricted grants from Acceleron , Actelion Pharmaceuticals , Bayer , OMT , and GSK . Funding Information: Financial/nonfinancial disclosures: The authors have reported to CHEST the following: C. D. V. has received fees for serving as a speaker, consultant, and an advisory board member from the following companies: Acceleron, Actelion, Bayer, Dompè, GSK, Janssen, MSD, Pfizer, and United Therapeutics. M. M. H. has received speaker fees, honoraria, or both for consultations from Acceleron, Actelion, Bayer, Janssen, MSD, and Pfizer. D. H. has received travel compensation from Actelion, Boehringer-Ingelheim, and Shire. D. P. has received fees for consultations from Actelion, Aspen, Biogen, Bayer, Boehringer Ingelheim, Johnson & Johnson, Novartis, Daiichi Sankyo, Sanofi, and Pfizer. N. B. received speaker fees from Bayer/MSD and Actelion/Janssen. K. M. O. has received speaker fees from Actelion, Bayer, and Lilly. H. A. G. has received honorariums for consultations, speaking at conferences, or both from Bayer HealthCare AG, Actelion, Encysive, Pfizer, Ergonex, Lilly, and Novartis. He is member of advisory boards for Bayer HealthCare AG, Pfizer, GSK, Actelion, Lilly, Merck, Encysive, and Ergonex. He also has received governmental grants from the German Research Foundation (DFG), Excellence Cluster Cardiopulmonary Research (ECCPS), State Government of Hessen (LOEWE), and the German Ministry for Education and Research (BMBF). M. Held has received speaker fees and honoraria for consultations from Actelion, Bayer, Boehringer Ingelheim Pharma, Encysive, Glaxo Smith Kline, Lilly, Janssen, Novartis, Pfizer, Nycomed, Roche, and Servier. H. K. has received speaker fees and honoraria for consultations from Actelion, Bayer, GSK, Lilly, Novartis, Pfizer, and United Therapeutics and research grants from Actelion. T. J. L. has received speaker fees, honoraria for consultations, and research funding from Actelion, Acceleron Pharma, Bayer, GSK, Janssen-Cilag, MSD, and Pfizer. S. R. has received honoraria for lectures, consultancy, or both from Actavis, Actelion, Bayer, GSK, Lilly, Novartis, Pfizer, and United Therapeutics. D. D. declares honoraria for lectures, consultancy, or both from Actelion, Bayer, GSK, Novartis, Pfizer, and Servier; participation in clinical trials for Actelion, Bayer, GSK, and Novartis; and research support to his institution from Actelion. R. B. has received fees from GSK, UT, Dompè, Bayer, Ferrer, MSD, and AOP Orphan Pharmaceuticals. M. C. has received fees for consulting from GSK and speaker fees from Bayer and Pfizer. M. Halank has received speaker fees and/or honoraria for consultations from Acceleron, Actelion, AstraZeneca, Bayer, BayerChemie, GSK, Janssen, MSD and Novartis. A. V.-N. reports receiving lecture fees from Actelion, Bayer, GlaxoSmithKline, Lilly, and Pfizer; serves on the advisory board of Actelion and Bayer; and serves on steering committees for Actelion, Bayer, GlaxoSmithKline, and Pfizer. D. S. received fees for lectures, consulting, research support, or a combination thereof to his institution from Actelion, Bayer, GSK, and Pfizer. R. E. has received speaker fees and honoraria for consultations from Actelion, Bayer, GSK, Lilly, Novartis, Pfizer, and United Therapeutics. J. S. R. G. has received speaker fees and honoraria for consultations from Acceleron, Actelion, Bayer, Complexa, GSK, MSD, Pfizer, and United Therapeutics. M. D. has received investigator, speaker, consultant, or steering committee member fees from Actelion, Aventis Pharmaceuticals, Bayer, Eli Lilly, Encysive, Gilead (Myogen), GlaxoSmithKline, Nippon Shyniaku, Novartis, Pfizer, Schering, and United Therapeutics; educational grants from Actelion, GlaxoSmithKline, Pfizer, and Therabel; and research grants from Actelion, Pfizer, and GlaxoSmithKline. She is holder of the Actelion Chair for Pulmonary Hypertension and of the GSK chair for research and education in pulmonary vascular pathology at the Catholic University of Leuven. J. C. has received fees for consultancies and lectures from Actelion, Bayer, GSK, United Therapeutics, and Pfizer as well as equipment and educational grants from Actelion. C. O. has received speaker fees and honoraria for consultations from Actelion, Bayer, GSK, Lilly, Novartis, and Pfizer. H. K. has received honoraria for lectures, consultancy, or both from Actelion-Janssen, Amicus Therapeutics, and Bristol Meyers Squibb. O. D. has or had consultancy relationships, has received research funding (last 3 years), or both from AbbVie, Actelion, Acceleron Pharma, Amgen, AnaMar, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, Catenion, Competitive Corpus, Drug Development International Ltd, CSL Behring, ChemomAb, Ergonex, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, Italfarmaco, iQone, iQvia, Kymera Therapeutics, Lilly, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Target Bio Science, and UCB in the area of potential treatments of scleroderma and its complications including PH. In addition, he has a patent mir-29 for the treatment of systemic sclerosis issued (US8247389, EP2331143). E. G. has received honoraria for consultations, speaking at conferences, or both from Bayer/MSD, Actelion/Janssen, GWT-TUD, and OMT/United Therapeutics. None declared (A. S.). Publisher Copyright: © 2021 The AuthorsBackground: Pulmonary hypertension (PH) in COPD is a poorly investigated clinical condition. Research Question: Which factors determine the outcome of PH in COPD? Study Design and Methods: We analyzed the characteristics and outcome of patients enrolled in the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) with moderate or severe PH in COPD as defined during the 6th PH World Symposium who received medical therapy for PH and compared them with patients with idiopathic pulmonary arterial hypertension (IPAH). Results: The population included incident patients with moderate PH in COPD (n = 68), with severe PH in COPD (n = 307), and with IPAH (n = 489). Patients with PH in COPD were older, predominantly male, and treated mainly with phosphodiesterase-5 inhibitors. Despite similar hemodynamic impairment, patients with PH in COPD achieved a worse 6-min walking distance (6MWD) and showed a more advanced World Health Organization functional class (WHO FC). Transplant-free survival rates at 1, 3, and 5 years were higher in the IPAH group than in the PH in COPD group (IPAH: 94%, 75%, and 55% vs PH in COPD: 86%, 55%, and 38%; P = .004). Risk factors for poor outcomes in PH in COPD were male sex, low 6MWD, and high pulmonary vascular resistance (PVR). In patients with severe PH in COPD, improvements in 6MWD by ≥ 30 m or improvements in WHO FC after initiation of medical therapy were associated with better outcomes. Interpretation: Patients with PH in COPD were functionally more impaired and had a poorer outcome than patients with IPAH. Predictors of death in the PH in COPD group were sex, 6MWD, and PVR. Our data raise the hypothesis that some patients with severe PH in COPD may benefit from PH treatment. Randomized controlled studies are necessary to explore this hypothesis further. Trial Registry: ClinicalTrials.gov; No.: NCT01347216; URL: www.clinicaltrials.govpublishersversionPeer reviewe

A revised host galaxy association for GRB 020819B: a high-redshift dusty starburst, not a low-redshift gas-poor spiral

The purported spiral host galaxy of GRB 020819B at z = 0.41 has been seminal in establishing our view of the diversity of long-duration gamma-ray burst environments: Optical spectroscopy of this host provided evidence that gamma-ray bursts (GRBs) can form even at high metallicities, whereas millimetric observations suggested that GRBs may preferentially form in regions with minimal molecular gas. We report new observations from the Very Large Telescope (Multi Unit Spectroscopic Explorer and X-shooter), which demonstrate that the purported host is an unrelated foreground galaxy. The probable radio afterglow is coincident with a compact, highly star forming, dusty galaxy at z = 1.9621. The revised redshift naturally explains the apparent non-detection of CO (3–2) line emission at the afterglow site from the Atacama Large Millimetre Observatory. There is no evidence that molecular gas properties in GRB host galaxies are unusual, and limited evidence that GRBs can form readily at a super-Solar metallicity

Medical treatment of pulmonary hypertension in adults with congenital heart disease : updated and extended results from the International COMPERA-CHD Registry

Funding Information: The authors are indebted to the COMPERA investigators and their staff. We explicitly thank Dr. Claudia S. Copeland for the professional editing of the final draft of the manuscript. Funding: COMPERA is funded by unrestricted grants from Acceleron, Actelion Pharmaceuticals (Janssen), Bayer, OMT and GSK. These companies were not involved in data analysis or the writing of this manuscript. Funding Information: ICMJE uniform disclosure form (available at https:// dx.doi.org/10.21037/cdt-21-351). The series “Current Management Aspects in Adult Congenital Heart Disease (ACHD): Part IV” was commissioned by the editorial office without any funding or sponsorship. Dr. DH reports non-financial support from Actelion, Boehringer-Ingelheim, and Shire, outside the submitted work; Dr. DP reports personal fees from Actelion, Biogen, Aspen, Bayer, Boehringer Ingelheim, Daiichi Sankyo, and Sanofi, outside the submitted work; Dr. MD reports personal fees from Actelion, Bayer, GSK and MSD, outside the submitted work; Dr. HAG reports personal fees from Actelion, Bayer, Gilead, GSK, MSD, Pfizer and United Therapeutics, outside the submitted work; Dr. MG reports personal fees from Actelion, Bayer and GSK, outside the submitted work; Dr. MMH reports personal fees from Acceleron, Actelion, Bayer, MSD and Pfizer, outside the submitted work; Dr. CDV reports personal fees from Actelion, Bayer, GSK, MSD, Pfizer, and United Therapeutics, outside the submitted work; Dr. RE reports personal fees from Actelion, Boehringer Ingelheim, OMT, Bayer, and Berlin Chemie; grants from Actelion and Boehringer Ingelheim, outside the submitted work; Dr. MH reports grants and personal fees from Actelion, personal fees from Bayer, Berlin Chemie, Boehringer Ingelheim, GSK, Janssen, Novartis and MSD, outside the submitted work; Dr. MH reports personal fees from Acceleron, Actelion, AstraZeneca, Bayer, BERLIN CHEMIE, GSK, MSD, Novartis and OMT, outside the submitted work; Dr. HW reports personal fees from Action, Bayer, Biotest, Boehringer, GSK, Pfizer, and Roche, outside the submitted work; Dr. DS reports personal fees from Actelion, Bayer, and GSK, outside the submitted work; Dr. LS reports personal fees from Actelion, Bayer, and MSD, outside the submitted work; Dr. SU reports grants from Swiss National Science Foundation, Zurich Lung, Swiss Lung, and Orpha Swiss, grants and personal fees from Actelion SA/Johnson & Johnson, Switzerland, and MSD Switzerland, outside the submitted work; Dr. TJL reports personal fees from Actelion, Janssen-Cilag, BMS, MSD, and OMT GmbH, outside the submitted work; Dr. LB reports personal fees from Actelion, outside the submitted work; Dr. MC reports personal fees from Boehringer Ingelheim Pharma GmbH, Roche Pharma, and Boehringer Ingelheim, outside the submitted work; Dr. HW reports personal fees from Boehringer Ingelheim, and Roche, outside the submitted work. Dr. EG reports personal fees from Actelion, Janssen, Bayer, MSD, Bial, OrPha Swiss GmbH, OMT and Medscape, outside the submitted work; Dr. SR reports personal fees from Actelion, Bayer, GSK, Pfizer, Novartis, Gilead, MSD, and United Therapeutics, outside the submitted work. The authors have no other conflicts of interest to declare. Publisher Copyright: © Cardiovascular Diagnosis and Therapy. All rights reserved.Background: Pulmonary arterial hypertension (PAH) is common in congenital heart disease (CHD). Because clinical-trial data on PAH associated with CHD (PAH-CHD) remain limited, registry data on the long-term course are essential. This analysis aimed to update information from the COMPERA-CHD registry on management strategies based on real-world data. Methods: The prospective international pulmonary hypertension registry COMPERA has since 2007 enrolled more than 10,000 patients. COMPERA-CHD is a sub-registry for patients with PAH-CHD Results: A total of 769 patients with PAH-CHD from 62 specialized centers in 12 countries were included into COMPERA-CHD from January 2007 through September 2020. At the last follow-up in 09/2020, patients [mean age 45.3±16.8 years; 512 (66%) female] had either post-tricuspid shunts (n=359; 46.7%), pre-tricuspid shunts (n=249; 32.4%), complex CHD (n=132; 17.2%), congenital left heart or aortic valve or aortic disease (n=9; 1.3%), or miscellaneous CHD (n=20; 2.6%). The mean 6-minute walking distance was 369±121 m, and 28.2%, 56.0%, and 3.8% were in WHO functional class I/II, III or IV, respectively (12.0% unknown). Compared with the previously published COMPERA-CHD data, after 21 months of followup, the number of included PAH-CHD patients increased by 91 (13.4%). Within this group the number of Eisenmenger patients rose by 39 (16.3%), the number of “Non-Eisenmenger PAH” patients by 45 (26.9%). Currently, among the 674 patients from the PAH-CHD group with at least one follow-up, 450 (66.8%) received endothelin receptor antagonists (ERA), 416 (61.7%) PDE-5 inhibitors, 85 (12.6%) prostacyclin analogues, and 36 (5.3%) the sGC stimulator riociguat. While at first inclusion in the COMPERA-CHD registry, treatment was predominantly monotherapy (69.3%), this has shifted to favoring combination therapy in the current group (53%). For the first time, the nature, frequency, and treatment of significant comorbidities requiring supportive care and medication are described. Conclusions: Analyzing “real life data” from the international COMPERA-CHD registry, we present a comprehensive overview about current management modalities and treatment concepts in PAH-CHD. There was an trend towards more aggressive treatment strategies and combination therapies. In the future, particular attention must be directed to the “Non-Eisenmenger PAH” group and to patients with complex CHD, including Fontan patients.publishersversionPeer reviewe

Idiopathic pulmonary arterial hypertension phenotypes determined by cluster analysis from the COMPERA registry

Funding Information: Marius M. Hoeper has received fees for lectures and/or consultations from Acceleron, Actelion, Bayer, MSD, and Pfizer. Nicola Benjamin has received fees for lectures and/or consultations from Actelion. Ekkehard Grünig has received fees for lectures and/or consultations from Actelion, Bayer, GSK, MSD, United Therapeutics, and Pfizer. Karen M. Olsson has received fees for lectures and/or consultations from Actelion, Bayer, United Therapeutics, GSK, and Pfizer. C. Dario Vizza has received fees from Actelion, Bayer, GSK, MSD, Pfizer, and United Therapeutics Europe. Anton Vonk-Noordegraaf has received fees for lectures and/or consultation from Actelion, Bayer, GSK, and MSD. Oliver Distler has/had a consultancy relationship with and/or has received research funding from 4-D Science, Actelion, Active Biotec, Bayer, Biogen Idec, Boehringer Ingelheim Pharma, BMS, ChemoAb, EpiPharm, Ergonex, espeRare foundation, GSK, Genentech/Roche, Inventiva, Lilly, medac, MedImmune, Mitsubishi Tanabe, Pharmacyclics, Pfizer, Sanofi, Serodapharm, and Sinoxa in the area of potential treatments of scleroderma and its complications including pulmonary arterial hypertension. In addition, Prof Distler has a patent for mir-29 for the treatment of systemic sclerosis licensed. Christian Opitz has received fees from Actelion, Bayer, GSK, Pfizer, and Novartis. J. Simon R. Gibbs has received fees for lectures and/or consultations from Actelion, Bayer, Bellerophon, GSK, MSD, and Pfizer. Marion Delcroix has received fees from Actelion, Bayer, GSK, and MSD. H. Ardeschir Ghofrani has received fees from Actelion, Bayer, Gilead, GSK, MSD, Pfizer, and United Therapeutics. Doerte Huscher has received fees for lectures and consultations from Actelion. David Pittrow has received fees for consultations from Actelion, Biogen, Aspen, Bayer, Boehringer Ingelheim, Daiichi Sankyo, and Sanofi. Stephan Rosenkranz has received fees for lectures and/or consultations from Actelion, Bayer, GSK, Pfizer, Novartis, Gilead, MSD, and United Therapeutics. Martin Claussen reports honoraria for lectures from Boehringer Ingelheim Pharma GmbH and Roche Pharma and for serving on advisory boards from Boehringer Ingelheim, outside the submitted work. Heinrike Wilkens reports personal fees from Boehringer and Roche during the conduct of the study and personal fees from Bayer, Biotest, Actelion, GSK, and Pfizer outside the submitted work. Juergen Behr received grants from Boehringer Ingelheim and personal fees for consultation or lectures from Actelion, Bayer, Boehringer Ingelheim, and Roche. Hubert Wirtz reports personal fees from Boehringer Ingelheim and Roche outside the submitted work. Hening Gall reports personal fees from Actelion, AstraZeneca, Bayer, BMS, GSK, Janssen-Cilag, Lilly, MSD, Novartis, OMT, Pfizer, and United Therapeutics outside the submitted work. Elena Pfeuffer-Jovic reports personal fees from Actelion, Boehringer Ingelheim, Novartis, and OMT outside the submitted work. Laura Scelsi reports personal fees from Actelion, Bayer, and MSD outside the submitted work. Siliva Ulrich reports grants from Swiss National Science Foundation, Zurich Lung, Swiss Lung, and Orpha Swiss, and grants and personal fees from Actelion SA/Johnson & Johnson Switzerland and MSD Switzerland outside the submitted work. The remaining authors have no conflicts of interest to disclose. Funding Information: This work was supported by the German Centre of Lung Research (DZL). COMPERA is funded by unrestricted grants from Acceleron , Actelion Pharmaceuticals , Bayer , OMT , and GSK . These companies were not involved in data analysis or the writing of this manuscript. Publisher Copyright: © 2020 The Authors Copyright: Copyright 2020 Elsevier B.V., All rights reserved.The term idiopathic pulmonary arterial hypertension (IPAH) is used to categorize patients with pre-capillary pulmonary hypertension of unknown origin. There is considerable variability in the clinical presentation of these patients. Using data from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension, we performed a cluster analysis of 841 patients with IPAH based on age, sex, diffusion capacity of the lung for carbon monoxide (DLCO; <45% vs ≥45% predicted), smoking status, and presence of comorbidities (obesity, hypertension, coronary heart disease, and diabetes mellitus). A hierarchical agglomerative clustering algorithm was performed using Ward's minimum variance method. The clusters were analyzed in terms of baseline characteristics; survival; and response to pulmonary arterial hypertension (PAH) therapy, expressed as changes from baseline to follow-up in functional class, 6-minute walking distance, cardiac biomarkers, and risk. Three clusters were identified: Cluster 1 (n = 106; 12.6%): median age 45 years, 76% females, no comorbidities, mostly never smokers, DLCO ≥45%; Cluster 2 (n = 301; 35.8%): median age 75 years, 98% females, frequent comorbidities, no smoking history, DLCO mostly ≥45%; and Cluster 3 (n = 434; 51.6%): median age 72 years, 72% males, frequent comorbidities, history of smoking, and low DLCO. Patients in Cluster 1 had a better response to PAH treatment than patients in the 2 other clusters. Survival over 5 years was 84.6% in Cluster 1, 59.2% in Cluster 2, and 42.2% in Cluster 3 (unadjusted p < 0.001 for comparison between all groups). The population of patients diagnosed with IPAH is heterogenous. This cluster analysis identified distinct phenotypes, which differed in clinical presentation, response to therapy, and survival.publishersversionPeer reviewe

Global Tipping Points Report 2023: Ch1.2: Cryosphere tipping points.

Drastic changes in our planet’s frozen landscapes have occurred over recent decades, from Arctic sea ice decline and thawing of permafrost soils to polar amplification, the retreat of glaciers and ice loss from the ice sheets. In this chapter, we assess multiple lines of evidence for tipping points in the cryosphere – encompassing the ice sheets on Greenland and Antarctica, sea ice, mountain glaciers and permafrost – based on recent observations, palaeorecords, numerical modelling and theoretical understanding. With about 1.2°C of global warming compared to pre-industrial levels, we are getting dangerously close to the temperature thresholds of some major tipping points for the ice sheets of Greenland and West Antarctica. Crossing these would lock in unavoidable long-term global sea level rise of up to 10 metres. There is evidence for localised and regional tipping points for glaciers and permafrost and, while evidence for global-scale tipping dynamics in sea ice, glaciers and permafrost is limited, their decline will continue with unabated global warming. Because of the long response times of these systems, some impacts of crossing potential tipping points will unfold over centuries to millennia. However, with the current trajectory of greenhouse gas (GHG) emissions and subsequent anthropogenic climate change, such largely irreversible changes might already have been triggered. These will cause far-reaching impacts for ecosystems and humans alike, threatening the livelihoods of millions of people, and will become more severe the further global warming progresses

DNA Methylation Analysis of Chromosome 21 Gene Promoters at Single Base Pair and Single Allele Resolution

Differential DNA methylation is an essential epigenetic signal for gene regulation, development, and disease processes. We mapped DNA methylation patterns of 190 gene promoter regions on chromosome 21 using bisulfite conversion and subclone sequencing in five human cell types. A total of 28,626 subclones were sequenced at high accuracy using (long-read) Sanger sequencing resulting in the measurement of the DNA methylation state of 580427 CpG sites. Our results show that average DNA methylation levels are distributed bimodally with enrichment of highly methylated and unmethylated sequences, both for amplicons and individual subclones, which represent single alleles from individual cells. Within CpG-rich sequences, DNA methylation was found to be anti-correlated with CpG dinucleotide density and GC content, and methylated CpGs are more likely to be flanked by AT-rich sequences. We observed over-representation of CpG sites in distances of 9, 18, and 27 bps in highly methylated amplicons. However, DNA sequence alone is not sufficient to predict an amplicon's DNA methylation status, since 43% of all amplicons are differentially methylated between the cell types studied here. DNA methylation in promoter regions is strongly correlated with the absence of gene expression and low levels of activating epigenetic marks like H3K4 methylation and H3K9 and K14 acetylation. Utilizing the single base pair and single allele resolution of our data, we found that i) amplicons from different parts of a CpG island frequently differ in their DNA methylation level, ii) methylation levels of individual cells in one tissue are very similar, and iii) methylation patterns follow a relaxed site-specific distribution. Furthermore, iv) we identified three cases of allele-specific DNA methylation on chromosome 21. Our data shed new light on the nature of methylation patterns in human cells, the sequence dependence of DNA methylation, and its function as epigenetic signal in gene regulation. Further, we illustrate genotype–epigenotype interactions by showing novel examples of allele-specific methylation

Pulmonary Hypertension in Adults with Congenital Heart Disease: Real-World Data from the International COMPERA-CHD Registry

Introduction: Pulmonary hypertension (PH) is a common complication in patients with congenital heart disease (CHD), aggravating the natural, post-operative, or post-interventional course of the underlying anomaly. The various CHDs differ substantially in characteristics, functionality, and clinical outcomes among each other and compared with other diseases with pulmonary hypertension. Objective: To describe current management strategies and outcomes for adults with PH in relation to different types of CHD based on real-world data. Methods and results: COMPERA (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension) is a prospective, international PH registry comprising, at the time of data analysis, >8200 patients with various forms of PH. Here, we analyzed a subgroup of 680 patients with PH due to CHD, who were included between 2007 and 2018 in 49 specialized centers for PH and/or CHD located in 11 European countries. At enrollment, the patients’ median age was 44 years (67% female), and patients had either pre-tricuspid shunts, post-tricuspid shunts, complex CHD, congenital left heart or aortic disease, or miscellaneous other types of CHD. Upon inclusion, targeted therapies for pulmonary arterial hypertension (PAH) included endothelin receptor antagonists, PDE-5 inhibitors, prostacyclin analogues, and soluble guanylate cyclase stimulators. Eighty patients with Eisenmenger syndrome were treatment-naïve. While at inclusion the primary PAH treatment for the cohort was monotherapy (70% of patients), with 30% of the patients on combination therapy, after a median observation time of 45.3 months, the number of patients on combination therapy had increased significantly, to 50%. The use of oral anticoagulants or antiplatelets was dependent on the underlying diagnosis or comorbidities. In the entire COMPERA-CHD cohort, after follow-up and receiving targeted PAH therapy (n = 511), 91 patients died over the course of a 5-year follow up. The 5-year Kaplan–Meier survival estimate for CHD associated PH was significantly better than that for idiopathic PAH (76% vs. 54%; p < 0.001). Within the CHD associated PH group, survival estimates differed particularly depending on the underlying diagnosis and treatment status. Conclusions: In COMPERA-CHD, the overall survival of patients with CHD associated PH was dependent on the underlying diagnosis and treatment status, but was significantly better as than that for idiopathic PAH. Nevertheless, overall survival of patients with PAH due to CHD was still markedly reduced compared with survival of patients with other types of CHD, despite an increasing number of patients on PAH-targeted combination therapy