D-dimer and fibrinogen indicate ischemic risk in patients with atrial fibrillation after percutaneous coronary intervention.

BACKGROUND: This study aimed to evaluate the association of antiphospholipid antibodies (aPL) and conventional markers of coagulation with ischemic and bleeding risk in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). METHODS: In this prospective two-center observational cohort study, patients with AF and an indication for oral anticoagulation (OAC) were enrolled after PCI. Blood was drawn on day 1-3 after PCI. Dilute Russell's viper venom time was used to determine lupus anticoagulant (LA) in OAC-free plasma. Anti-cardiolipin (aCL) IgG, IgM, and anti-ß2-Glycoprotein 1 (aß2GP1) IgG were analyzed by enzyme-linked immunosorbent assay (ELISA). Fibrinogen (FIB), d-dimer, and prothrombin fragment 1 and 2 (PF 1 + 2) were measured in citrated plasma. The primary ischemic outcome was time to major adverse cardiovascular events (MACE; death, myocardial infarction, or stroke) assessed at 6 months. Bleeding was defined according to International Society on Thrombosis and Haemostasis. RESULTS: 158 patients were enrolled between May 2020 and May 2021 on day 1-3 after PCI. The median age was 78 years (interquartile range [IQR] 72-82), 111 (70%) were male, and 39 (25%) presented with acute coronary syndrome. D-dimer was elevated in 74 (47%) patients, FIB was increased in 40 (25%) and PF1 + 2 in 68 (43%) patients. 32 (20%) patients had ≥ 1 antiphospholipid antibody elevated (aPL; LA: 19 [12%], aCL: 14 [9%], aß2GP1: 2 [1%]). The presence of aPL was neither significantly associated with MACE (HR 1.46, 95% CI [0.39-5.49], p = 0.579), nor bleeding (HR 1.07 [0.30-3.84], p = 0.917). Elevated d-dimer was significantly associated with higher risk for MACE (HR 5.06 [1.09-23.41], p = 0.038) and major bleeding (HR 7.04 [1.58-31.47], p = 0.011). Elevated D-dimer increased the predictive capacity of HAS-BLED for major bleedings (HAS-BLED: AUC 0.71 [0.60-0.83] vs. HAS-BLED + d-dimer: AUC 0.79 [0.70-0.88]; p = 0.025). Increased levels of FIB were associated with higher risk for MACE (HR 3.65 [1.11-11.96], p = 0.033). CONCLUSION: Biomarkers of coagulation might be suitable to assess ischemic and bleeding risk in patients with AF following PCI.

Urinary calprotectin as a diagnostic tool for detecting significant bacteriuria.

Pyuria in dipstick examination serves as the most widespread screening tool for urinary tract infections (UTI). The absence of pyuria, however, does not exclude UTI. We investigated the diagnostic value of urinary calprotectin, a mediator protein of the innate immune system, which is released by leukocytes, for the detection of UTI and compared it with dipstick pyuria. Since even low numbers of leukocytes in the urine significantly increase urinary calprotectin concentrations, calprotectin might be a more sensitive marker than pyuria detected by dipstick. All 162 patients were prospectively included and underwent a urine dipstick, urine culture, quantification of proteinuria and determination of calprotectin in the urine. Urinary calprotectin was determined using an enzyme-linked immunosorbent assay (ELISA). UTI was defined as urine cultures with detection of one or a maximum of two uropathogenic bacteria with ≥ 105 colony-forming units per millilitre (CFU/ml). Exclusion criteria were acute kidney injury, chronic renal insufficiency and tumors of the urinary tract. 71 (43.8%) patients had a UTI. Of the 91 patients without UTI, 23 had a contamination and 19 had evidence of ≥ 105 CFU/ml considered to be asymptomatic bacteriuria. The median calprotectin concentration in patients with UTI and pyuria was significantly higher than in patients with UTI and without pyuria (5510.4 vs. 544.7 ng/ml). In ROC analyses, calprotectin revealed an area under the curve (AUC) of 0.70 for the detection of significant bacteriuria. Pyuria in dipstick examinations provided an AUC of 0.71. There was no significant difference between these AUCs in the DeLong test (p = 0.9). In patients with evidence of significant bacteriuria but without pyuria, a significantly higher calprotectin concentration was measured in the urine than in patients with neither pyuria nor UTI (544.7 ng/ml vs 95.6 ng/ml, p = 0.029). Urinary calprotectin is non-inferior to dipstick pyuria in the detection of UTI.

Native hepatic T1-time as a non-invasive predictor of diastolic dysfunction and a monitoring tool for disease progression and treatment response in patients with pulmonary hypertension.

AIMS: Hepatic T1-time derived from cardiac magnetic resonance imaging (cMRI) reflects venous congestion and may provide a simple alternative to invasive end-diastolic elastance (Eed) for assessment of right ventricular (RV) diastolic function. We investigated the association of native hepatic T1-time with single-beat Eed and the value of hepatic T1-time for longitudinal monitoring in pulmonary hypertension (PH). METHODS AND RESULTS: We retrospectively enrolled 85 patients with suspected PH (59% female; 78 with PH diagnosed; 7 with PH excluded) who underwent standard right heart catheterization and cMRI within 24 h between 2015 and 2020. Hepatic T1-time showed moderate to strong correlations (rho >0.3, P ≤ 0.002) with pulmonary vascular resistance, native myocardial T1-time, Eed, RV size and function, brain natriuretic peptide (BNP) level, and 6-min walk distance, and a significant association with functional class (Kruskal-Wallis P < 0.001). Eed, myocardial T1-time, and BNP were independently linked to hepatic T1-time in multivariable regression. Hepatic T1-time > 598 ms predicted elevated Eed with 72.9% sensitivity and 82.1% specificity. Hepatic T1-time was superior to Eed in predicting clinical worsening. In 16 patients with follow-up assessments, those with decreasing hepatic T1-time (7 patients) showed significant hemodynamic improvements, whereas those with increasing hepatic T1-time (9 patients) did not. In a second retrospective cohort of 27 patients with chronic thromboembolic PH undergoing balloon pulmonary angioplasty, hepatic T1-time decreased significantly and hemodynamics improved after the procedure. CONCLUSIONS: Hepatic T1-time predicts RV diastolic dysfunction and prognosis, and may be useful for monitoring disease progression and treatment response in PH.

Natural proteome diversity links aneuploidy tolerance to protein turnover.

Accessing the natural genetic diversity of species unveils hidden genetic traits, clarifies gene functions and allows the generalizability of laboratory findings to be assessed. One notable discovery made in natural isolates of Saccharomyces cerevisiae is that aneuploidy-an imbalance in chromosome copy numbers-is frequent1,2 (around 20%), which seems to contradict the substantial fitness costs and transient nature of aneuploidy when it is engineered in the laboratory3-5. Here we generate a proteomic resource and merge it with genomic1 and transcriptomic6 data for 796 euploid and aneuploid natural isolates. We find that natural and lab-generated aneuploids differ specifically at the proteome. In lab-generated aneuploids, some proteins-especially subunits of protein complexes-show reduced expression, but the overall protein levels correspond to the aneuploid gene dosage. By contrast, in natural isolates, more than 70% of proteins encoded on aneuploid chromosomes are dosage compensated, and average protein levels are shifted towards the euploid state chromosome-wide. At the molecular level, we detect an induction of structural components of the proteasome, increased levels of ubiquitination, and reveal an interdependency of protein turnover rates and attenuation. Our study thus highlights the role of protein turnover in mediating aneuploidy tolerance, and shows the utility of exploiting the natural diversity of species to attain generalizable molecular insights into complex biological processes.

Accuracy of Event Rate and Effect Size Estimation in Major Cardiovascular Trials: A Systematic Review.

Importance: For the design of a randomized clinical trial (RCT), estimation of the expected event rate and effect size of an intervention is needed to calculate the sample size. Overestimation may lead to an underpowered trial. Objective: To evaluate the accuracy of published estimates of event rate and effect size in contemporary cardiovascular RCTs. Evidence Review: A systematic search was conducted in MEDLINE for multicenter cardiovascular RCTs associated with MeSH (Medical Subject Headings) terms for cardiovascular diseases published in the New England Journal of Medicine, JAMA, or the Lancet between January 1, 2010, and December 31, 2019. Identified trials underwent abstract review; eligible trials then underwent full review, and those with insufficiently reported data were excluded. Data were extracted from the original publication or the study protocol, and a random-effects model was used for data pooling. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline. The primary outcome was the accuracy of event rate and effect size estimation. Accuracy was determined by comparing the observed event rate in the control group and the effect size with their hypothesized values. Linear regression was used to determine the association between estimation accuracy and trial characteristics. Findings: Of the 873 RCTs identified, 374 underwent full review and 30 were subsequently excluded, resulting in 344 trials for analysis. The median observed event rate was 9.0% (IQR, 4.3% to 21.4%), which was significantly lower than the estimated event rate of 11.0% (IQR, 6.0% to 25.0%) with a median deviation of -12.3% (95% CI, -16.4% to -5.6%; P < .001). More than half of the trials (196 [61.1%]) overestimated the expected event rate. Accuracy of event rate estimation was associated with a higher likelihood of refuting the null hypothesis (0.13 [95% CI, 0.01 to 0.25]; P = .03). The median observed effect size in superiority trials was 0.91 (IQR, 0.74 to 0.99), which was significantly lower than the estimated effect size of 0.72 (IQR, 0.60 to 0.80), indicating a median overestimation of 23.1% (95% CI, 17.9% to 28.3%). A total of 216 trials (82.1%) overestimated the effect size. Conclusions and Relevance: In this systematic review of contemporary cardiovascular RCTs, event rates of the primary end point and effect sizes of an intervention were frequently overestimated. This overestimation may have contributed to the inability to adequately test the trial hypothesis.

Qualitative Exploration of Anesthesia Providers' Perceptions Regarding Philips Visual Patient Avatar in Clinical Practice.

The Philips Visual Patient Avatar, a user-centered visualization technology, offers an alternative approach to patient monitoring. Computer-based simulation studies indicate that it increases diagnostic accuracy and confidence, while reducing perceived workload. About three months after the technology's integration into clinical practice, we conducted an assessment among anesthesia providers to determine their views on its strengths, limitations, and overall perceptions. This single-center qualitative study at the University Hospital of Zurich examined anesthesia providers' perceptions of the Philips Visual Patient Avatar after its implementation. The study included an online survey to identify medical personnel's opinions on the technology's strengths and areas for improvement, which were analyzed using thematic analysis. A total of 63 of the 377 invited anesthesia providers (16.7%) responded to the survey. Overall, 163 comments were collected. The most prevalent positive themes were good presentation of specific parameters (16/163; 9.8%) and quick overview/rapid identification of problems (15/163; 9.2%). The most common perceived area for improvement was the ability to adjust the visualization thresholds of Visual Patient Avatar, which represent the physiological upper and lower vital-sign limits (33/163; 20.3%). The study showed that users consider Philips Visual Patient Avatar a valuable asset in anesthesia, allowing for easier identification of underlying problems. However, the study also revealed a user desire for the ability to freely adjust the thresholds of the Visual Patient Avatar by the handling caregivers, which were fixed to the departmental standard during the study.

Low on-clopidogrel ADP- and TRAP-6-induced platelet aggregation in patients with atrial fibrillation undergoing percutaneous coronary intervention: an observational pilot study.

High on-clopidogrel platelet reactivity (HPR) associates with ischemic risk in patients after percutaneous intervention (PCI). This study aimed to evaluate the association of HPR as assessed by multiple electrode aggregometry (MEA) with ischemic, thromboembolic, and bleeding risk in patients with atrial fibrillation (AF) undergoing PCI. Patients with AF and an indication for oral anticoagulation (OAC) were included in this prospective cohort study on day 1-3 after PCI. Platelet aggregation [U] was analyzed by MEA. HPR and low platelet reactivity (LPR) were defined as ADP-induced aggregation ≥ 46 U and ≤ 18 U, respectively. TRAP-6-induced aggregation reference was 94-156 U. The primary outcome was time to all-cause death, myocardial infarction, or stroke at 6 months. The secondary outcome was time to non-major clinically relevant bleedings or major bleedings. 159 patients were enrolled between May 2020 and May 2021. The median age was 78 years (interquartile range 72-82) and 111 (70%) were male. Median ADP- and TRAP-induced aggregation were 12 (6-17) and 49 (35-68) U, respectively. 147 (93%) patients had a low overall aggregability. HPR was detected in 2 patients (1%) and 125 (79%) had LPR. ADP-induced aggregation did not significantly associate with the primary outcome (r = 0.081, p = 0.309) but correlated inversely with bleeding risk (r = - 0.201, p = 0.011). HPR status as assessed by MEA among patients with AF after PCI was rare and overall aggregability was low. Conventional cut-off values for HPR might be inappropriate for these patients. ADP-induced aggregation might be helpful to identify patients at risk for bleeding.

Endothelial Overexpression of TGF-ß-Induced Protein Impairs Venous Thrombus Resolution: Possible Role in CTEPH.

Endothelial cells play a critical role during venous thrombus remodeling, and unresolved, fibrotic thrombi with irregular vessels obstruct the pulmonary artery in patients with chronic thromboembolic pulmonary hypertension (CTEPH). This study sought to identify endothelial mediators of impaired venous thrombus resolution and to determine their role in the pathogenesis of the vascular obstructions in patients with CTEPH. Endothelial cells outgrown from pulmonary endarterectomy specimens (PEA) were processed for mRNA profiling, and nCounter gene expression and immunohistochemistry analysis of PEA tissue microarrays and immunoassays of plasma were used to validate the expression in CTEPH. Lentiviral overexpression in human pulmonary artery endothelial cells (HPAECs) and exogenous administration of the recombinant protein into C57BL/6J mice after inferior Vena cava ligation were employed to assess their role for venous thrombus resolution. RT2 PCR profiler analysis demonstrated the significant overexpression of factors downstream of transforming growth factor beta (TGFß), that is TGFß-Induced Protein (TGFBI or BIGH3) and transgelin (TAGLN), or involved in TGFß signaling, that is follistatin-like 3 (FSTL3) and stanniocalcin-2 (STC2). Gene expression and immunohistochemistry analysis of tissue microarrays localized potential disease candidates to vessel-rich regions. Lentiviral overexpression of TGFBI in HPAECs increased fibrotic remodeling of human blood clots in vitro, and exogenous administration of recombinant TGFBI in mice delayed venous thrombus resolution. Significantly elevated plasma TGFBI levels were observed in patients with CTEPH and decreased after PEA. Our findings suggest that overexpression of TGFBI in endothelial promotes venous thrombus non-resolution and fibrosis and is causally involved in the pathophysiology of CTEPH.

Environmental and economic impact of sustainable anaesthesia interventions: a single-centre retrospective observational study.

BACKGROUND: Anaesthesia contributes substantially to the environmental impact of healthcare. To reduce the ecological footprint of anaesthesia, a set of sustainability interventions was implemented in the University Hospital Zurich, Switzerland. This study evaluates the environmental and economic implications of these interventions. METHODS: This was a single-centre retrospective observational study. We analysed the environmental impact and financial implications of changes in sevoflurane, desflurane, propofol, and plastic consumption over 2 yr (April 2021 to March 2023). The study included pre-implementation, implementation, and post-implementation phases. RESULTS: After implementation of sustainability measures, desflurane use was eliminated, there was a decrease in the consumption of sevoflurane from a median (inter-quartile range) of 25 (14-39) ml per case to 11 (6-22) ml per case (P<0.0001). Propofol consumption increased from 250 (150-721) mg per case to 743 (370-1284) mg per case (P<0.0001). Use of plastics changed: in the first quarter analysed, two or more infusion syringes were used in 62% of cases, compared with 74% of cases in the last quarter (P<0.0001). Two or more infusion lines were used in 58% of cases in the first quarter analysed, compared with 68% of cases in the last quarter (P<0.0001). This resulted in an 81% reduction in overall environmental impact from 3 (0-7) to 1 (0-3) CO2 equivalents in kg per case (P<0.0001). The costs during the final study phase were 11% lower compared with those in the initial phase: from 25 (13-41) to 21 (14-31) CHF (Swiss francs) per case (P<0.0001). CONCLUSIONS: Implementing sustainable anaesthesia interventions can significantly reduce the environmental impact and cost of anaesthesia.

User Perceptions of Visual Clot in a High-Fidelity Simulation Study: Mixed Qualitative-Quantitative Study.

BACKGROUND: Viscoelastic hemostatic assays, such as rotational thromboelastometry (ROTEM) or thromboelastography, enable prompt diagnosis and accelerate targeted treatment. However, the complex interpretation of the results remains challenging. Visual Clot-a situation awareness-based visualization technology-was developed to assist clinicians in interpreting viscoelastic tests. OBJECTIVE: Following a previous high-fidelity simulation study, we analyzed users' perceptions of the technology, to identify its strengths and limitations from clinicians' perspectives. METHODS: This is a mixed qualitative-quantitative study consisting of interviews and a survey. After solving coagulation scenarios using Visual Clot in high-fidelity simulations, we interviewed anesthesia personnel about the perceived advantages and disadvantages of the new tool. We used a template approach to identify dominant themes in interview responses. From these themes, we defined 5 statements, which were then rated on Likert scales in a questionnaire. RESULTS: We interviewed 77 participants and 23 completed the survey. We identified 9 frequently mentioned topics by analyzing the interview responses. The most common themes were "positive design features," "intuitive and easy to learn," and "lack of a quantitative component." In the survey, 21 respondents agreed that Visual Clot is easy to learn and 16 respondents stated that a combination of Visual Clot and ROTEM would help them manage complex hemostatic situations. CONCLUSIONS: A group of anesthesia care providers found Visual Clot well-designed, intuitive, and easy to learn. Participants highlighted its usefulness in emergencies, especially for clinicians inexperienced in coagulation management. However, the lack of quantitative information is an area for improvement.

SARS-CoV-2 vaccination in inflammatory bowel disease patients is not associated with flares: a retrospective single-centre Swiss study.

INTRODUCTION: Vaccination hesitancy is an important barrier to vaccination among IBD patients. The development of adverse events is the main concern reported. The purpose of this monocentric study was to assess SARS-CoV-2 vaccination safety in IBD patients by evaluating the postvaccination flare risk and incidence of overall adverse events. METHODS: Surveys were handed out on three consecutive months to each patient presenting at the Crohn-Colitis Centre, where they documented their vaccination status and any side effects experienced after vaccination.Dates of flares occurring in 2021 were recorded from their electronic medical records. Baseline and IBD characteristics and flare incidence were compared between the vaccinated and unvaccinated patients, and among the vaccinated population before and after their vaccination doses. The characteristics of patients who developed side effects and of those who did not were compared. RESULTS: We enrolled 396 IBD patients, of whom 91% were vaccinated. The proportion of patients who experienced flares was statistically not different between the vaccinated and the unvaccinated population (1.8 vs 2.6 flares per 100 person-months (p = 0.28)). Among vaccinated patients, there was no difference across the prevaccination, 1 month post any vaccination, and more than 1 month after any vaccination periods, and between the Spikevax and Cominarty subgroups. Overall, 46% of patients reported vaccination side effects, mostly mild flu-like symptoms. CONCLUSION: SARS-CoV-2 vaccination with mRNA vaccines seems safe, with mostly mild side effects. The IBD flare risk is not increased in the month following any vaccination.

Persistent complement dysregulation with signs of thromboinflammation in active Long Covid.

Long Covid is a debilitating condition of unknown etiology. We performed multimodal proteomics analyses of blood serum from COVID-19 patients followed up to 12 months after confirmed severe acute respiratory syndrome coronavirus 2 infection. Analysis of >6500 proteins in 268 longitudinal samples revealed dysregulated activation of the complement system, an innate immune protection and homeostasis mechanism, in individuals experiencing Long Covid. Thus, active Long Covid was characterized by terminal complement system dysregulation and ongoing activation of the alternative and classical complement pathways, the latter associated with increased antibody titers against several herpesviruses possibly stimulating this pathway. Moreover, markers of hemolysis, tissue injury, platelet activation, and monocyte-platelet aggregates were increased in Long Covid. Machine learning confirmed complement and thromboinflammatory proteins as top biomarkers, warranting diagnostic and therapeutic interrogation of these systems.

Oxonium ion scanning mass spectrometry for large-scale plasma glycoproteomics.

Protein glycosylation, a complex and heterogeneous post-translational modification that is frequently dysregulated in disease, has been difficult to analyse at scale. Here we report a data-independent acquisition technique for the large-scale mass-spectrometric quantification of glycopeptides in plasma samples. The technique, which we named 'OxoScan-MS', identifies oxonium ions as glycopeptide fragments and exploits a sliding-quadrupole dimension to generate comprehensive and untargeted oxonium ion maps of precursor masses assigned to fragment ions from non-enriched plasma samples. By applying OxoScan-MS to quantify 1,002 glycopeptide features in the plasma glycoproteomes from patients with COVID-19 and healthy controls, we found that severe COVID-19 induces differential glycosylation in IgA, haptoglobin, transferrin and other disease-relevant plasma glycoproteins. OxoScan-MS may allow for the quantitative mapping of glycoproteomes at the scale of hundreds to thousands of samples.

Pediatric Anesthesia Providers' Perspective on the Real-Life Implementation of the Philips Visual Patient Avatar: A Qualitative Study.

The Philips Visual Patient Avatar represents an alternative method of patient monitoring that, according to computer-based simulation studies, enhances diagnostic accuracy and confidence and reduces workload. After its clinical integration, we assessed pediatric anesthesia providers' perspectives on this technology. This is a single-center qualitative study, conducted at the University Hospital Zurich using in-depth individual interviews. We aimed to identify the advantages and limitations of the Visual Patient Avatar in pediatric anesthesia and to assess children's and parents' reactions from caregivers' perspectives. Thematic analysis was used to identify the dominant themes. Fourteen members of the institution's pediatric anesthesia team were interviewed. The most prevalent themes were children's positive reactions towards the Visual Patient Avatar (92.9%) and enhanced speed in problem identification (71.4%). Additionally, 50% of participants reported finding the Visual Patient Avatar useful for diverting children's attention during anesthesia induction, and 50% suggested that its vital sign thresholds should be adaptable for different age groups. The study revealed that the Visual Patient Avatar was recognized as a tool in pediatric anesthesia, enabling prompt identification of underlying issues and receiving positive feedback from both children and parents. The most commonly voiced wish for improvement in the study was the ability to customize the Visual Patient Avatar's thresholds for different age groups.

User Perceptions of Avatar-Based Patient Monitoring for Intensive Care Units: An International Exploratory Sequential Mixed-Methods Study.

Visual Patient Avatar ICU is an innovative approach to patient monitoring, enhancing the user's situation awareness in intensive care settings. It dynamically displays the patient's current vital signs using changes in color, shape, and animation. The technology can also indicate patient-inserted devices, such as arterial lines, central lines, and urinary catheters, along with their insertion locations. We conducted an international, multi-center study using a sequential qualitative-quantitative design to evaluate users' perception of Visual Patient Avatar ICU among physicians and nurses. Twenty-five nurses and twenty-five physicians from the ICU participated in the structured interviews. Forty of them completed the online survey. Overall, ICU professionals expressed a positive outlook on Visual Patient Avatar ICU. They described Visual Patient Avatar ICU as a simple and intuitive tool that improved information retention and facilitated problem identification. However, a subset of participants expressed concerns about potential information overload and a sense of incompleteness due to missing exact numerical values. These findings provide valuable insights into user perceptions of Visual Patient Avatar ICU and encourage further technology development before clinical implementation.

Cellular control of protein levels: A systems biology perspective.

How cells regulate protein levels is a central question of biology. Over the past decades, molecular biology research has provided profound insights into the mechanisms and the molecular machinery governing each step of the gene expression process, from transcription to protein degradation. Recent advances in transcriptomics and proteomics have complemented our understanding of these fundamental cellular processes with a quantitative, systems-level perspective. Multi-omic studies revealed significant quantitative, kinetic and functional differences between the genome, transcriptome and proteome. While protein levels often correlate with mRNA levels, quantitative investigations have demonstrated a substantial impact of translation and protein degradation on protein expression control. In addition, protein-level regulation appears to play a crucial role in buffering protein abundances against undesirable mRNA expression variation. These findings have practical implications for many fields, including gene function prediction and precision medicine.

[Chronic thromboembolic pulmonary hypertension]. / Chronisch thromboembolische pulmonale Hypertonie (Gruppe 4).

Chronic thromboembolic pulmonary disease (CTEPD) is an important late complication of acute pulmonary embolism, in which the thrombi transform into fibrous tissue, become integrated into the vessel wall, and lead to chronic obstructions. CTEPD is differentiated into cases without pulmonary hypertension (PH), characterized by a mean pulmonary arterial pressure up to 20 mmHg and a form with PH. Then, it is still referred to as chronic thromboembolic pulmonary hypertension (CTEPH).When there is suspicion of CTEPH, initial diagnostic tests should include echocardiography and ventilation/perfusion scan to detect perfusion defects. Subsequently, referral to a CTEPH center is recommended, where further imaging diagnostics and right heart catheterization are performed to determine the appropriate treatment.Currently, three treatment modalities are available. The treatment of choice is pulmonary endarterectomy (PEA). For non-operable patients or patients with residual PH after PEA, PH-targeted medical therapy, and the interventional procedure of balloon pulmonary angioplasty (BPA) are available. Increasingly, PEA, BPA, and pharmacological therapy are combined in multimodal concepts.Patients require post-treatment follow-up, preferably at (CTE)PH centers. These centers are required to perform a minimum number of PEA surgeries (50/year) and BPA interventions (100/year).