Drivers and recent trends of hospitalisation costs related to acute pulmonary embolism.

BACKGROUND AND AIMS: The socio-economic burden imposed by acute pulmonary embolism (PE) on European healthcare systems is largely unknown. We sought to determine temporal trends and identify cost drivers of hospitalisation for PE in Germany. METHODS AND RESULTS: We analysed the totality of reimbursed hospitalisation costs in Germany (G-DRG system) in the years 2016-2020. Overall, 484 884 PE hospitalisations were coded in this period. Direct hospital costs amounted to a median of 3572 (IQR, 2804 to 5869) euros, resulting in average total reimbursements of 710 million euros annually. Age, PE severity, comorbidities and in-hospital (particularly bleeding) complications were identified by multivariable logistic regression as significant cost drivers. Use of catheter-directed therapy (CDT) constantly increased (annual change in the absolute proportion of hospitalisations with CDT + 0.40% [95% CI + 0.32% to + 0.47%]; P < 0.001), and it more than doubled in the group of patients with severe PE (28% of the entire population) over time. Although CDT use was overall associated with increased hospitalisation costs, this association was no longer present (adjusted OR 1.02 [0.80-1.31]) in patients with severe PE and shock; this was related, at least in part, to a reduction in the median length of hospital stay (for 14.0 to 8.0 days). CONCLUSIONS: We identified current and emerging cost drivers of hospitalisation for PE, focusing on severe disease and intermediate/high risk of an adverse early outcome. The present study may inform reimbursement decisions by policymakers and help to guide future health economic analysis of advanced treatment options for patients with PE.

Optimizing antithrombotic therapy in patients with coexisting cardiovascular and gastrointestinal disease.

Balancing the safety and efficacy of antithrombotic agents in patients with gastrointestinal disorders is challenging because of the potential for interference with the absorption of antithrombotic drugs and for an increased risk of bleeding. In this Review, we address considerations for enteral antithrombotic therapy in patients with cardiovascular disease and gastrointestinal comorbidities. For those with gastrointestinal bleeding (GIB), we summarize a general scheme for risk stratification and clinical evidence on risk reduction approaches, such as limiting the use of concomitant medications that increase the risk of GIB and the potential utility of gastrointestinal protection strategies (such as proton pump inhibitors or histamine type 2 receptor antagonists). Furthermore, we summarize the best available evidence and potential gaps in our knowledge on tailoring antithrombotic therapy in patients with active or recent GIB and in those at high risk of GIB but without active or recent GIB. Finally, we review the recommendations provided by major medical societies, highlighting the crucial role of teamwork and multidisciplinary discussions to customize the antithrombotic regimen in patients with coexisting cardiovascular and gastrointestinal diseases.

Fibrinolytic Agents in Thromboembolic Diseases: Historical Perspectives and Approved Indications.

Fibrinolytic agents catalyze the conversion of the inactive proenzyme plasminogen into the active protease plasmin, degrading fibrin within the thrombus and recanalizing occluded vessels. The history of these medications dates to the discovery of the first fibrinolytic compound, streptokinase, from bacterial cultures in 1933. Over time, researchers identified two other plasminogen activators in human samples, namely urokinase and tissue plasminogen activator (tPA). Subsequently, tPA was cloned using recombinant DNA methods to produce alteplase. Several additional derivatives of tPA, such as tenecteplase and reteplase, were developed to extend the plasma half-life of tPA. Over the past decades, fibrinolytic medications have been widely used to manage patients with venous and arterial thromboembolic events. Currently, alteplase is approved by the U.S. Food and Drug Administration (FDA) for use in patients with pulmonary embolism with hemodynamic compromise, ST-segment elevation myocardial infarction (STEMI), acute ischemic stroke, and central venous access device occlusion. Reteplase and tenecteplase have also received FDA approval for treating patients with STEMI. This review provides an overview of the historical background related to fibrinolytic agents and briefly summarizes their approved indications across various thromboembolic diseases.

Circulating miR-let7a levels predict future diagnosis of chronic thromboembolic pulmonary hypertension.

Distinct patterns of circulating microRNAs (miRNAs) were found to be involved in misguided thrombus resolution. Thus, we aimed to investigate dysregulated miRNA signatures during the acute phase of pulmonary embolism (PE) and test their diagnostic and predictive value for future diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH). Microarray screening and subsequent validation in a large patient cohort (n = 177) identified three dysregulated miRNAs as potential biomarkers: circulating miR-29a and miR-720 were significantly upregulated and miR-let7a was significantly downregulated in plasma of patients with PE. In a second validation study equal expression patterns for miR-29a and miR-let7a regarding an acute event of recurrent venous thromboembolism (VTE) or deaths were found. MiR-let7a concentrations significantly correlated with echocardiographic and laboratory parameters indicating right ventricular (RV) dysfunction. Additionally, circulating miR-let7a levels were associated with diagnosis of CTEPH during follow-up. Regarding CTEPH diagnosis, ROC analysis illustrated an AUC of 0.767 (95% CI 0.54-0.99) for miR-let7a. Using logistic regression analysis, a calculated patient-cohort optimized miR-let7a cut-off value derived from ROC analysis of ≥ 11.92 was associated with a 12.8-fold increased risk for CTEPH. Therefore, miR-let7a might serve as a novel biomarker to identify patients with haemodynamic impairment and as a novel predictor for patients at risk for CTEPH.

Modelling Costs of Interventional Pulmonary Embolism Treatment: Implications of US Trends for a European Healthcare System.

BACKGROUND: Catheter-directed treatment (CDT) of acute pulmonary embolism (PE) is entering a growth phase in Europe following a steady increase in the United States (US) in the past decade, but the potential economic impact on European healthcare systems remains unknown. METHODS AND RESULTS: We built two statistical models for the monthly trend of proportion of CDT among patients with severe (intermediate- or high-risk) PE in the US. The conservative model was based on admission data from the National Inpatient Sample (NIS) 2016-2020, and the model reflecting increasing access to advanced treatment from the PERTTM national quality assurance database registry 2018-2021. By applying these models to the forecast of annual PE-related hospitalizations in Germany, we calculated the annual number of severe PE cases and the expected increase in CDT use for the period 2025-2030. The NIS-based model yielded a slow increase, reaching 3.1% (95% CI 3.0-3.2%) among all hospitalizations with PE in 2030; in the PERT-based model, increase would be steeper, reaching 8.7% (8.3-9.2%). Based on current reimbursement rates, we estimated an increase of annual costs for PE-related hospitalizations in Germany ranging from 15.3 to 49.8 million euros by 2030. This calculation does not account for potential cost savings, including those from reduced length of hospital stay. CONCLUSION: Our approach and results, which may be adapted to other European healthcare systems, provide a benchmark for healthcare costs expected to result from CDT. Data from ongoing trials on clinical benefits and cost savings are needed to determine cost-effectiveness and inform reimbursement decisions.

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.

Prospective Multicenter International Registry of Ultrasound-Facilitated Catheter-Directed Thrombolysis in Intermediate-High and High-Risk Pulmonary Embolism (KNOCOUT PE).

BACKGROUND: Prior clinical trials have demonstrated the efficacy of ultrasound-facilitated catheter-directed thrombolysis (USCDT) for the treatment of acute intermediate-risk pulmonary embolism (PE) using reduced thrombolytic doses and shorter infusion durations. However, utilization and safety of such strategies in broader PE populations remain unclear. The KNOCOUT PE (The EKoSoNic Registry of the Treatment and Clinical Outcomes of Patients With Pulmonary Embolism) registry is a multicenter international registry designed to study the treatment of acute PE with USCDT, with focus on safety outcomes. METHODS: The KNOCOUT PE prospective cohort included 489 patients (64 sites internationally) with acute intermediate-high or high-risk PE treated with USCDT between March 2018 and June 2020. Principal safety outcomes were independently adjudicated International Society on Thrombosis and Haemostasis major bleeding at 72 hours post-treatment and mortality within 12 months of treatment. Additional outcomes included change in right ventricular/left ventricular ratio and quality of life measures over 12 months. RESULTS: Mean alteplase (r-tPA [recombinant tissue-type plasminogen activator]) infusion duration was 10.5 hours. Mean total r-tPA dose was 18.1 mg, with 31.0% of patients receiving ≤12 mg. Major bleeding events within 72 hours occurred in 1.6% (8/489) of patients. One patient experienced worsening of a preexisting subdural hematoma after USCDT and therapeutic anticoagulation, which ultimately required surgery. All-cause mortality at 30 days was 1.0% (5/489). Improvement in PE quality of life score was observed with a 41.1% (243/489, 49.7%) and 44.2% (153/489, 31.3%) mean relative reduction by 3 and 12 months, respectively. CONCLUSIONS: In a prospective observational cohort study of patients with intermediate-high and high-risk PE undergoing USCDT, mean r-tPA dose was 18 mg, and the rates of major bleeding and mortality were low. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03426124.

Clinical Course and Management of Patients with Emergency Surgery Treated with Direct Oral Anticoagulants or Vitamin K Antagonists-Results of the German Prospective RADOA-Registry.

(1) Background: The clinical management of anticoagulated patients treated with direct oral anticoagulants (DOAC) or Vitamin K antagonists (VKA) needing emergency surgery is challenging. (2) Methods: The prospective German RADOA registry investigated treatment strategies in DOAC- or VKA-treated patients needing emergency surgery within 24 h after admission. Effectiveness was analysed by clinical endpoints including major bleeding. Primary observation endpoint was in hospital mortality until 30 days after admission. (3) Results: A total of 78 patients were included (DOAC: 44; VKA: 34). Median age was 76 years. Overall, 43% of the DOAC patients and 79% of the VKA patients were treated with prothrombin complex concentrates (PCC) (p = 0.002). Out of the DOAC patients, 30% received no hemostatic treatment compared to 3% (1/34) of the VKA patients (p = 0.002), and 7% of the DOAC patients and 21% of the VKA patients developed major or clinically relevant non-major bleeding at the surgical site (p = 0.093). In-hospital mortality was 13% with no significant difference between the two treatment groups (DOAC: 11%, VKA: 15%; p > 0.20). (4) Conclusions: The 30-day in-hospital mortality rate was comparable between both patient groups. VKA patients required significantly more hemostatic agents than DOAC patients in the peri- and postoperative surgery period.

Contribution of pressure and flow changes to resistance reduction after pulmonary arterial hypertension treatment: a meta-analysis of 3898 patients.

Background: Pulmonary arterial hypertension (PAH)-targeted therapies exert significant haemodynamic changes; however, systematic synthesis is currently lacking. Methods: We searched PubMed, CENTRAL and Web of Science for studies evaluating mean pulmonary artery pressure (mPAP), cardiac index/cardiac output (CI/CO) and pulmonary vascular resistance (PVR) of PAH-targeted therapies either in monotherapy or combinations as assessed by right heart catheterisation in treatment-naïve PAH patients. We performed a random-effects meta-analysis with meta-regression. Results: We included 68 studies (90 treatment groups) with 3898 patients (age 47.4±13.2 years, 74% women). In studies with small PVR reduction (<4 WU), CI/CO increase (R2=62%) and not mPAP reduction (R2=24%) was decisive for the PVR reduction (p<0.001 and p=0.36, respectively, in the multivariable meta-regression model); however, in studies with large PVR reduction (>4 WU), both CI/CO increase (R2=72%) and mPAP reduction (R2=35%) contributed significantly to the PVR reduction (p<0.001 and p=0.01, respectively). PVR reduction as a percentage of the pre-treatment value was more pronounced in the oral+prostanoid intravenous/subcutaneous combination therapy (mean difference -50.0%, 95% CI -60.8- -39.2%), compared to oral combination therapy (-41.7%, -47.6- -35.8%), prostanoid i.v./s.c. monotherapy (-31.8%, -37.6- -25.9%) and oral monotherapy (-21.6%, -25.4- -17.8%). Changes in haemodynamic parameters were significantly associated with changes in functional capacity of patients with PAH as expressed by the 6-min walking distance. Conclusion: Combination therapies, especially with the inclusion of parenteral prostanoids, lead to remarkable haemodynamic improvement in treatment-naïve PAH patients and may unmask the contribution of mPAP reduction to the overall PVR reduction in addition to the increase in CO.

Ultrasound-assisted catheter-directed thrombolysis in a patient with COVID-19 infection and bilateral intermediate-to-high-risk pulmonary embolism: a case report.

Background: Acute pulmonary embolism (PE) is a common cardiovascular disorder, potentially associated with high morbidity and mortality rates. Case summary: Herein, we report on a patient with COVID-19 infection and bilateral PE, who presented after cardiovascular resuscitation with return of spontaneous circulation. Initially, an acute coronary syndrome was suspected but bedside echocardiography showed dilatation of the right ventricle (RV) and RV dysfunction, helping to establish the diagnosis of acute intermediate-to-high-risk PE, which was subsequently confirmed by contrast-enhanced computed tomography pulmonary angiography. The patient was successfully treated using low-dose (12 mg of tissue plasminogen) ultrasound-assisted catheter-directed thrombolysis, which resulted in prompt clinical improvement and reversal of RV dysfunction without bleeding complications. Discussion: This case demonstrates the importance of echocardiography for the differential diagnosis of PE and of catheter-directed thrombolysis for its treatment in patients with intermediate-to-high-risk and high-risk PEs.

Healthcare resource utilisation and associated costs after low-risk pulmonary embolism: pre-specified analysis of the Home Treatment of Pulmonary Embolism (HoT-PE) study.

BACKGROUND: Pulmonary embolism (PE) and its sequelae impact healthcare systems globally. Low-risk PE patients can be managed with early discharge strategies leading to cost savings, but post-discharge costs are undetermined. PURPOSE: To define healthcare resource utilisation and overall costs during follow-up of low-risk PE. METHODS: We used an incidence-based, bottom-up approach and calculated direct and indirect costs over 3-month follow-up after low-risk PE, with data from the Home Treatment of Patients with Low-Risk Pulmonary Embolism (HoT-PE) cohort study. RESULTS: Average 3-month costs per patient having suffered low-risk PE were 7029.62 €; of this amount, 4872.93 € were associated with PE, accounting to 69.3% of total costs. Specifically, direct costs totalled 3019.33 €, and of those, 862.64 € (28.6%) were associated with PE. Anticoagulation (279.00 €), rehospitalisations (296.83 €), and ambulatory visits (194.95 €) comprised the majority of the 3-month direct costs. The remaining costs amounting to 4010.29 € were indirect costs due to loss of productivity. CONCLUSION: In a patient cohort with acute low-risk PE followed over 3 months, the majority of costs were indirect costs related to productivity loss, whereas direct, PE-specific post-discharge costs were low. Effective interventions are needed to reduce the burden of PE and associated costs, especially those related to productivity loss.

Change of Intraocular Pressure Over 5 Years and its Relationship to Cardiovascular Parameters: Results From the Gutenberg Health Study.

Purpose: To investigate the longitudinal change in intraocular pressure (IOP) over 5 years and its relationship with cardiovascular parameters in a population-based sample in Germany. Methods: The Gutenberg Health Study is a prospective, observational, single-center cohort study. The sample was equally stratified for sex, residence, and age decade. IOP was measured with noncontact tonometry at baseline and at 5-year follow-up. Cardiovascular parameters, including body mass index (BMI), systolic blood pressure, and diabetes status, were assessed. Participants without IOP measurement at one time point, who were taking IOP-lowering medications, or who had ophthalmic surgery during the 5-year follow-up interval were excluded, as well as those with glaucoma diagnosis. Univariable and multivariable linear regression analyses were conducted. Results: This analysis included 9633 participants (48.9% female). The mean IOP increased from 14.04 ± 2.78 mmHg at baseline to 14.77 ± 2.92 mmHg at 5-year follow-up (P < 0.001). In multivariable linear regression analyses, an increase in BMI was associated with an increase in IOP over time (P < 0.001), whereas a higher baseline BMI was associated with a lower IOP change (P < 0.001). Higher age and male sex were associated with higher IOP change (P < 0.001). A change in systolic blood pressure was associated with IOP change, whereas baseline systolic blood pressure and diabetes status were not associated. Conclusions: This population-based study found a relationship between IOP change over 5 years and BMI and systolic blood pressure change, respectively. These findings suggest the importance of monitoring cardiovascular risk factors in IOP management.

Prevalence and Prognostic Role of Lymphedema in Patients with Deep Venous Thrombosis and Thrombophlebitis.

Background: Deep venous thrombosis (DVT) poses a substantial disease burden. Lymphedema may present with similar symptoms making the diagnosis process more difficult. Data on the epidemiology of lymphedema are lacking. Methods: The German nationwide inpatient sample served to analyze all patients hospitalized owing to DVT and/or thrombophlebitis (referred to as DVT) of the legs in Germany between 2005 and 2020. We stratified these patients for additional lymphedema and analyzed the impact of lymphedema on adverse in-hospital events. Results: Overall, 1,136,574 hospitalizations related to DVT were recorded in Germany during 2005-2020 (53.3% women; 51.3% aged ≥70 years). Lymphedema was coded in 9974 (0.9%) patient-cases (82.0% not elsewhere classified, 17.7% secondary lymphedema). Annual numbers of hospitalizations with lymphedema among DVT patients increased from 450 (2005) to 613 (2016) (ß 0.57; 95% confidence interval [CI]: 0.48-0.66], p < 0.001) and decreased thereafter. Despite similar age, DVT patients with lymphedema had higher prevalence of cardiovascular diseases, chronic organ failure, and all types of investigated cancer. Prevalence of pulmonary embolism (PE) with shock/CPR (4.1% vs. 1.5%), acute renal failure (6.7% vs. 2.5%), and stroke (5.2% vs. 4.2%) was higher in DVT patients with lymphedema than without. Lymphedema was independently associated with PE with shock/CPR (OR: 2.1; 95% CI: 1.9-2.3) as well as death (OR: 1.3; 95% CI: 1.2-1.4). Conclusions: Comorbidity conditions like cancer, obesity, and cardiovascular risk factors, and also infectious complications, were more prevalent in DVT patients with lymphedema than in those without. Lymphedema was independently associated with severe in-hospital complications, particularly when its genesis was related to severe comorbidities.

Functional capacity and dyspnea during follow-up after acute pulmonary embolism.

BACKGROUND: Dissecting the determinants of functional capacity during long-term follow-up after acute pulmonary embolism (PE) can help to better characterize a patient population with persisting limitation. METHODS: In a prospective cohort study, consecutive unselected survivors of acute PE underwent 3- and 12-month follow-up, including six-minute walking distance (6MWD) and dyspnea assessment with the modified Medical Research Council (mMRC) scale. We used reference equations adjusting for age, sex, and anthropometric measurements to define abnormal 6MWD. RESULTS: Overall, 323 of 363 (89.0%) patients had at least one recorded 6MWD value at one year. At 3 months, the prevalence of abnormal 6MWD was 21.9% and at 12 months it was 18.3%. At 3 and 12 months, 58.8% and 52.1% with abnormal 6MWD did not report dyspnea, respectively. On average and during follow-up, 6MWD significantly improved with time, while the mMRC dyspnea scale did not. Abnormal 6MWD was associated with younger age (odds ratio per decade, 0.91; 95% CI, 0.88-0.94), higher body mass index (1.10; 1.03-1.17), smoking (3.53; 1.34-9.31), intermediate- or high-risk PE (3.21; 1.21-8.56), and higher mMRC grading (2.28; 1.59-3.27). Abnormal 6MWD at 3 months was associated with the prospectively defined endpoint of post-PE impairment (3.72; 1.50-9.28) and with poor disease-specific and generic health-related quality of life. CONCLUSION: Three months after PE, 37% of patients reported dyspnea and 22% had abnormal 6MWD. After a year, 20% still had abnormal 6MWD. Dyspnea correlated with abnormal 6MWD, but over 50% of patients with abnormal 6MWD did not report dyspnea. Abnormal 6MWD predicted subsequent post-pulmonary embolism impairment and worse long-term quality of life. CLINICAL TRIAL REGISTRATION: German Clinical Trials Register Identifier DRKS00005939.

Cumulative social disadvantage and cardiovascular disease burden and mortality.

AIMS: To investigate the association between cumulative social disadvantage and cardiovascular burden and mortality in a large cohort of the general population. METHODS AND RESULTS: Cross-sectional (n = 15 010, aged 35 to 74 years, baseline investigation period 2007 to 2012) and longitudinal data (5- and 10-year follow-ups from 2012 to 2022) from the Gutenberg Health Study were used to investigate the association between individual socioeconomic status (SES, measured via a validated questionnaire) and cardiovascular disease (CVD, composite of atrial fibrillation, coronary artery disease, myocardial infarction, stroke, chronic heart failure, peripheral artery disease, and/or venous thromboembolism) risk and mortality. Subjects with prevalent CVD had a lower SES sum score, as well as lower education, occupation, and household net-income scores (all P < 0.0001). Logistic regression analysis showed that a low SES (vs. high, defined by validated cut-offs) was associated with 19% higher odds of prevalent CVD [odds ratio (OR) 1.19, 95% CI 1.01; 1.40] in the fully adjusted model. At 5-year follow-up, low SES was associated with both increased cardiovascular [hazard ratio (HR) 5.36, 2.24; 12.82] and all-cause mortality (HR 2.23, 1.51; 3.31). At 10-year follow-up, low SES was associated with a 68% higher risk of incident CVD (OR 1.68, 1.12; 2.47) as well as 86% higher all-cause mortality (HR 1.86, 1.55; 2.24). In general, the education and occupation scores were stronger related to risk of CVD and death than the household net-income score. Low SES was estimated to account for 451.45 disability-adjusted life years per 1000 people (years lived with disability 373.41/1000 and years of life lost 78.03/1000) and an incidence rate of 11 CVD cases and 3.47 CVD deaths per 1000 people per year. The population attributable fraction for CVD incidence after 5 years was 4% due to low SES. CONCLUSION: Despite universal healthcare access, cumulative social disadvantage remains associated with higher risk of CVD and mortality. Dimensions of education and occupation, but not household net income, are associated with outcomes of interest.

Low socioeconomic status is associated with higher risk of incident cardiovascular disease (CVD) and mortality in a large cohort of the general population even after comprehensive adjustment for associated variables. Education and occupation may be more important regarding CVD and mortality risk as compared to the household net income. From a public health perspective, policies should strengthen efforts to reduce socioeconomic inequalities by ensuring equal access to education and employment.

A multidisciplinary pulmonary embolism response team (PERT): first experience from a single center in Germany.

BACKGROUND: Over the last few years, the concept of multidisciplinary pulmonary embolism response teams (PERTs) has emerged to encounter the increasing variety and complexity in managing acute pulmonary embolism (PE). PURPOSE: To investigate PERT's composition and added clinical value in a university center in Germany. METHODS: Over 4 years (01/2019-11/2022), patients with confirmed PE were enrolled in a prospective single-center cohort study (PERT Mainz). We investigated the composition of PERT and compared, after propensity score matching, patients with acute PE before and after the initiation of PERT at our Medical University Centre. The primary outcome was in-hospital PE-related mortality. RESULTS: From 2019 to 2022, 88 patients with acute PE with a PERT decision were registered. Of those, 13 (14.8%) patients died during the in-hospital stay. Patients evaluated by a PERT had a median age of 68; 48.9% were females, and 21.7% suffered from malignancy. Right ventricular dysfunction was present in 76.1% of all patients. In total, 42.0% were classified as intermediate-high-risk PE and 11.4% as high-risk PE. First PERT contact mainly originated from emergency departments (33.3%) and intensive care units (30.0%), followed by chest pain units (21.3%) and regular wards (12.0%). The participation rate of medical specialties demonstrated that cardiologists (100%) or cardiac/vascular surgeons (98.6%) were included in almost all PERT consultations, followed by radiologists (95.9%) and anesthesiologists (87.8%). Compared to the PERT era, more patients in the pre-PERT era were classified as simplified pulmonary embolism severity index (sPESI) ≥ 1 (78.4% vs 71.6%) and as high-risk PE according to ESC 2019 guidelines (18.2% vs. 11.4%). In the pre-PERT era, low- and intermediate-low patients with PE received more frequently advanced reperfusion therapies such as systemic thrombolysis or surgical embolectomy compared to the PERT era (10.7% vs. 2.5%). Patients in the pre-PERT were found to have a considerably higher all-cause mortality and PE-related mortality rate (31.8% vs. 14.8%) compared to patients in the PERT era (22.7% vs. 13.6%). After propensity matching (1:1) by including parameters as age, sex, sPESI, and ESC risk classes, univariate regression analyses demonstrated that the PE management based on a PERT decision was associated with lower risk of all-cause mortality (OR, 0.37 [95%CI 0.18-0.77]; p = 0.009). For PE-related mortality, a tendency for reduction was observed (OR, 0.54 [95%CI 0.24-1.18]; p = 0.121). CONCLUSION: PERT implementation was associated with a lower risk of all-cause mortality rate in patients with acute PE. Large prospective studies are needed further to explore the impact of PERTs on clinical outcomes.

Cardiac, possible cardiac, and likely non-cardiac origin of chest pain : A hitherto underestimated parameter in German chest pain units.

BACKGROUND: Current guidelines emphasize the diagnostic value of non-cardiac or possibly cardiac chest pain. The goal of this analysis was to determine whether German chest pain units (CPUs) adequately address conditions with "atypical" chest pain in existing diagnostic structures. METHOD: A total of 11,734 patients from the German CPU registry were included. The analyses included mode of admission, critical time intervals, diagnostic steps, and differential diagnoses. RESULTS: Patients with unspecified chest pain were younger, more often female, were less likely to have classic cardiovascular risk factors and tended to present more often as self-referrals. Patients with acute coronary syndrome (ACS) mostly had prehospital medical contact. Overall, there was no difference between these two groups regarding the time from the onset of first symptoms to arrival at the CPU. In the CPU, the usual basic diagnostic measures were performed irrespective of ACS as the primary working diagnosis. In the non-ACS group, further ischemia-specific diagnostics were rarely performed. Extra-cardiac differential diagnoses were not specified. CONCLUSION: The establishment of broader awareness programs and opening CPUs for low-threshold evaluation of self-referring patients should be discussed. Regarding the rigid focus on the clarification of cardiac causes of chest pain, a stronger interdisciplinary approach should be promoted.

[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).

Pharmacological Treatments in Heart Failure With Mildly Reduced and Preserved Ejection Fraction: Systematic Review and Network Meta-Analysis.

BACKGROUND: Medical treatment for heart failure (HF) with preserved ejection (HFpEF) and with mildly reduced ejection fraction (HFmrEF) has weaker evidence compared with reduced ejection fraction, despite recent trials with an angiotensin receptor neprilysin inhibitor (ARNI) and sodium-glucose cotransporter-2 inhibitors (SGLT2i). OBJECTIVES: We aimed to estimate the aggregate therapeutic benefit of drugs for HFmrEF and HFpEF. METHODS: We performed a systematic review of MEDLINE, CENTRAL, and Web of Science for randomized trials including patients with HF and left ventricular ejection fraction (LVEF) >40%, treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (analyzed together as renin-angiotensin system inhibitors [RASi]), beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), digoxin, ARNI, and SGLT2i. An additive component network meta-analysis was performed. The primary outcome was a composite of cardiovascular (CV) death and first hospitalization for heart failure (HHF); secondary outcomes were CV death, total HHF, and all-cause mortality. RESULTS: We identified 13 studies with a total of 29,875 patients and a mean LVEF of 56.3% ± 8.7%. ARNI, MRA, and SGLT2i separately, but not RASi, BB, or digoxin, reduced the primary composite outcome compared with placebo. The combination of ARNI, BB, MRA, and SGLT2i was the most effective (HR: 0.47 [95% CI: 0.31-0.70]); this was largely explained by the triple combination of ARNI, MRA, and SGLT2i (HR: 0.56 [95% CI 0.43-0.71]). Results were similar for CV death (HR: 0.63 [95% CI 0.43-0.91] for ARNI, MRA, and SGLT2i) or total HHF (HR: 0.49 [95% CI 0.33-0.71] for ARNI, MRA, and SGLT2i) alone. In a subgroup analysis, only SGLT2i had a consistent benefit among all LVEF subgroups, whereas the triple combination had the greatest benefit in HFmrEF, robust benefit in patients with LVEF 50% to 59%, and a statistically marginal benefit in patients with LVEF ≥60%. CONCLUSIONS: In patients with HF and LVEF>40%, the quadruple combination of ARNI, BB, MRA, and SGLT2i provides the largest reduction in the risk of CV death and HHF; driven by the robust effect of the triple combination of ARNI, MRA, and SGLT2i. The benefit was more pronounced in HFmrEF patients.