Traps N' Clots: NET-Mediated Thrombosis and Related Diseases.

In-hospital outcomes of catheter-directed thrombolysis in patients with pulmonary embolism.

AbstractAimsCatheter-directed treatment of acute pulmonary embolism (PE) is technically advancing. Recent guidelines acknowledge this treatment option for patients with overt or imminent haemodynamic decompensation, particularly when systemic thrombolysis is contraindicated. We investigated patients with PE who underwent catheter-directed thrombolysis (CDT) in the German nationwide inpatient cohort.Methods and resultsData from hospitalizations with PE (International Classification of Disease code I26) between 2005 and 2016 were collected by the Federal Office of Statistics in Germany. Patients with PE who underwent CDT (OPS 8-838.60 or OPS code 8-83b.j) were compared with patients receiving…

Home treatment of patients with low-risk pulmonary embolism with the oral factor Xa inhibitor rivaroxaban: Rationale and design of the HoT-PE Trial

SummaryPulmonary embolism (PE) is a potentially life-threatening acute cardiovascular syndrome. However, more than 95 % of patients are haemodynamically stable at presentation, and among them are patients at truly low risk who may qualify for immediate or early discharge. The Home Treatment of Pulmonary Embolism (HoT-PE) study is a prospective international multicentre single-arm phase 4 management (cohort) trial aiming to determine whether home treatment of acute lowrisk PE with the oral factor Xa inhibitor rivaroxaban is feasible, effective, and safe. Patients with confirmed PE, who have no right ventricular dysfunction or free floating thrombi in the right atrium or ventricle, are eligib…

Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism

The optimal N-terminal pro-brain natriuretic peptide (NT-proBNP) cut-off value for risk stratification of pulmonary embolism remains controversial. In this study we validated and compared different proposed NT-proBNP cut-off values in 688 normotensive patients with pulmonary embolism. During the first 30 days, 28 (4.1%) patients reached the primary outcome (pulmonary embolism-related death or complications) and 29 (4.2%) patients died. Receiver operating characteristic analysis yielded an area under the curve of 0.70 (0.60-0.80) for NT-proBNP. A cut-off value of 600 pg·mL(-1) was associated with the best prognostic performance (sensitivity 86% and specificity 50%) and the highest odds ratio…

Venous thromboembolism in patients hospitalized for hip joint replacement surgery

Venous thromboembolism (VTE) is a potentially life-threatening disease. Major transient risk factors include trauma, surgery, and immobilization. Patients undergoing hip joint replacement (HJR) are characterized by a high risk of postoperative VTE, but data on the time trends of VTE rates in this population are sparse.In an analysis of the German nationwide inpatient sample, we included all hospitalizations for elective primary HJR in Germany from 2005 to 2016. Time trends of the surgical procedure, overall death rates, and VTE rates were analysed, and predictors of VTE identified.Overall, 1,885,839 inpatients with elective primary HJR (59.1% women, 51.4% ≥70 years) were included in the ana…

A prospective cohort study to identify and evaluate endotypes of venous thromboembolism: Rationale and design of the Genotyping and Molecular Phenotyping in Venous ThromboEmbolism project (GMP-VTE)

Abstract Several clinical, genetic and acquired risk factors for venous thromboembolism (VTE) have been identified. However, the molecular pathophysiology and mechanisms of disease progression remain poorly understood. This is reflected by uncertainties regarding the primary and secondary prevention of VTE and the optimal duration of antithrombotic therapy. A growing body of literature points to clinically relevant differences between VTE phenotypes (e.g. deep vein thrombosis (DVT) versus pulmonary embolism (PE), unprovoked versus provoked VTE). Extensive links to cardiovascular, inflammatory and immune-related morbidities are testament to the complexity of the disease. The GMP-VTE project …

Outcome of patients with right heart thrombi: the Right Heart Thrombi European Registry

Our aim was the assessment of the prognostic significance of right heart thrombi (RiHT) and their characteristics in pulmonary embolism in relation to established prognostic factors.138 patients (69 females) aged (mean±sd) 62±19 years with RiHT were included into a multicenter registry. A control group of 276 patients without RiHT was created by propensity scoring from a cohort of 963 contemporary patients. The primary end-point was 30-day pulmonary embolism-related mortality; the secondary end-point included 30-day all-cause mortality. In RiHT patients, pulmonary embolism mortality was higher in 31 patients with systolic blood pressure <90 mmHg than in 107 normotensives (42% versus 12%,…

Sex-specific differences in the presentation, clinical course, and quality of life of patients with acute venous thromboembolism according to baseline risk factors. Insights from the PREFER in VTE

Abstract Introduction Sex and the presence of specific provoking risk factors, along with age, influence the presentation and prognosis of venous thromboembolism (VTE). We investigated the presentation, course and quality of life in women and men with acute VTE classified according to their VTE provoking factors. Methods PREFER in VTE is an international, non-interventional registry of patients with a first episode of acute symptomatic VTE. Baseline provoking factors were classified as follows: major transient, minor transient, active cancer, and none identifiable. The primary outcome was recurrent VTE. Quality of life and treatment satisfaction were secondary outcomes. Results Of 3,455 pat…

The optimal imaging test for diagnosis of acute pulmonary embolism: a second chance for lung scintigraphy?

Ventilation–perfusion scintigraphy may continue to be the first-line diagnostic method for pulmonary embolism in institutions that can ensure its uninterrupted availability and the expertise in its interpretationhttps://bit.ly/2y3Dlhx

Diagnosis of Cerebral Venous Thrombosis: The Complementary Value of Imaging Methods.

Thrombotic complications of vaccination against SARS-CoV-2: what pharmacovigilance reports tell us – and what they don't

In the present issue of the Journal [1], Smadja et al. present an analysis of global pharmacovigilance reports of thrombotic events following severe acute respiratory distress syndrome coronavirus (SARS-CoV)-2 vaccination. More specifically, the authors analysed the data entered into the World Health Organization (WHO) Global Database for Individual Case Safety Reports (VigiBase) between December 13, 2020 and March 16, 2021, covering, at that time, a population of almost 362 million vaccinated individuals across the world. The study focuses on three of the coronavirus disease (COVID)-19 vaccines available to date, namely the Pfizer-BioNtech (BNT162b2), Moderna (mRNA-1273), and OxfordAstraZe…

Survival Benefit of Obese Patients With Pulmonary Embolism.

To investigate the impact of obesity and underweight on adverse in-hospital outcomes in pulmonary embolism (PE).Patients diagnosed as having PE based on International Statistical Classification of Diseases and Related Health Problems, 10th Revision, German Modification code I26 in the German nationwide inpatient database were stratified for obesity, underweight, and normal weight/overweight (reference group) and compared regarding adverse in-hospital outcomes.From January 1, 2011, through December 31, 2014, 345,831 inpatients (53.3% females) 18 years and older were included in this analysis; 8.6% were obese and 0.5% were underweight. Obese patients were younger (67.0 vs 73.0 years), were mo…

Lemierre Syndrome: Clinical Update and Protocol for a Systematic Review and Individual Patient Data Meta-analysis.

Lemierre syndrome usually affects otherwise healthy adolescents or young adults and occurs at an overall rate of 1 to 10 cases per million person-years with an estimated fatality rate of 4 to 9%. Diagnostic criteria remain debated and include acute neck/head bacterial infection (often tonsillitis caused by anaerobes at high potential for sepsis and vascular invasion, notably Fusobacterium necrophorum) complicated by local vein thrombosis, usually involving the internal jugular vein, and systemic septic embolism. Medical treatment is based on antibiotic therapy with anaerobic coverage, anticoagulant drugs and supportive care in case of sepsis. Surgical procedures can be required, including d…

Antithrombotics and new interventions for venous thromboembolism: Exploring possibilities beyond factor IIa and factor Xa inhibition.

Abstract Direct oral anti–activated factor X and antithrombin agents have largely replaced vitamin K antagonists as the standard of care in treatment of venous thromboembolism. However, gaps in efficacy and safety persist, notably in end‐stage renal disease, implantable heart valves or assist devices, extracorporeal support of the circulation, and antiphospholipid syndrome. Inhibition of coagulation factor XI (FXI) emerges as a promising new therapeutic target. Antisense oligonucleotides offer potential advantages as a prophylactic or therapeutic modality, with one dose‐finding trial in orthopedic surgery already published. In addition, monoclonal antibodies blocking activation and/or activ…

Definition of tachycardia for risk stratification of pulmonary embolism

Tachycardia is a reliable predictor of adverse outcomes in normotensive patients with acute pulmonary embolism (PE). However, different prognostic relevant heart rate thresholds have been proposed. The aim of the study was to investigate the prognostic performance of different thresholds used for defining tachycardia in normotensive PE patients.We performed a post-hoc analysis of normotensive patients with confirmed PE consecutively included in a single-centre and a multi-centre registry. An adverse outcome was defined as PE-related death, need for mechanical ventilation, cardiopulmonary resuscitation or administration of catecholamines.Of 1567 patients (median age: 72 [IQR, 59-79] years; f…

Ultrasound-Assisted Catheter-Directed Thrombolysis in High-Risk and Intermediate-High-Risk Pulmonary Embolism: Results From a Single-Center Cohort

We present our single-center results on ultrasound-assisted thrombolysis (USAT) in patients with pulmonary embolism (PE) at intermediate high risk (IHR) and high risk (HR). Our study consisted of 75 patients with PE who underwent USAT (60 at IHR and 15 at HR). The median time delay from symptoms to USAT was 5 days. Ultrasound-assisted thrombolysis resulted in improvements in tricuspid annular plane systolic excursion; pulmonary artery (PA) systolic and mean pressures; Qanadli score; right to left ventricle diameter ratio and right to left atrial diameter ratio; and diameters of main, right, and left PA regardless of the baseline risk status ( P < .0001 for all). Death was documented in …

Survival and recurrent venous thromboembolism in patients with first proximal or isolated distal deep vein thrombosis and no pulmonary embolism

Essentials The long-term risk of recurrence and death after distal deep vein thrombosis (DVT) is uncertain. We included subjects with first proximal or isolated distal DVT (IDDVT) and no pulmonary embolism. The risk of symptomatic and asymptomatic recurrence is lower after IDDVT (vs. proximal). IDDVT may be associated with a lower long-term risk of death, especially after unprovoked DVT. SummaryBackground A few studies have focused on the risk of recurrence after first acute isolated distal deep vein thrombosis (IDDVT) compared with proximal DVT (PDVT), whereas the incremental risk of death has never been explored beyond the first 3 years after acute event. Methods Our single-center cohort …

Chronic thromboembolic disease following pulmonary embolism: more work ahead

Early discharge and home treatment of patients with low-risk pulmonary embolism with the oral factor Xa inhibitor rivaroxaban: an international multicentre single-arm clinical trial.

Abstract Aims To investigate the efficacy and safety of early transition from hospital to ambulatory treatment in low-risk acute PE, using the oral factor Xa inhibitor rivaroxaban. Methods and results We conducted a prospective multicentre single-arm investigator initiated and academically sponsored management trial in patients with acute low-risk PE (EudraCT Identifier 2013-001657-28). Eligibility criteria included absence of (i) haemodynamic instability, (ii) right ventricular dysfunction or intracardiac thrombi, and (iii) serious comorbidities. Up to two nights of hospital stay were permitted. Rivaroxaban was given at the approved dose for PE for ≥3 months. The primary outcome was sympto…

AB0691 INCREASED CARDIOVASCULAR RISK IN MIXED CONNECTIVE TISSUE DISEASE: EVALUATION OF MACROVASCULAR INVOLVEMENT AND ITS PREDICTORS BY AORTIC PULSE WAVE VELOCITY

Background: Macrovascular involvement and cardiovascular (CV) risk have not been sufficiently studied in patients with mixed connective tissue disease (MCTD). In particular, the gold standard assessment method of aortic stiffness carotid-femoral pulse wave velocity (cfPWV) (1) has never been evaluated in patients with this disease. Objectives: Aims of the present study were to examine cfPWV in MCTD and to evaluate its associations with MCTD associated parameters and traditional CV risk factors. Methods: cfPWV measurements were performed in 43 MCTD patients and 107 healthy controls. The difference between cfPWV in the two groups was statistically examined and subsequently controlled for the …

2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS)

Guidelines summarize and evaluate available evidence with the aim of assisting health professionals in proposing the best management strategies for an individual patient with a given condition. Guidelines and their recommendations should facilitate decision making of health professionals in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible health professional(s) in consultation with the patient and caregiver as appropriate.

Evaluation of the predictive value of the bleeding prediction score VTE‐BLEED for recurrent venous thromboembolism

Abstract Introduction VTE‐BLEED is a validated score for identification of patients at increased risk of major bleeding during extended anticoagulation for venous thromboembolism (VTE). It is unknown whether VTE‐BLEED high‐risk patients also have an increased risk for recurrent VTE, which would limit the potential usefulness of the score. Methods This was a post hoc analysis of the randomized, double‐blind, placebo‐controlled PADIS‐PE trial that randomized patients with a first unprovoked pulmonary embolism (PE) initially treated during 6 months to receive an additional 18‐month of warfarin vs. placebo. The primary outcome of this analysis was recurrent VTE during 2‐year follow‐up after ant…

Sex-specific differences in pulmonary embolism

Abstract Introduction Sex-specific differences regarding risk factors, symptoms and prognosis have been reported for several cardiovascular diseases. For patients with pulmonary embolism (PE), sex-specific data are limited and inconsistent. We aimed to investigate sex-specific differences in PE. Materials and methods Over a 10-year period (01/2003–09/2013), patients with confirmed PE were enrolled in a prospective single-centre cohort study. Results We prospectively examined 569 PE patients (55.9% women). Men more often had cancer (20.7% vs. 13.5%, p = 0.024) and unprovoked PE (61.0% vs. 47.5%, p = 0.001) while women more frequently presented with risk factors for venous thromboembolism suc…

A review of venous thromboembolism in COVID‐19: A clinical perspective

Abstract Coronavirus disease‐19 (COVID‐19) started in Wuhan, China in December 2019 and spread to all around the world in a short period of time. Hospitalized patients with COVID‐19 mostly could suffer from an abnormal coagulation activation risk with increased venous thrombosis events and a poor clinical course. The reported incidence rates of thrombotic complications in hospitalized COVID‐19 patients vary between 2.6 and 85% (both in non‐critically ill and critically ill patients). The risk of venous thromboembolism is not known in non‐hospitalized patients with COVID‐19. There are numerous studies and guidelines for administration of thromboprophylaxis for COVID‐19 cases. All hospitalize…

Risk-adapted management of pulmonary embolism

The presence and severity of right ventricular (RV) dysfunction is a key determinant of prognosis in the acute phase of pulmonary embolism (PE). Risk-adapted treatment strategies continue to evolve, tailoring initial management to the clinical presentation and the functional status of the RV. Beyond pharmacological and, if necessary, mechanical circulatory support, systemic thrombolysis remains the mainstay of treatment for hemodynamically unstable patients; in contrast, it is not routinely recommended for intermediate-risk PE. Catheter-directed pharmacomechanical reperfusion treatment represents a promising option for minimizing bleeding risk; for reduced-dose intravenous thrombolysis, the…

Isolated Pulmonary Embolism Is Associated With a High Risk of Arterial Thrombotic Disease

Background Isolated PE is associated with a higher burden of atherosclerotic disease than other manifestations of VTE. Research Question We hypothesized that the presence of isolated PE may signal a chronically elevated risk of arterial thrombotic disease. Study Design and Methods Data from the VTEval Study, a prospective cohort study enrolling individuals with clinical suspicion and imaging-based diagnosis or exclusion of VTE, were analyzed. Patients with PE received whole-leg ultrasonography to assess presence of DVT. Regularized logistic regression identified features that discriminate between isolated PE and other VTE phenotypes at clinical presentation. Survival analyses were performed…

Introduction to the Special Issue: ‘Update on Pulmonary Embolism’

Potential Involvement of Osteopontin in Inflammatory and Fibrotic Processes in Pulmonary Embolism and Chronic Thromboembolic Pulmonary Hypertension

Background Inflammation and incomplete thrombus resolution leading to obstructive fibrotic remodelling are considered critical mechanisms for the development of chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism (PE). Osteopontin (OPN) is involved in a variety of biological processes including inflammation and tissue fibrosis. Methods OPN plasma concentrations were measured in 70 CTEPH and 119 PE patients. Tissue material from 6 CTEPH patients removed during pulmonary endarterectomy and murine venous thrombi induced by subtotal ligation of the inferior vena cava in C57BL/6 mice were analysed by (immuno)histochemistry. Results CTEPH patients had higher OPN plasma…

Sex-specific and age-related seasonal variations regarding incidence and in-hospital mortality of pulmonary embolism in Germany

Background Studies have reported seasonal variations regarding the incidence and the short-term mortality of pulmonary embolism (PE). The aim of this study was to identify sex-specific and age-related differences in seasonal patterns regarding hospitalisations and mortality of PE patients. Methods We analysed the impact of seasons on incidence and in-hospital mortality of male and female hospitalised PE patients in Germany (2005–2015) based on the German nationwide inpatient sample. Results The German nationwide inpatient sample comprised 885 806 hospitalisations due to PE (2005–2015). Seasonal variations of both incidence (p=0.021) and in-hospital mortality (p<0.001) were of significant ma…

Validation of a Model for Identification of Patients at Intermediate to High Risk for Complications Associated With Acute Symptomatic Pulmonary Embolism

For patients with acute symptomatic pulmonary embolism (PE), the Bova score classifies their risk for PE-related complications within 30 days after diagnosis. The original Bova score was derived from 2,874 normotensive patients with acute PE who participated in one of six prospective PE studies.We retrospectively assessed the validity of the Bova risk model in normotensive patients with acute PE diagnosed in an academic urban ED. Two clinician investigators used baseline data for the model's four prognostic variables to stratify patients into the three Bova risk stages (I-III) for 30-day PE-related complications. Intraclass correlation coefficient (ICC) and the κ statistic were used to asse…

Management of Pulmonary Embolism: Results from the German Chest Pain Unit Registry.

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Since 2008, specialized chest pain units (CPUs) were implemented across Germany ensuring structured diagnostics in acute chest pain. This study aims to analyze the management of pulmonary embolism (PE) patients in such certified CPUs. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Data were retrieved from 13,902 patients enrolled in the German CPU registry and analyzed for the diagnosis of PE including patient characteristics, critical time intervals, diagnostic workup, treatment, and prognosis. PE patients were compared to the overall CPU patient cohort. Only patients with a complete 3-month follow-up were included. &lt;b&gt;&lt;i&gt;Resu…

Thrombolytic therapy for submassive pulmonary embolism.

Approximately 10% of all patients with acute pulmonary embolism (PE) die within the first three months after diagnosis. However, PE is not universally life-threatening, but covers a wide spectrum of clinical severity and death risk. Thrombolytic treatment is indicated patients with acute massive PE who are at high risk for early death, i.e. those patients who present with arterial hypotension and shock. On the other hand, low molecular-weight heparin or fondaparinux is adequate treatment for most normotensive patients with PE. Recombinant tissue plasminogen activator, given as 100 mg infusion over 2 h, is the treatment of choice for patients with PE, although older regimens using urokinase …

Management of Pulmonary Embolism

Pulmonary embolism (PE) remains a major contributor to global disease burden. Risk-adapted treatment and follow-up contributes to a favorable outcome. Age-adjusted cutoff levels increase D-dimer specificity and may decrease overuse of imaging procedures and overdiagnosis of PE. Primary systemic fibrinolysis has an unfavorable risk-benefit ratio in intermediate-risk PE; catheter-directed techniques are an option for patients with hemodynamic decompensation and high bleeding risk. New oral anticoagulant agents are effective and safe alternatives to standard anticoagulation regimens. Recent trial data do not support insertion of cava filters in patients who can receive anticoagulant treatments…

Comparison of risk assessment strategies for not-high-risk pulmonary embolism

We compared the prognostic performance of the 2014 European Society of Cardiology (ESC) risk stratification algorithm with the previous 2008 ESC algorithm, the Bova score and the modified FAST score (based on a positive heart-type fatty acid-binding protein (H-FABP) test, syncope and tachycardia, modified using high-sensitivity troponin T instead of H-FABP) in 388 normotensive pulmonary embolism patients included in a single-centre cohort study.Overall, 25 patients (6.4%) had an adverse 30-day outcome. Regardless of the score or algorithm used, the rate of an adverse outcome was highest in the intermediate-high-risk classes, while all patients classified as low-risk had a favourable outcome…

Pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension.

Management and outcome of patients with operable chronic thromboembolic pulmonary hypertension (CTEPH) who underwent pulmonary endarterectomy (PEA) at a large German referral center were investigated.In Germany, 394 PEAs were performed in 2014 and 2015 with an in-hospital mortality rate of 5.8%. Of these, 253 patients (64.2%) were treated at the Kerckhoff Clinic, Bad Nauheim, and 237 (93.7%; median age, 62 years [interquartile range [IQR], 52-72 years]; 46.0% female) were included in the present analysis.On referral, 52 patients (22.0%) were treated with pulmonary arterial hypertension-specific drugs and 95 (40.4%) were treated with non-vitamin K-dependent oral anticoagulants, and 14 (5.9%)…

Psoriasis and its impact on the clinical outcome of patients with pulmonary embolism

Abstract Background Venous thromboembolism (VTE) is common and associated with high morbidity and mortality. Although chronic inflammation was not categorized as a traditional risk factor for VTE, chronic inflammation might increase the risk to develop VTE events. While studies confirmed an increased cardiovascular morbidity and mortality in psoriatic patients, data regarding the influence of psoriasis on patients' cardiovascular profile and on prognosis of patients with pulmonary embolism (PE) are sparse. Purpose We aimed to investigate the impact of psoriasis on prognosis of PE patients. Methods Hospitalized PE patients were stratified for psoriasis and the impact of psoriasis on outcome …

Trends in thrombolytic treatment and outcomes of acute pulmonary embolism in Germany.

Abstract Aims Pulmonary embolism (PE) is the third most common cardiovascular cause of death; systemic thrombolysis is potentially lifesaving treatment in patients presenting with haemodynamic instability. We investigated trends in the use of systemic thrombolysis and the outcome of patients with acute PE. Methods and results We analysed data on the characteristics, comorbidities, treatment, and in-hospital outcome of 885 806 PE patients in Germany between 2005 and 2015. Incidence of acute PE was 99/100 000 population/year and increased from 85/100 000 in 2005 to 109/100 000 in 2015 [β 0.32 (0.26–0.38), P &amp;lt; 0.001]. During the same period, in-hospital case fatality rates decreased fro…

Frage zur Lyseindikation bei Lungenembolie

Die S2 Leitlinie „Diagnostik und Therapie der Beinund Beckenvenenthrombose und der Lungenembolie“ besagt, dass Patienten mit niedrigem Risiko (hamodynamisch stabil, keine rechtsventrikulare Dysfunktion) wie bei einer Venenthrombose antikoaguliert werden, Patienten mit hohem Risiko systemisch lysiert werden. Patienten mit mittlerem Risiko, d.h. hamodynamisch stabil mit rechtsventrikularer Dysfunktion, sollen in „ausgewahlten Fallen“ einer systemischen Thrombolyse zugefuhrt werden. Gibt es neue Daten bzw. Empfehlungen, wie in solchen Fallen pragmatisch vorgegangen werden kann?

Differential impact of syncope on the prognosis of patients with acute pulmonary embolism: a systematic review and meta-analysis

Aims Controversial reports exist in the literature regarding the prognostic role and therapeutic implications of syncope in patients with acute pulmonary embolism (PE). We conducted a systematic review and meta-analysis to investigate the association between syncope and short-term adverse outcomes, taking into account the presence or absence of haemodynamic compromise at acute PE presentation. Methods and results The literature search identified 1664 studies, 29 of which were included for a total of 21 956 patients with PE (n = 3706 with syncope). Syncope was associated with higher prevalence of haemodynamic instability [odds ratio (OR) 3.50; 95% confidence interval (CI) 2.67-4.58], as well…

Diagnosis of pulmonary embolism: progress after many YEARS

The 2019 ESC Guidelines on the Diagnosis and Management of Acute Pulmonary Embolism

COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-Up

Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis. In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy. Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who hav…

Course of D-Dimer and C-Reactive Protein Levels in Survivors and Nonsurvivors with COVID-19 Pneumonia: A Retrospective Analysis of 577 Patients

Ambulatory treatment of low-risk pulmonary embolism in fragile patients: a subgroup analysis of the multinational Home Treatment of Pulmonary Embolism (HoT-PE) Trial

Pulmonary embolism is the third most frequent acute cardiovascular disease with an annual incidence of approximately 100 cases per 100 000 population and an annual mortality of ≥7 deaths per 100 000 population in the European region [1, 2]. Initial management is adjusted to the risk of in-hospital death or early complications, which depend both on the severity of pulmonary embolism and the presence of comorbidities [3]. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors hav…

In-hospital outcomes of catheter-directed thrombolysis in patients with pulmonary embolism

Abstract Background and purpose Catheter-directed treatment of acute pulmonary embolism (PE) is technically advancing. Recent guidelines acknowledge this treatment option for patients with overt or imminent haemodynamic decompensation, particularly when systemic thrombolysis is contraindicated or has failed. We investigated baseline characteristics and in-hospital outcomes of patients with PE who underwent catheter-directed thrombolysis (CDT) in the German nationwide inpatient cohort. Methods Data from hospitalizations with PE between 2005 and 2016 were collected by the Federal Office of Statistics (Statistisches Bundesamt) in Germany and included in this analysis. Patients with PE who unde…

Home treatment of pulmonary embolism: are all the questions answered now after the HOME-PE trial?

Temporal Trends in the Prevalence of Infective Endocarditis in Germany Between 2005 and 2014

Infective endocarditis (IE) is a potentially life-threatening disease. Little is known about temporal trends in its prevalence in Germany. In 2009, recommendations for antibiotic prophylaxis were deescalated in the revised European Society of Cardiology guideline to include only patients at high risk of IE. We selected patients with the discharge diagnosis of IE based on the International Classification of Diseases code I33 in the nationwide database of the Federal Statistical Office of Germany. We identified 94,364 patients with a diagnosis of IE from January 2005 to December 2014. Mean prevalence was 11.6 per 100,000 citizens per year in this 10-year-period. The annual IE prevalence showe…

Venous thromboembolism in patients hospitalized for knee and hip joint replacement surgery

Abstract Background Venous thromboembolism (VTE) is a frequent acute cardiovascular disease, leading to significant morbidity and mortality worldwide. Major trauma, surgery, immobilisation and joint replacements are major provoking factors for VTE. In particular, patients undergoing knee and hip joint replacement surgery are at high risk of developing VTE perioperatively, even in the era of established pharmacological thromboprophylaxis. Without thromboprophylaxis, as many as 20–60% of patients may develop perioperative VTE. Purpose As recent studies indicate an increasing number of total knee and hip replacement surgeries in European countries and the United States, aims of our study were …

Response to ‘Detecting right ventricular dysfunction in patients diagnosed with low-risk pulmonary embolism: is routine computed tomographic pulmonary angiography sufficient?’

Magnetic resonance direct thrombus imaging for pre-operative assessment of acute thrombosis in chronic thromboembolic pulmonary hypertension

Pulmonary Embolism: Contemporary Medical Management and Future Perspectives

Pulmonary embolism (PE) contributes substantially to the global disease burden. A key determinant of early adverse outcomes is the presence (and severity) of right ventricular dysfunction. Consequently, risk-adapted management strategies continue to evolve, tailoring acute treatment to the patients' clinical presentation, hemodynamic status, imaging and biochemical markers, and comorbidity. For subjects with hemodynamic instability or 'high-risk' PE, immediate systemic reperfusion treatment with intravenous thrombolysis is indicated; emerging approaches such as catheter-directed pharmacomechanical reperfusion might help to minimize the bleeding risk. Currently, direct, non-vitamin K-depende…

Identification of intermediate-risk patients with acute symptomatic pulmonary embolism

The identification of normotensive patients with acute pulmonary embolism (PE) at high risk of adverse PE-related clinical events (i.e. intermediate-risk group) is a major challenge. We combined individual patient data from six studies involving 2874 normotensive patients with PE. We developed a prognostic model for intermediate-risk PE based on the clinical presentation and the assessment of right ventricular dysfunction and myocardial injury. We used a composite of PE-related death, haemodynamic collapse or recurrent PE within 30 days of follow-up as the main outcome measure. The primary outcome occurred in 198 (6.9%) patients. Predictors of complications included systolic blood pressure …

P5017Factors associated with a negative D-dimer test in patients diagnosed with acute symptomatic pulmonary embolism

Abstract Background The recommended diagnostic strategy for suspected acute pulmonary embolism (PE) combines the assessment of pre-test probability, D-dimer level, and -if indicated- computed tomography pulmonary angiography. Purpose To evaluate the frequency and potential explanations for negative D-dimer tests in patients diagnosed with acute PE. Methods The multicentre Follow-up of Acute Pulmonary Embolism (FOCUS) cohort study prospectively enrolled 1,100 consecutive patients diagnosed with acute symptomatic PE; two-year follow-up is ongoing. The items of the Simplified revised Geneva Score and the D-dimer levels at diagnosis have been prospectively collected, but they did not necessaril…

Vorapaxar in the secondary prevention of atherothrombotic events

BACKGROUND: Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. METHODS: We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients …

Possible misclassification of cardiovascular risk by SCORE in antisynthetase syndrome: results of the pilot multicenter study RI.CAR.D.A

Abstract Objectives To test the ability of an established traditional cardiovascular (CV) risk prediction score [Systematic COronary Risk Evaluation (SCORE)] and its EULAR modified version (mSCORE) to identify antisynthetase syndrome (ASyS) patients at high CV risk and to examine for the first time associations of CV and cerebrovascular surrogate markers with clinical and immunological ASyS parameters. Methods SCORE/mSCORE and the gold standard marker of aortic stiffness [carotid-femoral pulse wave velocity (cfPWV)] were examined in ASyS patients and healthy controls. Moreover, sonography of the common- (CCA) and internal- (ICA) carotid arteries was performed in subsets of both groups, eval…

Thrombosis

Background— Thrombosis is the common pathology underlying ischemic heart disease, ischemic stroke, and venous thromboembolism (VTE). The Global Burden of Disease Study 2010 (GBD 2010) documented that ischemic heart disease and stroke collectively caused 1 in 4 deaths worldwide. GBD 2010 did not report data for VTE as a cause of death and disability. Objective— To review the literature on the global burden of disease caused by VTE. Approach and Results— We performed a systematic review of the literature on the global disease burden because of VTE in low-, middle-, and high-income countries. Studies from Western Europe, North America, Australia, and Southern Latin America (Argentina) yielded…

Dabigatran after Short Heparin Anticoagulation for Acute Intermediate-Risk Pulmonary Embolism: Rationale and Design of the Single-Arm PEITHO-2 Study

AbstractPatients with intermediate-risk pulmonary embolism (PE) may, depending on the method and cut-off values used for definition, account for up to 60% of all patients with PE and have an 8% or higher risk of short-term adverse outcome. Although four non-vitamin K-dependent direct oral anticoagulants (NOACs) have been approved for the treatment of venous thromboembolism, their safety and efficacy as well as the optimal anticoagulation regimen using these drugs have not been systematically investigated in intermediate-risk PE. Moreover, it remains unknown how many patients with intermediate-high-risk and intermediate-low-risk PE were included in most of the phase III NOAC trials. The ongo…

Risk stratification of normotensive pulmonary embolism based on the sPESI — Does it work for all patients?

Trends in pregnancy outcomes in patients with pulmonary hypertension: still a long way to go

Prediction of bleeding events in patients with venous thromboembolism on stable anticoagulation treatment.

Attempts at identifying patients with an elevated risk of bleeding while on anticoagulation following acute venous thromboembolism (VTE) have largely been unsuccessful thus far. We sought to develop a clinical prediction score for bleeding during stable anticoagulation treatment after acute VTE.We performed a post hoc analysis of the pooled RE-COVER studies, two double-blind randomised “sister” trials evaluating dabigatran versus standard treatment in 5107 VTE patients.A score was derived from patients randomised to dabigatran using logistic regression analysis covering the complete follow-up period. The final model, named VTE-BLEED, included six variables and yielded a c-statistic of 0.72 …

Lungenembolie: Weniger Rezidive durch längere orale Antikoagulation

Bei Patienten mit einer Lungenembolie reduziert eine Antikoagulation uber 3–6 Monate das Rezidivrisiko. Unklar ist bislang, ob dieser Effekt auch nach dem Ende der Therapie erhalten bleibt. Aktuell wurde der Nutzen einer zusatzlichen Behandlung mit Warfarin uber 18 Monate nach einer initalen 6-monatigen Therapie mit Vitamin-K-Antagonisten untersucht.

Pharmacokinetics of Direct Oral Anticoagulants in Emergency Situations: Results of the Prospective Observational RADOA-Registry

Thrombosis and haemostasis 122(4), 552-559 (2022). doi:10.1055/a-1549-6556

Global public awareness about atrial fibrillation

Essentials Early recognition of atrial fibrillation helps in stroke prevention. Survey in 10 countries to assess public awareness of atrial fibrillation. Overall global awareness of atrial fibrillation was 48%. Less than 46% of participants were aware atrial fibrillation leads to stroke. Background Atrial fibrillation (AF) is an important cause of ischemic stroke that often remains undetected until stroke occurs. Awareness of the risk factors and symptoms is important so that AF can be diagnosed and thromboprophylaxis given. However, the extent of public awareness of AF is uncertain. We assessed public awareness of AF across six continents and compared it with that of other thrombotic and n…

Lysed Erythrocyte Membranes Promote Vascular Calcification

Background: Intraplaque hemorrhage promotes atherosclerosis progression, and erythrocytes may contribute to this process. In this study we examined the effects of red blood cells on smooth muscle cell mineralization and vascular calcification and the possible mechanisms involved. Methods: Erythrocytes were isolated from human and murine whole blood. Intact and lysed erythrocytes and their membrane fraction or specific erythrocyte components were examined in vitro using diverse calcification assays, ex vivo by using the murine aortic ring calcification model, and in vivo after murine erythrocyte membrane injection into neointimal lesions of hypercholesterolemic apolipoprotein E–deficient mi…

Reduced-Dose Intravenous Thrombolysis for Acute Intermediate–High-risk Pulmonary Embolism: Rationale and Design of the Pulmonary Embolism International THrOmbolysis (PEITHO)-3 trial

Intermediate-high-risk pulmonary embolism (PE) is characterized by right ventricular (RV) dysfunction and elevated circulating cardiac troponin levels despite apparent hemodynamic stability at presentation. In these patients, full-dose systemic thrombolysis reduced the risk of hemodynamic decompensation or death but increased the risk of life-threatening bleeding. Reduced-dose thrombolysis may be capable of improving safety while maintaining reperfusion efficacy. The Pulmonary Embolism International THrOmbolysis (PEITHO)-3 study (ClinicalTrials.gov Identifier: NCT04430569) is a randomized, placebo-controlled, double-blind, multicenter, multinational trial with long-term follow-up. We will c…

Comprehensive platelet phenotyping supports the role of platelets in the pathogenesis of acute venous thromboembolism - results from clinical observation studies

Background: The pathogenesis of arterial and venous thrombosis is in large part interlaced. How much platelet phenotype relates to acute venous thromboembolism (VTE) independent of the underlying cardiovascular profile is presently poorly investigated.Methods: Platelet count and mean platelet volume (MPV), platelet aggregation in whole blood and platelet rich plasma (PRP), platelet-dependent thrombin generation (TG) and platelet surface activation markers were measured under standardized conditions. Machine learning was applied to identify the most relevant characteristics associated with VTE from a large array (N = 58) of clinical and plateletrelated variables.Findings: VTE cases (N = 159)…

Chronisch thromboembolische pulmonale Hypertonie: Empfehlungen der Kölner Konsensus Konferenz 2016

The 2015 European Guidelines on Pulmonary Hypertension did not cover only pulmonary arterial hypertension (PAH), but also other significant subgroups of pulmonary hypertension (PH). In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany to discuss open and controversial issues surrounding the practical implementation of the European Guidelines. Several working groups were initiated, one of which was dedicated to the diagnosis and treatment of chronic thromboembolic pulmonary hypertension (CTEPH). In ev…

A model for estimating the health economic impact of earlier diagnosis of chronic thromboembolic pulmonary hypertension

Background Diagnostic delay of chronic thromboembolic pulmonary hypertension (CTEPH) exceeds 1 year, contributing to higher mortality. Health economic consequences of late CTEPH diagnosis are unknown. We aimed to develop a model for quantifying the impact of diagnosing CTEPH earlier on survival, quality-adjusted life-years (QALYs) and healthcare costs. Material and methods A Markov model was developed to estimate lifelong outcomes, depending on the degree of delay. Data on survival and quality of life were obtained from published literature. Hospital costs were assessed from patient records (n=498) at the Amsterdam UMC – VUmc, which is a Dutch CTEPH referral center. Medication costs were ba…

Home treatment of fragile patients with acute pulmonary embolism: a subgroup analysis of the multinational home treatment of pulmonary embolism (HoT-PE) trial

Abstract Background and aims Subgroup analyses of randomized trials and cohort studies on direct oral anticoagulants (DOACs) suggested that single direct drug treatment may be effective and safe in elderly and “fragile” patients with acute pulmonary embolism (PE). In a post-hoc analysis of HoT-PE, a prospective multicenter management trial, we studied whether early discharge and home treatment of acute PE is effective and safe in these patients. Methods HoT-PE enrolled patients with acute PE classified as being at low risk based on the modified Hestia criteria and the absence of right ventricular dysfunction. The primary efficacy outcome was symptomatic recurrent VTE, or PE-related death wi…

Antithrombotic Therapy in COVID-19: Systematic Summary of Ongoing or Completed Randomized Trials

ABSTRACTEndothelial injury and microvascular/macrovascular thrombosis are common pathophysiologic features of coronavirus disease-2019 (COVID-19). However, the optimal thromboprophylactic regimens remain unknown across the spectrum of illness severity of COVID-19. A variety of antithrombotic agents, doses and durations of therapy are being assessed in ongoing randomized controlled trials (RCTs) that focus on outpatients, hospitalized patients in medical wards, and critically-ill patients with COVID-19. This manuscript provides a perspective of the ongoing or completed RCTs related to antithrombotic strategies used in COVID-19, the opportunities and challenges for the clinical trial enterpri…

Temporal trends and predictors of inhospital death in patients hospitalised for heart failure in Germany.

Abstract Aims We investigated trends in incidence, case fatality rate, patient characteristics and adverse inhospital events of patients hospitalised for heart failure in Germany. Methods and results The German nationwide inpatient sample (2005–2016) was used for this analysis. Patients hospitalised due to heart failure were selected for analysis. Temporal trends in the incidence of hospitalisations, case fatality rate and treatments were analysed and predictors of inhospital death were identified. The analysis comprised a total number of 4,539,140 hospitalisations (52.0% women, 81.0% aged ≥70 years) due to heart failure. Although hospitalisations increased from 381 (2005) to 539 per 100,00…

Impact of Systemic Atherosclerosis on Clinical Characteristics and Short-Term Outcomes in Patients with Deep Venous Thrombosis or Thrombophlebitis

Venous thromboembolism (VTE) and atherosclerosis are accompanied by substantial cardiovascular mortality; links between both disease entities were reported. We aimed to investigate the impact of systemic atherosclerosis on adverse outcomes in patients with deep venous thrombosis or thrombophlebitis (DVT) and to identify differences in DVT patients with and without systemic atherosclerosis.The German nationwide inpatient sample was used for this analysis. Patients admitted for DVT were included in this study and stratified by systemic atherosclerosis (composite of coronary artery disease, myocardial infarction, ischemic stroke, and/or atherosclerotic arterial diseases). We compared DVT patie…

Pulmonary embolism: risk assessment and management.

Acute pulmonary embolism (PE) poses a significant burden on health and survival. Its severity ranges from asymptomatic, incidentally discovered subsegmental thrombi to massive, pressor-dependent PE complicated by cardiogenic shock and multisystem organ failure. Rapid and accurate risk stratification is therefore of paramount importance to ensure the highest quality of care. This article critically reviews currently available and emerging tools for risk-stratifying acute PE, and particularly for distinguishing between elevated (intermediate) and low risk among normotensive patients. We focus on the potential value of risk assessment strategies for optimizing severity-adjusted management. Apa…

Risk factors for chronic thromboembolic pulmonary hypertension – Importance of thyroid disease and function

Abstract Introduction Although a number of risk factors for chronic thromboembolic pulmonary hypertension (CTEPH) have been reported, the exact prevalence is controversial and varies between published cohorts. The aim of the present study was to investigate the prevalence of risk factors in operable CTEPH patients with special emphasis on thyroid disease and function. Material and methods Overall, 228 CTEPH patients (47.7% female; median age 63 [IQR 52–72] years) scheduled for pulmonary endarterectomy between 01/2014 and 12/2015 were studied. Prevalence of risk factors was assessed, and patients were classified according to their thyroid function based on laboratory measurements. Results As…

COVID-19 as a Potential Trigger for Immune Thrombotic Thrombocytopenic Purpura and Reason for an Unusual Treatment: A Case Report

AbstractImmune thrombotic thrombocytopenic purpura (iTTP) is a rare autoimmune disorder characterized by severely reduced activity of the von Willebrand factor (VWF)-cleaving protease ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) due to autoantibodies. This leads to the development of pathogenic multimers of VWF, causing a thrombotic microangiopathy with decreased number of platelets, hemolysis, and life-threatening tissue ischemia of mostly brain, heart, and kidneys. Standard treatment of iTTP involves daily plasma exchange to remove ultra large multimers of VWF, inhibitors, substituting ADAMTS13, and the accompaniment of an immunosuppressive …

Center for Thrombosis and Hemostasis Mainz.

Trends in Pulmonary Embolism Outcomes

Acute pulmonary embolism (PE), a potentially life-threatening manifestation of venous thromboembolism (VTE), represents a major threat to the health and occasionally the life of a large number of patients worldwide. A systematic review of the published data, performed on the occasion of World

Survival and quality of life after early discharge in low-risk pulmonary embolism.

IntroductionEarly discharge of patients with acute low-risk pulmonary embolism requires validation by prospective trials with clinical and quality-of-life outcomes.MethodsThe multinational Home Treatment of Patients with Low-Risk Pulmonary Embolism with the Oral Factor Xa Inhibitor Rivaroxaban (HoT-PE) single-arm management trial investigated early discharge followed by ambulatory treatment with rivaroxaban. The study was stopped for efficacy after the positive results of the predefined interim analysis at 50% of the planned population. The present analysis includes the entire trial population (576 patients). In addition to 3-month recurrence (primary outcome) and 1-year overall mortality, …

Combination Therapy with Oral Treprostinil for Pulmonary Arterial Hypertension:A Double-Blind Placebo-controlled Clinical Trial

Rationale: Oral treprostinil improves exercise capacity in patients with pulmonary arterial hypertension (PAH), but the effect on clinical outcomes was unknown.\ud \ud Objectives: To evaluate the effect of oral treprostinil compared with placebo on time to first adjudicated clinical worsening event in participants with PAH who recently began approved oral monotherapy.\ud \ud Methods: In this event-driven, double-blind study, we randomly allocated 690 participants (1:1 ratio) with PAH to receive placebo or oral treprostinil extended-release tablets three times daily. Eligible participants were using approved oral monotherapy for over 30 days before randomization and had a 6-minute-walk dista…

Akute Lungenembolie – Eine kritische Übersicht über aktuelle Leitlinien und Empfehlungen

Die akute Lungenembolie (LE) ist eine haufige und potenziell lebensbedrohliche Erkrankung. Dieser Artikel bietet eine kritische Ubersicht uber die aktuellen Leitlinien und Empfehlungen fur das Management der akuten LE. Die Symptome und klinischen Zeichen sind unspezifisch und umfassen Dyspnoe, Brustschmerzen, Hamoptyse, Synkope, arterielle Hypotension und Schock. Bei Patienten mit klinischem Verdacht auf akute LE sollte umgehend das Vorliegen eines hohen Risikos aufgrund hamodynamischer Instabilitat festgestellt oder ausgeschlossen werden. Dies wird ein risikoadaptiertes diagnostisches und therapeutisches Vorgehen ermoglichen. Nach Semiquantifizierung der klinischen Wahrscheinlichkeit einer…

Therapeutic Advances in Emergency Cardiology: Acute Pulmonary Embolism.

Background Acute pulmonary embolism (PE) requires rapid diagnosis and early and appropriate treatment, often under conditions of hemodynamic instability. The therapeutic strategy should optimally integrate the therapeutic arsenal in a multidisciplinary but unitary approach. Areas of uncertainty The short list of the major uncertainties associated with acute PE should include limited general public awareness on venous thromboembolism, acute hemodynamic support not based on evidence from randomized clinical trials, with few updates lately, mainly linked to extracorporeal membrane oxygenation, thrombolytic therapy having firm indications only in high-risk PE, without clear strategies for parti…

Hämodynamische Definition der pulmonalen Hypertonie: Kommentar zu der vorgeschlagenen Änderung durch das 6th World Symposium on Pulmonary Hypertension

ZusammenfassungDie Ende 2015 veröffentlichten ESC/ERS-Leitlinien und andere internationale Empfehlungen definierten die pulmonale Hypertonie (PH) bisher durch einen invasiv gemessenen mittleren pulmonal arteriellen Druck (mPAP) ≥ 25 mmHg in Ruhe. Auf dem 6th World Symposium on Pulmonary Hypertension in Nizza wurde eine Modifikation dieser hämodynamischen Definition im Sinne einer Senkung des Schwellenwertes auf &gt; 20 mmHg vorgeschlagen. Für die präkapilläre PH wird zusätzlich ein pulmonaler Gefäßwiderstand (PVR) ≥ 3 Wood-Einheiten (WE) gefordert. Diese Änderung muss im Hinblick auf die zugrunde liegende Rationale und mögliche Konsequenzen kritisch hinterfragt werden; es bedarf daher einer…

History of deep vein thrombosis is a discriminator for concomitant atrial fibrillation in pulmonary embolism.

Pulmonary embolism (PE) is the consequence of deep vein thrombosis (DVT) in 70% of all cases. Although, PE and DVT are commonly related to risk factors of Virchow's triad, both entities are linked to cardiovascular risk factors, but risk factors seem differently important in both entities.We aimed to investigate clinical profile and outcome of patients with PE history stratified by concomitant DVT.Data from the observational multi-center thrombEVAL-study were analyzed.The sample (N=2,318) comprised 295 PE patients, of whom 69.2% (N=204) had DVT. Individuals without DVT were older and had higher prevalence of concomitant atrial fibrillation (AF), chronic lung diseases, coronary artery diseas…

Quality of Life 3 and 12 Months Following Acute Pulmonary Embolism

BACKGROUND Few data are available on the long-term course and predictors of quality of life (QoL) following acute pulmonary embolism (PE). RESEARCH QUESTION What are the kinetics and determinants of disease-specific and generic health-related QoL 3 and 12 months following an acute PE? STUDY DESIGN AND METHODS The Follow-up after Acute Pulmonary Embolism (FOCUS) study prospectively followed up consecutive adult patients with objectively diagnosed PE. Patients were considered for study who completed the Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire at predefined visits 3 and 12 months following PE. The course of disease-specific QoL as assessed using the PEmb-QoL and the impact …

Evaluation of oral anticoagulation therapy: Rationale and design of the thrombEVAL study programme

Since decades, oral anticoagulation (OAC) with vitamin K antagonists (VKA) is an established therapy for both prevention and treatment of thromboembolism in daily clinical routine. Increasing life expectancy, demographic changes, and novel oral anticoagulants have led to an increasing complexity of medical therapy. However, data on quality and management of VKA therapy with phenprocoumon in current medical care are limited. Our aim is to investigate the quality of OAC with VKA in current health care and to evaluate the potential for improvements.The investigator-initiated thrombEVAL study programme comprises two cohorts of patients treated with vitamin K antagonists for oral anticoagulation…

Optimizing the Personalized, Risk-Adjusted Management of Pulmonary Embolism: An Integrated Clinical Trial Programme

Acute pulmonary embolism (PE) contributes significantly to the global burden of cardiovascular disease. The severity of the acute PE event determines the expected estimated risk of early death. This risk is influenced by the degree of dysfunction of the right ventricle (RV), as assessed by the presence of acute RV pressure overload on imaging and/or elevated cardiac biomarkers, and by demographic and clinical factors, including relevant comorbidities. Haemodynamic instability and cardiogenic shock is at the top of the PE severity spectrum, as it represents the most extreme manifestation of RV failure and a key determinant of poor prognosis. Ideally, risk-adjusted treatment should implement:…

P2772The rule-out criteria for chronic thromboembolic pulmonary hypertension can identify patients without haemodynamic abnormalities and functional limitation 3 and 12 months after acute PE

Abstract Background Up to one-third of patients report persisting hemodynamic abnormalities and functional limitation over long-term follow-up after acute pulmonary embolism (PE). Purpose We tested whether a validated algorithm designed to rule-out chronic thromboembolic pulmonary hypertension (CTEPH) after acute PE can be used for identifying patients at lower risk of presenting with persisting symptoms and echocardiographic abnormalities. Methods The multicentre Follow-up of Acute Pulmonary Embolism (FOCUS) cohort study prospectively enrolled 1,100 consecutive patients diagnosed with acute symptomatic PE; two-year follow-up is ongoing. We focused on the scheduled visits for 3- and 12-mont…

Incidence of acute pulmonary embolism in COVID-19 patients: Systematic review and meta-analysis.

Highlights • Acute pulmonary embolism (PE) is a frequent complication of COVID-19 infection. • The in-hospital incidence of acute PE among COVID-19 patients is higher in ICU patients. • Computed tomography angiography (CTPA) is infrequently performed.

Sex-specific differences in the distal versus proximal presenting location of acute deep vein thrombosis

Abstract Background and aims Women present with pulmonary embolism (PE) more often than men, while the opposite is true for proximal deep vein thrombosis (DVT). We investigated whether sex-specific differences exist in the presenting location of acute symptomatic DVT among patients without concomitant PE. Methods We tested our hypothesis in a meta-analysis of studies selected by systematically reviewing PubMed, Embase, and the grey literature. Thereafter, we analysed data of a single-center cohort including patients with first isolated acute DVT to assess the additional impact of age and provoking risk factors on the presenting location of DVT. Results We identified 7 studies for a total of…

Improved identification of thrombolysis candidates amongst intermediate-risk pulmonary embolism patients: implications for future trials.

Defining a “higher-risk” population among intermediate-risk patients with pulmonary embolism included in PEITHO http://ow.ly/JM7u30hcSgN

Pulmonary embolism hotline 2012. Recent and expected trials.

SummaryManagement of acute pulmonary embolism (PE) has advanced considerably in the past year, and progress is expected to continue in 2013. To help determine the optimal management strategy for normotensive patients with intermediate-risk PE, the Pulmonary Embolism Thrombolysis (PEITHO) study completed enrolment of 1006 patients with evidence of right ventricular dysfunction (by echocardiography or computed tomography) plus a positive troponin test. Patients have been randomised to thrombolytic treatment with tenecteplase versus placebo, and the effects on clinical end points (death or haemodynamic collapse) assessed at 7 and 30 days. The results are expected in spring 2013; long-term foll…

Determinants of diagnostic delay in chronic thromboembolic pulmonary hypertension: results from the European CTEPH Registry.

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterised by chronic thrombi in the pulmonary arterial bed, causing pulmonary hypertension [1–3]. CTEPH is diagnosed in ∼3% of patients who survive a symptomatic acute pulmonary embolism (PE) [4]. While the surgical removal of chronic fibrotic thrombotic vascular occlusions by pulmonary endarterectomy (PEA) may cure most patients with CTEPH by normalising pulmonary artery hemodynamics and improving symptoms, patients who remain not operated or do not undergo balloon pulmonary angioplasty have severe functional limitations, and poor quality of life and survival [5, 6]. Since the natural course of CTEPH involves progressive remodell…

Predicting Venous Thromboembolism in Primary Care

Mid-regional pro-atrial natriuretic peptide and copeptin as indicators of disease severity and therapy response in CTEPH

Background Chronic thromboembolic pulmonary hypertension (CTEPH) leads to right heart failure. Pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA) restore pulmonary haemodynamics and allow cardiac recovery. This study examined the relationship of copeptin and mid-regional pro-atrial natriuretic peptide (MR-proANP) levels to disease severity and therapy response. Methods This observational cohort study included 125 patients (55 PEA/70 BPA) who underwent treatment and completed a 6-/12-month follow-up. Biomarkers, measured at baseline, prior to every BPA and at follow-up, were compared to 1) severe disease at baseline (right atrial pressure (RAP) ≥8 mmHg and cardiac index ≤2…

Thrombolyse bei akuter Lungenembolie – Risikostratifizierung, risikoadaptierte Diagnostik und Therapie

Die Strategien zur Risikostratifizierung und risikoadaptierten Diagnostik und Therapie von Patienten mit akuter Lungenembolie befinden sich derzeit in einer Phase des Umbruchs. Fur die neuen europaischen Leitlinien, die Mitte des Jahres 2014 erscheinen sollen, werden umfangreiche Uberarbeitungen unter anderem auch hinsichtlich der Indikation zur Thrombolyse bei normotensiven Patienten mit „intermediarem“ Risiko erwartet. In diesem Artikel werden die Empfehlungen zur Thrombolyse bei Patienten mit akuter Lungenembolie zusammengefasst unter besonderer Berucksichtigung aktueller Studiendaten zur thrombolytischen Therapie bei Patienten mit „intermediarem“ Risiko.

Recent Randomized Trials of Antithrombotic Therapy for Patients With COVID-19

Endothelial injury and microvascular/macrovascular thrombosis are common pathophysiological features of coronavirus disease-2019 (COVID-19). However, the optimal thromboprophylactic regimens remain unknown across the spectrum of illness severity of COVID-19. A variety of antithrombotic agents, doses, and durations of therapy are being assessed in ongoing randomized controlled trials (RCTs) that focus on outpatients, hospitalized patients in medical wards, and patients critically ill with COVID-19. This paper provides a perspective of the ongoing or completed RCTs related to antithrombotic strategies used in COVID-19, the opportunities and challenges for the clinical trial enterprise, and ar…

Early switch to oral anticoagulation in patients with acute intermediate-risk pulmonary embolism (PEITHO-2) : a multinational, multicentre, single-arm, phase 4 trial

BACKGROUND: Current guidelines recommend a risk-adjusted treatment strategy for the management of acute pulmonary embolism. This is a particular patient category for whom optimal treatment (anticoagulant treatment, reperfusion strategies, and duration of hospitalisation) is currently unknown. We investigated whether treatment of acute intermediate-risk pulmonary embolism with parenteral anticoagulation for a short period of 72 h, followed by a switch to a direct oral anticoagulant (dabigatran), is effective and safe. METHODS: We did a multinational, multicentre, single-arm, phase 4 trial at 42 hospitals in Austria, Belgium, France, Germany, Italy, Netherlands, Romania, Slovenia, and Spain. …

Pharmacological Agents Targeting Thromboinflammation in COVID-19: Review and Implications for Future Research.

AbstractCoronavirus disease 2019 (COVID-19), currently a worldwide pandemic, is a viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The suspected contribution of thrombotic events to morbidity and mortality in COVID-19 patients has prompted a search for novel potential options for preventing COVID-19-associated thrombotic disease. In this article by the Global COVID-19 Thrombosis Collaborative Group, we describe novel dosing approaches for commonly used antithrombotic agents (especially heparin-based regimens) and the potential use of less widely used antithrombotic drugs in the absence of confirmed thrombosis. Although these therapies may have direct…

2014 ESC Guidelines on the diagnosis and management of acute pulmonary embolism

ACS : acute coronary syndrome AMPLIFY : Apixaban for the Initial Management of Pulmonary Embolism and Deep-Vein Thrombosis as First-line Therapy aPTT : activated partial thromboplastin time b.i.d. : bis in diem (twice daily) b.p.m. : beats per minute BNP : brain natriuretic peptide BP : blood pressure CI : confidence interval CO : cardiac output COPD : chronic obstructive pulmonary disease CPG : Committee for Practice Guidelines CRNM : clinically relevant non-major CT : computed tomographic/tomogram CTEPH : chronic thromboembolic pulmonary hypertension CUS : compression venous ultrasonography DSA : digital subtraction angiography DVT : deep vein thrombosis ELISA : enzyme-linked immunosorben…

Sex-specific differences in chronic thromboembolic pulmonary hypertension. Results from the European CTEPH registry

BACKGROUND: Women are more susceptible than men to several forms of pulmonary hypertension, but have better survival. Sparse data are available on chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: We investigated sex-specific differences in the clinical presentation of CTEPH, performance of pulmonary endarterectomy (PEA), and survival. RESULTS: Women constituted one-half of the study population of the European CTEPH registry (N = 679) and were characterized by a lower prevalence of some cardiovascular risk factors, including prior acute coronary syndrome, smoking habit, and chronic obstructive pulmonary disease, but more prevalent obesity, cancer, and thyroid diseases. The med…

Endothelial Leptin Receptor Deletion Promotes Cardiac Autophagy and Angiogenesis Following Pressure Overload by Suppressing Akt/mTOR Signaling.

Background: Cardiac remodeling is modulated by overnutrition or starvation. The adipokine leptin mediates energy balance between adipose tissue and brain. Leptin and its receptors are expressed in the heart. Methods and Results: To examine the importance of endothelial leptin signaling in cardiac hypertrophy, transverse aortic constriction was used in mice with inducible endothelium-specific deletion of leptin receptors (End.LepR-KO) or littermate controls (End.LepR-WT). End.LepR-KO was associated with improved left ventricular function (fractional shortening, 28.4% versus 18.8%; P =0.0114), reduced left ventricular dilation (end-systolic inner left ventricular diameter, 3.59 versus 4.08 m…

P2540Sex-specific differences in the clinical presentation, surgical complications, and course of chronic thromboembolic pulmonary hypertension

Abstract Background Women are more susceptible to develop several forms of pulmonary hypertension, but they may have better survival rates than men. Sparse data are available concerning sex-specific differences in chronic thromboembolic pulmonary hypertension (CTEPH). Purpose and methods We investigated sex-specific differences in the clinical presentation of CTEPH, functional parameters, exposure to pulmonary endarterectomy (PEA), and survival. Results Women constituted half of the study population (N=679 treatment-naïve patients from the European CTEPH registry) and were characterized by a lower prevalence of some cardiovascular risk factors (e.g. prior acute coronary syndrome, smoking ha…

Riociguat treatment in patients with pulmonary arterial hypertension: Final safety data from the EXPERT registry

OBJECTIVE: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice. METHODS: EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping ri…

The predictive value of heart-type fatty acid-binding protein is independent from symptom duration in normotensive patients with pulmonary embolism.

Heart-type fatty acid-binding protein (H-FABP) is a useful biomarker for risk stratification of patients with pulmonary embolism (PE). In patients with acute myocardial infarction, H-FABP plasma concentrations rise after 30 minutes and return to normal within 20-24 hours. We tested whether the predictive value of H-FABP is affected by the duration of symptoms prior to diagnosis in patients with PE.We prospectively studied 257 consecutive normotensive patients with confirmed symptomatic PE.Patients with acute (24 hours; n=150) symptom onset presented more often with syncope (28.7% vs. 6.5%; p0.001) compared to patients with symptoms ≥ 24 hours (n=107); other baseline characteristics, comorbi…

Systemic Thrombolytic Therapy for Acute Pulmonary Embolism: Who Is a Candidate?

Pulmonary embolism (PE) is a major cause of both acute and long-term morbidity for a large number of patients worldwide, and massive PE is frequently fatal. Right ventricular (RV) dysfunction is a key determinant of prognosis in the acute phase of PE. Patients with clinically overt RV failure, that is, with cardiogenic shock or persistent hypotension at presentation (acute high-risk PE), are clearly in need of immediate reperfusion treatment with systemic thrombolysis or, alternatively, surgical or catheter-directed techniques. On the other hand, within the large group of patients presenting without hemodynamic instability, the bleeding risk of full-dose intravenous thrombolytic treatment h…

Risk stratification of normotensive pulmonary embolism: prognostic impact of copeptin

The prognostic value of copeptin, the C-terminal fragment of the precursor protein of vasopressin which is released upon stress, and hypotension in pulmonary embolism is unknown, especially if combined with biomarkers reflecting different pathophysiological axes such as myocardial injury (high-sensitivity troponin T (hsTnT)) and stretch (N-terminal pro-brain natriuretic peptide (NT-proBNP)).We prospectively studied 268 normotensive pulmonary embolism patients included in a single-centre cohort study.Patients with an adverse 30-day outcome (5.6%) had higher copeptin levels than patients with a favourable course (median (interquartile range) 51.8 (21.6–90.8) versus 13.2 (5.9–39.3) pmol·L−1; p…

Progress in the management of acute pulmonary embolism.

Purpose of review Pulmonary embolism is a major contributor to global disease burden worldwide. The 2014 guidelines of the European Society of Cardiology, endorsed by the European Respiratory Society, emphasize the need for initial and advanced risk stratification as well as risk-adapted treatment to ensure the highest quality of care. This review summarizes the progress in pulmonary embolism diagnosis, risk assessment, and treatment. Recent findings Major advances of the past 12 months include age-related biomarker cutoff levels for optimising pulmonary embolism diagnosis and risk stratification; detection of (isolated) subsegmental pulmonary embolism by computed tomographic pulmonary angi…

Age-sex specific pulmonary embolism-related mortality in the USA and Canada, 2000-18: an analysis of the WHO Mortality Database and of the CDC Multiple Cause of Death database

Contains fulltext : 232738.pdf (Publisher’s version ) (Closed access) BACKGROUND: Pulmonary embolism (PE)-related mortality is decreasing in Europe. However, time trends in the USA and Canada remain uncertain because the most recent analyses of PE-related mortality were published in the early 2000s. METHODS: For this retrospective epidemiological study, we accessed medically certified vital registration data from the WHO Mortality Database (USA and Canada, 2000-17) and the Multiple Cause of Death database produced by the Division of Vital Statistics of the US Centers for Disease Control and Prevention (CDC; US, 2000-18). We investigated contemporary time trends in PE-related mortality in th…

Evaluation of VTE-BLEED for predicting intracranial or fatal bleeding in stable anticoagulated patients with venous thromboembolism.

VTE-BLEED predicts fatal and/or intracranial bleeding in patients with venous thromboembolism treated with long-term anticoagulants http://ow.ly/3hqg30iXK5a

Tailoring anticoagulant treatment of patients with atrial fibrillation using a novel bleeding risk score

ObjectivesCurrent international guidelines advocate the application of bleeding risk scores only to identify modifiable risk factors, but not to withhold treatment in patients at high risk of bleeding. VTE-BLEED (ActiVe cancer, male with uncontrolled hyperTension, anaEmia, history of BLeeding, agE and rEnal Dysfunction) is a simple bleeding risk score that predicts major bleeding (MB) in patients with venous thromboembolism, but has never been evaluated in patients with atrial fibrillation (AF). We sought to evaluate VTE-BLEED in patients with AF included in the Randomised Evaluation of Long-term anticoagulant therapY (RE-LY) trial, to assess whether score classes (high vs low bleeding risk…

Thrombosis and thromboembolism related to COVID‐19: A clarion call for obtaining solid estimates from large‐scale multicenter data

Abstract The clinical spectrum of coronavirus disease 2019 (COVID‐19) is wide, ranging from minor, nonspecific symptoms to severe pneumonia, acute respiratory distress syndrome, multiorgan involvement, and shock. In severe cases, the acute systemic inflammatory response, coagulation activation, and diffuse endothelial damage may, in combination with hypoxia, immobilization, and underlying risk factors, result in potentially life‐threatening venous and arterial thrombotic events. The first data from single‐center retrospective studies suggest that thrombotic events are a key aspect of COVID‐19‐associated morbidity and mortality. We have planned and will be launching the COvid REgistry on THR…

Prognostic impact of copeptin in pulmonary embolism: a multicentre validation study.

To externally validate the prognostic impact of copeptin, either alone or integrated in risk stratification models, in pulmonary embolism (PE), we performed a post hoc analysis of 843 normotensive PE patients prospectively included in three European cohorts.Within the first 30 days, 21 patients (2.5%, 95% CI 1.5–3.8) had an adverse outcome and 12 (1.4%, 95% CI 0.7–2.5) died due to PE. Patients with copeptin ≥24 pmol·L−1 had a 6.3-fold increased risk for an adverse outcome (95% CI 2.6–15.5, p&lt;0.001) and a 7.6-fold increased risk for PE-related death (95% CI 2.3–25.6, p=0.001). Risk classification according to the 2014 European Society of Cardiology (ESC) guideline algorithm identified 248…

Low-molecular-weight heparin to prevent recurrent venous thromboembolism in pregnancy: Rationale and design of the Highlow study, a randomised trial of two doses

Summary Background Women with a history of venous thromboembolism (VTE) have a 2% to 10% absolute risk of VTE recurrence during subsequent pregnancies. Therefore, current guidelines recommend that all pregnant women with a history of VTE receive pharmacologic thromboprophylaxis. The optimal dose of low-molecular-weight heparin (LMWH) for thromboprophylaxis is unknown. In the Highlow study (NCT 01828697; www.highlowstudy.org ), we compare a fixed low dose of LMWH with an intermediate dose of LMWH for the prevention of pregnancy-associated recurrent VTE. We present the rationale and design features of this study. Methods The Highlow study is an investigator-initiated, multicentre, internation…

Trends in mortality related to pulmonary embolism in the European Region, 2000-15: analysis of vital registration data from the WHO Mortality Database

Summary Background European estimates of the burden imposed by pulmonary embolism are not available to this date. We aimed to assess pulmonary embolism-related mortality and time trends in the WHO European Region. Methods We analysed vital registration data from the WHO Mortality Database (2000–15) covering subregions of the WHO European Region: Eastern Europe, Northern Europe, Southern Europe, Western Europe, and Central Asia. Deaths were considered pulmonary embolism-related if International Classification of Disease-10 code for acute pulmonary embolism (I26) or any code for deep or superficial vein thrombosis was listed as the primary cause of death. We used locally estimated scatterplot…

Quality of life and functional limitations after pulmonary embolism and its prognostic relevance

Abstract Background While the importance of patients’ quality of life (QoL) in chronic cardiac or pulmonary disease is uncontroversial, the burden of an acute pulmonary embolism (PE) on QoL has received little attention thus far. Objectives We aimed to validate the German PEmb‐QoL questionnaire, identify associations between QoL and clinical/functional parameters, and investigate the prognostic relevance of QoL for long‐term survival in survivors of an acute PE episode. Patients/Methods Patients were invited for a clinical follow‐up visit including assessment of QoL using the German PEmb‐QoL questionnaire 6 months after an objectively confirmed PE at a single center. Internal consistency re…

Prevalence of pulmonary embolism in 127 945 autopsies performed in cancer patients in the United States between 2003 and 2019

Abstract Background Pulmonary embolism (PE) is a potentially fatal disease, but data on the incidence of fatal PE in cancer patients are scant. Objective We sought to estimate the proportion of cancer patients with PE at autopsy. Methods For this retrospective cohort study, all autopsy reports of cancer patients were retrieved from PALGA: Dutch Pathology Registry and used for data extraction. The primary outcome was PE at time of autopsy, defined as any clot obstructing a pulmonary artery. The secondary outcome was venous thromboembolism, defined as the composite of thrombotic PE, deep vein thrombosis, splanchnic vein thrombosis, or internal jugular vein thrombosis. Results A total of 9571 …

The Prognostic Value of Renal Function in Acute Pulmonary Embolism—A Multi-Centre Cohort Study

Background Haemodynamic alterations caused by acute pulmonary embolism (PE) may affect multi-organ function including kidneys. This multi-centre, multinational cohort study aimed to validate the prognostic significance of estimated glomerular filtration rate (eGFR) and its potential additive value to the current PE risk assessment algorithms. Methods The post hoc analysis of pooled prospective cohort studies: 2,845 consecutive patients (1,424 M/1,421 F, 66 ± 17 years) with confirmed acute PE and followed up for 180 days. We tested prognostic value of pre-specified eGFR level ≤60 mL/min/1.73 m2 calculated on admission according to the Modification of Diet in Renal Disease study equation. Th…

A targeted proteomics investigation of the obesity paradox in venous thromboembolism

Abstract The obesity paradox, the controversial finding that obesity promotes disease development but protects against sequelae in patients, has been observed in venous thromboembolism (VTE). The aim of this investigation was to identify a body mass–related proteomic signature in VTE patients and to evaluate whether this signature mediates the obesity paradox in VTE patients. Data from the Genotyping and Molecular Phenotyping in Venous ThromboEmbolism Project, a prospective cohort study of 693 VTE patients, were analyzed. A combined end point of recurrent VTE or all-cause death was used. Relative quantification of 444 proteins was performed using high-throughput targeted proteomics technolo…

Protein expression profiling suggests relevance of noncanonical pathways in isolated pulmonary embolism

Abstract Patients with isolated pulmonary embolism (PE) have a distinct clinical profile from those with deep vein thrombosis (DVT)-associated PE, with more pulmonary conditions and atherosclerosis. These findings suggest a distinct molecular pathophysiology and the potential involvement of alternative pathways in isolated PE. To test this hypothesis, data from 532 individuals from the Genotyping and Molecular Phenotyping of Venous ThromboEmbolism Project, a multicenter prospective cohort study with extensive biobanking, were analyzed. Targeted, high-throughput proteomics, machine learning, and bioinformatic methods were applied to contrast the acute-phase plasma proteomes of isolated PE pa…

Prevention of early complications and late consequences after acute pulmonary embolism: Focus on reperfusion techniques

Pulmonary embolism (PE) is a major cause of acute cardiovascular mortality and long-term morbidity. Right ventricular (RV) dysfunction is the key determinant of prognosis in the acute phase of PE, and residual RV dysfunction is associated with the development of post-PE functional impairment, chronic thromboembolic disease, and higher costs of treatment over the long term. Patients with clinically overt RV failure, i.e. hemodynamic collapse at presentation (high-risk PE), necessitate immediate thrombolytic treatment to relieve the obstruction in the pulmonary circulation; surgical or catheter-directed removal of the thrombus can be an alternative option. For patients with a high risk of ble…

Letter by Tziakas et al Regarding Article, “Aortic Valve Stenosis: From Basic Mechanisms to Novel Therapeutic Targets”

Prognostic value of right ventricular dysfunction or elevated cardiac biomarkers in patients with low-risk pulmonary embolism: a systematic review and meta-analysis

Abstract Aims Patients with acute pulmonary embolism (PE) classified as low risk by the Pulmonary Embolism Severity Index (PESI), its simplified version (sPESI), or the Hestia criteria may be considered for early discharge. We investigated whether the presence of right ventricular (RV) dysfunction may aggravate the early prognosis of these patients. Methods and results We did a systematic review and meta-analysis of studies including low-risk patients with acute PE to investigate the prognostic value of RV dysfunction. Diagnosis of RV dysfunction was based on echocardiography or computed tomography pulmonary angiography. In addition, we investigated the prognostic value of elevated troponin…

Power of the Wilcoxon–Mann–Whitney test for non‐inferiority in the presence of death‐censored observations

In clinical trials with patients in a critical state, death may preclude measurement of a quantitative endpoint of interest, and even early measurements, for example for intention-to-treat analysis, may not be available. For example, a non-negligible proportion of patients with acute pulmonary embolism will die before 30 day measurements on the efficacy of thrombolysis can be obtained. As excluding such patients may introduce bias, alternative analyses, and corresponding means for sample size calculation are needed. We specifically consider power analysis in a randomized clinical trial setting in which the goal is to demonstrate noninferiority of a new treatment as compared to a reference t…

Impact of obesity on adverse in-hospital outcomes in patients undergoing percutaneous mitral valve edge-to-edge repair using MitraClip® procedure - Results from the German nationwide inpatient sample

Background and aim: The number of percutaneous edge-to-edge mitral regurgitation (MR) valve repairs with MitraClip® implantations increased exponentially in recent years. Studies have suggested an obesity survival paradox in patients with cardiovascular diseases. We investigated the influence of obesity on adverse in-hospital outcomes in patients with MitraClip® implantation. Methods and results: We analyzed data on characteristics of patients and in-hospital outcomes for all percutaneous mitral valve repairs using the edge-to-edge MitraClip®-technique in Germany 2011–2015 stratified for obesity vs. normal-weight/over-weight. The nationwide inpatient sample comprised 13,563 inpatients under…

High-sensitivity troponin I for risk stratification in normotensive pulmonary embolism

While numerous studies have confirmed the prognostic role of high-sensitivity troponin T (hsTnT) in pulmonary embolism (PE), high-sensitivity troponin I (hsTnI) is inappropriately studied. This study aimed to investigate the prognostic relevance of hsTnI in normotensive PE, establish the optimal cut-off value for risk stratification and to compare the prognostic performances of hsTnI and hsTnT. Based on data from 459 consecutive PE patients enrolled in a single-centre registry, receiver operating characteristic analysis was used to identify an optimal hsTnI cut-off value for prediction of in-hospital adverse outcomes (PE-related death, cardiopulmonary resuscitation or vasopressor treatment)…

Increased Lymphangiogenesis and Lymphangiogenic Growth Factor Expression in Perivascular Adipose Tissue of Patients with Coronary Artery Disease

Experimental and human autopsy studies have associated adventitial lymphangiogenesis with atherosclerosis. An analysis of perivascular lymphangiogenesis in patients with coronary artery disease is lacking. Here, we examined lymphangiogenesis and its potential regulators in perivascular adipose tissue (PVAT) surrounding the heart (C-PVAT) and compared it with PVAT of the internal mammary artery (IMA-PVAT). Forty-six patients undergoing coronary artery bypass graft surgery were included. Perioperatively collected C-PVAT and IMA-PVAT were analyzed using histology, immunohistochemistry, real time PCR, and PVAT-conditioned medium using cytokine arrays. C-PVAT exhibited increased PECAM-1 (platele…

Variation of platelet function in clinical phenotypes of acute venous thromboembolism – Results from the GMP‐VTE project

Background The role of platelets in the pathogenesis of venous thromboembolism (VTE) is receiving increasing attention; however, limited information is available on platelet function in the acute phase of the disease. Objective To characterize platelet function according to VTE phenotypes. Patients/Methods In total, 154 subjects (isolated pulmonary embolism [iPE], n = 28; isolated deep vein thrombosis [iDVT], n = 35; DVT+PE, n = 91) were included. In this study platelet function analyzer (PFA)-200, light transmission aggregometry (LTA), thrombin generation (TG) in presence (PRP) and absence (PFP) of platelets and platelet flow cytometry were investigated. LASSO regression was used to select…