Background: There is ambiguity whether frail patients with atrial fibrillation (AF) managed with vitamin K antagonists (VKAs) should be switched to a non-vitamin K oral anticoagulant (NOAC).Methods... Show moreBackground: There is ambiguity whether frail patients with atrial fibrillation (AF) managed with vitamin K antagonists (VKAs) should be switched to a non-vitamin K oral anticoagulant (NOAC).Methods: We conducted a pragmatic, multicenter, open-label, randomized controlled superiority trial. Older AF patients living with frailty (age >= 75 years plus a Groningen Frailty Indicator (GFI) score >= 3) were randomized to switch from INR-guided VKA treatment to a NOAC or to continued VKA treatment. Patients with a glomerular filtration rate <30 mLmin(-1)1.73 m(-2) or with valvular AF were excluded. Follow-up was 12 months. The cause-specific hazard ratio (HR) was calculated for occurrence of the primary outcome which was a major or clinically relevant non-major bleeding complication, whichever came first, accounting for death as a competing risk. Analyses followed the intention-to-treat principle. Secondary outcomes included thromboembolic events.Results: Between January 2018 and June 2022, a total of 2,621 patients were screened for eligibility and 1,330 patients were randomized (mean age 83 years, median GFI 4). After randomization 6 patients in the switch to NOAC arm and 1 patient in the continue with VKA arm were excluded due to the presence of exclusion criteria, leaving 662 patients switched from a VKA to a NOAC and 661 patients continued VKAs in the intention-to-treat population. After 163 primary outcome events (101 in the switch arm, 62 in the continue arm), the trial was stopped for futility according to a prespecified futility analysis. The HR for our primary outcome was 1.69 (95% CI 1.23-2.32). The HR for thromboembolic events was 1.26 (95% CI 0.60 to 2.61).Conclusions: Switching INR-guided VKA treatment to a NOAC in frail older patients with AF was associated with more bleeding complications compared to continuing VKA treatment, without an associated reduction in thromboembolic complications. Show less
Cohen, A.T.; Creeper, K.J.; Alikhan, R.; Er, C.; Connors, J.M.; Huisman, M.V.; ... ; Becattini, C. 2024
Background In patients with acute venous thromboembolism (VTE), the rates of recurrence and major bleeding are highest during the first weeks of anticoagulation. The CARAVAGGIO trial demonstrated... Show moreBackground In patients with acute venous thromboembolism (VTE), the rates of recurrence and major bleeding are highest during the first weeks of anticoagulation. The CARAVAGGIO trial demonstrated noninferiority of apixaban to dalteparin for treatment of cancer-associated VTE without an increased risk of major bleeding. We compared the early time course of VTE recurrence and major bleeding events of apixaban compared with dalteparin at 7, 30, and 90 days of treatment in patients with cancer-associated VTE.Methods The study design of the CARAVAGGIO trial has been described. Eligible patients were randomly assigned to receive monotherapy with either apixaban or dalteparin for 6 months. The primary efficacy outcome was the incidence of objectively confirmed recurrent VTE. The primary safety outcome was major bleeding.Results In 1,155 patients, recurrent VTE after 7, 30, and 90 days occurred in 6 (1%), 15 (2.6%), and 27 (4.7%) patients in the apixaban arm versus 5 (0.9%), 20 (3.5%), and 36 (6.2%) patients respectively in the dalteparin arm. By day 7, 30, and 90, major bleeding events had occurred in 3 (0.5%), 9 (1.6%), and 16 (2.8%) patients in the apixaban group versus 5 (0.9%), 11 (1.9%), and 17 (2.9%) patients in the dalteparin group.Conclusion The frequencies of recurrent VTE and major bleeding events at 7, 30, and 90 days of apixaban compared with dalteparin were similar in patients with cancer-associated VTE. This supports the use of apixaban for the initiation and early phase of anticoagulant therapy in cancer-associated VTE. Show less
Supplemental Digital Content is Available in the Text.Background:Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) is a prospective... Show moreSupplemental Digital Content is Available in the Text.Background:Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) is a prospective registry of outcomes from patients with newly diagnosed AF at risk of stroke. In the propensity score (PS)-matched global population of phase 3 GLORIA-AF, at 3 years, dabigatran-treated patients experienced reduced risk for major bleeding, and similar risk for stroke and myocardial infarction, compared with vitamin K antagonist (VKA)-treated patients.Study Question:Do patients in Eastern Europe benefit from treatment with dabigatran versus VKA?Study Design:Descriptive analysis, without PS matching. To contextualize the Eastern Europe results of GLORIA-AF phase 3, we also descriptively analyzed the global population without PS matching. Consecutive patients with newly diagnosed AF and CHA2DS2-VASc-score >= 1 were enrolled until December 2016 in 38 countries (9 in Eastern Europe).Measures and Outcomes:Three-year outcomes with dabigatran and VKA.Results:In Eastern Europe, 1341 patients were eligible (6% of patients globally), and incidence rates (per 100 patient-years) for the following outcomes were numerically lower with dabigatran (N = 498) versus VKA (N = 466): major bleeding (0.26 vs. 0.90), all-cause death (2.04 vs. 3.50), and a composite of stroke, systemic embolism, myocardial infarction, life-threatening bleeding, and vascular death (1.37 vs. 1.92); stroke was comparable (0.51 vs. 0.50). All incidence rates were numerically lower in Eastern Europe versus the global population for both treatments. Chronic concomitant use of high bleeding risk medications (eg, nonsteroidal anti-inflammatories) was lower in Eastern Europe (dabigatran 3.8%, VKA 9.3%) than globally (dabigatran 14.8%, VKA 20.6%) and persistence with dabigatran was higher in Eastern Europe (76%) than globally (64%).Conclusions:Dabigatran was associated with numerically reduced major bleeding, all-cause death, and cardiovascular (CV) composite, with comparable risk of stroke versus VKA, in Eastern Europe. Limitations of this descriptive analysis include few CV events (n = 11 for stroke, in the dabigatran and VKA groups combined) and a lack of statistical analysis and PS matching, which precludes definitive conclusions; however, the CV outcomes in Eastern Europe were consistent with the beneficial impact of dabigatran versus VKA in the statistically analyzed global population with PS matching. Show less
Geersing, G.J.; Takada, T.; Klok, F.A.; Büller, H.R.; Courtney, D.M.; Freund, Y.; ... ; Es, N. van 2024
BackgroundThe recently published 4-level Pulmonary Embolism Clinical Probability Score (4PEPS) integrates different aspects from currently available diagnostic strategies to further reduce imaging... Show moreBackgroundThe recently published 4-level Pulmonary Embolism Clinical Probability Score (4PEPS) integrates different aspects from currently available diagnostic strategies to further reduce imaging testing in patients with clinically suspected pulmonary embolism (PE).AimTo externally validate the performance of 4PEPS in an independent cohort.MethodsIn this post-hoc analysis of the prospective diagnostic management YEARS study, the primary outcome measures were discrimination, calibration, efficiency (proportion of imaging tests potentially avoided), and failure rate (venous thromboembolism (VTE) diagnosis at baseline or follow-up in patients with a negative 4PEPS algorithm). Multiple imputation was used for missing 4PEPS items. Based on 4PEPS, PE was considered ruled out in patients with a very low clinical pre-test probability (CPTP) without D-dimer testing, in patients with a low CPTP and D-dimer <1000 μg/L, and in patients with a moderate CPP and D-dimer below the age-adjusted threshold.ResultsOf the 3465 patients, 474 (14 %) were diagnosed with VTE at baseline or during 3-month follow-up. Discriminatory performance of the 4PEPS items was good (area under ROC-curve, 0.82; 95%CI, 0.80–0.84) as was calibration. Based on 4PEPS, PE could be considered ruled out without imaging in 58 % (95%CI 57–60) of patients (efficiency), for an overall failure rate of 1.3 % (95%CI 0.86–1.9).ConclusionIn this retrospective external validation, 4PEPS appeared to safely rule out PE with a high efficiency. Nevertheless, although not exceeding the failure rate margin by ISTH standards, the observed failure rate in our analysis appeared to be higher than in the original 4PEPS derivation and validation study. This highlights the importance of a prospective outcome study. Show less
Background and aimsCancer provides challenges to the continuity of anticoagulant treatment in patients with atrial fibrillation (AF), e.g. through cancer-related surgery or complications. We aimed... Show moreBackground and aimsCancer provides challenges to the continuity of anticoagulant treatment in patients with atrial fibrillation (AF), e.g. through cancer-related surgery or complications. We aimed to provide data on the incidence and reasons for interrupting and discontinuing anticoagulant treatment in AF patients with cancer and to assess its contribution to the risk of thromboembolism (TE) and major bleeding (MB).MethodsThis retrospective study identified AF patients with cancer in two hospitals between 2012 and 2017. Data on anticoagulant treatment, TE and MB were collected during two-year follow-up. Incidence rates (IR) per 100 patient-years and adjusted hazard ratios (aHR) were obtained for TE and MB occurring during on- and off-anticoagulant treatment, during interruption and after resumption, and after permanent discontinuation.Results1213 AF patients with cancer were identified, of which 140 patients permanently discontinued anticoagulants and 426 patients experienced one or more interruptions. Anticoagulation was most often interrupted or discontinued due to cancer-related treatment (n = 441, 62 %), bleeding (n = 129, 18 %) or end of life (n = 36, 5 %). The risk of TE was highest off-anticoagulation and during interruptions, with IRs of 19 (14–25)) and 105 (64–13), and aHRs of 3.1 (1.9–5.0) and 4.6 (2.4–9.0), respectively. Major bleeding risk were not only increased during an interruption, but also in the first 30 days after resumption, with IRs of 33 (12–72) and 30 (17–48), and aHRs of 3.3 (1.1–9.8) and 2.4 (1.2–4.6), respectively.ConclusionsInterruption of anticoagulation therapy harbors high TE and MB risk in AF patients with cancer. The high incidence rates call for better (periprocedural) anticoagulant management strategies tailored to the cancer setting. Show less
BackgroundPulmonary infarction (PI) is relatively common in pulmonary embolism (PE). The association between PI and persistent symptoms or adverse events is largely unknown.AimTo evaluate the... Show moreBackgroundPulmonary infarction (PI) is relatively common in pulmonary embolism (PE). The association between PI and persistent symptoms or adverse events is largely unknown.AimTo evaluate the predictive value of radiological PI signs at acute PE diagnosis on 3-month outcomes.MethodsWe studied a convenience cohort with computed tomographypulmonary angiography (CTPA)-confirmed PE for whom extensive 3-month follow-up data were available. The CTPAs were re-evaluated for signs of suspected PI. Associations with presenting symptoms, adverse events (recurrent thrombosis, PE-related readmission and mortality) and self-reported persistent symptoms (dyspnea, pain and post-PE functional impairment) at 3-month follow-up were investigated using univariate Cox regression analysis.ResultsAt re-evaluation of the CTPAs, 57 of 99 patients (58 %) had suspected PI, comprising a median of 1 % (IQR 1–3) of total lung parenchyma. Patients with suspected PI more often presented with hemoptysis (11 % vs. 0 %) and pleural pain (OR 2.7, 95%CI 1.2–6.2), and with more proximal PE on CTPA (OR 1.6, 95%CI 1.1–2.4) than patients without suspected PI. There was no association with adverse events, persistent dyspnea or pain at 3-month follow-up, but signs of PI predicted more functional impairment (OR 3.03, 95%CI 1.01–9.13). Sensitivity analysis with the largest infarctions (upper tertile of infarction volume) yielded similar results.ConclusionsPE patients radiologically suspected of PI had a different clinical presentation than patients without those signs and reported more functional limitations after 3 months of follow-up, a finding that could guide patient counselling. Show less
Zhai, Z.W.; Boon, G.J.A.M.; Staring, M.; Dam, L.F. van; Kroft, L.J.M.; Girón, I.H.; ... ; Stoel, B.C. 2023
The shape and distribution of vascular lesions in pulmonary embolism (PE) and chronic thromboembolic pulmonary hypertension (CTEPH) are different. We investigated whether automated quantification... Show moreThe shape and distribution of vascular lesions in pulmonary embolism (PE) and chronic thromboembolic pulmonary hypertension (CTEPH) are different. We investigated whether automated quantification of pulmonary vascular morphology and densitometry in arteries and veins imaged by computed tomographic pulmonary angiography (CTPA) could distinguish PE from CTEPH. We analyzed CTPA images from a cohort of 16 PE patients, 6 CTEPH patients, and 15 controls. Pulmonary vessels were extracted with a graph-cut method, and separated into arteries and veins using deep-learning classification. Vascular morphology was quantified by the slope (α) and intercept (β) of the vessel radii distribution. To quantify lung perfusion defects, the median pulmonary vascular density was calculated. By combining these measurements with densities measured in parenchymal areas, pulmonary trunk, and descending aorta, a static perfusion curve was constructed. All separate quantifications were compared between the three groups. No vascular morphology differences were detected in contrast to vascular density values. The median vascular density (interquartile range) was −567 (113), −452 (95), and −470 (323) HU, for the control, PE, and CTEPH group. The static perfusion curves showed different patterns between groups, with a statistically significant difference in aorta-pulmonary trunk gradient between the PE and CTEPH groups (p = 0.008). In this proof of concept study, not vasculature morphology but densities differentiated between patients of three groups. Further technical improvements are needed to allow for accurate differentiation between PE and CTEPH, which in this study was only possible statistically by measuring the density gradient between aorta and pulmonary trunk. Show less
Hendriks, S.V.; Hout, W.B. van den; Bemmel, T. van; Bistervels, I.M.; Eijsvogel, M.; Faber, L.M.; ... ; YEARS Investigators 2023
Background Venous thromboembolism constitutes substantial health care costs amounting to approximately 60 million euros per year in the Netherlands. Compared with initial hospitalization, home... Show moreBackground Venous thromboembolism constitutes substantial health care costs amounting to approximately 60 million euros per year in the Netherlands. Compared with initial hospitalization, home treatment of pulmonary embolism (PE) is associated with a cost reduction. An accurate estimation of cost savings per patient treated at home is currently lacking.Aim The aim of this study was to compare health care utilization and costs during the first 3 months after a PE diagnosis in patients who are treated at home versus those who are initially hospitalized.Methods Patient-level data of the YEARS cohort study, including 383 normotensive patients diagnosed with PE, were used to estimate the proportion of patients treated at home, mean hospitalization duration in those who were hospitalized, and rates of PE-related readmissions and complications. To correct for baseline differences within the two groups, regression analyses was performed. The primary outcome was the average total health care costs during a 3-month follow-up period for patients initially treated at home or in hospital.Results Mean hospitalization duration for the initial treatment was 0.69 days for those treated initially at home (n = 181) and 4.3 days for those initially treated in hospital (n = 202). Total average costs per hospitalized patient were €3,209 and €1,512 per patient treated at home. The adjusted mean difference was €1,483 (95% confidence interval: €1,181–1,784).Conclusion Home treatment of hemodynamically stable patients with acute PE was associated with an estimated net cost reduction of €1,483 per patient. This difference underlines the advantage of triage-based home treatment of these patients. Show less
BackgroundCancer is suggested to confer thromboembolic and bleeding risk in patients with atrial fibrillation (AF).ObjectivesWe aimed to describe current anticoagulant practice in patients with AF... Show moreBackgroundCancer is suggested to confer thromboembolic and bleeding risk in patients with atrial fibrillation (AF).ObjectivesWe aimed to describe current anticoagulant practice in patients with AF and active cancer, present incidences of thromboembolic and bleeding complications, and evaluate the association between cancer type or anticoagulant management strategy with AF-related complications.MethodsThis retrospective study identified patients with AF and active cancer in 2 hospitals between January 1, 2012, and December 31, 2017. Follow-up lasted for 2 years. Data on cancer and anticoagulant treatment were collected. The outcomes of interest included ischemic stroke or transient ischemic attack (TIA) and clinically relevant nonmajor bleeding (CRNMB/MB). Incidence rates (IRs) per 100 patient-years and subdistribution hazard ratios (SHRs) with corresponding 95% Cis were estimated.ResultsWe identified 878 patients with AF who developed cancer (cohort 1) and 335 patients with cancer who developed AF (cohort 2). IRs for ischemic stroke/TIA and MB/CRNMB were 3.9 (2.8-5.3) and 15.7 (13.3-18.5) for cohort 1 and 4.0 (2.2-6.7) and 16.7 (12.6-21.7) for cohort 2. 14.2% (cohort 1) and 19.1% (cohort 2) of patients with a CHA2DS2-VASc score of ≥2 did not receive anticoagulant treatment. Withholding anticoagulants was associated with thromboembolic complications (SHR: 5.1 [3.20-8.0]). In nonanticoagulated patients with a CHA2DS2-VASc score of <2, IRs for stroke/TIA were 4.5 (0.75-15.0; cohort 1) and 16.0 (5.1-38.7; cohort 2).ConclusionPatients with AF and active cancer experience high rates of thromboembolic and bleeding complications, underlying the complexity of anticoagulant management in these patients. Our data suggest that the presence of cancer is an important factor in determining the indication for anticoagulants in patients with a low CHA2DS2-VASc score. Show less
Background: Patients with osteosarcoma (OS) and Ewing sarcoma (ES) are considered to have a high venous thromboembolism (VTE) risk, although the exact incidence and prognostic impact are under... Show moreBackground: Patients with osteosarcoma (OS) and Ewing sarcoma (ES) are considered to have a high venous thromboembolism (VTE) risk, although the exact incidence and prognostic impact are under-researched in general as well as in relevant age groups. Aims: To study the impact of VTE and major bleeding (MB) in OS and ES patients, subdivided in children, Ad-olescents Young Adults (AYAs; aged 18-39) and older adults. Methods: Retrospective single-center chart review in 519 OS and 165 ES patients treated between 1980 and 2018. Patients were followed from sarcoma diagnosis until an outcome of interest (VTE, MB) or death occurred. Cu-mulative incidences were estimated with death as competing risk. Cox models were used to determine prognostic impact. Results: Five-year cumulative incidences of VTE were 12 % (95%CI 9.1-15) for OS and 6.7 % (95%CI 3.5-11) for ES patients, mostly happening in patients >= 18 years; the most frequent VTE presentation was catheter-related upper-extremity thrombosis (OS: 18/65, ES: 7/11). Five-year cumulative incidences for MB were 5.8 % (95% CI 4.0-8.1) in OS and 5.4 % (95%CI 2.5-9.8) in ES patients. 192 OS and 77 ES AYAs were included, who faced similar VTE and MB incidences as older adults. In OS, VTE and MB were both associated with mortality (adjusted HRs 2.0 [95%CI 1.4-2.9] and 2.4 [95%CI 1.4-4.0], respectively), whereas in ES this association was only present for MB (aHR 3.4 [95%CI 1.2-9.6]). Conclusions: VTE is a frequent complication in adult OS and to a lesser extent in ES patients, while the rate of MB was comparably high in both sarcoma types. Show less
Background The 'Atrial fibrillation Better Care' (ABC) pathway has been proposed to streamline a more holistic or integrated care approach to atrial fibrillation (AF) management. We aimed to... Show moreBackground The 'Atrial fibrillation Better Care' (ABC) pathway has been proposed to streamline a more holistic or integrated care approach to atrial fibrillation (AF) management. We aimed to analyse the impact of adherence to the ABC pathway on the risk of major adverse outcomes in a contemporary prospective global cohort of patients with AF.Methods Patients enrolled Phase II and III of the GLORIA-AF Registry with complete data on ABC pathway adherence and follow-up were included in this post-hoc analysis between November 2011 and December 2014 for Phase II, and between January 2014 and December 2016 for Phase III. The primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACEs). Multivariable Cox-regression and delay of event (DoE) analyses were used to evaluate the association between adherence to the ABC pathway and the risk of outcomes.Findings We included 24,608 patients in this analysis (mean age: 70.2 (10.3) years, 10,938 (44.4%) females). Adherence to the ABC pathway was associated with a significant risk reduction for the primary outcome, with greatest magnitude observed for full ABC pathway adherence (adjusted Hazard Ratio [aHR] 0.54, 95% Confidence Interval [CI]: 0.44-0.67, p < 0.0001). ABC pathway adherence was also associated with reduced risk of mortality (aHR: 0.89, 95% CI: 0.79-1.00, p = 0.048), thromboembolism (aHR: 0.78, 95% CI: 0.65-0.94, p = 0.0078), and MACE (aHR: 0.82, 95% CI: 0.71-0.95, p = 0.0071). An increasing number of ABC criteria attained was associated with longer event-free survival in the DoE analysis.Interpretation Adherence to the ABC pathway in patients with AF was associated with a reduced risk of major adverse events, including mortality, thromboembolism and MACE. This underlines the importance of using the ABC pathway in the clinical care of patients with AF. (C) 2022 The Author(s). Published by Elsevier Ltd. Show less
BackgroundRight ventricular (RV) function plays a critical role in the pathophysiology and acute prognosis of pulmonary embolism (PE). We analyzed the temporal changes of RV function in the cohort... Show moreBackgroundRight ventricular (RV) function plays a critical role in the pathophysiology and acute prognosis of pulmonary embolism (PE). We analyzed the temporal changes of RV function in the cohort of a prospective multicentre study investigating if an early switch to oral anticoagulation in patients with intermediate-risk PE is effective and safe. MethodsEchocardiographic and laboratory examinations were performed at baseline (PE diagnosis), 6 days and 6 months. Echocardiographic parameters were classified into categories representing RV size, RV free wall/tricuspid annulus motion, RV pressure overload and right atrial (RA)/central venous pressure. ResultsRV dysfunction based on any abnormal echocardiographic parameter was present in 84% of patients at baseline. RV dilatation was the most frequently abnormal finding (40.6%), followed by increased RA/central venous pressure (34.6%), RV pressure overload (32.1%), and reduced RV free wall/tricuspid annulus motion (20.9%). As early as day 6, RV size remained normal or improved in 260 patients (64.7%), RV free wall/tricuspid annulus motion in 301 (74.9%), RV pressure overload in 297 (73.9%), and RA/central venous pressure in 254 (63.2%). At day 180, the frequencies slightly increased. The median NT-proBNP level decreased from 1448 pg/ml at baseline to 256.5 on day 6 and 127 on day 180. ConclusionIn the majority of patients with acute intermediate-risk PE switched early to a direct oral anticoagulant, echocardiographic parameters of RV function normalised within 6 days and remained normal throughout the first 6 months. Almost one in four patients, however, continued to have evidence of RV dysfunction over the long term. Show less
BackgroundRight ventricular (RV) function plays a critical role in the pathophysiology and acute prognosis of pulmonary embolism (PE). We analyzed the temporal changes of RV function in the cohort... Show moreBackgroundRight ventricular (RV) function plays a critical role in the pathophysiology and acute prognosis of pulmonary embolism (PE). We analyzed the temporal changes of RV function in the cohort of a prospective multicentre study investigating if an early switch to oral anticoagulation in patients with intermediate-risk PE is effective and safe. MethodsEchocardiographic and laboratory examinations were performed at baseline (PE diagnosis), 6 days and 6 months. Echocardiographic parameters were classified into categories representing RV size, RV free wall/tricuspid annulus motion, RV pressure overload and right atrial (RA)/central venous pressure. ResultsRV dysfunction based on any abnormal echocardiographic parameter was present in 84% of patients at baseline. RV dilatation was the most frequently abnormal finding (40.6%), followed by increased RA/central venous pressure (34.6%), RV pressure overload (32.1%), and reduced RV free wall/tricuspid annulus motion (20.9%). As early as day 6, RV size remained normal or improved in 260 patients (64.7%), RV free wall/tricuspid annulus motion in 301 (74.9%), RV pressure overload in 297 (73.9%), and RA/central venous pressure in 254 (63.2%). At day 180, the frequencies slightly increased. The median NT-proBNP level decreased from 1448 pg/ml at baseline to 256.5 on day 6 and 127 on day 180. ConclusionIn the majority of patients with acute intermediate-risk PE switched early to a direct oral anticoagulant, echocardiographic parameters of RV function normalised within 6 days and remained normal throughout the first 6 months. Almost one in four patients, however, continued to have evidence of RV dysfunction over the long term. Show less
Bavalia, R.; Stals, M.A.M.; Mulder, F.I.; Bistervels, I.M.; Coppens, M.; Faber, L.M.; ... ; Holleman, F. 2022
BackgroundThe Pulmonary Embolism Severity Index (PESI) and the simplified PESI (sPESI) are validated scores for mortality prediction in patients with pulmonary embolism (PE). National Early Warning... Show moreBackgroundThe Pulmonary Embolism Severity Index (PESI) and the simplified PESI (sPESI) are validated scores for mortality prediction in patients with pulmonary embolism (PE). National Early Warning Score (NEWS) is a general prognostic risk score for multiple clinical settings. We investigated whether the NEWS had a comparable performance with the PESI and sPESI, for predicting intensive care unit (ICU) admission and death in patients with acute PE. MethodsIn haemodynamically stable patients with confirmed PE from the YEARS Study (2013-2015), we evaluated the performance of the NEWS, PESI and sPESI for predicting 7-day ICU admission and 30-day mortality. Receiver operating characteristic curves were plotted and the area under the curve (AUC) was calculated. ResultsOf 352 patients, 12 (3.4%) were admitted to the ICU and 5 (1.4%) died. The AUC of the NEWS for ICU admission was 0.80 (95% CI 0.66 to 0.94) and 0.92 (95% CI 0.82 to 1.00) for 30-day mortality. At a threshold of 3 points, NEWS yielded a sensitivity and specificity of 92% and 53% for ICU admission and 100% and 52% for 30-day mortality. The AUC of the PESI was 0.64 (95% CI 0.48 to 0.79) for ICU admission and 0.94 (95% CI 0.87 to 1.00) for mortality. At a threshold of 66 points, PESI yielded a sensitivity of 75% and a specificity of 38% for ICU admission. For mortality, these were 100% and 37%, respectively. The performance of the sPESI was similar to that of PESI. ConclusionIn comparison with PESI and sPESI, NEWS adequately predicted 7-day ICU admission as well as 30-day mortality, supporting its potential relevance for clinical practice. Show less
Bavalia, R.; Stals, M.A.M.; Mulder, F.I.; Bistervels, I.M.; Coppens, M.; Faber, L.M.; ... ; Holleman, F. 2022
BackgroundThe Pulmonary Embolism Severity Index (PESI) and the simplified PESI (sPESI) are validated scores for mortality prediction in patients with pulmonary embolism (PE). National Early Warning... Show moreBackgroundThe Pulmonary Embolism Severity Index (PESI) and the simplified PESI (sPESI) are validated scores for mortality prediction in patients with pulmonary embolism (PE). National Early Warning Score (NEWS) is a general prognostic risk score for multiple clinical settings. We investigated whether the NEWS had a comparable performance with the PESI and sPESI, for predicting intensive care unit (ICU) admission and death in patients with acute PE. MethodsIn haemodynamically stable patients with confirmed PE from the YEARS Study (2013-2015), we evaluated the performance of the NEWS, PESI and sPESI for predicting 7-day ICU admission and 30-day mortality. Receiver operating characteristic curves were plotted and the area under the curve (AUC) was calculated. ResultsOf 352 patients, 12 (3.4%) were admitted to the ICU and 5 (1.4%) died. The AUC of the NEWS for ICU admission was 0.80 (95% CI 0.66 to 0.94) and 0.92 (95% CI 0.82 to 1.00) for 30-day mortality. At a threshold of 3 points, NEWS yielded a sensitivity and specificity of 92% and 53% for ICU admission and 100% and 52% for 30-day mortality. The AUC of the PESI was 0.64 (95% CI 0.48 to 0.79) for ICU admission and 0.94 (95% CI 0.87 to 1.00) for mortality. At a threshold of 66 points, PESI yielded a sensitivity of 75% and a specificity of 38% for ICU admission. For mortality, these were 100% and 37%, respectively. The performance of the sPESI was similar to that of PESI. ConclusionIn comparison with PESI and sPESI, NEWS adequately predicted 7-day ICU admission as well as 30-day mortality, supporting its potential relevance for clinical practice. Show less
Kaptein, F.H.J.; Hulle, T. van der; Braken, S.J.E.; Gennep, E.J. van; Buijs, J.T.; Burgmans, M.C.; ... ; Klok, F.A. 2022
BACKGROUND Renal cell carcinoma (RCC) can be complicated by a venous tumor thrombus (TT), of which the optimal management is unknown.OBJECTIVES This study sought to assess the prevalence of TT in... Show moreBACKGROUND Renal cell carcinoma (RCC) can be complicated by a venous tumor thrombus (TT), of which the optimal management is unknown.OBJECTIVES This study sought to assess the prevalence of TT in RCC, its current management, and its association with venous thromboembolism (VTE), arterial thromboembolism (ATE), major bleeding (MB), and mortality.METHODS Patients diagnosed with RCC between 2010 and 2019 in our hospital were included and followed from RCC diagnosis until 2 years after, or until an outcome of interest (VTE, ATE, and MB) or death occurred, depending on the analysis. Cumulative incidences were estimated with death as a competing risk. Cause-specific hazard models were used to identify predictors and the prognostic impact.RESULTS Of the 647 patients, 86 had a TT (prevalence 13.3%) at RCC diagnosis, of which 34 were limited to the renal vein, 37 were limited to the inferior vena cava below the diaphragm, and 15 extended above the diaphragm; 20 patients started therapeutic anticoagulation and 45 underwent thrombectomy with/without anticoagulation. During follow-up (median 24.0 [IQR: 7.0-24.0] months), 17 TT patients developed a VTE, 0 developed an ATE, and 11 developed MB. TT patients were more often diagnosed with VTE (adjusted HR: 6.61; 95% CI: 3.18-13.73) than non-TT patients, with increasing VTE risks in more proximal TT levels. TT patients receiving anticoagulation still developed VTE (HR: 0.56; 95% CI: 0.13-2.48), at the cost of more MB events (HR: 3.44; 95% CI: 0.95-12.42) compared with those without anticoagulation.CONCLUSIONS Patients with RCC-associated TT were at high risk of developing VTE. Future studies should establish which of these patients benefit from anticoagulation therapy. (c) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Show less
Kortekaas, K.A.; Exter, P.L. den; Beeres, S.L.M.A.; Palmen, M.; Jukema, J.W.; Huisman, M.V.; Tops, L.F. 2022
Left ventricular assist device (LVAD) implantation as destination therapy (DT) is a valuable treatment option in patients with end-stage heart failure ineligible for heart transplant. However, this... Show moreLeft ventricular assist device (LVAD) implantation as destination therapy (DT) is a valuable treatment option in patients with end-stage heart failure ineligible for heart transplant. However, this therapy can be complicated by life-threatening pump thrombosis (PT). This case series reports our single-center experience with a structured systemic thrombolysis protocol in case of PT. Consecutive patients undergoing DT LVAD (HVAD, Medtronic, Framingham, MA) implantation between 2010 and April 2021 at our institution were reviewed and those with PT identified. Clinical, laboratory and LVAD specific data were collected and analyzed retrospectively. All patients with PT were treated with systemic thrombolysis according to a structured bedside protocol. Treatment was defined successful if a patient was alive at 30 days follow-up and free of recurrent PT, stroke or device exchange. Fourteen out of 94 patients experienced a PT after LVAD implantation (11%). Systemic thrombolysis was successful in 10 of 14 patients (71%) at 30 days. Two patients died within 30 days due to a hemothorax and multi-organ failure. In three patients treatment was complicated by a major bleeding; twice a hemothorax (one fatal) and one right calf bleeding. No intracerebral hemorrhage was observed. Three patients experienced a thrombotic complication within 30 days; all recurrent PT. Eleven of the 14 DT patients were discharged home after a limited hospital stay after thrombolysis (average of 11 days). In conclusion, systemic thrombolysis may be a reasonable option for life-threatening PT in this vulnerable DT group in whom device exchange is often impossible due to comorbidity. Show less
Introduction: Application of the chronic thromboembolic pulmonary hypertension (CTEPH) rule out criteria (manual electrocardiogram [ECG] reading and N-terminal pro-brain natriuretic peptide ... Show moreIntroduction: Application of the chronic thromboembolic pulmonary hypertension (CTEPH) rule out criteria (manual electrocardiogram [ECG] reading and N-terminal pro-brain natriuretic peptide [NTproBNP] test) can rule out CTEPH in pulmonary embolism (PE) patients with persistent dyspnea (InShape II algorithm). Increased pulmonary pressure may also be identified using automated ECG-derived ventricular gradient optimized for right ventricular pressure overload (VG-RVPO). Method: A predefined analysis of the InShape II study was performed. The diagnostic performance of the VG-RVPO for the detection of CTEPH and the incremental diagnostic value of the VG-RVPO as new rule-out criteria in the InShape II algorithm were evaluated. Results: 60 patients were included; 5 (8.3%) were ultimately diagnosed with CTEPH. The mean baseline VG-RVPO (at time of PE diagnosis) was -18.12 mV.ms for CTEPH patients and - 21.57 mV.ms for non-CTEPH patients (mean difference 3.46 mV.ms [95%CI -29.03 to 35.94]). The VG-RVPO (after 3-6 months follow-up) normalized in patients with and without CTEPH, without a clear between-group difference (mean Delta VG-RVPO of -8.68 and - 8.42 mV.ms respectively; mean difference of -0.25 mV.ms, [95%CI -12.94 to 12.44]). The overall predictive accuracy of baseline VG-RVPO, follow-up RVPO and Delta VG-RVPO for CTEPH was moderate to poor (ROC AUC 0.611, 0.514 and 0.539, respectively). Up to 76% of the required echocardiograms could have been avoided with VG-RVPO criteria replacing the InShape II rule-out criteria, however at cost of missing up to 80% of the CTEPH diagnoses. Conclusion: We could not demonstrate (additional) diagnostic value of VG-RVPO as standalone test or as on top of the InShape II algorithm. Show less
Background: Clinical complexity is common in atrial fibrillation (AF) patients. We assessed the impact of clinical complexity on oral anticoagulant (OAC) treatment patterns and major adverse... Show moreBackground: Clinical complexity is common in atrial fibrillation (AF) patients. We assessed the impact of clinical complexity on oral anticoagulant (OAC) treatment patterns and major adverse outcomes in a contemporary cohort of AF patients. Methods: The GLORIA-AF Phase II and III Registry enrolled newly diagnosed AF patients with at least one stroke risk factor. Among patients with CHA(2)DS(2)-VASc score >= 2, we defined four domains of perceived clinical complexity: frail elderly (age >= 75 years and body mass index <23 kg/m(2)), chronic kidney disease (CKD, creatinine clearance <60 mL/min), history of bleeding, and those with >= 2 of the above conditions. We evaluated the associations between clinical complexity domains and antithrombotic treatment prescription, risk of OAC discontinuation, and major adverse outcomes. Results: Among the 29,625 patients included (mean age 69.6 +/- 10.7 years, 44.2% females), 9,504 (32.1%) presented with at least one complexity criterion. Clinical complexity was associated with lower OAC prescription, with stronger associations in frail elderly (odds ratio [OR]: 0.47, 95% confidence interval [CI]: 0.36-0.62) and those with >= 2 complexity domains (OR: 0.50, 95% CI: 0.44-0.57). Risk of OAC discontinuation was higher among frail elderly (hazard ratio [HR]: 1.30, 95% CI: 1.00-1.69), CKD (HR: 1.10, 95% CI: 1.02-1.20), and those with >= 2 complexity domains (HR: 1.39, 95% CI: 1.23-1.57). Clinical complexity was associated with higher risk of the primary outcome of all-cause death, thromboembolism, and major bleeding, with the highest magnitude in those with >= 2 criteria (HR: 1.63, 95% CI: 1.43-1.86). Conclusion: In AF patients, clinical complexity influences OAC treatment management, and increases the risk of poor clinical outcomes. These patients require additional efforts, such as integrated care approach, to improve their management and prognosis. Show less
