Predicting intracranial bleeding during anticoagulation for venous thromboembolism within different time frames: Findings from the RIETE registry.

BACKGROUND: The risk of intracranial bleeding during anticoagulation for venous thromboembolism (VTE) is substantial and persists beyond the initial treatment phase. We aimed to refine risk-assessment through phase-specific prognostic scores. METHODS: We identified data from 77,786 VTE patients in the RIETE registry from March 2009 to October 2023 to develop two prognostic scores for intracranial bleeding. Multivariable Cox regression was used to analyze distinct variables for the early (≤90 days) and late (>90 days) phases, with comparative validation against existing scores (modified ACCP, RIETE, VTE-BLEED, and CHAP). RESULTS: Intracranial bleeding occurred in 411 patients (0.53 %), with 208 cases in the early phase and 203 in the late phase. The 30-day mortality was 45 % and 35 %, respectively. Shared significant predictors for both phases include baseline abnormal mental status, brain cancer, recent intracranial bleeding, and epilepsy. Unique to early-phase bleeding were body weight, non-brain cancer, hypertension, dementia, thrombocytopenia, renal insufficiency, and thrombolytic therapy. Advanced age, pulmonary embolism initially, prior stroke, depression, treatment with direct oral anticoagulants, and use of corticosteroids predicted late-phase bleeding. Both prognostic scores showed a c-statistic of 0.68, outperforming existing scores. CONCLUSIONS: The study introduces two temporal prognostic scores for intracranial bleeding during anticoagulation for VTE. By discerning specific risk factors pertinent to each treatment phase, these scores outperform traditional models, offering an advanced tool for clinical decision-making. They hold significant potential for optimizing anticoagulation management and reducing bleeding-related mortality.

Surgery Versus Thrombolytic Therapy for the Management of Left-Sided Prosthetic Valve Thrombosis Without Hemodynamic Compromise: A Systematic Review and Meta-Analysis.

BACKGROUND: The optimal strategy in prosthetic heart valve thrombosis (PVT) remains controversial, with no randomized trials and conflicting observational data. We performed a systematic review and meta-analysis of evidence comparing systemic thrombolysis and cardiac surgery in PVT. METHODS AND RESULTS: We searched PubMed, the Cochrane Library, and Embase for studies on treatment strategies in patients with left-sided PVT since 2000. The primary outcome was death, and the secondary outcomes were major bleeding and thromboembolism during follow-up (International Prospective Register of Systematic Reviews No. CRD42022384092). We identified 2298 studies, of which 16 were included, comprising 1389 patients with PVT (mean age, 50.4±9.3 years; 60.0% women). Among them, 67.2% were New York Heart Association stage III/IV at admission. Overall, 48.1% were treated with systemic thrombolysis and 51.9% with cardiac surgery. The mortality rate was 10.8% in the thrombolysis group and 15.3% in the surgery group. The pooled risk difference for death with systemic thrombolysis was 1.13 (exact CI, 0.74-1.79; ζ2=0.89; P<0.001) versus cardiac surgery. Rates of both transient ischemic attack and non-central nervous system embolism were higher in the thrombolysis group (P=0.002 and P=0.02, respectively). Treatment success, major bleeding, and stroke were similar between groups. Sensitivity analysis including studies that used low-dose or slow-infusion thrombolysis showed that the mortality rate was lower, and treatment success was higher, in patients referred to systemic thrombolysis, with similar rates of other secondary outcomes. CONCLUSIONS: There is evidence to suggest that thrombolysis might be the preferred option for the management of PVT without cardiogenic shock, pending future randomized controlled trials or larger observational studies.

Comparative analysis of COVID-19-associated venous thromboembolism outcomes: evolution from 2020 to 2021-2022.

Patients with COVID-19 are at an increased risk for venous thromboembolism (VTE). With the advent of vaccinations and novel treatments from 2020 through 2022, the landscape of COVID-19 has evolved. Notably, the effects of such interventions on the outcomes of COVID-19-associated VTE have not been thoroughly examined. Data from the RIETE registry were analyzed to evaluate 90-day VTE-related outcomes (all-cause mortality, major bleeding, and VTE recurrences) in patients with COVID-19-associated VTE. We compared the periods before and after the widespread introduction of COVID-19 vaccines: March to December 2020 (pre-vaccine period) and March 2021 to December 2022 (post-vaccine period). Statistical analysis included mixed-effects parametric survival-time models. Among 1,620 patients with COVID-19-associated VTE, most (74.1%) were identified during 2020 period. The analysis revealed a more than two-fold increase in the risk of death within 90 days (adjusted hazard ratio [HR]: 2.27; 95% confidence interval, CI: 1.18-4.38) and major bleeding (adjusted HR: 2.91; 95%CI: 1.08-7.84) for patients from the 2020 period compared to those from the 2021-2022 period. Inpatient subgroup analysis confirmed the observed mortality differences. The frequency of recurrent VTE was low (1.1 vs. 0.7%, respectively), and did not show significant variation between the two periods. Our research provides a comparative perspective on the clinical outcomes of COVID-19-associated VTE before and after the introduction of vaccines. Our findings reveal a significant decrease in the incidence of 90-day mortality and major bleeding in patients with COVID-19-associated VTE in the 2021-2022 period.

Risk of recurrence after discontinuing anticoagulation in patients with COVID-19- associated venous thromboembolism: a prospective multicentre cohort study.

Background: The clinical relevance of recurrent venous thromboembolism (VTE) after discontinuing anticoagulation in patients with COVID-19-associated VTE remains uncertain. We estimated the incidence rates and mortality of VTE recurrences developing after discontinuing anticoagulation in patients with COVID-19-associated VTE. Methods: A prospective, multicenter, non-interventional study was conducted between March 25, 2020, and July 26, 2023, including patients who had discontinued anticoagulation after at least 3 months of therapy. All patients from the registry were analyzed during the study period to verify inclusion criteria. Patients with superficial vein thrombosis, those who did not receive at least 3 months of anticoagulant therapy, and those who were followed for less than 15 days after discontinuing anticoagulation were excluded. Outcomes were: 1) Incidence rates of symptomatic VTE recurrences, and 2) fatal PE. The rate of VTE recurrences was defined as the number of patients with recurrent VTE divided by the patient-years at risk of recurrent VTE during the period when anticoagulation was discontinued. Findings: Among 1106 patients with COVID-19-associated VTE (age 62.3 ± 14.4 years; 62.9% male) followed-up for 12.5 months (p25-75, 6.3-20.1) after discontinuing anticoagulation, there were 38 VTE recurrences (3.5%, 95% confidence interval [CI]: 2.5-4.7%), with a rate of 3.1 per 100 patient-years (95% CI: 2.2-4.2). No patient died of recurrent PE (0%, 95% CI: 0-7.6%). Subgroup analyses showed that patients with diagnosis in 2021-2022 (vs. 2020) (Hazard ratio [HR] 2.86; 95% CI 1.45-5.68) or those with isolated deep vein thrombosis (vs. pulmonary embolism) (HR 2.31; 95% CI 1.19-4.49) had significantly higher rates of VTE recurrences. Interpretation: In patients with COVID-19-associated VTE who discontinued anticoagulation after at least 3 months of treatment, the incidence rate of recurrent VTE and the case-fatality rate was low. Therefore, it conceivable that long-term anticoagulation may not be required for many patients with COVID-19-associated VTE, although further research is needed to confirm these findings. Funding: Sanofi and Rovi, Sanofi Spain.

Integration of Extracorporeal Membrane Oxygenation into the Management of High-Risk Pulmonary Embolism: An Overview of Current Evidence.

High-risk pulmonary embolism (PE) refers to a large embolic burden causing right ventricular failure and hemodynamic instability. It accounts for approximately 5% of all cases of PE but contributes significantly to overall PE mortality. Systemic thrombolysis is the first-line revascularization therapy in high-risk PE. Surgical embolectomy or catheter-directed therapy is recommended in patients with an absolute contraindication to systemic thrombolysis. Extracorporeal membrane oxygenation (ECMO) provides respiratory and hemodynamic support for the most critically ill PE patients with refractory cardiogenic shock or cardiac arrest. The complex management of these individuals requires urgent yet coordinated multidisciplinary care. In light of existing evidence regarding the utility of ECMO in the management of high-risk PE patients, a number of possible indications for ECMO utilization have been suggested in the literature. Specifically, in patients with refractory cardiac arrest, resuscitated cardiac arrest, or refractory shock, including in cases of failed thrombolysis, venoarterial ECMO (VA-ECMO) should be considered, either as a bridge to percutaneous or surgical embolectomy or as a bridge to recovery after surgical embolectomy. We review here the current evidence on the use of ECMO as part of the management strategy for the highest-risk presentations of PE and summarize the latest data in this indication.

External validation of the PE-SARD risk score for predicting early bleeding in acute pulmonary embolism in the RIETE Registry.

INTRODUCTION: The PE-SARD score (syncope, anemia, renal dysfunction) was developed to predict the risk of major bleeding in the acute phase of pulmonary embolism (PE). METHODS: We analyzed data from 50,686 patients with acute PE included in the RIETE registry to externally validate the PE-SARD score. We calculated the overall reliability of the PE-SARD score, as well as discrimination and calibration for predicting the risk of major bleeding at 30 days. The performance of PE-SARD was compared to the BACS and PE-CH models. RESULTS: During the first 30 days, 640 patients (1.3 %) had a major bleeding event. The incidence of major bleeding within 30 days was 0.6 % in the PE-SARD-defined low-risk group, 1.5 % in the intermediate-risk group, and 2.5 % in the high-risk group, for an OR of 2.22 (95 % CI, 2.02-2.43) for the intermediate-risk group (vs low-risk group), and 3.94 for the high-risk group (vs low-risk group). The corresponding sensitivity was 81.1 % (intermediate/high vs low risk), and specificity was 85.9 % (95 % CI, 85.8-86.1) (low/intermediate vs high risk). The applicability of PE-SARD was consistent across clinically relevant patient subgroups and over shorter time periods of follow-up (i.e., 3 and 7 days). The C-index was 0.654 and calibration was excellent. The PE-SARD bleeding score improved the major bleeding risk prediction compared with the BACS and PE-CH scores. CONCLUSIONS: The PE-SARD score identifies PE patients with a higher risk of bleeding, which could assist providers for potentially adjusting PE management, in a framework of shared decision-making with individual patients.

Incidence of atrial fibrillation in cryptogenic stroke with patent foramen ovale closure: protocol for the prospective, observational PFO-AF study.

INTRODUCTION: After closure of patent foramen ovale (PFO) due to stroke, atrial fibrillation (AF) occurs in up to one in five patients. However, data are sparse regarding the possible pre-existence of AF in these patients prior to PFO closure, and about recurrence of AF in the long term after the procedure. No prospective study to date has investigated these topics in patients with implanted cardiac monitor (ICM). The PFO-AF study (registered with ClinicalTrials.gov under the number NCT04926142) will investigate the incidence of AF occurring within 2 months after percutaneous closure of PFO in patients with prior stroke. AF will be identified using systematic ICM. Secondary objectives are to assess incidence and burden of AF in the 2 months prior to, and up to 2 years after PFO closure. METHODS AND ANALYSIS: Prospective, multicentre, observational study including 250 patients with an indication for PFO closure after stroke, as decided by interdisciplinary meetings with cardiologists and neurologists. Patients will undergo implantation of a Reveal Linq device (Medtronic). Percutaneous PFO closure will be performed 2 months after device implantation. Follow-up will include consultation, ECG and reading of ICM data at 2, 12 and 24 months after PFO closure. The primary endpoint is occurrence of AF at 2 months, defined as an episode of AF or atrial tachycardia/flutter lasting at least 30 s, and recorded by the ICM and/or any AF or atrial tachycardia/flutter documented on ECG during the first 2 months of follow-up. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee 'Comité de Protection des Personnes (CPP) Sud-Méditerranéen III' on 2 June 2021 and registered with ClinicalTrials.gov (NCT04926142). Findings will be presented in national and international congresses and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04926142.

Home treatment versus early discharge for the outpatient management of acute pulmonary embolism: A non-interventional, post-hoc cohort analysis.

INTRODUCTION: We prospectively investigated whether home treatment of pulmonary embolism (PE), is as effective and safe as the recommended early discharge management in terms of outcomes at 3 months. METHODS: We performed a post hoc analysis of prospectively and consecutively recorded data in acute PE patients from a tertiary care facility between January 2012 and November 2021. Home treatment was defined as discharge to home directly from the emergency department (ED) after <24 h stay. Early discharge was defined as in-hospital stay of ≥24 h and ≤48 h. Primary efficacy and safety outcomes were a composite of PE-related death or recurrent venous thrombo-embolism, and major bleeding, respectively. Outcomes between groups were compared using penalized multivariable models. RESULTS: In total, 181 patients (30.6 %) were included in the home treatment group and 463 (69.4 %) patients in the early discharge group. Median duration of ED stay was 8.1 h (IQR, 3.6-10.2 h) in the home treatment group, and median length of hospital stay was 36.4 h (IQR, 28.7-40.2) in the early discharge group. The adjusted rate of the primary efficacy outcome was 1.90 % (95 % CI, 0.16-15.2) vs 2.05 % (95 % CI, 0.24-10.1) for home treatment vs early discharge (hazard ratio (HR) 0.86 (95 % CI, 0.27-2.74). The adjusted rates of the primary safety outcome did not differ between groups at 3 months. CONCLUSIONS: In a non-randomized cohort of selected acute PE patients, home treatment provided comparable rates of adverse VTE and bleeding events to the recommended early discharge management, and appears to have similar clinical outcomes at 3 months.

Trends in management and outcomes of pulmonary embolism with a multidisciplinary response team.

Multidisciplinary pulmonary embolism (PE) response teams have garnered widespread adoption given the complexities of managing acute PE and provide a platform for assessment of trends in therapy and outcomes. We describe temporal trends in PE management and outcomes following the deployment of such a team. All consecutive patients managed by our multidisciplinary PE response team activated by the Emergency Department were included over a 5-year calendar period. We examined temporal trends in management and rates of a composite primary endpoint (all-cause-death, major bleeding, recurrent venous thromboembolism, and readmission) at 30 days and 6 months. We assessed 425 patients between 2015 and 2019. We observed an increase in PE acuity and use of systemic thrombolysis. The primary endpoint at 30 days decreased from 16.3% in 2015 to 7.1% in 2019 (adjusted rate ratio per period, 0.63; 95%CI, 0.47-0.84), driven by a decrease in the adjusted rate of major bleeding. Among 406 patients with complete follow-up, the adjusted rate ratio per year for the primary outcome at 6 months was 0.37 (95%CI, 0.19-0.71), driven by a decrease in all-cause mortality. We observed evidence of temporal changes in clinical presentation, therapeutic strategies, and outcomes for acute PE, in parallel to, but not necessarily because of, the implementation of a multidisciplinary response team. Over time, major bleeding, mortality and readmission rates decreased, despite an increase in PE risk category.

An Update on the Management of Acute High-Risk Pulmonary Embolism.

Hemodynamic instability and right ventricular (RV) dysfunction are the key determinants of short-term prognosis in patients with acute pulmonary embolism (PE). High-risk PE encompasses a wide spectrum of clinical situations from sustained hypotension to cardiac arrest. Early recognition and treatment tailored to each individual are crucial. Systemic fibrinolysis is the first-line pulmonary reperfusion therapy to rapidly reverse RV overload and hemodynamic collapse, at the cost of a significant rate of bleeding. Catheter-directed pharmacological and mechanical techniques ensure swift recovery of echocardiographic parameters and may possess a better safety profile than systemic thrombolysis. Further clinical studies are mandatory to clarify which pulmonary reperfusion strategy may improve early clinical outcomes and fill existing gaps in the evidence.

Catheter-based therapy for acute pulmonary embolism: An overview of current evidence.

Systemic thrombolysis for acute pulmonary embolism reduces the risk of death and cardiovascular collapse but is associated with an increased rate of bleeding. The desire to minimize the risk of bleeding events has driven the development of catheter-based strategies for pulmonary reperfusion in pulmonary embolism. These catheter-based strategies utilize lower-dose fibrinolytic regimens or purely mechanical thromboaspiration to expedite removal of the embolus. The most comprehensive data on catheter-based techniques come from trials of ultrasound-facilitated catheter fibrinolysis. This technique relieves right ventricular pressure overload with a lower risk of major bleeding and intracranial haemorrhage than historical rates observed with systemic fibrinolysis in intermediate- to high-risk pulmonary embolism. Two aspiration thrombectomy devices recently demonstrated significant reductions in right ventricle/left ventricle ratio and a low major adverse event rate in patients with intermediate-risk pulmonary embolism. However, further research is required to determine the optimal application of ultrasound-facilitated catheter fibrinolysis and other catheter-based therapies in patients with acute pulmonary embolism.

Extended Anticoagulation After Pulmonary Embolism: A Multicenter Observational Cohort Analysis.

Background Pulmonary embolism (PE) has a long-term risk of adverse events, which can be prevented by extended anticoagulation. We compared clinical characteristics and outcomes between patients treated with 2-year extended anticoagulation and those who were not, in a population who had completed an initial phase of 3 to 6 months of anticoagulant therapy after acute PE. Methods and Results Observational cohort analysis of patients with PE who survived an initial phase of 3 to 6 months anticoagulation. Primary efficacy outcome was all-cause death or recurrent venous thromboembolism. Primary safety outcome was major bleeding. In total, 858 (71.5%) patients were treated with and 341 (28.5%) were treated without extended anticoagulant therapy during the active study period. Age <65 years, intermediate-high or high-risk index PE, normal platelet count, and the absence of concomitant antiplatelet treatment were independently associated with the prescription of extended anticoagulation. The mean duration of the active phase was 2.1±0.3 years. The adjusted rate of the primary efficacy outcome was 2.1% in the extended group and 7.7% in the nonextended group (P<0.001) for patients treated with extended anticoagulant therapy. Rate of bleeding were similar between the extended anticoagulant group and the nonextended group. Conclusions Extended oral anticoagulation over 2 and a half years after index PE seems to provide a net clinical benefit compared with no anticoagulation in patients with PE selected to receive extended anticoagulation. Randomized clinical trials are warranted to explore the potential benefit of extended anticoagulation in patients with PE, especially those with transient provoking factors but residual risk.

Optimal reperfusion strategy in acute high-risk pulmonary embolism requiring extracorporeal membrane oxygenation support: a systematic review and meta-analysis.

BACKGROUND: The optimal pulmonary revascularisation strategy in high-risk pulmonary embolism (PE) requiring implantation of extracorporeal membrane oxygenation (ECMO) remains controversial. METHODS: We conducted a systematic review and meta-analysis of evidence comparing mechanical embolectomy and other strategies, including systemic thrombolysis, catheter-directed thrombolysis or ECMO as stand-alone therapy, with regard to mortality and bleeding outcomes. RESULTS: We identified 835 studies, 17 of which were included, comprising 327 PE patients. Overall, 32.4% were treated with mechanical pulmonary reperfusion (of whom 85.9% had surgical embolectomy), while 67.6% received other strategies. The mortality rate was 22.6% in the mechanical reperfusion group and 42.8% in the "other strategies" group. The pooled odds ratio for mortality with mechanical reperfusion was 0.439 (95% CI 0.237-0.816) (p=0.009; I2=35.2%) versus other reperfusion strategies and 0.368 (95% CI 0.185-0.733) (p=0.004; I2=32.9%) for surgical embolectomy versus thrombolysis. The rate of bleeding in patients under ECMO was 22.2% in the mechanical reperfusion group and 19.1% in the "other strategies" group (OR 1.27, 95% CI 0.54-2.96; I2=7.7%). The meta-regression model did not identify any relationship between the covariates "more than one pulmonary reperfusion therapy", "ECMO implantation before pulmonary reperfusion therapy", "clinical presentation of PE" or "cancer-associated PE" and the associated outcomes. CONCLUSIONS: The results of the present meta-analysis and meta-regression suggest that mechanical reperfusion, notably by surgical embolectomy, may yield favourable results regardless of the timing of ECMO implantation in the reperfusion timeline, independent of thrombolysis administration or cardiac arrest presentation.

Prevalence and severity of cognitive dysfunction in patients referred for transcatheter aortic valve implantation (TAVI): clinical and cognitive impact at 1 year.

AIM: We estimated the proportion and severity of cognitive disorders in an unselected population of patients referred for transcatheter aortic valve implantation (TAVI). Second, we describe clinical and cognitive outcomes at 1 year. METHODS: Eligible patients were aged ≥ 70 years, with symptomatic aortic stenosis and an indication for TAVI. The Montreal Cognitive Assessment (MoCA) was used to assess cognitive dysfunction (CD), defined as no CD if score ≥ 26, mild CD if 18-25; moderate CD if 10-18, and severe CD if < 10. We assessed survival and in-hospital complications at 6 months and 1 year. RESULTS: Between June 2019 and October 2020, 105 patients were included; 21 (20%) did not undergo TAVI, and thus, 84 were analyzed; median age 85 years, 53.6% females, median EuroScore 11.5%. Median MoCA score was 22 (19-25); CD was excluded in 18 (21%), mild in 50 (59.5%), moderate in 15 (19%) and severe in 1. Mean MoCA score at follow-up was 21.9(± 4.69) and did not differ significantly from baseline (21.79 (± 4.61), p = 0.73). There was no difference in success rate, in-hospital complications, or death across CD categories. CONCLUSION: The clinical course of patients with mild or moderate CD is not different at 1 year after TAVI compared to those without cognitive dysfunction.

Available Bleeding Scoring Systems Poorly Predict Major Bleeding in the Acute Phase of Pulmonary Embolism.

We aimed to compare six available bleeding scores, in a real-life cohort, for prediction of major bleeding in the early phase of pulmonary embolism (PE). We recorded in-hospital characteristics of 2754 PE patients in a prospective observational multicenter cohort contributing 18,028 person-days follow-up. The VTE-BLEED (Venous Thrombo-Embolism Bleed), RIETE (Registro informatizado de la enfermedad tromboembólica en España; Computerized Registry of Patients with Venous Thromboembolism), ORBIT (Outcomes Registry for Better Informed Treatment), HEMORR2HAGES (Hepatic or Renal Disease, Ethanol Abuse, Malignancy, Older Age, Reduced Platelet Count or Function, Re-Bleeding, Hypertension, Anemia, Genetic Factors, Excessive Fall Risk and Stroke), ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation), and HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile International Normalized Ratio, Elderly, Drugs/Alcohol) scores were assessed at baseline. International Society on Thrombosis and Haemostasis (ISTH)-defined bleeding events were independently adjudicated. Accuracy of the overall original 3-level and newly defined optimal 2-level outcome of the scores were evaluated and compared. We observed 82 first early major bleedings (3.0% (95% CI, 2.4-3.7)). The predictive power of bleeding scores was poor (Harrel's C-index from 0.57 to 0.69). The RIETE score had numerically higher model fit and discrimination capacity but without reaching statistical significance versus the ORBIT, HEMORR2HAGES, and ATRIA scores. The VTE-BLEED and HAS-BLED scores had significantly lower C-index, integrated discrimination improvement, and net reclassification improvement compared to the others. The rate of observed early major bleeding in score-defined low-risk patients was high, between 15% and 34%. Current available scoring systems have insufficient accuracy to predict early major bleeding in patients with acute PE. The development of acute-PE-specific risk scores is needed to optimally target bleeding prevention strategies.

An Original Risk Score to Predict Early Major Bleeding in Acute Pulmonary Embolism: The Syncope, Anemia, Renal Dysfunction (PE-SARD) Bleeding Score.

BACKGROUND: Improved prediction of the risk of early major bleeding in pulmonary embolism (PE) is needed to optimize acute management. RESEARCH QUESTION: Does a simple scoring system predict early major bleeding in acute PE patients, identifying patients with either high or low probability of early major bleeding? STUDY DESIGN AND METHODS: From a multicenter prospective registry including 2,754 patients, we performed post hoc multivariable logistic regression analysis to build a risk score to predict early (up to hospital discharge) major bleeding events. We validated the endpoint model internally, using bootstrapping in the derivation dataset by sampling with replacement for 500 iterations. Performances of this novel score were compared with that of the VTE-BLEED (Venous Thrombo-Embolism Bleed), RIETE (Registro informatizado de la enfermedad tromboembólica en España; Computerized Registry of Patients with Venous Thromboembolism), and BACS (Bleeding, Age, Cancer, and Syncope) models. RESULTS: Multivariable regression identified three predictors for the occurrence of 82 major bleeds (3.0%; 95% CI, 2.39%-3.72%): Syncope (+1.5); Anemia, defined as hemoglobin <12 g/dL (+2.5); and Renal Dysfunction, defined as glomerular filtration rate <60 mL/min (+1 point) (SARD). The PE-SARD bleeding score was calculated by summing all the components. Overall, 52.2% (95% CI, 50.29%-54.11%) of patients were classified as low bleeding-risk (score, 0 point), 35.2% (95% CI, 33.39%-37.04%) intermediate-risk (score, 1-2.5 points), and 12.6% (95% CI, 9.30%-16.56%) high-risk (score >2.5 points). Observed bleeding rates increased with increasing risk group, from 0.97% (95% CI, 0.53%-1.62%) in the low-risk to 8.93% (95% CI, 6.15%-12.44%) in the high-risk group. C-index was 0.74 (95% CI, 0.73-0.76) and Brier score 0.028 in the derivation cohort. Similar values were calculated from internal bootstrapping. Performance of the PE-SARD score was better than that observed with the VTE-BLEED, RIETE, and BACS scores, leading to a high proportion of bleeding-risk reclassification in patients who bled and those who did not. INTERPRETATION: The PE-SARD bleeding risk score is an original, user-friendly score to estimate risk of early major bleeding in patients with acute PE.

Impact of early (<7 days) pacemaker implantation after cardiac surgery on long-term pacemaker dependency.

OBJECTIVE: We aimed to investigate pacemaker dependency after at least 1 year in patients with early (<7 days) implantation, compared to those who received a pacemaker ≥7 days after cardiac surgery. Secondary endpoints were length of hospital stay and in-hospital complications. METHODS: Retrospective analysis of 108 consecutive patients who received a pacemaker after cardiac surgery between 06/2012 and 06/2018. Characteristics and outcomes were compared between patients with early (<7 days) and late (≥7 days) implantation. Patients were followed up with evaluation of pacemaker dependency between April and June 2019. We identified predictors of dependency by logistic regression. RESULTS: In total, 63.9% were men, average age 71.9 ± 11.8 years; 32 (29.6%) had early implantation, and 76 (70.4%) late implantation. After a median 3.2 years [IQR 1.9, 4.5] of follow-up, 30 patients (27.8%) had died, and there was no difference in pacemaker dependency among survivors (66.7% vs. 46.5%, early vs. late respectively, p = .15). Patients in the early group had a shorter length of stay (11.5 [9.0, 14.0] vs. 15.0 [11.5, 20] days, p = .002) and less often had new-onset atrial fibrillation (AF) post-surgery (22.7% vs. 47.8%, p = .05). The only significant predictor of dependency was aortic valve replacement surgery (OR = 4.70, 95% CI [1.36 to 16.24]). CONCLUSION: Early implantation of a permanent pacemaker (<7 days after cardiac surgery) does not impact on the proportion of patients with long-term (>12 months) pacemaker dependency, but is associated with shorter length of stay and less frequent new-onset AF. These findings warrant prospective confirmation in randomized trials.

Renal dysfunction improves risk stratification and may call for a change in the management of intermediate- and high-risk acute pulmonary embolism: results from a multicenter cohort study with external validation.

BACKGROUND: Renal dysfunction influences outcomes after pulmonary embolism (PE). We aimed to determine the incremental value of adding renal dysfunction, defined by estimated glomerular filtration rate (eGFR), on top of the European Society of Cardiology (ESC) prognostic model, for the prediction of 30-day mortality in acute PE patients, which in turn could lead to the optimization of acute PE management. METHODS: We performed a multicenter, non-interventional retrospective post hoc analysis based on a prospectively collected cohort including consecutive confirmed acute PE stratified per ESC guidelines. We first identified which of three eGFR formulae most accurately predicted death. Changes in global model fit, discrimination, calibration and reclassification parameters were evaluated with the addition of eGFR to the prognostic model. RESULTS: Among 1943 patients (mean age 67.3 (17.1), 50.4% women), 107 (5.5%) had died at 30 days. The 4-variable Modification of Diet in Renal Disease (eGFRMDRD4) formula predicted death most accurately. In total, 477 patients (24.5%) had eGFRMDRD4 < 60 ml/min. Observed mortality was higher for intermediate-low-risk and high-risk PE in patients with versus without renal dysfunction. The addition of eGFRMDRD4 information improved model fit, discriminatory capacity, and calibration of the ESC model. Reclassification parameters were significantly increased, yielding 18% reclassification of predicted mortality (p < 0.001). Predicted mortality reclassifications across risk categories were as follows: 63.1% from intermediate-low risk to eGFR-defined intermediate-high risk, 15.8% from intermediate-high risk to eGFR-defined intermediate-low risk, and 21.0% from intermediate-high risk to eGFR-defined high risk. External validation in a cohort of 14,234 eligible patients from the RIETE registry confirmed our findings with a significant improvement of Harrell's C index and reclassification parameters. CONCLUSION: The addition of eGFRMDRD4-derived renal dysfunction on top of the prognostic algorithm led to risk reclassification within the intermediate- and high-risk PE categories. The impact of risk stratification integrating renal dysfunction on therapeutic management for acute PE requires further studies.