Thromboembolic Events In Patients Research Articles

P997Risk of stroke and mortality in patients with atrial fibrillation and insulin dependent versus non-insulin dependent diabetes mellitus

Abstract Funding Acknowledgements Pfizer pharmaceutical corporation Background Diabetes is a known risk factor for thromboembolic events in patients with non-valvular atrial fibrillation (NVAF). Whether patients on insulin therapy are at an increased risk for stroke compered to patients treated solely by oral antidiabetic medications is not yet established. Aim To assess the risk of ischemic stroke and mortality in patients with NVAF and diabetes mellitus (DM) treated by insulin vs. oral antidiabetic treatment. Methods A prospective, historical cohort study based on the Clalit Health Services (CHS) electronic medical records database, including all individuals age ≥ 21 years with a first diagnosis of NVAF between January 2010 to December 2016 and a minimal follow-up period of 1 year. Patients were divided into two groups based on their diabetes therapy regiment (insulin vs. oral antidiabetic medications). Results Overall study population included 12,231 patients with AF and DM, of them 3510 (28.7%) had an insulin-requiring diabetes. The median age was 72.4 years (IQR 65-80) in the insulin- treated group and 75.2 (IQR 68-83) in the orally treated group, with a slight majority of women in both groups, 51.6% and 53.5% respectively. Patients in the insulin group had significantly higher co-morbidity rates including hypertension (HTN) (93.6% vs. 91.2%; p < 0.001), congestive heart failure (CHF) (38% vs. 22.2%%; p < 0.001), previous cerebrovascular accident/ transient ischemic attack (CVA/TIA) (23.1% vs.14.5%; p < 0.001) and vascular diseases (62.1% vs. 46.5%; p < 0.001). Moreover, patient on insulin therapy were significantly less treated with anticoagulation medications at baseline compered to patients not treated with insulin (38.9% vs. 46.6%; p < 0.001). The incidence of stroke per 100 person-years was 2.62 in the insulin-treated group and 2.02 in the oral-treated group. Although, diabetes patients on insulin therapy had a significantly increased risk for stroke compared to patients not treated with insulin in the univariate analysis (HR: 1.34; 95%CI: 1.13- 1.60), this association was not found to be significant after adjusting for confounding variables (HR: 1.17; 95%CI: 0.96- 1.41). The rate of mortality per 100 person-years was 19 in the insulin-treated group and 12.6 in the oral-treated group. The risk for overall mortality was significantly higher in the insulin-treated group compared to the non-insulin group (HR: 1.38; 95%CI: 1.29- 1.48), as found in the multivariate Cox model, adjusted for age, gender, Creatinine clearance, HTN, CHF , CVA/TIA, vascular diseases, duration of diabetes and use of anticoagulation therapy. Conclusion In this cohort of patients with newly diagnosed NVAF and DM, patients on insulin are at increased risk of all cause mortality and a have a trend of increased risk of stroke after accounting for other recognized risk factors for stroke and mortality in this population.

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

SummaryBackgroundTranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding.MethodsWe did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124.FindingsBetween July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98).InterpretationWe found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial.FundingUK National Institute for Health Research Health Technology Assessment Programme.

P1360Association between left atrial appendage dysfunction and thromboembolic risk in nonvalvular atrial fibrillation

Abstract Background/Introduction: Atrial fibrillation (AF) is associated with higher risk for thromboembolism , and the discriminative ability of the widely used CHA2DS2-VASc scores for risk stratification is modest. Although the presence of thrombus in the LAA is the most powerful predictors for thromboembolic risk, they are often absent in patients with AF and prior stroke. AF may be related to myocardial fibrosis, and even though left atrial fibrosis is associated with mechanical dispersion, this phenomenon is not well studied in LAA. We hypothesized that detection of LAA dysfunction and mechanical dispersion using strain echocardiography is useful in the identification of cardiac thromboembolism. Purpose The aim of this study was to determine the association of LAA mechanics assessed using strain analysis with previous thromboembolic events in patients with nonvalvular AF and to assess the potential incremental significance of LAA mechanical dispersion over the traditional risk stratification scheme. Methods A group of 116 patients with AF referred for TEE was prospectively analyzed. LAA strain and mechanical dispersion in parallel with other conventional TEE parameters were analyzed in terms of their association with previous embolic stroke and peripheral embolization. Results Patients with embolic events had a higher mean CHA2DS2-VASc score, higher incidence of LAA dense SEC or thrombi, and other clinical data were comparable. Patients with embolic events had greater impairment in the LA standard parameters, and lower global and regional LAA longitudinal strain than those of the controls. LAA MD was significantly higher in patients with embolization than in those without it (18.91 ± 7.19 %vs 13.8 ± 5.54%; P < .001). In ROC analysis, cut-off values for LAA MD,LAEF, LAA GLS for the presence of dense SEC/ thrombus were >20.21 % (p = 0.0076), ≤31.11 % (p = 0.017), and ≤ 7.31 % (p = 0.014), respectively. LAA MD, LAEF, LAA thrombus and CHA2DS2-VASc scores were independently associated with the presence of thromboembolism in multivariate analyses, and LAA MD had additional significance over the CHA2DS2-VASc score. Conclusion LAA MD, LAA thrombi and LAEF had statistically significant meaning for the presence of prior embolism that was independent of the standard planimetric and volumetric measurements. What’s more, LAA MD had an incremental value over CHA2DS2-VASc score in risk stratification and warrants testing in a larger study. Abstract Figure. ROC curves for LAA parameters

Venous thromboembolic events in patients with brain metastases: the PICOS score

Aim of studyVenous thromboembolic events (VTEs) are significant complications in patients with systemic malignancies. Thrombosis risk is poorly defined for patients with brain metastasis, and available risk calculation scores are not validated for these patients. MethodsWe identified 811 patients with brain metastasis followed at our institution and reviewed electronic charts retrospectively for the occurrence of VTEs, along with candidate risk factors. Risk factors were tested in univariate and multivariate analyses and finally integrated in a score model for risk estimation. An independent cohort of 346 patients with brain metastasis was available for validation. ResultsVTEs were documented in 97 of 811 patients (12.0%). Primary tumours with high thrombogenicity (p = 0.02, hazard ratio 1.7, 95% confidence interval (CI) = 1.1–2.8), dexamethasone (p = 0.011, hazard ratio 2.27, 95% CI = 1.5–4.5), chemotherapy (p = 0.005, hazard ratio 3.4, 95% CI = 1.6–7.5), body mass index > 35 kg/m2 (p = 0.002, hazard ratio 3.4, 95% CI = 1.6–7.5) and immobilisation (p = 0.003, hazard ratio 2.4, 95% CI = 1.3–4.3) were confirmed to be independently associated with VTEs. We derived a score model for VTE risk estimation, the thrombogenic primary, immobilization, chemotherapy, obesity, steroid (PICOS) score (0–7 points). Receiver-operating characteristic curve analysis demonstrated its prognostic accuracy (area under the curve [AUC] = 0.71, 95% CI = 0.64–0.77), and its value for the evaluation of VTE risk was superior to that of other scores such as the Khorana (AUC = 0.51) or CONKO (AUC = 0.52) scores. The potential value of the PICOS score was confirmed in the validation cohort (AUC = 0.72, 95% CI = 0.63–0.82). ConclusionsThe PICOS score may become a helpful tool for the identification of patients with brain metastasis at high risk for VTEs and for stratification in controlled studies.

Involvement of ADAMTS13 and von Willebrand factor in thromboembolic events in patients infected with SARS‐CoV‐2

Involvement of ADAMTS13 and von Willebrand factor in thromboembolic events in patients infected with SARS‐CoV‐2

Inherited Risk Factors of Thromboembolic Events in Patients with Primary Nephrotic Syndrome.

Background and objectives. Venous thromboembolic events (VTEs) are among the most important complications of nephrotic syndrome (NS). We conducted a study that aimed to determine the prevalence of inherited risk factors for VTE in NS and to identify which factors are independent predictors of VTE. Materials and Methods. Thirty-six consecutive patients with primary NS that underwent percutaneous kidney biopsy between January 2017 and December 2017 were enrolled in this retrospective, observational study. VTEs were the primary outcome. Baseline demographic and biochemical data were collected from medical records, and genetic testing was done for polymorphisms of Factor V, PAI, MTHFR, and prothrombin genes. Results. The incidence of VTE was 28%, and the median time to event was 3 months (IQR: 2–9). The prevalence of inherited risk factors was 14% for Factor V Leiden mutation, 5.6% for prothrombin G20210A, 44.5% for PAI, and 27.8% for each of the two polymorphisms of the MTHFR gene. On multivariate analysis, the presence of at least two mutations was independently associated with the risk of VTE (HR, 8.92; 95% confidence interval, CI: 1.001 to 79.58, p = 0,05). Conclusions. These findings suggest that genetic testing for inherited thrombophilia in NS could play an important role in detecting high-risk patients that warrant prophylactic anticoagulation.

Impact of antithrombotic therapy on the outcomes with focus on bleeding and thromboembolic events in patients undergoing pancreticoduodenectomy.

We investigated perioperative outcomes of pancreaticoduodenectomy (PD) in patients receiving antithrombotic therapy (ATT) with a focus on the incidence of perioperative bleeding and thromboembolic complications. A total of 77 patients who underwent PD at our institution between 2013 and 2019 were retrospectively reviewed. Clinical findings and surgical outcomes including bleeding and thromboembolic complications were compared in patients with or without ATT. Interruption of ATT and perioperative heparin bridging were based on our hospital protocol. Among ATT (30) and non-ATT (47) groups, ATT group had a significantly higher age and history of cardiocerebrovascular diseases. No significant difference was observed in intraoperative and post-pancreatectomy haemorrhage (PPH) between the groups. ATT group was associated with a significantly higher rate of post-operative complications, Clavien-Dindo classification ≥II and thromboembolic events. Operative mortality in ATT and non-ATT groups was 2 (6.7%) and 1 (2.1%), respectively. There was no significant association between ATT and excessive intraoperative blood loss (≥1000 mL), PPH (≥grade B) and thromboembolic complications (Clavien-Dindo classification ≥II). In patients with ATT, PD is a feasible procedure with no major impact on intraoperative bleeding or PPH.

Extent of Late Gadolinium Enhancement Predicts Thromboembolic Events in Patients With Hypertrophic Cardiomyopathy.

Thromboembolic complications such as ischemic stroke or peripheral arterial thromboembolism are known complications in hypertrophic cardiomyopathy (HCM). We sought to assess the clinical and cardiovascular magnetic resonance (CMR) characteristics of patients with HCM suffering from thromboembolic events and analyzed the predictors of these unfavorable outcomes.Methods and Results:The 115 HCM patients underwent late gadolinium enhanced (LGE) CMR and were included in the study. Follow-up was 5.6±3.6 years. The primary endpoint was the occurrence of thromboembolic events (ischemic stroke or peripheral arterial thromboembolism). It occurred in 17 (14.8%) patients (event group, EG), of whom 64.7% (11) were men. During follow-up, 10 (8.7%) patients died. Patients in the EG showed more comorbidities, such as heart failure (EG 41.2% vs. NEG (non-event group) 14.3%, P<0.01) and atrial fibrillation (AF: EG 70.6% vs. NEG 36.7%, P<0.01). Left atrial end-diastolic volume was significantly higher in the EG (EG 73±24 vs. NEG 50±33 mL/m2, P<0.01). Both the presence and extent of LGE were enhanced in the EG (extent% EG 23±15% vs. NEG 8±9%, P<0.0001). No patient without LGE experienced a thromboembolic event. Multivariate analysis revealed AF and LGE extent as independent predictors. LGE extent (>14.4%) is an independent predictor for thromboembolic complications in patients with HCM and might therefore be considered as an important risk marker. The risk for thromboembolic events is significantly elevated if accompanied by AF.

Trends in Prevalence of Non-Valvular Atrial Fibrillation and Anticoagulation Therapy in a Japanese Region - Analysis Using the National Health Insurance Database.

Direct oral anticoagulants (DOACs) are effective in reducing thromboembolism events in patients with non-valvular atrial fibrillation (NVAF). However, little is known about trends in NVAF prevalence and DOAC prescriptions in daily clinical practice. This study investigated the current status and trends in NVAF prevalence and DOAC prescriptions in a region of Japan.Methods and Results:Annual data for the 4 years from May 2014 to May 2017 in the Tsugaru region of Aomori Prefecture, Japan, were obtained for analysis from the Japanese National Health Insurance database ("Kokuho" database [KDB]). The prevalence of NVAF in subjects aged 40-74 years increased gradually over the 4-year study period (1,094/57,452 [1.90%] in 2014, 1,055/56,018 [1.88%] in 2015, 1,072/54,256 [1.98%] in 2016, and 1,154/52,341 [2.20%] in 2017). The proportion of NVAF patients prescribed warfarin decreased (42%, 33%, 24%, and 21% in 2014, 2015, 2016, and 2017, respectively), the proportion of those prescribed DOACs increased (30%, 42%, 50%, and 57%, respectively), and the proportion not prescribed an oral anticoagulant (OAC) decreased (28%, 25%, 26%, and 22%, respectively). However, 17% of patients with a CHADS2score ≥2 were not prescribed an OAC in 2017. By using the KDB we found that the prevalence of NVAF has increased gradually from 2014 to 2017. In the Tsugaru region in Japan, DOACs prescriptions increased and warfarin prescriptions decreased over the 4-year period.

Resuming Anticoagulation Following Hospitalization for Gastrointestinal Bleeding Is Associated with Reduced Thromboembolic Events and Improved Mortality: Results from a Systematic Review and Meta-Analysis.

Systemic anticoagulants are widely prescribed for prevention and treatment of thromboembolism, but are commonly complicated by gastrointestinal bleeding (GIB). Limited data exist on the management of anticoagulation after hospitalization for GIB and the subsequent risks of recurrent GIB, thromboembolism, and mortality. We performed a systematic review and meta-analysis of studies to determine risk of recurrent GIB, thromboembolism, and mortality after resuming anticoagulation following GIB. PubMed, EMBASE, and Scopus were searched for randomized controlled trials and cohort studies in patients with atrial fibrillation, venous thromboembolism, or valvular heart disease who received long-term warfarin or direct oral anticoagulants before experiencing GIB. Studies were included if data were available on anticoagulation management and outcomes of recurrent GIB, thromboembolism, and mortality following GIB. A total of 5354 studies were reviewed of which 10 were included in the meta-analysis. There were 2080 patients who resumed anticoagulation and 2296 patients who discontinued anticoagulation post-index GIB. Resumption of anticoagulation was associated with a significant increase in recurrent GIB (OR 1.646, 95% CI 1.035-2.617, p = 0.035). There was a significant decrease in thromboembolic events in patients who resumed anticoagulation compared to those who did not (OR 0.340, 95% CI 0.178-0.652, p = 0.001, I2 = 62.7%). Resumption of anticoagulation was associated with a significant reduction in all-cause mortality (OR 0.499, 95% CI 0.419-0.595, p < 0.0001). While resumption of anticoagulation following index GIB was associated with a significant increase in recurrent GIB, it was also associated with a significant decrease in thromboembolic events and all-cause mortality.

A Pharmacogenetically Guided Acenocoumarol Dosing Algorithm for Chilean Patients: A Discovery Cohort Study

BackgroundVitamin K antagonists (VKA) are used as prophylaxis for thromboembolic events in patients with cardiovascular diseases. The most common VKA are warfarin and acenocoumarol. These drugs have a narrow therapeutic margin and high inter-individual response variability due to clinical and pharmacogenetic variables.ObjectiveThe authors aim to develop an algorithm comprised of clinical and genetic factors to explain the variability in the therapeutic dose of acenocoumarol among Chilean patientsMethodologyDNA was obtained from 304 patients as a discovery cohort with an international normalized ratio (INR) range of 2.0–3.0. The non-genetic (demographic and clinical) variables were also recorded. Genotype analyses were performed using real-time PCR for VKORC1 (rs9923231), VKORC1 (rs7294), GGCx (rs11676382), CYP4F2 (rs2108622), ABCB1 (rs1045642), CYP2C9*2 (rs1799853), ApoE (rs429358), and CYP2C9*3 (rs1057910).ResultsThe clinical variables that significantly influenced the weekly therapeutic dose of VKA were age, sex, body mass index (BMI), and initial INR, collectively accounting for 19% of the variability, and the genetic variables with a significant impact were VKORC1 (rs9923231), CYP2C9*2 (rs1799853), and CYP2C9*3 (rs1057910), explaining for another 37% of the variability.ConclusionWe developed an algorithm that explains 49.99% of the variability in therapeutic VKA dosage in the Chilean population studied. Factors that significantly affected the dosage included VKORC1, CYP2C9*2, and CYP2C9*3 polymorphisms, as well as age, sex, BMI, and initial INR.

Thromboembolic Events in Patients with Concomitant Aortic Valve Surgery and Left Ventricular Assist Device Implantation, an IMACS Database Analysis

Patients with significant aortic regurgitation at time of left ventricular assist device (LVAD) implantation, frequently need concomitant aortic valve (AV) replacement (AVR) or AV repair. The aim of this study was to investigate the risk for thromboembolic events (TE) in patients with concomitant continuous-flow LVAD and AV surgery. We used the international multicenter registry data from the International Society of Heart and Lung Transplantation Mechanically Assisted Circulation Support (IMACS) registry of LVAD patients, implanted between January 2013 until September 2017. Differences between AVR, AV repair and non-AVR/repair patients were analyzed. In total, 785 (5.1%) out of the total 15267 patients (mean age 56±13 years, 79% male) received concomitant AVR/repair during LVAD surgery (mean age 60±11 years, 89% male); 386(2.5%) patients had biological prosthesis, 71 (0.5%) mechanical prosthesis and 328 (2.1%) AV repair. Follow-up was complete in 644 out of 785 (82%) patients, with a median follow-up of 11.8 months [IQR 4.8-23.4]. In total, TE occurred in 3135 cases; 2976 out of 12317 (24%) in patients without AV surgery, 73 out of 316 (23%) with a biological prosthesis, 73 out of 267 (27%) with an AV repair, and 13 out of 61 (21%) with mechanical prosthesis. The Figure shows that early (90-day) post LVAD, TE rate was significantly higher in the mechanical prosthesis group compared to the remaining cohort. However, at 2-years of follow-up, none of the concomitant surgery modalities were associated with higher TE rates. In patients treated with concomitant AVR or AV repair during LVAD surgery, a significant higher rate of early TE's was found in the mechanical prosthesis group. However, after 2-year follow-up, this differences was no longer significant. Caution in the early postoperative period is warranted when concomitant mechanical prosthesis is scheduled.

Therapeutic strategies for thrombosis: new targets and approaches.

Antiplatelet agents and anticoagulants are a mainstay for the prevention and treatment of thrombosis. However, despite advances in antithrombotic therapy, a fundamental challenge is the side effect of bleeding. Improved understanding of the mechanisms of haemostasis and thrombosis has revealed new targets for attenuating thrombosis with the potential for less bleeding, including glycoprotein VI on platelets and factor XIa of the coagulation system. The efficacy and safety of new agents are currently being evaluated in phase III trials. This Review provides an overview of haemostasis and thrombosis, details the current landscape of antithrombotic agents, addresses challenges with preventing thromboembolic events in patients at high risk and describes the emerging therapeutic strategies that may break the inexorable link between antithrombotic therapy and bleeding risk.

Impact of direct-acting oral anticoagulants and warfarin on postendoscopic GI bleeding and thromboembolic events in patients undergoing elective endoscopy

An increasing number of patients are undergoing GI endoscopic procedures with active prescriptions for direct oral anticoagulants (DOACs). DOACs have been associated with a higher risk of GI bleeding (GIB) compared with warfarin. Our aims were to compare the risk of postendoscopic GIB and thromboembolic (TE) events among patients on DOACs versus warfarin. We conducted a retrospective cohort study of patients aged 18 years or older in a large integrated health care system in Southern California, who had undergone an outpatient GI endoscopic procedure and were taking a DOAC or warfarin between January 1, 2013, and October 1, 2019. We compared bleeding and thrombosis risk in the 30 days after the endoscopic procedure between the warfarin and DOAC groups using multivariate logistic regression analysis adjusted for covariates. Between January 1, 2013, and October 1, 2019, we identified 6765 outpatient GI endoscopic procedures in which patients received preprocedure prescriptions for either a DOAC (1587) or warfarin (5178). Overall, there was no significant difference in postprocedure GIB (odds ratio [OR], 1.165; 95% confidence interval [CI], 0.88-1.55; P= .291) or TE (OR, 0.929; 95% CI, 0.64-1.35; P= .703) between the DOAC and warfarin groups). Subgroup analysis revealed a higher risk of GIB associated with DOAC specifically with EGD procedures (OR, 1.8; 95% CI, 1.15-2.83; P= .011). There was no significant difference in the overall postendoscopic risk of GIB and TE events among patients with preprocedure use of DOACs compared with patients on warfarin. There may be a higher risk of GIB in patients taking DOACs and undergoing EGD.

A novel clock-face method for characterizing peridevice leaks after left atrial appendage occlusion.

To propose a novel method for mapping leak location and frequency to a clock-face representation of the left atrial appendage (LAA) ostium. LAA occlusion with the Watchman device (WD) is an established therapy to reduce thromboembolic events in patients with atrial fibrillation (AF) and intolerance to long-term oral anticoagulation. Postimplantation leaks are known sequelae, but leak locations and characteristics are poorly described. We retrospectively reviewed 101 consecutive WD implants from April 2015 to February 2018. Leak locations from 6-week post-implant transesophageal echocardiograms were mapped to a clock-face representation of the LAA ostium: 12:00 as cranial near the limbus, 3:00 as anterior toward the pulmonary artery, 6:00 as caudal near the mitral annulus, and 9:00 as posterior. Patient demographics, LAA dimensions, and procedural characteristics were also collected. Thirty-four patients had ≥1 leak totaling 45 leaks at 6-week follow-up. Baseline patient demographics showed a mean age 77, CHA2 DS2 VASc 4.69, and 64% of patients with permanent AF. No patient had a detectable leak at the time of implant. At 6 weeks, mean leak size was 2.67 ± 0.89 mm with no leak over 5 mm (largest 4.60 mm). Most leaks occurred along the posterior 6:00-12:00 segment (39/45) and the 6:00-9:00 quadrant (16/45). Six-week post-WD implant leaks localize to the posterior LAA ostium. This could result from the elliptical LAA orifice, differential LAA tissue composition, or implantation technique. This study provides a novel method for describing the location of post-implant leaks and serves as the basis for further investigations.

Left atrial appendage mechanical dispersion provides incremental value for thromboembolic risk stratification over CHA2DS2-VASc Score in nonvalvular atrial fibrillation

BackgroundLeft atrial appendage (LAA) dysfunction is associated with increased risk of thromboembolic events. However, little is known about LAA mechanical dispersion (MD) would provide additional information toward thromboembolism over the CHA2DS2-VASc score. The aim of this study was to determine the association of LAA mechanics as assessed by speckle-tracking imaging with thromboembolic events in patients with nonvalvular atrial fbrillation (AF). MethodsA total of 116 consecutive patients with AF referred for transesophageal echocardiography (TEE) were prospectively enrolled. Of these, 17(14.7%) patients had prior embolic events. Using speckle-tracking echocardiography (STE), we measured the LAA strain in each of 24 segments in mid-esophageal TEE views obtained at 0°, 45°, 90° and 135°. LAA MD was defined as the standard deviation (SD) of time to peak positive strain corrected by the R-R interval. ResultsPatients with embolism had lower LAA global longitudinal strain (GLS) (8.56 ± 2.62% vs 11.37 ± 5.54%, p = 0.002) and higher LAA MD (16.90 ± 6.67% vs 12.10 ± 3.94%; P = 0.010) than those without embolism. LAA MD >13.1% differentiated patients with embolism from controls, with an area under the curve (AUC) of 0.709(p = 0.004). LAA MD was independently associated with the presence of thromboembolism in multivariate analysis (odds ratio, 1.24; 95% confidence interval, 1.08–1.42; P = 0.002). The model based on CHA2DS2-VASc score for discrimination of patients with embolism was significantly improved by adding LAA MD (P < 0.01). ConclusionLAA MD obtained from strain echocardiography was significantly associated with a prior history of embolic events and had incremental diagnostic value over CHA2DS2VASc score, suggesting that LAA MD may be useful in refining thromboembolic risk stratification in patients with AF.

Why optional inferior vena cava filters are not always retrieved? A real world 19 years experience in a Swiss tertiary care university hospital.

Background: inferior vena cava filters (IVCF) are widely used to prevent thromboembolic events in patients not suitable for anticoagulation (AC). Although new generations of filters are optional and therefore retrievable, most of them become permanent. Aim of our study was to evaluate real life IVCF management in a tertiary hospital including retrieval rates and reasons for permanent filtering.Materials and methods: Electronic charts from patients receiving IVCF in a Swiss university hospital, during 1999–2017, were retrospectively identified. Patients were classified in two groups, according to filter retrieval (RG) or not (NRG). Type and reasons of filter placement were assessed. Retrieval, complications, and mortality rates were calculated. Reasons of non-retrieval were analyzed.Results: 920 patients received an IVCF during 1999–2017. Filters were retrieved in 372 patients (40.65%). Subjects in the NRG were significantly older, more chronically ill, and presented higher mortality rate at 12 months following filter insertion (29.60% vs. 4.30%; p < 0.001). Reasons for non-retrieval included lack of follow-up (22.34%), persistent contraindications to AC (20.51%), technical issues (17.40%), and severe morbidity with short life expectancy (17.22%). Overall, complication rates after filter placement was 18.58%. Most reported complication was filter thrombosis (15.60%).Conclusions: In a real life setting, optional IVCF are still too often left in place indefinitely. Need for a systematic follow-up to ensure prompt filter retrieval is warranted. IVCF are not retrieved mostly in chronically and more severely ill patients, likely accounting for higher mortality in these subjects.

Between a Rock and a Hard Place: How to Use Antithrombotics in Patients Undergoing Transcatheter Aortic Valve Replacement

Transcatheter aortic valve replacement (TAVR) has become the preferred method for management of severe aortic stenosis in patients who are at high and intermediate surgical risk, and has recently gained approval from the Food and Drug Administration in the US for use in patients at low risk for surgery. Thrombocytopenia and thromboembolic events in patients undergoing TAVR is associated with increased morbidity and mortality, and yet there is insufficient evidence supporting the current guideline-mediated therapy for antithrombotics post-TAVR. In this article, the authors review current guidelines for antithrombotic therapy in patients undergoing TAVR, studies evaluating antiplatelet regimens, and studies evaluating the use of platelet function testing after TAVR. They also offer a potential link between thrombocytopenia and antiplatelet treatments in patients undergoing TAVR.

Klippel Trenaunay Weber syndrome in pregnancy

Klippel Trenaunay Weber syndrome (KTW) is a rare disorder, which occurs, in one in 27500 live births.1 It is a congenital neuroectodermal disorder1 and is characterized by the triad of symptoms such as port wine stain, bone and soft tissue hypertrophy and varicose veins. It is also associated with arteriovenous malformation.2 Due to the complexity of this disease, it is a real challenge to the anaesthetist and the obstetrician. We report a case of a KTW syndrome patient in her first pregnancy who was transferred to us from a district general hospital for the delivery. She had all the features along with multiple vascular anomalies and thrombocytopaenia. She underwent an elective caesarean section under general anaesthesia. Her intraoperative period was uneventful. At her post-operative day one she had a sudden cardiac arrest due to massive pulmonary embolism. This case highlights the high risk of thromboembolic events in patients with KTW syndrome.

P598 Incidence of venous thromboembolic events in patients with ulcerative colitis treated with tofacitinib in the ulcerative colitis clinical development programme: An update as of May 2019

Abstract Background Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of UC. In data analysed from a large, ongoing (data cut-off February 2019 [a]; database unlocked; data may be subject to change), post-authorisation safety study in patients with RA (≥50 years; ≥1 cardiovascular risk factor; enrolled on a stable dose of MTX), the incidence rate (IRs; unique patients with events per 100 pt-years [PY]) of pulmonary embolism (PE) in patients treated with tofacitinib 10mg BID (0.54 [95% CI] 0.32, 0.87]) was numerically higher compared with 5 mg BID (0.27 [0.12, 0.52]) and statistically different from TNFi (0.09 [0.02, 0.26]). Corresponding IRs for deep vein thrombosis (DVT) were 0.38 (0.20, 0.67), 0.30 (0.14, 0.55) and 0.18 (0.07, 0.39).1 UC is a known risk factor for DVT and PE. Subsequently, updates to the tofacitinib prescribing information have been made, with venous thromboembolism added as a warning and adverse drug reaction. Here, we provide an update on the incidence of DVT and PE in the tofacitinib UC clinical development programme, as of May 2019.2 Methods DVT and PE events were evaluated from 4 randomised placebo-controlled studies (Phase [P]2/P3 induction studies and P3 maintenance study) and an ongoing, open-label, long-term extension (OLE) study.3,4 Three cohorts were analysed: Induction, Maintenance and Overall (patients receiving tofacitinib 5 or 10mg BID in P2/P3/OLE studies; patients were categorised based on the average daily dose: predominant dose [PD] 5 or 10 mg BID). Results 1157 patients were evaluated for DVT and PE, with 2581 PY of tofacitinib exposure and up to 6.8 years’ treatment. In the Induction and Maintenance Cohorts, 2 patients had DVT and 2 had PE; all were receiving placebo at the time of the event (tables). In the Overall Cohort, DVT occurred in 1 pt and PE in 4 patients during the OLE study, after ≥7 months of treatment; all patients had received PD 10 mg BID (83% of Overall Cohort received PD 10 mg BID) and had other (non-UC) risk factors for venous thrombosis (tables). Conclusion IRs in the Overall Cohort have remained stable since the previously reported data cut.2 All of the events in tofacitinib patients (PD 10 mg BID) occurred during the OLE study and all had other (non-UC) risk factors for thromboembolic events. This analysis is limited by sample size and duration of drug exposure; further study is needed. [a] The tofacitinib 10mg BID arm of the study was discontinued in February 2019 and patients who re-consented and chose to remain in the study were switched to the 5 mg BID arm. References