Embolic Events Research Articles

Rationale and design of a randomized clinical trial evaluating the efficacy of mechanical neuroprotection in reducing the risk of silent brain infarcts associated with percutaneous left atrial appendage closure: study protocol for a LAAC-SBI trial

BackgroundLeft atrial appendage closure (LAAC) procedures prevent cardioembolic stroke in patients with atrial fibrillation who have contraindications to oral anticoagulant medications. However, these procedures carry certain risks of peri-procedural complications. One such complication is silent brain infarcts (SBI), which can lead to cognitive impairment and mood disturbances. The implementation of mechanical neuroprotection systems during LAAC procedures may reduce the risk of SBI and associated cognitive and mood disorders.MethodsThe LAAC-SBI trial is a prospective, multicenter, randomized, and double-blind interventional study. The study aims to enroll a total of 240 patients, with 120 patients allocated to each group. The study group will evaluate the use of the Sentinel CPS during LAAC, while the control group will undergo LAAC procedures without the Sentinel CPS. The primary endpoint of the study is the number of new SBIs or stroke foci detected by diffusion-weighted magnetic resonance imaging (DW MRI). Secondary endpoints include deterioration of cognitive function, development of dementia syndrome, and occurrence of depressive disorders. These endpoints will be assessed using questionnaire tools such as the Montreal Cognitive Assessment (MoCA), Trail Making Test (TMT), Controlled Oral Word Association Test (COWAT), and Hospital Anxiety and Depression Scale (HADS). The observational period for patients in the study is 2 years.DiscussionIf the study demonstrates a favorable outcome with reduced incidence of SBI and improved cognitive and mood outcomes in patients receiving cerebral protection devices during LAAC, it will have significant implications for clinical management standards. This would support the use of neuroprotection devices not only for LAAC but also in procedures such as atrial fibrillation ablation or transcatheter mitral valve interventions, where the risk of embolic events and subsequent brain injury may also be present.Trial registrationClinicalTrials.gov NCT05369195. Registration on 11.05.2022.

Management and outcomes of superficial vein thrombosis: a single-center retrospective study

BackgroundGuidelines suggest but cannot recommend the optimal management of superficial vein thrombosis (SVT). ObjectivesTo identify the prevalence of asymptomatic deep vein thrombosis (DVT) at the time of SVT diagnosis, and to report the treatment and 3-month complications of patients with only SVT more than 3 cm from deep vein junction (or unknown distance). MethodsWe performed a single-center retrospective review of patients referred to the Ottawa Hospital thrombosis unit with ultrasound (US)-diagnosed SVT, and followed patients with only SVT for 3 months. ResultsThree hundred sixteen patients with SVT were included. Of the 218 patients without DVT symptoms at presentation, 19 (8.7%; 95% CI, 5.7%-13.2%) were found to have asymptomatic concomitant DVT (11 proximal and 8 distal), and 45 (20.6%) had SVT within 3 cm of the saphenofemoral or saphenopopliteal junctions. Among the 192 patients diagnosed with SVT only, we observed 3-month thrombotic complications in 56 (29.2%; 95% CI, 23.2%-36.0%) patients, with a total of 69 events: 11 (5.7%) DVTs, 2 (1.0%) pulmonary embolisms, 37 (19.2%) SVT extensions, and 19 (9.8%) SVT recurrences. Eighty-two percent (9/11) of the 3-month DVT and pulmonary embolism events occurred in patients who initially received conservative management. Therapeutic treatment doses were most effective. ConclusionAt the time of SVT diagnosis, many patients had asymptomatic DVT and SVT near the deep venous system, supporting the systematic use of initial US in patients clinically diagnosed with SVT. The observed differences in 3-month complication rates, according to the treatment provided, highlight the need for large-scale randomized controlled trials to establish optimal management.

Direct oral anticoagulants versus vitamin K antagonists for left ventricular thrombus: a systematic review and meta-analysis

Abstract Introduction Left ventricular thrombi (LVTs) increase the risk of stroke and systemic embolism and are commonly seen after acute myocardial infarction. While vitamin K antagonists (VKAs) are the recommended first-line treatment for LVT, direct oral anticoagulants (DOACs) are being used as an alternative. However, the comparative efficacy and safety of DOACs and VKAs in LVT treatment are unclear. Purpose We conducted a systematic review with meta-analysis to evaluate the impact of DOACs compared with VKAs therapy in patients with LVT. Methods PubMed, Embase, and Cochrane were systematically searched for studies that compared DOACs versus VKAs and reported efficacy and safety endpoints. We performed meta-analyses with fixed or random effect models based on the level of heterogeneity determined by the Cochrane Q-test and I2 statistics. Results Three randomised controlled trials (RCTs) and 29 cohort studies were included, with 4,400 patients assigned to either DOACs (1,307 patients) or VKAs (3,093 patients). Our findings indicate that DOACs therapy did not significantly reduce stroke/systemic embolic events (OR 0.90; 95% CI 0.65-1.26; p=0.54; I2=33%), stroke (OR 0.90; 95% CI 0.59-1.36; p=0.60; I2=7%), systemic embolic events (OR 0.65; 95% CI 0.39-1.06; p=0.08; I2=0%), thrombus resolution (OR 1.11; 95% CI 0.92-1.33; p=0.27; I2=0%), minor bleeding (OR 0.68; 95% CI 0.39-1.18; p=0.17; I2=0%), major bleeding (OR 0.84; 95% CI 0.47-1.49; p=0.54; I2=16%), or all-cause mortality (OR 1.01; 95% CI 0.75-1.36; p=0.97; I2=0%) compared to VKAs. However, DOACs therapy was associated with a statistically significant reduction in any bleeding (OR 0.72; 95% CI 0.55-0.96; p=0.02; I2=0%) and clinically relevant bleeding (OR 0.62; 95% CI 0.41-0.92; p=0.02; I2=0%) compared to VKAs therapy. Our subgroup analysis of patients treated with apixaban revealed no significant differences between DOACs and VKAs therapies for stroke, clinically relevant bleeding, and all-cause mortality. Conversely, rivaroxaban therapy was associated with a statistically significant reduction in systemic embolic events and clinically relevant bleeding compared to VKAs therapy. Conclusion DOACs therapy was not associated with reduced efficacy and safety endpoints compared to VKAs therapy, except for fewer haemorrhagic events. Rivaroxaban therapy had a significant reduction in systemic embolic and hemorrhagic events. These findings support the superiority of DOACs over VKAs therapy for LVT.PRISMA Flow-ChartForest plot of odds ratios (OR)

Clinical impact of valvular strands or Lambl's excrescences in the real-world practice

Abstract Background Due to recent advancements in high-resolution echo systems, valvular strands or Lambl’s excrescences are frequently observed in daily clinical practice. However, it can be challenging to differentiate these valvular structures as fibroelastomas or infective endocarditis. Although those redundant cardiac tissues are reported to cause embolic events, the incidence or outcomes of valvular strands and Lambl’s excrescences have not been well investigated. Purpose To investigate the clinical impact of valvular strands or Lambl’s excrescences (VS/LEs) on clinical outcomes. Methods We searched our hospital’s institutional echocardiography database for transthoracic echocardiography (TTE), or transesophageal echocardiography (TEE) reports with VS/LEs between 2018 and 2022. Patients diagnosed with infectious endocarditis or overt papillary fibroelastoma were excluded. Clinical outcomes of all-cause death, ischemic stroke, systemic embolism, or surgical resection were evaluated from the electronic medical chart. We analyzed the cumulative incidences of each clinical outcome for the entire cohort, and we compared cases assessed by TEE (With TEE) and cases confirmed by TTE only (TTE only). Results From the 53799 TTE and 3186 TEE tests, we found 340 reports from 174 cases with VS/LEs (With TEE, 67 cases, and TTE only, 107 cases). Only one stroke case was suspected of aortic valve strand origin for stroke at the index TEE or TTE. Surgical resection was performed in two cases (one each in With TEE and TTE only groups) within 30 days from the first detection of the VS/LEs. The median follow-up period was 355 days. We observed all-cause death in 8 cases (6.1%: With TEE, 1 case [1.6%] and TTE only, 7 cases [8.6%], P=0.09). Ischemic stroke occurred in 6 cases (5.0%: With TEE, 3 cases [6.5%], TTE only, 3 cases [4.1%], P=0.27). None of the deaths were associated with embolic events. We performed landmark analysis at 30 days for surgical resection, and five cases underwent surgical treatment at one year (With TEE, 5 cases, and TTE only, no case). All surgical resections for the VS/LEs were performed concurrently with other cardiac operations. Conclusions In this study, we observed that most VS/LEs were managed non-invasively and rarely associated with embolic events, especially TTE-only detected VS/LEs.

Left atrial strain and risk of systemic embolic event in rheumatic mitral stenosis with sinus rhythm

Abstract Backgrounds Stroke and systemic embolism might be an important complication of rheumatic mitral stenosis (MS) even though patients are in sinus rhythm (SR), but the risk of embolic events in this population are not well studied. Purpose We aimed to evaluate the risk factors of embolic events in patients with rheumatic MS and SR. Methods From the multi-center retrospective registry of 2426 patients with rheumatic MS, we included patients with rheumatic MS and SR (n=583) between January 2000 and December 2021. After exclusion of patients who had history of systemic embolic events, taking the anticoagulants, combined significant aortic valve dysfunction, and a history of valve surgery. We finally analyzed 443 patients. The primary outcome was defined as composite of stroke, transient ischemic attack, noncentral nervous system embolism. Results Among 448 patients (77.1% female; mean age, 52.3 ± 10.1 years), systemic embolic events developed in 38 (8.4 %) patients with annual incidence rate of 4.6/100 person-year during mean follow-up period of 96.4 ± 61.1 months (median 94.2 months). Patients who had systemic embolic events were significantly older and had higher the prevalence of hypertension and diabetes than those who did not, without significant differences in left atrial (LA) dimensions, volumes, pulmonary artery systolic pressure. Instead, LA strain was significantly impaired in patients with systemic embolic events (19.1 ± 9.3 vs. 15.5 ± 8.07, p= 0.034). In the multivariate analysis, LA strain was independent predictors of systemic embolic events [HR 0.96, 95 % CI: 0.93-0.99; P = 0.021], after adjustment for confounding factors. The impaired LA strain (LA reservoir strain < 16.6 %) also had incremental prognostic value for development of systemic embolic events over clinical factors and traditional echocardiographic parameters (Figure). Conclusions Impaired LA strain is a predictor of stroke and systemic embolism in patients with rheumatic MS in SR. Considering the risk for embolism, oral anticoagulation might be considered in patients with rheumatic MS in SR and impaired LA strain.Figure

Association of device detected atrial high rate episodes with embolic events

Abstract Background Subclinical atrial fibrillation (AFib) is a common etiology of embolic events such as embolic strokes of undetermined source. With the advent of cardiac implantable electronic devices (CIED), there has been increased detection of subclinical AFib, or atrial high rate episodes (AHRE) in asymptomatic patients without a known diagnosis of AFib. The clinical significance of AHRE detected with CIED remains poorly characterized with studies reporting conflicting results. The purpose of this meta-analysis is to evaluate the association of AHRE with cerebrovascular accidents (CVA), transient ischemic attacks (TIA), and systemic embolic events. Methods A literature search was conducted for studies reporting on the association of subclinical AFib or AHRE with CVA, TIA, and systemic embolic events. The search included the following databases: Ovid MEDLINE, EMBASE, Google Scholar, and Web of Science. The search was not restricted to time or publication status. Results A total of 19 studies and 50,968 patients (12,879 with AHRE vs 38,089 without AHRE) were included. Mean follow-up was 32 months, mean age was 72 years old, 53.3% were male. Patients with device detected AHRE had increased risk of composite endpoint of CVA, TIA, and systemic embolic events (OR 2.98, 95% CI 2.03-4.39; P<0.01). Subgroup analysis by maximum AHRE burden demonstrated that both maximum AHRE burden >24 hours and burden <24 hours are associated with increased risk of CVA, TIA, and systemic embolic events (OR 4.82, 95% CI 2.07-11.24; p<0.01; OR 1.55, 95% CI 1.11-2.15; p<0.01). The overall effect size is larger for maximum AHRE burden >24 hours compared to <24 hours (Z=3.64 vs Z=2.61). Conclusions Our results suggest that AHRE detected with CIED is associated with increased risk of CVA, TIA, and systemic embolic events regardless of maximum AHRE burden >24 hours or <24 hours. Additional studies are required to determine the utility anticoagulation therapy for treatment of asymptomatic patients with device detected AHRE.

Risk and benefits of baseline antiplatelet therapy in 58,598 patients with atrial fibrillation randomized to NOACs vs warfarin

Abstract Background The efficacy and safety of NOAC versus warfarin (W) may differ in AF pts receiving antiplatelet therapy (APT) at baseline. Moreover, prior individual trial-specific analyses examining the treatment effect of NOAC vs. W as a function of APT are underpowered for interaction testing. Purpose We evaluated outcomes by randomized anticoagulant stratified by baseline APT in a pooled individual pt-level meta-analysis of 4 pivotal RCTs of NOAC vs. W in AF: RE-LY, ROCKET-AF, ARISTOTLE, and ENGAGE AF-TIMI 48. Methods Pts were stratified by use of APT vs. no APT at baseline. Pts randomized to low-dose NOAC not globally approved (edoxaban 30/15 mg or dabigatran 110 mg) were excluded. The primary efficacy and safety outcomes were stroke/systemic embolic events (S/SEE) and major bleeding, respectively; ischemic stroke (IS), intracranial hemorrhage (ICH), major GI bleeding and all-cause mortality (ACM) were secondary outcomes. Each outcome was assessed by randomized treatment using a Cox model stratified by trial with adjustment for age, sex, weight, CrCl, smoking status, HTN, DM, CAD, prior MI, PAD, and prior stroke. Interaction testing was performed by APT at baseline. Results Of 58,598 pts, 19,774 (34%) were on APT at baseline (92% aspirin only, 5% P2Y12 only, 3% DAPT). Pts treated with APT had greater prevalence of CAD (41% vs. 24%), prior MI (22% vs. 11%), and PAD (6% vs. 4%) (p<0.001 for each). Reflective of these baseline differences, the annualized event rate for each outcome was higher in the APT vs. no APT group (Figure). The treatment effect (HR) of NOAC vs. W for all 6 clinical outcomes was consistent irrespective of baseline APT (p-interaction [aHR] for each = NS; Figure). However, the absolute risk reduction (ARR) for NOAC vs. W differed for ICH and major GI bleeding as a function of baseline APT (Figure). Specifically, for ICH, a greater absolute benefit was seen with NOAC vs. W in those on APT at baseline (ARR 0.6% vs. 0.3%; p-int = 0.007). Conversely, for major GI bleeding, NOAC vs. W was associated with greater absolute risk in those on APT (ARR -0.6% vs. -0.2%; p-int = 0.04). Conclusions The treatment effect of NOAC vs. W is consistent irrespective of APT at baseline for S/SEE, major bleeding, and ACM. Given higher rates of bleeding in AF pts treated with both APT and anticoagulation, concomitant APT should be avoided when possible. In pts requiring concomitant APT, NOAC instead of W should be considered owing to greater absolute safety benefit for ICH, which should be weighed against individual patient-specific risk factors for GI bleeding.

Cardioembolic events and death predictors in patients with intraventricular thrombus

Abstract Background There is poor evidence about the optimal medical treatment and length of anticoagulation for the management of intraventricular thrombus (IVT). Current ESC guidelines recommend continuation of anticoagulation for up to 6 months. Purpose The objective of this study was to identify predictors of events during follow-up in patients with IVT in order to infer the best therapy in this clinical scenario. Methods All patients with IVT in our tertiary hospital between 2005 and 2021 were retrospectively analyzed. Patients were classified into 2 groups, according to whether they developed (group 1) or not (group 2) the combined event of death, myocardial infarction, stroke or embolism during the first 6 months. A multivariate logistic regression analysis was performed to identify independent risk factors of clinical events. Results 195 patients were included, of whom 40 (24.1%) presented the combined event at 6 months. There were no differences in age (68.5±15.6 vs 65±13.7 years; p=0.167) or gender distribution (80% men vs 84.9%; p=0.463) between the groups. A history of peripheral vascular disease (22% vs 7.1%; p=0.007), atrial fibrillation (AF) (22% vs 6.3%; p= 0.004) and stroke (34.2% vs 11.8%; p=0.001) were more frequent in group 1. The echocardiogram showed more frequently a mobile thrombus (43.2% vs 23%; p=0.017) with the presence of outgrowths (19.4% vs 5.6%; p=0.012) in the group with events. In addition, these patients had worse ventricular function (LVEF 33.6% vs 40.4%; p=0.002). Regarding treatment, the use of P2Y12 inhibitors was lower in group 1 (36.6% vs. 58.3%, p=0.016). There were no differences in the use of anticoagulants (85.4% vs 87.4%, p=0.737) or in the time until the thrombus clearance (median 119 vs 147 days, p=0.152). The presence of outgrowths in the thrombus, the ejection fraction, and a history of stroke were independently associated with the development of events at 6 months (Table). Considering a cut-off point of one-year follow-up instead, only 7 patients more had events. The presence of outgrowths was the only factor that maintained the independent association with the development of events (OR 9.3 (95%CI 1.6-54.7); p=0.01) during this time frame. Conclusions Cardiovascular events after IVT diagnosis are concentrated in the first 6 months. The presence of outgrowths attached to the thrombus, the lower ejection fraction, and a history of stroke were independent predictors of events at 6 months. In addition, the presence of outgrowths maintained its strong association at one year. Therefore, a more aggressive antithrombotic treatment may be considered in the presence of these factors.

One-year clinical outcomes and the impact of procedural configurations in patients with left atrial appendage occlusion

Abstract Background To evaluate the long-term clinical performance, the impact of procedural configurations and post-procedure medications in atrial fibrillation patients with percutaneous left atrial appendage occlusion (LAAO). Methods The RECORD study was a prospective, all-comers registry conducted in 39 Chinese centers that consecutively enrolling patients who received LAAO between 1st April 2019 and 31st October 2020 with minimum inclusion and exclusion criteria. Events including any death, any stroke, systemic embolism and bleeding event were collected at 1 year and adjudicated by an independent clinical event committee. Cox proportional hazard models with multivariable adjustments were applied to estimate hazard ratios (HRs) for each outcome. Results Of the 3,096 participants, 3,082 successfully received an LAAO implant and 3,013 (97.8%) completed the 1-year follow-up. Participants had a high risk of stroke (mean CHA2DS2-VASc score of 4.0) and a moderate-to-high risk of bleeding (mean HAS-BLED score of 2.4). Local anesthetic was performed in 1,287 (41.6%) patients and fluoroscopy guidance in 492 (16.0%) patients. In 1295 (42.0%) cases, one-stage combination procedures of LAAO and radiofrequency ablation or cryoablation (CA) were performed. At 1 year, the composite ischemic endpoint of death, stroke, and systemic embolism occurred in 133 (4.51%) patients. Any life-threatening, disabling or major bleeding events occurred in 71 (2.36%) patients. There was no significant association between the type of anesthesia (general versus local), modality of image guidance (TEE, ICE, or fluoroscopy) with the ischemic or bleeding events. Combination procedures of LAAO plus CA was associated with a significantly lower rate of death, stroke, or systemic embolism than performing LAAO only (3.5% versus 5.2%, HRadjusted:0.69, 95%CI:0.48-0.98, P=0.041). The commonest antithrombotic strategy was OAC | APT | APT (38.1%; corresponded to medication prescribed at discharge | 45 days | 6 months), followed by OAC | OAC | APT (27.0%). Compared with OAC | APT | APT, the OAC | OAC | APT group was associated with a higher risk of life-threatening, disabling or major bleeding (1.2% versus 2.5%, HRadjusted:0.50, 95%CI: 0.25-0.99, P=0.47); whereas the risk of death, stroke and SE was numerically similar (2.9% versus 3.0%, HRadjusted:1.05, 95%CI: 0.61-1.78, P=0.867). There was no significant difference between OAC | APT | APT and OAC+APT | APT | APT groups regarding ischemic events; however, in patients with HAS-BLED ≥ 3, OAC | APT | APT was associated with lower rates of life-threatening, disabling or major bleeding events (1.1% versus 4.8%, HRadjusted:4.55, 95%CI: 1.31-15.81, P=0.017). Conclusion In Chinese centers, patients with a WATCHMAN LAAO device had low rates of ischemic and bleeding events at 1 year. One-stage combination procedures of LAAO and catheter ablation was associated with a significantly lower rate of ischemic events than performing LAAO only.Procedural configurations to outcomesPost-LAAO antithrombotic medications

Is pre-diabetes a predictor of events in patients with atrial fibrillation?

Abstract Introduction Diabetes mellitus (DM) not only increases the probability of presenting atrial fibrillation (AF), but it is also a predictor of ischemic stroke included in scales such as CHA2DS2VASc. However, there is limited information on the association between glycated hemoglobin (HbA1c) levels and ischemic, embolic or hemorrhagic events in patients with pre-diabetes and AF. Objectives This study aimed to investigate whether the presence of pre-diabetes in patients with AF increases the risk of ischemic events, hemorrhagic events, myocardial infarction or death. Methods We used data from the CardioCHUVI-AF registry, which included 18,285 patients with AF from a Galician health area between January 2014 and December 2019. Patients with valvular AF (n=376), with loss of follow-up (n=97), without information on baseline characteristics (n=48) and without data on HbA1c (12,473) were excluded. The final cohort consisted of 5,291 patients, 2,993 were non-diabetics (56.6%) and 2,298 with known diabetes (43.4%). This final cohort was classified according to HbA1c in diabetics if HbA1c is more than 6.5% (n= 1,546; 29.2%), pre-diabetics when HbA1c is between 5.7 and 6.4% (n =2,233; 42.2%) and non-diabetics if HbA1c was less than 5.7% (n = 1,512; 28.6%). Competing hazards regression analysis for non-fatal events (with death as the competing event) and conventional Cox regression for mortality were performed. Results 2,993 non-diabetic patients with AF and HbA1c data were followed for 4.1 ± 1.6 years. The mean age was 73.0 ± 9.9 years, 47.4% were women, the mean CHA2DS2VASc score was 2.9 ± 1.4 points, the mean HASBLED score was 2.5 ± 1.2 points, and 2,407 (80.4%) patients were under treatment with oral anticoagulants. In the Kaplan Meier curves, no was observed a higher rate of events in pre-diabetes patients in comparison with patients with normal glycemia. In the multivariate analysis, after adjusting for the CHA2DS2VASc and HASBLED scales, as well as for anticoagulant therapy, it was observed that pre-diabetes was not associated with an increased risk of mortality ( HR= 0.80; 95% CI, 0.60-1.08), ischemic stroke (HR= 0.99; 95% CI, 0.71-1.38), major hemorrhage (HR= 0.78; 95% CI, 0.60-1.02) or myocardial infarction (HR= 1.08; 95% CI, 0.65-1.79), compared with patients with normal glycemia. Conclusions In our registry, non-diabetic patients with atrial fibrillation do not have a higher risk of events when their glycated hemoglobin is in the pre-diabetes range.

Three-dimensional printer guided new morphological classification of left atrial appendage -rock, paper and scissors-

Abstract Background Cardiogenic embolism by left atrial thrombi is one of the most important atrial fibrillation (AF)-related clinical problems. In a previous survey, 91% of nonrheumatic AF-related left atrial thrombi was originated in the left atrial appendage (LAA). The WATCHMAN device was developed as a permanent implantable device to seal off the LAA to prevent cardiogenic embolism. It has been used in Japan since September 2019 only for patients who are at the high risk of bleeding events. The WATCHMAN family is the only left atrial appendage closure (LAAC) device in JAPAN. It is known that the LAA diameter of Asians is larger than that of non-Asians. Furthermore, the LAA of the Japanese are more complicated, compared to the Western. Whereas the four classifications from previous reports are widely used in the world, the classification differs with different physicians in the real-world practice. Purpose We aimed to identify the relationship between morphological features of LAA and clinical events such as ischemic stroke in Japanese patients. Methods The LAAC database of our institution was respectively analyzed. All LAAC cases were performed between February 2020 and February 2022. The three-dimensional printing of LAA was generated from cardiovascular computed tomography imaging data. The shapes of the LAA were classified into 3 morphological types: (1) The LAA with bi lobe was defined as "Scissors" type; (2) The one with complicated erasing branches was "Paper" type; (3) The simple one was "Rock" type. We retrospectively examined the relationship between the risk of ischemic stroke and the morphological features of the LAA. Results The cohort consisted of 63 consecutive patients (age, 73±8 years; male gender, 73%; BMI, 24±4 kg/m²; the size of WATCHMAN device, 29±42 mm). Of those, 14 (22%), 21 (33%) and 28 (44%) patients were divided into the Scissors, Paper and Rock types, respectively. All groups were identically matched for comorbidities. Table shows the patient characteristics and the results of univariate and multivariate analysis. There were 35 (56%) patients who had a history of ischemic stroke (4 vs. 9 vs. 22; Rock vs. Scissors vs. Paper types, p-value=0.01). In the multivariate analysis, the Paper type is the potential risk factor of ischemic stroke (p-value<0.01, respectively). Conclusions The morphological features of LAA by three-dimensional printing may be related to cardioembolic stroke. Patients with Paper type LAA were significantly more likely to have had a history of ischemic stroke. These results could have a relevant impact on the antithrombotic management of patients who are at the high risk of embolic and bleeding events and, moreover, LAAC could be the best option for these patients.Table 1Table 2

Repeated measurement of the novel atrial biomarker BMP10 improves risk stratification in anticoagulated patients with atrial fibrillation: Insights from the ARISTOTLE trial

Abstract Background Atrial fibrillation (AF) increases the risk of stroke, heart failure, and death. Biomarkers provide important prognostic information about these complications in AF. Recently, bone morphogenic protein 10 (BMP10), a protein mainly expressed in atrial tissue, was identified as a novel marker in AF for the risk of ischemic stroke. Purpose To assess the association between baseline characteristics with BMP10 concentrations, and if repeated BMP10 measurements at 2 months improve the prognostication of ischemic stroke or systemic embolism and other cardiovascular events in patients with AF. Methods BMP10 was measured in plasma samples collected at randomization and at 2 months in patients with AF who were randomized to apixaban or warfarin in the ARISTOTLE trial (n = 2878) with a median follow-up time of 1.8 years. BMP10 was analyzed with a prototype Elecsys immunoassay. The association of baseline variables with BMP10 at 2 months was evaluated with linear regression analysis. Cox-regression models adjusted for baseline characteristics and comorbidities including kidney function and BMP10-level at baseline were used in order to evaluate associations with outcomes. Results Median age was 70 (63.0-76.0) and 63% were male. The events during the follow up period were 34 ischemic strokes, 155 deaths and 99 hospitalizations for heart failure. Median concentration of BMP10 was 2.4 ng/mL at inclusion and 2.6 ng/mL at 2 months (median increase 7.8%, p<0.001). The Spearman correlation for BMP10 at baseline and 2 months was 0.71. The baseline variables most strongly associated with higher BMP10 levels at 2 months, in descending order of importance, were: higher BMI, female sex, worse kidney function, older age, AF-rhythm, diabetes, and randomized treatment. BMP10 levels at 2 months improved the risk stratification in models adjusted for clinical variables including baseline levels of BMP10. For ischemic stroke and death, the estimated associations were nonlinear (Figure) with increased risk with higher BMP10 levels (p=0.037 and p<0.001, respectively), whereas the association with HF hospitalization was linear with HR of 1.91 (p=0.012) comparing the third and first sample quartiles. Patients randomized to apixaban had approximately 2.2% lower BMP10 levels at 2 months compared to those randomized to warfarin (p<0.001). Conclusions In patients with AF, the level of the atrial biomarker BMP10 is consistently associated with the risk of stroke at baseline and after 2 months of treatment with warfarin or apixaban. Repeated compared to only one measurement of BMP10 further improves risk stratification. Apixaban as compared to warfarin is associated with a reduction in the BMP10 level, which is in accordance with the lower risk of stroke with apixaban as compared to warfarin.

Meta-analysis of cardiac imaging modalities for the diagnosis of left ventricular thrombus following acute myocardial infarction

Abstract Background The formation of left ventricular thrombus (LVT) in post-acute myocardial infarction (AMI) patient carries significant risk of systemic embolism. Hence, there is a need to adopt strategies aimed at accurate and early diagnosis of LVT in order to mitigate the risk of embolic events with anti-thrombotic therapy. We aimed to conduct a systematic review and meta-analysis to appraise the current literature on the various diagnostic modalities used in post-AMI LVT detection. Methods We conducted a comprehensive search in Medline, EMBASE, and Scopus using an appropriate keyword/MeSH term search strategy up to 31 December 2021. All studies reporting a comparison between at least two imaging modalities in the diagnosis of LVT in post-AMI patients were included. Results A total of 2039 patient from 11 studies published between 2006 and 2021 were studied. Across all study populations, a majority of patients were male (82.3%) and the overall incidence of LVT was 15.2%. Using delayed-enhancement cardiac magnetic resonance imaging (DE-CMR) as the gold standard reference, transthoracic echocardiogram (TTE) with ultrasound enhancing agent (UEA) had the highest sensitivity (0.886, 95% CI 0.667-0.967) and specificity (0.980, 95% CI 0.900-0.996), while cine-CMR had the best diagnostic performance in terms of positive likelihood ratio (LR+ 437, 95% CI 37.2-1890), negative likelihood ratio (LR- 0.246, 95% CI 0.118-0.423) and diagnostic odds ratio (DOR 2050, 95% CI 134-9590). The summary receiver operating characteristic curves (SROCs) of the three studied imaging modalities were plotted and the AUC values were 0.920, 0.974 and 0.989 for TTE without and with UEA, and cine-CMR. Conclusions The diagnostic modalities used for LVT detection examined in this study had good specificity but poor sensitivity when compared to DE-CMR. Post-AMI patients at higher risk of LVT formation may benefit from further imaging studies with DE-CMR if initial TTE were negative.

The importance of active rhythm monitoring in patients with renal infarction: Korean national health insurance registry

Abstract Background/Introduction Several studies reported that approximately 50% of renal infraction (RI) is caused by cardioembolic disease, particularly associated with atrial fibrillation (AF). However, in the Korean national health insurance database (NHIS), from 2013 to 2019, the prevalence of AF in patients with RI was only 15%. So, we aimed to analyze the incidence of newly developed AF in RI patients. Method This nationwide population-based retrospective cohort study included 5,200 patients with RI using the NHIS database from 2002 to 2012. We analyzed the incidence rate of AF during 12 months among the patients without previous history of AF. We selected clinical events after three months of RI diagnosis to exclude cases diagnosed by initial screening or with previously missed diagnosis of AF. The definition of RI, AF, and comorbidities use the ICD-10-CM codes. Result During the total follow-up period (median 2.5 years, interquartile range 1.04-4.25), AF occurred in 19.1% of RI patients (n=993). Most cases (n=837, 16.1%) occurred within a year, and the incidence of AF was 3.965 per 10,000 person-year. Patients with newly developed AF had a higher proportion of older age than those without AF (64.1 vs. 57.3 years, P<0.001). The prevalence of comorbidities, including hypertension (HTN), ischemic heart disease (IHD), and heart failure (HF), was higher in those with AF. The independent predictors of AF were age (adjusted hazard ratio [aHR] 1.05, 95% CI 1.04-1.05, P<0.001), male (aHR 1.26, 95% CI 1.09-1.45, P=0.002), body mass index (BMI) (aHR 1.04, 95% CI 1.02-1.06, P <0.001), current smoker (aHR 1.20, 95% CI 1.03-1.40, P =0.023), IHD (aHR 1.20, 95% CI 1.00-1.45, P =0.050) and HF (aHR 1.70, 95% CI 1.25-2.33, P =0.001). Additionally, the incidence of all-cause death was 14.264 per 10,000 person-year during the follow-up period. Conclusion Even if AF is not diagnosed in the initial screening after diagnosis of RI, the physician should consider active rhythm monitoring to detect subclinical AF for optimal management in these patients. Especially it might be helpful to reduce the burden of recurrent embolic events in those with risk factors, such as older age, male, higher BMI, current smoker, IHD, or HF.Cox regression analysisAtrial fibrillation cumulative incidence

Cardiac complications as a major predictor of in-hospital death in infective endocarditis using machine-learning algorithm analysis

Abstract Introduction Despite advances in diagnostic and therapeutic strategies, infective endocarditis (IE) remains associated with devastating outcomes with substantial mortality rate. In patients who develop cardiac complications, an early aggressive therapeutic strategy regarding surgical intervention may be warrant. The epidemiologic profile of IE has been changed, which highlights the need for studies with risk stratification of patients hospitalized with IE. Purpose The study aim is to investigate variables strongly associated with in-hospital death and define groups of patients at different risk profile based on values of explanatory variables. Methods A prospective cohort including 349 consecutive patients with IE admitted to a quaternary hospital. The diagnosis was based on the modified Duke criteria and modified European Society of Cardiology criteria from 2015. Data regarding predisposing conditions, laboratory, imaging results, treatment, and outcomes were described. The primary endpoint was in-hospital mortality due to any complication related to IE. Cardiac complications were defined as development or worsening heart failure, prosthesis rupture or perivalvular extension of infection. In-hospital death was analyzed through conditional inference trees and the composed nodes were discriminated in groups with different risks of death and by logistic regression model. Results The median age was 55 years, 59% of patients had native valve, 23.5% prosthetic valve and 35.5% intracardiac device-related IE. Rheumatic heart disease corresponded to 25%, 18% presented diabetes and 13.5% had chronic kidney disease as predisposing conditions. The main causative microorganism was Staphylococcus aureus (19%) and average C-reactive protein (CRP) at diagnosis was 72mg/L. During treatment, 123 (35%) had cardiac complications, 73 (21%) neurological complications, and 45 (13%) suffered embolic events. A total of 105 (47%) patients underwent cardiac surgery. The overall in-hospital mortality was 35.5%. On multivariable analysis, the independent predictors of death were increasing age, high CRP, neurologic and cardiac complications (Figure 1), with C statistic of the model 0.76 (CI 95% 0.70-0.82). According to the decision-tree analysis (Figure 2), patients with cardiac complications, CRP >71mg/L and age >43 years-old had 83.8% mortality rate, whereas those without cardiac or neurologic complications and CRP ≤51 had 7.1% in-hospital death. Among all predictors, cardiac complications showed the strongest association with the primary endpoint. Conclusions Cardiac and neurologic complications, elevated age and high CRP were independently associated with death. The machine-learning algorithm demonstrated that cardiac complications were the most important risk factor for in-hospital death. Early identification of patients who are at high risk of death can offer opportunity for more aggressive monitoring and approach to improve IE outcome.Logistic regression modelDecision-tree analysis

Long-term effectiveness and safety of edoxaban in patients with atrial fibrillation: 4-year follow-up of more than 13,000 patients from the ETNA-AF-Europe study

Abstract Background Direct, non-vitamin K antagonist oral anticoagulants (DOACs/NOACs) have become the first-choice therapy for stroke prevention in patients with atrial fibrillation (AF) at risk of stroke. Data on long-term effectiveness and safety of NOACs are scarce and not available from randomised clinical trials. Purpose We analysed 4-year outcome data in 13,632 European patients with AF treated with the NOAC, edoxaban. Methods This is the first report of the four-year follow-up information collected in the ETNA-AF-Europe (NCT02944019) study. It is a prospective registry, conducted in 825 centres enrolling edoxaban-treated patients in 10 European countries. Design and follow-up were agreed with the European Medicines Agency as part of the post-approval safety assessment of edoxaban. Key efficacy and safety outcomes were adjudicated. Results 13,164 patients (56.7% males) with AF treated with edoxaban (60 mg OD n=9617; 30 mg OD n=3042; missing dose n=505) were analysed: median (interquartile range [IQR]) age was 75 (68–80) years, weight 80 (70–90) kg, creatinine clearance (CrCl) 68.9 (52.7–87.9) mL/min, modified CHA2DS2-VASc and HAS-BLED scores 3 (2–4) and 2 (1–2), respectively in the overall population. Annualised all-cause and cardiovascular deaths in the overall population were 4.1%/year and 1.0%/year, respectively; higher in the edoxaban 30 mg vs 60 mg cohort (Figure 1). Annualised rates of stroke, transient ischaemic attack and systemic embolic events rates were <1% (0.6%/year, 0.3%/year and 0.1%/year, respectively); these proportions were similar between the two dose cohorts (Figure 1). The time-to-first event curves for all-cause death, stroke and major bleeding were almost linear throughout the 4-year follow-up (Figure 2), irrespective of dose cohort. Compared with patients receiving edoxaban 60 mg, those prescribed 30 mg were older (median [IQR] age: 80 [75–85] vs 73 [66–78] years), had greater frail proportion (27.0% vs 6.6%), a lower CrCl (46.1 [37.4–59.0] vs 75.9 [61.9–93.8] mL/min) and a higher CHA2DS2-VASc score (4 [3–5] vs 3 [2–4]). Annualised bleeding rate was 3.0%/year and higher in the 30 mg vs 60 mg cohort (Figure 1). Annualised major bleeding, intracranial haemorrhage (ICH) and major gastrointestinal (GI) bleeding rates were low (0.9%/year, 0.2%/year and 0.4%/year, respectively), with higher major bleeding and major GI bleeding rates in patients treated with edoxaban 30 mg OD (Figure 1). ICH rates were similar in both dose cohorts. Conclusion These findings illustrate the long-term effectiveness and safety of edoxaban. Treatment with edoxaban over 4 years in patients with AF is associated with a relatively low, linearly increasing rate of all-cause death and ischaemic stroke. Rates of bleeding and especially ICH rates were low.

Edge-to-edge repaire and the incidence of silent cerebral embolic events

Abstract Background Silent cerebral hits are present in the majority of patients (75-80%) undergoing TAVI. However, there is a lack of data on the rate of silent cerebral infarcts after percutaneous "edge-to-edge" procedure. Purpose To assess clinically overt stroke and silent cerebral embolic lesions detected by diffusion-weighted magnetic resonance imaging (DW-MRI) in patients after MitraClip implantation. Methods and results 85 patients underwent MitraClip implantation at our institution within a period of May 2016 – January 2023. Of these, 53 patients (62%) underwent DW-MRI pre (<24 hours) and post (24-48 hours) "edge-to-edge" procedure. No patients showed a significant decline in post-neurocognitive function (as assessed by the Montreal Cognitive Assessment [MoCA] score) compared with baseline. DW-MRI detected silent cerebral lesion in 11 patients (21%; 6 unilateral and 5 bilateral) after MitraClip implantation. Conclusions The rate of silent (assessed by DW-MRI) cerebral embolic events after MitraClip implantation was very low in our observational study (the largest study worldwide so far). Larger randomized trials including neuroimaging are needed to define the occurrence and consequences of cerebral damage during transcatheter treatment of mitral regurgitation. Future research is also needed to investigate the role of cerebrovasczlar protection devices during this procedure.

Role of thoracoabdominal imaging on diagnosis and management in patients with suspected infective endocarditis

Abstract Background/Introduction Embolic events (EEs) are a common complication of infective endocarditis (IE) and their presence can impact diagnosis and modify the therapeutic plan. Purpose The present study aimed to describe the role of thoracoabdominal imaging (TA-Im) on diagnosis and management of patients with suspected IE. Methods This study was conducted at a university hospital, from January 2014 to June 2022. EEs and IE were defined according to modified Duke criteria. Results Among 966 episodes with IE suspicion and TA-Im, 740 (77%) contrast-enhanced CT, 158 (16%) 18F-FDG PET/CT and 68 (7%) non-contrast-enhanced CT. The majority of patients (528; 55%) were without thoracoabdominal symptoms. At least one EE was found in 205 (21%) episodes. Based on TA-Im findings, the diagnosis was reclassified from rejected to possible or from possible to definite IE in 6 (1%) and 10 (1%) episodes, respectively [2 (0.5%) and 5 (1%) in asymptomatic episodes, respectively]. Table shows the type of embolic events and their impact on diagnosis in episodes with suspected IE. Among the 413 patients with possible or definite IE, at least one EE was found on TA-Im in 143 (35%) episodes. Together with the presence of left-side valvular vegetation >10mm, the results of TA-Im established a surgical indication (prevention of embolism) in 15 (4%) episodes, 7 of which were asymptomatic. Among the subgroup of episodes (n=127) with left-side vegetation >10mm, TA-Im established a surgical indication in 12% of episodes (15 patients), 10% among asymptomatic episodes (7 out of 73). Figure shows the changes in diagnostic classification and management due to TA-Im results in patients suspected (A) and those with IE (B). Conclusion TA-Im performed in asymptomatic patients with IE suspicion improved the diagnosis of IE in only a small proportion of patients; this proportion was similarly low in symptomatic patients. The role of systematic TA-Im in the clinical management of asymptomatic IE patients remains unclear, since it identified a new indication for valvular surgery in only a small proportion of patients. The scenario, where the benefit of TA-Im on management is a patient with a vegetation >10mm; in those patients, systematic TA-Im may lead to a new surgical indication in 10% of cases.Embolic eventsDiagnosis and mangement

Abstract 15998: Impact of Atrial Fibrillation Detected by Cardiac Implantable Electronic Devices on Embolic Stroke Events in Cancer Patients

Background: Cancer patients have a higher risk of atrial fibrillation (AF) than general population, however, the link between cancer and AF is not fully understood. The association between AF detected by implanted cardiac implantable electronic devices (CIEDs) and the incidence of embolic stroke events has been reported. However, little is known about the incidence of AF and embolic stroke events in Japanese cancer patients with CIEDs. Moreover, the cut-off value of new-onset AF duration detected by CIEDs for embolic stroke is still unknown, and a problem to be solved in the future. The aim of this study is to identify the incidence of embolic stroke in Japanese cancer patients with a CIED and to examine the risk factors of embolic stroke. Methods: We retrospectively analyzed the database of our CIEDs clinic. Every 6 months, AF events were checked by CIEDs. Patients who had a history of AF or had received anticoagulant therapies before a CIED implantation and who are prescribed anticoagulants after a CIED implantation were excluded. We examined the characteristics and incidence of embolic stroke events and investigated the relationship between new-onset AF detected by CIEDs and the incidence of embolic stroke. Results: We enrolled 138 consecutive cancer patients with CIEDs who had no prior AF and took no anticoagulant in this study (follow-up period, 76±48 months; age, 73±16 years). During the follow-up period, 13 patients (9.4%) had embolic stroke events. Receiver-operating characteristic curve analysis confirmed that 20 seconds was the best cut-off value of AF duration detected by CIEDs for embolic stroke events (AUC = 0.75). Multivariate analysis demonstrated that independent predictors for embolic stroke were left atrial diameter ≥ 40mm (P=0.018) and new-onset AF ≥ 20 seconds (P = 0.0082). Conclusions: AF episodes lasting for ≥ 20 seconds and enlarged left atrium were the risk factors of embolic stroke events. We consider examining AF burden carefully in this population.

Abstract 12823: As Anticoagulation Use Increases, Embolic Events Downtrend in Atrial Fibrillation Hospitalizations

Background: Direct oral anticoagulants and Left atrial appendage closure (LAAC) were approved for use in 2010 and 2015, respectively. Data on temporal changes in stroke prevention strategies and rates of embolic complications in atrial fibrillation (AF) in the 2010s decade are limited. Aims: Describe trends in long-term anticoagulation (AC), LAAC use, and in-hospital AF associated ischemic stroke (IS), transient ischemic attacks (TIA), and systemic embolic events (SEE) between 2010 and 2019. Methods: The national inpatient database was used to identify patients with AF from 2010 to 2019. Data were divided into 2 eras: 2010-2014 and 2015-2019. Results: A total of 40,787,136 inpatients with AF were identified: prevalence increased from 18,594,372 in 2010 to 2014 (46%; mean [SD] age 75.5 [12.0] years; 50.3% male) to 22,192,764 in 2015 to 2019 (54%; mean [SD] age 75.1 [11.8] years; 52.5% male). There was a marked increase in long-term AC use (27.2% to 40.2%; P=0.001) and rates of percutaneous LAAC procedures (0.01% to 0.6%; P <0.001) from 2015 to 2019. IS rates among patients with AF increased from 2010 to 2014 (3.5% to 3.8%; P=0.04), with no significant temporal change from 2015 to 2019 (P=0.84). TIA rates declined from 2010 to 2014 (1.2% to 1.0%; P=0.017) and continued a downtrend from 2015 to 2019 (0.9% to 0.7%; P=0.002). There was no temporal change in SEE or the composite outcome of all embolic events from 2010 to 2014, followed by a decline from 2015 to 2019 in SEE (0.5% to 0.4%; P 0.012) and all embolic events (5.1% to 4.8%; P 0.026) ( Figure 1 ). Mean rates of major bleeding events increased from 5.7% in 2010-2014 to 9.1% in 2015-2019 (P <0.001). Conclusion: In an inpatient AF population, the composite outcome of all embolic events and specifically SEE downtrend from 2015 to 2019, likely due to increased AC use. Further data assessing the risk-benefit ratio of available therapies for stroke prevention in inpatients with AF - AC and LAAC - are needed to optimize personalized strategies.