Impact of gender in patients with device-related thrombosis after left atrial appendage closure - A sub-analysis from the multicenter EUROC-DRT-registry.

BACKGROUND: Device-related thrombosis (DRT) is a common finding after left atrial appendage closure (LAAC) and is associated with worse outcomes. As women are underrepresented in clinical studies, further understanding of sex differences in DRT patients is warranted. METHODS AND RESULTS: This sub-analysis from the EUROC-DRT-registry compromises 176 patients with diagnosis of DRT after LAAC. Women, who accounted for 34.7% (61/176) of patients, were older (78.0 ± 6.7 vs. 74.9 ± 9.1 years, p = .06) with lower rates of comorbidities. While DRT was detected significantly later in women (173 ± 267 vs. 127 ± 192 days, p = .01), anticoagulation therapy was escalated similarly, mainly with initiation of novel oral anticoagulant (NOAC), vitamin K antagonist (VKA) or heparin. DRT resolution was achieved in 67.5% (27/40) of women and in 75.0% (54/72) of men (p = .40). In the remaining cases, an intensification/switch of anticoagulation was conducted in 50.% (9/18) of men and in 41.7% (5/12) of women. Final resolution was achieved in 72.5% (29/40) cases in women, and in 81.9% (59/72) cases in men (p = .24). Women were followed-up for a similar time as men (779 ± 520 vs. 908 ± 687 days, p = .51). Kaplan-Meier analysis revealed no difference in mortality rates in women (Hazard Ratio [HR]: 1.73, 95%-Confidence interval [95%-CI]: .68-4.37, p = .25) and no differences in stroke (HR: .83, 95%-CI: .30-2.32, p = .72) within 2 years after LAAC. CONCLUSION: Evaluation of risk factors and outcome revealed no differences between men and women, with DRT in women being diagnosed significantly later. Women should be monitored closely to assess for DRT formation/resolution. Treatment strategies appear to be equally effective.

Comparative data on left atrial appendage occlusion efficacy and clinical outcomes by age group in the Amplatzer™ Amulet™ Occluder Observational Study.

AIMS: Left atrial appendage occlusion (LAAO) may be considered for patients with non-valvular atrial fibrillation (NVAF) and a relative/formal contraindication to anticoagulation. This study aimed to summarize the impact of aging on LAAO outcomes at short and long-term follow-up. METHODS AND RESULTS: We compared subjects aged <70, ≥70 and <80, and ≥80 years old in the prospective, multicentre Amplatzer™ Amulet™ Occluder Observational Study (Abbott, Plymouth, MN, USA). Serious adverse events (SAEs) were reported from implant through a 2-year post-LAAO visit and adjudicated by an independent clinical events committee. Overall, 1088 subjects were prospectively enrolled. There were 265 subjects (24.4%) <70 years old, 491 subjects (45.1%) ≥70 and <80 years old, and 332 subjects (30.5%) ≥80 years old, with the majority (≥80%) being contraindicated to anticoagulation. As expected, CHA2DS2-VASc and HAS-BLED Scores increased with age. Implant success was high (≥98.5%) across all groups, and the proportion of subjects with a procedure- or device-related SAE was similar between groups. At follow-up, the observed ischaemic stroke rate was not significantly different between groups, and corresponding risk reductions were 62, 56, and 85% when compared with predicted rates for subjects <70, ≥70 and <80, and ≥80 years old, respectively. Major bleeding and mortality rates increased with age, while the incidence of device-related thrombus tended to increase with age. CONCLUSIONS: Despite the increased risk for ischaemic stroke with increasing age in AF patients, LAAO reduced the risk for ischaemic stroke compared with the predicted rate across all age groups without differences in procedural SAEs.

Symptomatic vs. non-symptomatic device-related thrombus after LAAC: a sub-analysis from the multicenter EUROC-DRT registry.

BACKGROUND: Device-related thrombus (DRT) after left atrial appendage closure (LAAC) is associated with adverse outcomes, i.e. ischemic stroke or systemic embolism (SE). Data on predictors of stroke/SE in the context of DRT are limited. AIMS: This study aimed to identify predisposing factors for stroke/SE in DRT patients. In addition, the temporal connection of stroke/SE to DRT diagnosis was analyzed. METHODS: The EUROC-DRT registry included 176 patients, in whom DRT after LAAC were diagnosed. Patients with symptomatic DRT, defined as stroke/SE in the context of DRT diagnosis, were compared against patients with non-symptomatic DRT. Baseline characteristics, anti-thrombotic regimens, device position, and timing of stroke/SE were compared. RESULTS: Stroke/SE occurred in 25/176 (14.2%) patients diagnosed with DRT (symptomatic DRT). Stroke/SE occurred after a median of 198 days (IQR 37-558) after LAAC. In 45.8% stroke/SE occurred within one month before/after DRT diagnosis (DRT-related stroke). Patients with symptomatic DRT had lower left ventricular ejection fractions (50.0 ± 9.1% vs. 54.2 ± 11.0%, p = 0.03) and higher rates of non-paroxysmal atrial fibrillation (84.0% vs. 64.9%, p = 0.06). Other baseline parameters and device positions were not different. Most ischemic events occurred among patients with single antiplatelet therapy (50%), however, stroke/SE was also observed under dual antiplatelet therapy (25%) or oral anticoagulation (20%). CONCLUSION: Stroke/SE are documented in 14.2% and occur both in close temporal relation to the DRT finding and chronologically independently therefrom. Identification of risk factors remains cumbersome, putting all DRT patients at substantial risk for stroke/SE. Further studies are necessary to minimize the risk of DRT and ischemic events.

Clinical and echocardiographic risk factors for device-related thrombus after left atrial appendage closure: an analysis from the multicenter EUROC-DRT registry.

BACKGROUND: Data on Device-related Thrombus (DRT) after left atrial appendage closure (LAAC) remain scarce. This study aimed to investigate risk factors for DRT from centers reporting to the EUROC-DRT registry. METHODS: We included 537 patients (112 with DRT and 425 without DRT) who had undergone LAAC between 12/2008 and 04/2019. Baseline and implantation characteristics, anti-thrombotic treatment and clinical outcomes were compared between both groups in uni- and multivariate analyses. Additional propensity-score matching (PSM) was conducted to focus on the role of implantation characteristics. RESULTS: Patients with DRT showed higher rates of previous stroke/transient ischemic attack (TIA) (49.1% vs. 34.7%, p < 0.01), spontaneous echocardiographic contrast (SEC) (44.9% vs. 27.7%, p < 0.01) and lower left atrial appendage (LAA) peak emptying velocity (35.4 ± 18.5 vs. 42.4 ± 18.0 cm/s, p = 0.02). Occluders implanted in DRT patients were larger (25.5 ± 3.8 vs. 24.6 ± 3.5 mm, p = 0.03) and implanted deeper in the LAA (mean depth: 7.6 ± 4.7 vs. 5.7 ± 4.7 mm, p < 0.01). Coverage of the appendage ostium was achieved less often in DRT patients (69.5% vs. 81.5%, p < 0.01), while DRT patients were less frequently on oral anticoagulation (7.1% vs. 16.7%, p < 0.01). Multivariate analysis identified age, prior stroke/TIA and SEC as independent risk factors for DRT. After PSM, implantation depth was found to be predictive. Rates of stroke/TIA were higher in DRT patients (13.5% vs. 3.8%, Hazard Ratio: 4.21 [95%-confidence interval: 1.88-9.49], p < 0.01). CONCLUSIONS: DRT after LAAC is associated with adverse outcome and appears to be of multifactorial origin, depending on patient characteristics, anticoagulation regimen and device position.

Perioperative bridging of chronic oral anticoagulation in patients undergoing pacemaker implantation--a study in 200 patients.

OBJECTIVE: To assess the risk of bleeding and thromboembolism (TE) of bridging therapy with low molecular weight heparin (LMWH) in patients undergoing pacemaker implantation. BACKGROUND: Current guidelines on peri-procedural management of patients with chronic oral anticoagulation (OAC) give no explicit recommendations on how to treat patients undergoing pacemaker implantations. METHODS AND RESULTS Since 2000 all patients with chronic OAC undergoing pacemaker implantation were prospectively enrolled and treated following a pre- specified bridging regimen with enoxaparin using reduced LMWH doses in patients at non high TE risk and renal impairment. Patients were followed up for 30 days regarding bleeding complications, incidence of thromboembolism, length of therapy and adverse events following bridging therapy. 200 patients (age 78.4 ± 8.3 years; 60.5% male) were enrolled and treated with enoxaparin for a mean of 7.3 ± 4.2 days. 109 patients (54.4%) were assigned to high TE risk and 91 (45.6%) to non high TE risk. Renal insufficiency (CrCl of <50 ml/min) was present in 92 patients (46%). After risk stratification 72.5% of patients (n = 145) were treated with reduced LMWH doses. Outpatient treatment was feasible in 39 patients (19.5%). Nine bleeding complications were observed (4.5%; 95% confidence interval [CI] 2.1-8.4%), including one major bleed (0.5%; 95% CI 0.01%-2.75%) and eight minor bleeds (4%; 95% CI 1.74%-7.73%). No thromboembolic complications evolved due to bridging therapy (0%; 95% CI 0.0-1.49%). After multivariate regression analysis independent predictors for bleedings were the development of thrombozytopenia (hazard ratio [HR] 6.0, 95% CI 0.3-139.8; P = 0.002), the prevalence of congestive heart failure (HR 4.5, 95% CI 0.9-22.2; P = 0.01), high TE risk (HR 6.9, 95% CI 1.9-25.6; P = 0.03) and an increasing CHADS2 score (HR 2.3, 95% CI 1.0-5.4; P = 0.05). CONCLUSION: Oral anticoagulation can be safely interrupted before pacemaker implantation under overlapping therapy with enoxaparin. Reducing heparin doses in patients with low thromboembolic risk and renal insufficiency led to a low incidence of major bleeding without increasing thromboembolic events.

Device-Related Thrombus After Left Atrial Appendage Closure: Data on Thrombus Characteristics, Treatment Strategies, and Clinical Outcomes From the EUROC-DRT-Registry.

BACKGROUND: Left atrial appendage closure is an established therapy in patients with atrial fibrillation. Although device-related thrombosis (DRT) is relatively rare, it is potentially linked to adverse events. As data on DRT characteristics, outcome, and treatment regimen are scarce, we aimed to assess these questions in a multicenter approach. METHODS: One hundred fifty-six patients with the diagnosis of DRT after left atrial appendage closure were included in the multinational EUROC-DRT registry. Baseline characteristics included clinical and echocardiographic data. After inclusion, all patients underwent further clinical and echocardiographic follow-up to assess DRT dynamics, treatment success, and outcome. RESULTS: DRT was detected after a median of 93 days (interquartile range, 54­161 days) with 17.9% being detected >6 months after left atrial appendage closure. Patients with DRT were at high ischemic and bleeding risk (CHA2DS2-VASc 4.5±1.7, HAS-BLED 3.3±1.2) and had nonparoxysmal atrial fibrillation (67.3%), previous stroke (53.8%), and spontaneous echo contrast (50.6%). The initial treatment regimens showed comparable resolution rates (antiplatelet monotherapy: 57.1%, dual antiplatelet therapy: 85.7%, vitamin K antagonists: 80.0%, novel oral anticoagulants: 75.0%, and heparin: 68.6%). After intensification or switch of treatment, complete DRT resolution was achieved in 79.5% of patients. Two-year follow-up revealed a high risk of mortality (20.0%) and ischemic stroke (13.8%) in patients with DRT. Patients with incomplete DRT resolution showed numerically higher stroke rates and increased mortality rates (stroke: 17.6% versus 12.3%, P=0.29; mortality: 31.3% versus 13.1%, P=0.05). CONCLUSIONS: A substantial proportion of DRT is detected >6 months after left atrial appendage closure, highlighting the need for imaging follow-up. Patients with DRT appear to be at a high risk for stroke and mortality. While DRT resolution was achieved in most patients, incomplete DRT resolution appeared to identify patients at even higher risk. Optimal DRT diagnostic criteria and treatment regimens are warranted.

The Impact of CHA2DS2-VASc and HAS-BLED Scores on Clinical Outcomes in the Amplatzer Amulet Study.

OBJECTIVES: The aim of this study was to evaluate the impact of CHA2DS2-VASc and HAS-BLED scores on ischemic and bleeding events of patients enrolled in the Amplatzer Amulet Observational Study. BACKGROUND: Baseline CHA2DS2-VASc and HAS-BLED scores have been validated in atrial fibrillation patients to guide about anticoagulation but not in patients treated by left atrial appendage occlusion (LAAO). METHODS: Subjects were stratified according to CHA2DS2-VASc and HAS-BLED scores. Clinical outcomes were collected through 2 years and adjudicated by an independent committee. RESULTS: Subjects were considered at low (n = 156), moderate (n = 715), and high (n = 215) risk for ischemic stroke, corresponding to CHA2DS2-VASc scores of <3, 3 to 5, and ≥6, respectively. The annual rates of ischemic stroke were 1.1%, 2.0%, and 3.5%, respectively. When compared with the predicted rate, LAAO reduced the risk of ischemic stroke by 56%, 69%, and 68%. Device-related thrombus occurred in 0.7%, 1.5%, and 3.0% of subjects at low, moderate, and high risk for ischemic stroke, respectively. The HAS-BLED score was ≤3 in 629 subjects and >3 in 456 subjects, respectively. Non-peri-procedural major bleeding was reduced by 11% and 9% compared with predicted rates in the low and high bleeding risk groups, respectively. CONCLUSIONS: LAAO with the Amplatzer Amulet reduced the risk of ischemic stroke compared with the predicted rate, with a greater magnitude among patients at high thromboembolic risk without increasing the bleeding risk. (Amplatzer™Amulet™ Post-Market Study [Amulet™PMS]; NCT02447081).

Left atrial appendage occlusion for stroke despite oral anticoagulation (resistant stroke). Results from the Amplatzer Cardiac Plug registry.

INTRODUCTION AND OBJECTIVES: Despite the efficacy of oral anticoagulant (OAC) therapy, some patients continue to have a high residual risk and develop a stroke on OAC therapy (resistant stroke [RS]), and there is a lack of evidence on the management of these patients. The aim of this study was to analyze the safety and efficacy of left atrial appendage occlusion (LAAO) as secondary prevention in patients with nonvalvular atrial fibrillation who have experienced a stroke/transient ischemic attack despite OAC treatment. METHODS: We analyzed data from the Amplatzer Cardiac Plug multicenter registry on 1047 consecutive patients with nonvalvular atrial fibrillation undergoing LAAO. Patientes with previous stroke on OAC therapy as indication for LAAO were identified and compared with patients with other indications. RESULTS: A total of 115 patients (11%) with RS were identified. The CHA2DS2-VASc and the HAS-BLED score were significantly higher in the RS group (respectively 5.5±1.5 vs 4.3±1.6; P <.001; 3.9±1.3 vs 3.1±1.2; P <.001). No significant differences were observed in periprocedural major safety events (7.8 vs 4.5%; P=.1). With a mean clinical follow-up of 16.2±12.2 months, the observed annual stroke/transient ischemic attack rate for the RS group was 2.6% (65% risk reduction) and the observed annual major bleeding rate was 0% (100% risk reduction). CONCLUSIONS: Patients with RS undergoing LAAO showed similar safety outcomes to patients without RS, with a significant reduction in stroke/transient ischemic attack and major bleeding events during follow-up. Adequately powered controlled trials are needed to further investigate the use of LAAO in RS patients.

Bridging of oral anticoagulation with low-molecular-weight heparin: experience in 373 patients with renal insufficiency undergoing invasive procedures.

If surgery or another intervention is planned, current guidelines recommend bridging oral anticoagulation (OAC) with heparins in patients at elevated thromboembolic (TE) risk. While patients with renal impairment have a higher risk of bleeding and dosing of heparins is more difficult, there are no specific recommendations for bridging the latter patients. Hence, we aimed to investigate the efficacy and tolerability of using reduced low-molecular-weight heparin (enoxaparin) dosages for bridging of OAC. Three hundred twenty-two hospitalised and 51 ambulatory adult patients at moderate to high TE risk were enrolled. Patients with renal insufficiency (n=274 with creatinine clearance [CrCl] 30-50 ml/min and n=99 with CrCl 20-29 ml/min) received after discontinuation of OAC therapy enoxaparin 1mg/ kg once daily. Surgery was performed at international normalised ratio (INR) <1.5. Mean time between the last enoxaparin dose and procedure was 26.8 +/- 2.7 hours. Within 30 days of individual follow-up, no case of TE was observed (0 %; 95 % confidence interval [CI] 0- 0.9). A total of 30 bleeding events (8.0 %; CI 5.5-11.3) occurred (3 major [0.8 %; CI 0.2-2.3] and 27 minor [7.2 %; CI 4.8-10.4]). Bleeding events occurred in 6.5% (CI 3.9-10.2) of patients with CrCl 30-50 ml/min and in 12.1% (CI 6.4-20.2) of patients with CrCl 20-29 ml/min (p between groups =0.08). Logistic regression analysis identified the CHADS(2) score as the only independent haemorrhagic risk factor (p= 0.03). No heparin-induced thrombocytopenia (HIT-II) was reported. Bridging therapy could be performed in 51 (13.7%) ambulatory patients. In renally impaired patients undergoing bridging of OAC, the use of a priori reduced dosage of enoxaparin was not compromised by any TE events. It appeared well tolerated as the rate of major bleeds was low.

How useful is determination of anti-factor Xa activity to guide bridging therapy with enoxaparin? A pilot study.

Low-molecular-weight heparins (LMWH) are commonly used as peri-procedural bridging anticoagulants. The usefulness of measurement of anti-factor Xa activity (anti-Xa) to guide bridging therapy with LMWH is unknown. It was the objective of this study to determine levels of anti-Xa during standard bridging therapy with enoxaparin, and to examine predictors for residual anti-Xa. Consecutive patients receiving enoxaparin at a dosage of 1 mg/kg body weight/12 hours for temporary interruption of phenprocoumon were prospectively enrolled to the study. Blood-samples were obtained 14 hours after LMWH-application immediately pre- procedurally. Procedural details, clinical and demographic data were collected and subsequently analyzed. Seventy patients were included (age 75.2 +/- 10.8 years, Cr Cl 55.7 +/- 21.7ml/min, body mass index [BMI] 27.1 +/- 4.9). LMWH- therapy was for a mean of 4.2 +/- 1.6 days; overall anti-Xa was 0.58 +/- 0.32 U/ml. In 37 (52.8%) of patients anti-Xa was > or U/ml, including 10 (14.3%) patients with anti-Xa > 1U/ml. Linear regression analysis of single variables and logistic multivariable regression analysis failed to prove a correlation between anti-Xa and single or combined factors. No major bleeding, no thromboembolism and four (5.7%) minor haemorrhages were observed. When bridging OAC with therapeutic doses of enoxaparin a high percentage of patients undergo interventions with high residual anti-Xa. The levels of anti-Xa vary largely and are independent of single or combined clinical variables. Since the anti-Xa-related outcome of patients receiving bridging therapy with LMWH is not investigated, no firm recommendation on the usefulness of monitoring of anti-Xa can be given at this stage.

Contrast-free, echocardiography-guided left atrial appendage occlusion (LAAo): a propensity-matched comparison with conventional LAAo using the AMPLATZER™ Amulet™ device.

AIMS: Percutaneous left atrial appendage occlusion (LAAo) is commonly performed under fluoroscopy including the use of contrast dye. In this study, we aimed to assess feasibility and safety of contrast-free, 3D-echo-based LAAo with the use of the AMPLATZER™ Amulet™ device. METHODS AND RESULTS: We analyzed 20 patients (74 ± 10 years, 65% males) at an increased thromboembolic and bleeding risk (CHA2DS2VASC 4.0 ± 1.3; HAS-BLED 3.5 ± 0.9) with chronic renal failure (GFR 41 ± 21 ml/min) undergoing LAAo without the use of contrast dye at our center and compared the results with a propensity-matched cohort (1:1 matching) of conventionally treated patients receiving contrast agent. Contrast-free LAAo was associated with less radiation exposure (13.1 ± 19.2 vs. 32.9 ± 21.2 Gy*cm2, p < 0.01) and fluoroscopy time (5.0 ± 3.4 vs. 11.6 ± 4.9 min, p < 0.01). Procedural success rates were excellent in both groups (100%) without severe periprocedural complications (i.e. procedural death, stroke/systemic embolism, myocardial infarction, cardiac tamponade or major bleeding). CONCLUSIONS: Echocardiographically guided LAAo without the use of contrast dye appears safe and feasible. This approach appears to be associated with reduced radiation exposure and may represent an alternative to traditional LAAo, especially in patients in whom the avoidance of contrast dye is warranted.

Incidence, Characterization, and Clinical Impact of Device-Related Thrombus Following Left Atrial Appendage Occlusion in the Prospective Global AMPLATZER Amulet Observational Study.

OBJECTIVES: This study sought to report the incidence, characteristics, and clinical impact of device-related thrombus (DRT) following left atrial appendage occlusion (LAAO) with the AMPLATZER Amulet device (Abbott, Plymouth, Minnesota). BACKGROUND: DRT is a potential serious complication of LAAO, but the incidence and clinical impact of DRTs in a real-world setting are not well characterized. METHODS: A total of 1,088 patients were enrolled in a multicenter prospective study and followed for 1 year. All events were adjudicated by an independent committee, including the presence of DRT. Patients with DRT were reviewed for suboptimal device implantation and characterization of DRT formation. Multiple Cox regression was performed to identify predictors of DRT formation. RESULTS: Device implantation was successful in 1,078 (99%) patients, with 1-year follow-up completed in 96.3% of patients. A total of 18 DRTs occurred in 17 patients (1.7%/year), as a second DRT developed following complete resolution of an initial DRT in 1 patient. The left upper pulmonary vein ridge was not covered by the Amulet disc in 82% of DRT patients, indicating suboptimal implantation, with most thrombus developing in the untrabeculated area of the LAA ostium between the pulmonary vein ridge and the upper edge of the disc. Three (18%) DRT patients had an ischemic stroke, all within 3 months of DRT diagnosis. Patients with a DRT were at a greater risk for ischemic stroke or transient ischemic attack compared with non-DRT patients (hazard ratio: 5.27; 95% confidence interval: 1.58 to 17.55; p = 0.007). Larger LAA orifice width was a predictor of DRT formation (hazard ratio: 1.09; 95% confidence interval: 1.00 to 1.19; p = 0.04). CONCLUSIONS: Following LAAO with the AMPLATZER Amulet device, DRT was observed infrequently. Although the presence of DRT was associated with an increased rate of ischemic stroke or transient ischemic attack as compared with patients without DRT, the large majority of DRT patients (82%) did not experience any ischemic neurologic events.

A History of Percutaneous Left Atrial Appendage Occlusion with the PLAATO Device.

Percutaneous left atrial appendage occlusion was introduced as an alternative method for prevention of thromboembolism in patients with nonvalvular atrial fibrillation after extensive animal work in 2001. The first device was named Percutaneous Left Atrial Appendage Transcatheter Occlusion (PLAATO) and patented by the company Appriva. The device was invented by Michael Lesh, MD.

Periprocedural bridging therapy with low-molecular-weight heparin in chronically anticoagulated patients with prosthetic mechanical heart valves: experience in 116 patients from the prospective BRAVE registry.

BACKGROUND AND AIM OF THE STUDY: The study aim was to determine the safety and feasibility of a standardized bridging regimen in patients with mechanical heart valves at high thromboembolic risk, using low-molecular-weight heparin (LMWH). METHODS: Since the year 2000, all patients at the authors' institution, with mechanical heart valves and a need for periprocedural interruption of oral anticoagulation (OAC), were prospectively enrolled in this registry. Patients were treated with enoxaparin following a pre-specified, standardized bridging regimen. The main outcome measures were the incidence of hemorrhagic or thromboembolic events. The follow up period was 30 days after hospital discharge. RESULTS: A total of 116 patients was included (31 with mitral valve replacement, 76 aortic valve replacement, nine double valve replacement). Patients underwent either major surgery (n = 25), minor surgery (n = 36), pacemaker implantation (n = 21), or coronary catheterization (n = 34). Bridging therapy with enoxaparin was administered for a mean of 7.0 +/- 4.6 days. Eighteen patients (15.5%) were treated as outpatients. In 35 patients (34%) with renal impairment (creatinine clearance <50 ml/min), LMWH dosage was halved. No thromboembolic (95% CI 0-3.1%) and only one major bleeding complication occurred (0.86%; 95% CI 0.02-4.7%); minor bleeding occurred in 10 patients (8.6%; 95% CI 4.2-15.3%). The hemorrhages arose after a mean of 5.4 +/- 1.4 days LMWH therapy. CONCLUSION: Bridging therapy following a standardized LMWH-based regimen with enoxaparin was effective and relatively safe in a large cohort of patients with mechanical heart valves. Extended duration of LMWH therapy seems to promote the incidence of hemorrhage. Neither dose reduction in patients with renal impairment nor outpatient treatment affected the safety and efficacy of this bridging regimen. These findings warrant that more extensive studies be conducted to investigate the safety of this approach.

[Perioperative Bridging with Enoxaparin. Results of the Prospective BRAVE Registry with 779 Patients]. / Perioperative überbrückende Antikoagulation mit Enoxaparin. Ergebnisse des prospektiven BRAVE-Registers mit 779 Patienten.

BACKGROUND AND PURPOSE: Oral anticoagulant (OAC) therapy should be temporarily interrupted for an elective procedure or surgery, and perioperative prophylaxis with heparins should be initiated in patients who face a high or moderate risk of thrombosis. To date, the optimal heparin dose has not been established. The authors investigated the efficacy and safety of a risk-adapted regimen with the low-molecular-weight heparin enoxaparin in two different, body weight-adapted regimens. PATIENTS AND METHODS: In the own institution, adult patients were consecutively documented in the prospective BRAVE registry, if they required bridging therapy. Patients with moderate thromboembolic risk (35.7%) received, after interruption of OAC and reaching an International Normalized Ratio (INR) of 1.5, enoxaparin 1 mg/kg body weight daily, those with high risk (64.3%) enoxaparin 1 mg/kg body weight twice daily (in case of compromised renal function half this dose, respectively). Events were recorded at 30 days post intervention by on-site examination of the patient or telephone follow-up. RESULTS: Of 779 patients, none had a thromboembolic event. Enoxaparin was well tolerated. A total of four major bleedings in three patients (0.5%, all in the high-risk group), 46 minor bleedings (5.9%), and twelve cases of thrombocytopenia (1.5%, however, no heparin-induced thrombocytopenia [HIT] II) were noted. CONCLUSION: The absence of thromboembolic events confirms the efficacy of enoxaparin in perioperative bridging. The rate of major bleedings was low and, of note, no cases of HIT II were noted. Reducing the dose to half the standard was shown to be effective and well tolerated in patients with moderate risk. Likewise, enoxaparin in a reduced dose can be safely used in patients with renal insufficiency who require bridging.

Comparison of the Feasibility and Safety of First- versus Second-Generation AMPLATZER™ Occluders for Left Atrial Appendage Closure.

INTRODUCTION: Left atrial appendage closure (LAAC) is considered an alternative to oral anticoagulation therapy in patients with atrial fibrillation (AF). The aim of this study was to compare the safety and efficacy of the first- and second-generation AMPLATZER Devices for LAAC, AMPLATZER Cardiac Plug (ACP) versus AMPLATZER Amulet™. METHODS: Procedural data, such as fluoroscopy time, radiation dose, and contrast-dye, as well as VARC criteria and major adverse events (MAEs) were assessed for both devices. The rate of peridevice leaks was analyzed at echocardiographic follow-up. RESULTS: A total of 196 patients with AF underwent LAAC with the ACP (n = 99) or Amulet device (n = 97). The use of Amulet was associated with significantly lower fluoroscopy time (14.8 ± 7.4 min versus 10.6 ± 4.1 min; p < 0.001), lower radiation dose (4833 ± 3360 cGy⁎cm2 versus 3206 ± 2169 cGy⁎cm2; p < 0.001), and reduced amount of contrast-dye (150.2 ± 83.9 ml versus 128.8 ± 46.0 ml; p = 0.03). Furthermore, LAAC with Amulet devices resulted in lower device-resizing rates (3 versus 16 cases; p = 0.001). Peridevice leaks were less frequent in the Amulet group (12 versus 4; p = 0.03). MAE occurred in 6 ACP and 4 Amulet patients (p = 0.58). CONCLUSIONS: The Amulet device is associated with shorter fluoroscopy times and radiation dosages, reduced use of contrast-dye, lower recapture rates, and less peridevice leaks as compared to the ACP.

A comparison of two-dimensional and real-time 3D transoesophageal echocardiography and angiography for assessing the left atrial appendage anatomy for sizing a left atrial appendage occlusion system: impact of volume loading.

AIMS: Correct sizing of a left atrial appendage (LAA) closure system is important to avoid redeployment of the device and peri-device leaks. The aims of this study were to assess the significance of two-dimensional transoesophageal echocardiography (2D-TEE), real-time 3D transoesophageal echocardiography (RT 3D-TEE) and angiography for measuring the size of the LAA landing zone and to determine the impact on sizing an LAA closure device. Furthermore, we investigated the relevance of volume loading on LAA size. METHODS AND RESULTS: In a prospective study, 46 patients underwent 2D-TEE and RT 3D-TEE 24 hours prior to LAA closure, at the beginning of the procedure and just before the procedure after volume loading with an average of 1,035±246 ml. Angiography was performed immediately before the implantation. Maximal diameter (2.2±0.4 versus 2.3±0.4 cm; p<0.01), perimeter (6.5±1.0 versus 6.8±1.0 cm, p<0.01) and area (3.2±1.0 versus 3.5±1.1 cm², p<0.01) of the LAA increased significantly after volume loading. The highest correlation (R) between measurements and LAA device size was found for RT 3D-TEE-derived perimeter (R=0.97) and area (R=0.96), whereas the maximal diameter (R=0.78) measured by 2D-TEE and angiography (R=0.76) correlated less closely. Sizing based on an RT 3D-TEE-measured perimeter resulted only in 4% of undersizing the implanted device. Peri-device leaks occurred in seven cases (15%) and were associated with a lower compression of LAA devices (7±1.3% versus 14±3.2% for patients without leaks, p<0.001). CONCLUSIONS: Volume loading before LAA closure increases LAA dimensions significantly. RT 3D-TEE measurements show a closer correlation to LAA closure device size than 2D-TEE or angiographic measurements.

Left atrial appendage occlusion with the AMPLATZER Amulet device: periprocedural and early clinical/echocardiographic data from a global prospective observational study.

AIMS: The global, prospective AMPLATZER Amulet observational study documents real-world periprocedural, transoesophageal echocardiographic (TEE) and clinical outcomes from left atrial appendage occlusion (LAAO) using the AMPLATZER Amulet device. The aim of this report is to describe the periprocedural and early clinical/TEE results from this study. METHODS AND RESULTS: This multicentre prospective real-world registry included 1,088 patients (75±8.5 years, 64.5% male, CHA2DS2-VASc: 4.2±1.6, HAS-BLED: 3.3±1.1) with non-valvular atrial fibrillation; 82.8% of patients were considered to have an absolute or relative contraindication to long-term anticoagulation and 72.4% had had a previous major bleeding. Periprocedural results, clinical outcomes up to the first three months and the available TEE results from the first scheduled follow-up (one to three months post implant) are reported. Successful device implantation was achieved in 99.0% of patients. During the procedure and index hospitalisation, major adverse events occurred in 3.2% of patients. Patients were discharged on a single antiplatelet agent (23.0%), dual antiplatelets (54.3%) or an oral anticoagulant (18.9%). TEE follow-up 67±23 days post procedure in 673 patients showed adequate (<3 mm jet) occlusion of the appendage in 98.2% of patients and device thrombus in 10 patients (1.5%), as evaluated by core laboratory analysis. CONCLUSIONS: This large real-world prospective registry of catheter-based LAAO using the AMPLATZER Amulet device reports a high implant success rate and a low periprocedural complication rate in a population with a high risk of stroke and bleeding. Transoesophageal echo data confirm good closure rates during follow-up and low rates of device-associated thrombus.

Incidence and Clinical Impact of Device-Associated Thrombus and Peri-Device Leak Following Left Atrial Appendage Closure With the Amplatzer Cardiac Plug.

OBJECTIVES: Routine device surveillance after successful left atrial appendage closure is recommended to evaluate for intermediate to late complications. The aim of this study was to assess the incidence and clinical impact of these complications on cardiovascular events. METHODS: Centers participating in the Amplatzer Cardiac Plug multicenter study were requested to submit their post-procedural transesophageal echocardiograms for independent adjudication. Thirteen of 22 centers contributed all their post-procedural echocardiograms, which included 344 from 605 consecutive patients. These images were submitted to a core laboratory and reviewed by 2 independent experts for peri-device leak, device-associated thrombus, device embolization, device migration, left atrial appendage thrombus, and left atrial thrombus. Clinical events were prospectively collected by each center. RESULTS: Of the 344 transesophageal echocardiograms, 339 were deemed analyzable. Patients' mean age was 74.4 ± 7.5 years, and 67.3% were men. The mean CHADS2 score was 2.7 ± 1.3, the mean CHA2DS2-VASc score was 4.3 ± 1.5, and the mean HAS-BLED score was 3.0 ± 1.2. Amplatzer Cardiac Plug implantation was successful in all patients. Periprocedural major adverse events occurred in 2.4%. Median clinical follow-up duration was 355 days (range 179 to 622 days). Follow-up transesophageal echocardiography was performed after a median of 134 days (range 88 to 227 days). Device-associated thrombus was observed in 3.2% and peri-device leak in 12.5% (5.5% minimal, 5.8% mild, 0.6% moderate, 0.6% severe). Neither device-associated thrombus nor peri-device leak was associated with an increased risk for cardiovascular events. Independent predictors of device-associated thrombus were smoking (odds ratio: 5.79; p = 0.017) and female sex (odds ratio: 4.22; p = 0.027). CONCLUSIONS: Following successful left atrial appendage closure with the Amplatzer Cardiac Plug, the presence of peri-device leak was relatively low, and device-associated thrombus was infrequent. Neither was associated with increased risk for thromboembolism.

Patients with intracranial bleeding and atrial fibrillation treated with left atrial appendage occlusion: Results from the Amplatzer Cardiac Plug registry.

BACKGROUND: In patients with non-valvular atrial fibrillation (NVAF), intracranial bleeding (ICB) constitutes a very challenging situation in which the rate of both ischemic and hemorrhagic events is increased. In these patients, left atrial appendage occlusion (LAAO) might represent a very valid alternative. OBJECTIVES: To investigate the procedural safety and long-term outcome of patients undergoing LAAO therapy due to previous ICB. METHODS: Data from the Amplatzer Cardiac Plug multicenter registry on 1047 consecutive patients were analyzed. Patients with previous ICB as indication for LAAO were compared to patients with other indications. RESULTS: A total of 198 patients (18.9%) with previous ICB were identified. The CHA2DS2-VASc score was similar (4.5±1.5 vs. 4.4±1.6, p=0.687) and the HAS-BLED score was higher in patients with previous ICB compared to those without (3.5±1.1 vs. 3.1±1.2, p<0.001). No significant differences in peri-procedural major adverse events were observed (2.5 vs 5.4%, p=0.1). Patients with previous ICB were more frequently on single acetylsalicylic acid therapy after LAAO (42.4% vs. 28.3%; p<0.001). With an average follow-up of 1.3years, the observed annual stroke/TIA rate (procedure and follow-up) for patients with previous ICB was 1.4% (75% relative risk reduction). The observed annual major bleeding rate (procedure and follow-up) for patients with previous ICB was 0.7% (89% relative risk reduction). CONCLUSIONS: In patients with NVAF and previous ICB, LAAO seemed to be a safe procedure and was associated with a significant reduction in stroke/TIA and a remarkably low frequency of major bleeding during follow-up.