Embolization of percutaneous left atrial appendage closure devices: timing, management and clinical outcomes.

BACKGROUND: Left atrial appendage (LAA) occluder embolization is an infrequent but serious complication. OBJECTIVES: We aim to describe timing, management and clinical outcomes of device embolization in a multi-center registry. METHODS: Patient characteristics, imaging findings and procedure and follow-up data were collected retrospectively. Device embolizations were categorized according to 1) timing 2) management and 3) clinical outcomes. RESULTS: Sixty-seven centers contributed data. Device embolization occurred in 108 patients. In 70.4 % of cases, it happened within the first 24 h of the procedure. The device was purposefully left in the LA and the aorta in two (1.9 %) patients, an initial percutaneous retrieval was attempted in 81 (75.0 %) and surgery without prior percutaneous retrieval attempt was performed in 23 (21.3 %) patients. Two patients died before a retrieval attempt could be made. In 28/81 (34.6 %) patients with an initial percutaneous retrieval attempt a second, additional attempt was performed, which was associated with a high mortality (death in patients with one attempt: 2.9 % vs. second attempt: 21.4 %, p < 0.001). The primary outcome (bailout surgery, cardiogenic shock, stroke, TIA, and/or death) occurred in 47 (43.5 %) patients. Other major complications related to device embolization occurred in 21 (19.4 %) patients. CONCLUSIONS: The majority of device embolizations after LAA closure occurs early. A percutaneous approach is often the preferred method for a first rescue attempt. Major adverse event rates, including death, are high particularly if the first retrieval attempt was unsuccessful. CONDENSED ABSTRACT: This dedicated multicenter registry examined timing, management, and clinical outcome of device embolization. Early embolization (70.4 %) was most frequent. As a first rescue attempt, percutaneous retrieval was preferred in 75.0 %, followed by surgical removal (21.3 %). In patients with a second retrieval attempt a higher mortality (death first attempt: 2.9 % vs. death second attempt: 24.1 %, p < 0.001) was observed. Mortality (10.2 %) and the major complication rate after device embolization were high.

Persistent and Recurrent Device-Related Thrombus After Left Atrial Appendage Closure: Incidence, Predictors, and Outcomes.

BACKGROUND: Scarce data exist on the evolution of device-related thrombus (DRT) after left atrial appendage closure (LAAC). OBJECTIVES: This study sought to assess the incidence, predictors, and clinical impact of persistent and recurrent DRT in LAAC recipients. METHODS: Data were obtained from an international multicenter registry including 237 patients diagnosed with DRT after LAAC. Of these, 214 patients with a subsequent imaging examination after the initial diagnosis of DRT were included. Unfavorable evolution of DRT was defined as either persisting or recurrent DRT. RESULTS: DRT resolved in 153 (71.5%) cases and persisted in 61 (28.5%) cases. Larger DRT size (OR per 1-mm increase: 1.08; 95% CI: 1.02-1.15; P = 0.009) and female (OR: 2.44; 95% CI: 1.12-5.26; P = 0.02) were independently associated with persistent DRT. After DRT resolution, 82 (53.6%) of 153 patients had repeated device imaging, with 14 (17.1%) cases diagnosed with recurrent DRT. Overall, 75 (35.0%) patients had unfavorable evolution of DRT, and the sole predictor was average thrombus size at initial diagnosis (OR per 1-mm increase: 1.09; 95% CI: 1.03-1.16; P = 0.003), with an optimal cutoff size of 7 mm (OR: 2.51; 95% CI: 1.39-4.52; P = 0.002). Unfavorable evolution of DRT was associated with a higher rate of thromboembolic events compared with resolved DRT (26.7% vs 15.1%; HR: 2.13; 95% CI: 1.15-3.94; P = 0.02). CONCLUSIONS: About one-third of DRT events had an unfavorable evolution (either persisting or recurring), with a larger initial thrombus size (particularly >7 mm) portending an increased risk. Unfavorable evolution of DRT was associated with a 2-fold higher risk of thromboembolic events compared with resolved DRT.

High-density mapping for ablation of atypical atrial flutters - procedural characteristics related to outcome.

BACKGROUND: High-density (HD) mapping is increasingly used to characterize arrhythmic substrate for ablation of atypical atrial flutters (AAFl). However, results on clinical outcomes and factors that are associated with arrhythmia recurrence are scarce. METHODS: Single-center, prospective, observational cohort study that enrolled patients with catheter ablation for AAFl using a HD mapping system and a grid-shaped mapping catheter. Procedural characteristics, rates of atrial flutter recurrence, and factors that were associated with atrial flutter recurrence were evaluated. RESULTS: Sixty-one patients with a total of 94 AAFl were included in the cohort. HD mapping was used to successfully identify the flutter circuit of 80/94 AAFl. The circuit was not identified for 14/94 AAFl in 11 patients. Critical isthmuses were identified and ablated in 29 patients (48%). Acute procedural success was achieved in 52 patients (85%), and 37 patients (61%) remained free from atrial flutter recurrence during a follow up of 1.3 [1.0-2.1] years. Atrial flutter recurrence was univariably associated with presence of a non-identified flutter circuit (HR:2.6 95% CI [1.1-6.3], p = .04) and critical isthmus-targeted ablation (HR:0.4 [0.15-0.90], p = .03). In multivariable regression analyses, critical isthmus ablation remained significant (HR:0.4 [0.16-0.97], p = .04), whereas presence of a non-identified flutter did not (HR:2.4 [0.96-5.8], p = .06). CONCLUSION: HD mapping was successfully used to identify the majority of AAFl circuits. Ablation resulted in freedom from atrial flutter recurrence in 61% of the cohort. Successful identification of all flutter circuits and critical isthmuses appears to be beneficial for long-term outcomes.

Left Atrial Appendage Occlusion Under Miniaturized Transesophageal Echocardiographic Guidance and Conscious Sedation: Multicenter European Experience.

BACKGROUND: Left atrial appendage occlusion (LAAO) procedures are widely guided by standard transesophageal echocardiography (TEE) probes, requiring general anesthesia in most patients. The use of miniaturized TEE probes allows for LAAO guidance under local anesthesia and offers an attractive imaging alternative to standard TEE probes. OBJECTIVES: The aim of this study was to assess the safety and efficacy of miniaturized TEE probes for procedural guidance of LAAO. METHODS: Multicenter retrospective observational study of LAAO procedures performed under miniaturized TEE guidance and conscious sedation. The primary efficacy endpoint was technical success. The secondary efficacy endpoint was procedural success (technical success without major periprocedural complications). The safety outcome was a composite of major periprocedural complications. RESULTS: A total of 546 consecutive LAAO procedures were performed in 5 European centers. Technical success was achieved in 534 (98.0%) patients. Sixteen major periprocedural complications occurred in 15 (2.9%) patients, yielding a procedural success rate of 97.0%. Conversion to general anesthesia was required in 4 (0.7%) patients. Short-term imaging follow-up was available in 422 patients with an incidence of major (>5 mm) TEE-detected residual leaks of 0.7%, complete LAA occlusion of 82.2% on cardiac computed tomography, and device-related thrombus of 5%. As compared with procedural 2-dimensional imaging for device sizing, preprocedural assessment by 3-dimensional imaging resulted in improved technical success (100% vs 95.0%; P < 0.001). CONCLUSIONS: LAAO under conscious sedation and miniaturized TEE guidance is safe and feasible with a high rate of technical success and a low rate of periprocedural complications.

Long-term outcomes of successful left atrial appendage occlusion with focus on stroke prevention: 10-year follow-up of a single-center registry.

Background: Percutaneous left atrial appendage occlusion (LAAO) is an alternative to anticoagulation in the prevention of stroke in patients with nonvalvular atrial fibrillation, especially in patients with a contraindication for oral anticoagulation therapy (OAT). Objective: The study sought to obtain long-term patient outcomes after successful LAAO in everyday clinical practice. Methods: In this single-center registry spanning over 10 years, data of all consecutive patients that underwent percutaneous LAAO were collected. Observed thromboembolic and major bleeding event rates after successful LAAO during follow-up were compared with expected event rates based on CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age 65-74 years, sex category) and HAS-BLED (hypertension, abnormal renal or liver function, stroke, bleeding, labile international normalized ratio, elderly, drugs or alcohol) scores. Furthermore, anticoagulation and antiplatelet use during follow-up was evaluated. Results: Of 230 patients scheduled for LAAO (38% women, 69.5 ± 8.2 years of age, CHA2DS2-VASc score 3.9 ± 1.6, HAS-BLED score 2.9 ± 1.0), 218 patients had a successful implantation (95%) with a follow-up duration of 5.2 ± 3.1 years. The procedure was combined with catheter ablation in 52% of the patients. Fifty thromboembolic complications (24 ischemic stroke, 26 transient ischemic attack) were observed during follow-up in 40 (18%) of 218 patients. Ischemic strokes occurred with a rate of 2.1 per 100 patient-years, accounting for a 66% relative risk reduction compared with the CHA2DS2-VASc predicted event rate. Device-related thrombus was observed in 5 (2%) patients. Sixty-five nonprocedural major bleeding complications occurred in 24 (11%) of 218 patients with a rate of 5.7 per 100-patient years, which is comparable to estimated HAS-BLED-bleeding rates under OAT use. At end of follow-up 71% of all patients were on single antiplatelet or no antiplatelet or anticoagulation treatment, while 29% were on OAT. Conclusion: Thromboembolic event rates during long-term follow-up after successful LAAO remained consistently lower than expected supporting the efficacy of LAAO.

Hemostatic biomarkers and antithrombotic strategy in percutaneous left atrial interventions: State-of-the-art review.

Atrial septal defect, persistent foramen ovale and the left atrial appendage are nowadays often percutaneously closed with implantable devices. These interventions may be complicated by thromboembolic events and the perfect post-procedural antithrombotic management is still under investigation. The mechanisms leading to left atrial device-related thrombus and thromboembolic complications are not fully understood. Biomarkers of coagulation activation are elevated following percutaneous device placement, peaking within one month and returning to baseline values after three months. By contrast, platelet reactivity shows no post-procedural increase. This suggests that an optimal antithrombotic regimen should perhaps include (oral) anticoagulation therapy rather than the currently more frequently prescribed antiplatelet-based regimen. Furthermore, biomarkers of endothelial activation, fibrinolysis, and on-treatment platelet reactivity may be of value in predicting device-related thrombus and bleeding and guide future medical strategy, facilitating personalized medicine.

COMPARE LAAO: Rationale and design of the randomized controlled trial "COMPARing Effectiveness and safety of Left Atrial Appendage Occlusion to standard of care for atrial fibrillation patients at high stroke risk and ineligible to use oral anticoagulation therapy".

BACKGROUND: Left atrial appendage occlusion (LAAO) provides an alternative to oral anticoagulation (OAC) for stroke prevention in patients with atrial fibrillation (AF). In patients with a long-term or permanent contraindication for OAC randomized controlled trial (RCT) data is lacking. STUDY OBJECTIVES: To assess the efficacy and safety of LAAO in AF patients who are ineligible to use OAC. The co-primary efficacy endpoint is (1) time to first occurrence of stroke (ischemic, hemorrhagic, or undetermined) and (2) time to first occurrence of the composite of stroke, transient ischemic attack (TIA), and systemic embolism (SE). The primary safety endpoint is the 30-day rate of peri-procedural complications. STUDY DESIGN: This is a multicenter, investigator-initiated, open-label, blinded endpoint (PROBE), superiority-driven RCT. Patients with AF, a CHA2DS2-VASc score ≥2 for men and ≥3 for women and a long-term or permanent contraindication for OAC will be randomized in a 2:1 fashion to the device- or control arm. Patients in the device arm will undergo percutaneous LAAO and will receive post-procedural dual antiplatelet therapy (DAPT) per protocol, while those in the control arm will continue their current treatment consisting of no antithrombotic therapy or (D)APT as deemed appropriate by the primary responsible physician. In this endpoint-driven trial design, assuming a 50% lower stroke risk of LAAO compared to conservative treatment, 609 patients will be followed for a minimum of 1 and a maximum of 5 years. Cost-effectiveness and budget impact analyses will be performed to allow decision-making on reimbursement of LAAO for the target population in the Netherlands. SUMMARY: The COMPARE LAAO trial will investigate the clinical superiority in preventing thromboembolic events and cost-effectiveness of LAAO in AF patients with a high thromboembolic risk and a contraindication for OAC use. NCT TRIAL NUMBER: NCT04676880.

Predictors of Device-Related Thrombus Following Percutaneous Left Atrial Appendage Occlusion.

BACKGROUND: Device-related thrombus (DRT) has been considered an Achilles' heel of left atrial appendage occlusion (LAAO). However, data on DRT prediction remain limited. OBJECTIVES: This study constructed a DRT registry via a multicenter collaboration aimed to assess outcomes and predictors of DRT. METHODS: Thirty-seven international centers contributed LAAO cases with and without DRT (device-matched and temporally related to the DRT cases). This study described the management patterns and mid-term outcomes of DRT and assessed patient and procedural predictors of DRT. RESULTS: A total of 711 patients (237 with and 474 without DRT) were included. Follow-up duration was similar in the DRT and no-DRT groups, median 1.8 years (interquartile range: 0.9-3.0 years) versus 1.6 years (interquartile range: 1.0-2.9 years), respectively (P = 0.76). DRTs were detected between days 0 to 45, 45 to 180, 180 to 365, and >365 in 24.9%, 38.8%, 16.0%, and 20.3% of patients. DRT presence was associated with a higher risk of the composite endpoint of death, ischemic stroke, or systemic embolization (HR: 2.37; 95% CI, 1.58-3.56; P < 0.001) driven by ischemic stroke (HR: 3.49; 95% CI: 1.35-9.00; P = 0.01). At last known follow-up, 25.3% of patients had DRT. Discharge medications after LAAO did not have an impact on DRT. Multivariable analysis identified 5 DRT risk factors: hypercoagulability disorder (odds ratio [OR]: 17.50; 95% CI: 3.39-90.45), pericardial effusion (OR: 13.45; 95% CI: 1.46-123.52), renal insufficiency (OR: 4.02; 95% CI: 1.22-13.25), implantation depth >10 mm from the pulmonary vein limbus (OR: 2.41; 95% CI: 1.57-3.69), and non-paroxysmal atrial fibrillation (OR: 1.90; 95% CI: 1.22-2.97). Following conversion to risk factor points, patients with ≥2 risk points for DRT had a 2.1-fold increased risk of DRT compared with those without any risk factors. CONCLUSIONS: DRT after LAAO is associated with ischemic events. Patient- and procedure-specific factors are associated with the risk of DRT and may aid in risk stratification of patients referred for LAAO.

Efficacy and safety of the GOLD FORCE multicentre randomized clinical trial: multielectrode phased radiofrequency vs. irrigated radiofrequency single-tip catheter with contact force ablation for treatment of symptomatic paroxysmal atrial fibrillation.

AIMS: Pulmonary vein isolation (PVI) for atrial fibrillation (AF) has become increasingly safe and effective with the evolution of single-tip ablation catheters aided by contact force sensing (ST-CF) and single-shot devices such as the second-generation pulmonary vein ablation catheter (PVAC) Gold multi-electrode array. The multicentre randomized GOLD FORCE trial was conducted to evaluate non-inferiority of safety and efficacy of PVAC Gold PVI compared to ST-CF ablation for paroxysmal AF. METHODS AND RESULTS: The primary efficacy endpoint documented AF recurrence ≥30 s was assessed by time-to-first-event analysis after a 90-day blanking period using repeated 7-day Holters. Secondary endpoints include acute success and procedural characteristics. Safety endpoints included procedural complications, stroke/transient ischaemic attack (TIA), tamponade, bleeding, and access site complications. Two hundred and eight patients underwent randomization and PVI (103 assigned to PVAC Gold, 105 to ST-CF). Acute success rates were 95% and 97% for PVAC Gold and ST-CF, respectively. At 12 months, AF recurrence was observed in 46.6% of the PVAC Gold group and in 26.2% of the ST-CF group [absolute efficacy difference 20.4% (95% confidence interval, CI 7.5-33.2%), hazard ratio 2.05 (95% CI 1.28-3.29), P = 0.003]. PVAC Gold had significantly shorter procedure and ablation times. Complication rates were 5.7% and 4.9% for PVAC Gold and ST-CF, respectively (P = 0.782). CONCLUSION: In this multicentre randomized clinical trial, ablation with ST-CF and PVAC Gold ablation catheters non-inferiority for efficacy was not met. AF recurrence was significantly more frequent in the PVAC Gold group compared to single-tip contact force group. Both groups had similarly low rates of adverse events. PVAC Gold ablation had significantly shorter procedure and ablation times.

Impact of anticoagulation strategy after left atrial appendage occlusion in patients requiring direct current cardioversion.

INTRODUCTION: Current guidelines recommend adequate anticoagulation for at least 3 weeks pre- and 4 weeks post-direct current cardioversion (DCCV) to reduce thrombo-embolic risk in patients with atrial fibrillation (AF) lasting greater than 48 h. No specific recommendations exist for DCCV in patients that have undergone left atrial appendage occlusion (LAAO), many of whom are ineligible for anticoagulation. This study aims to observe the efficacy and safety of DCCV post-LAAO in everyday clinical practice. METHODS: This prospective multicenter registry included DCCVs in patients post-LAAO. Imaging strategy or anticoagulation treatment around DCCV were analyzed. Complications during 30-day follow-up were registered. DCCVs performed in accordance with current guidelines for the general AF population were compared to DCCVs performed deviating from these guidelines. RESULTS: In 93 patients (age 65 ± 17 years, CHA2 DS2 -VASC 3.0 ± 1.3) 284 DCCVs were performed between 2010 and 2018, in 271 sinus rhythm was restored. A wide variety of imaging or anticoagulation strategies around DCCV was observed; in 128 episodes strategies deviated from current guidelines. No thrombo-embolic events were observed after any DCCV during 30-day follow-up. In 34 DCCVs trans-esophageal echocardiography (TOE) was performed before DCCV to exclude cardiac thrombi and/or (re-)verify adequate device positioning. In two patients without post-LAAO imaging before DCCV, a device rotation or embolization was observed during scheduled TOE after LAAO. CONCLUSION: DCCV in AF patients after LAAO is highly effective. No thrombo-embolic events were observed in any patient in this observational cohort, regardless of the periprocedural anticoagulation or imaging strategy. Confirmation of adequate device positioning at least once before DCCV seems recommendable.

The WATCHMAN left atrial appendage closure device for patients with atrial fibrillation: current status and future perspectives.

INTRODUCTION: Atrial fibrillation (AF) is associated with an increased risk of stroke. Stroke prevention with oral anticoagulation (OAC) is recommended in AF patients at increased risk of stroke. The left atrial appendage (LAA) is the main source of thrombus formation in AF patients. The WATCHMAN percutaneous LAA closure (LAAC) device may serve as an alternative to OAC overcoming disadvantages including the risk of (major) bleeding. AREAS COVERED: This review will focus on LAAC with the Watchman device for stroke prevention in AF patients. Current status, available literature, clinical safety and efficacy will be summarized. Furthermore, the future perspectives of Watchman will be discussed. EXPERT OPINION: LAAC with Watchman appears a promising, safe, and effective alternative to OAC. Ongoing and future studies to consolidate the position of Watchman should focus on comparative safety and efficacy of different LAAC devices, patient selection, various post-procedural antithrombotic regimens, head-to-head comparisons with NOAC, better understanding of device-related thrombus, and the role of the LAA in the propagation of non-valvular AF. This research may attribute to a paradigm shift in which LAAC no longer serves as a 'last resort' treatment for AF patients ineligible for OAC but may serve as a second-line or even first-line treatment option for AF patients.

Postprocedural Management: Anticoagulation and Beyond.

Excluding the left atrial appendage in patients with nonvalvular atrial fibrillation is a mechanical way to decrease stroke risk. During endothelialization, the closure device is exposed to circulating blood, which might activate the coagulation cascade. In excessive proportions, possibly resulting in the development of device-related thrombus, requiring a bridging period with optimal antithrombotic treatment. Initial protocol treatment is less suitable for patients with contraindications to anticoagulation. Less intensive antithrombotic regimens investigated suggest safety and efficacy, however further research is required. A tailored treatment, considering bleeding and thromboembolic risk based on patient/procedural characteristics in every patient, is probably the best approach.

Prehospital Prasugrel Versus Ticagrelor in Real-World Patients With ST-Elevation Myocardial Infarction Referred for Primary PCI: Procedural and 30-Day Outcomes.

OBJECTIVES: Pretreatment with P2Y12 inhibitors before primary percutaneous coronary intervention (PPCI) can reduce the incidence of major adverse cardiovascular event (MACE) rate in ST-segment elevation myocardial infarction (STEMI) patients. We investigated differences in coronary reperfusion and clinical outcomes between prehospital administration of prasugrel vs ticagrelor in a historical cohort analysis. METHODS AND RESULTS: We conducted a retrospective analysis of prospectively collected data of 533 STEMI patients, directly referred by the ambulance for PPCI, and pretreated with either prasugrel (2013-2014) or ticagrelor (2015-2016). The primary outcome measurement was coronary and myocardial reperfusion prior to and after intervention. Secondary outcome measurements included MACE and stent thrombosis (ST) at 30 days. The median time from first medical contact to balloon was 82 minutes. There was no significant difference in preprocedural and postprocedural coronary reperfusion (TIMI flow grade 3) and postprocedural ST-segment elevation resolution between the prasugrel and ticagrelor groups. No significant differences in MACE and ST rates were found between the groups. No fatal or intracranial bleedings were reported up to 30-day follow-up. CONCLUSIONS: Prehospital administration of both prasugrel and ticagrelor in STEMI patients is safe, without differences in preprocedural and postprocedural reperfusion and short-term clinical outcomes.