Interventional Left Atrial Appendage Closure Research Articles

A comparison of conventional and advanced 3D imaging techniques for percutaneous left atrial appendage closure.

Understanding complex cardiac anatomy is essential for percutaneous left atrial appendage (LAA) closure. Conventional multi-slice computed tomography (MSCT) and transesophageal echocardiography (TEE) are now supported by advanced 3D printing and virtual reality (VR) techniques for three-dimensional visualization of volumetric data sets. This study aimed to investigate their added value for LAA closure procedures. Ten patients scheduled for interventional LAA closure were evaluated with MSCT and TEE. Patient-specific 3D printings and VR models were fabricated based on MSCT data. Ten cardiologists then comparatively assessed LAA anatomy and its procedure relevant surrounding structures with all four imaging modalities and rated their procedural utility on a 5-point Likert scale questionnaire (from 1 = strongly agree to 5 = strongly disagree). Device sizing was rated highest in MSCT (MSCT: 1.9 ± 0.8; TEE: 2.6 ± 0.9; 3D printing: 2.5 ± 1.0; VR: 2.5 ± 1.1; p < 0.01); TEE, VR, and 3D printing were superior in the visualization of the Fossa ovalis compared to MSCT (MSCT: 3.3 ± 1.4; TEE: 2.2 ± 1.3; 3D printing: 2.2 ± 1.4; VR: 1.9 ± 1.3; all p < 0.01). The major strength of VR and 3D printing techniques was a superior depth perception (VR: 1.6 ± 0.5; 3D printing: 1.8 ± 0.4; TEE: 2.9 ± 0.7; MSCT: 2.6 ± 0.8; p < 0.01). The visualization of extracardiac structures was rated less accurate in TEE than MSCT (TEE: 2.6 ± 0.9; MSCT: 1.9 ± 0.8, p < 0.01). However, 3D printing and VR insufficiently visualized extracardiac structures in the present study. A true 3D visualization in VR or 3D printing provides an additional value in the evaluation of the LAA for the planning of percutaneous closure. In particular, the superior perception of depth was seen as a strength of a 3D visualization. This may contribute to a better overall understanding of the anatomy. Clinical studies are needed to evaluate whether a more comprehensive understanding through advanced multimodal imaging of patient-specific anatomy using VR may translate into improved procedural outcomes.

Intracerebral hemorrhage under platelet inhibition and oral anticoagulation in patients with cerebral amyloid angiopathy

Die Durchführung einer oralen Antikoagulation ist bei Patienten mit einer zerebralen Amyloidangiopathie eine therapeutische Herausforderung. Die Assoziation der zerebralen Amyloidangiopathie mit Lobärblutungen, eine hohe Mortalität intrazerebraler Blutungen insbesondere unter oraler Antikoagulation sowie das hohe Rezidivrisiko solcher Blutungen erfordern eine strenge und interdisziplinäre Risiko-Nutzen-Abwägung. Vitamin-K-Antagonisten erhöhen das Risiko für die mit intrazerebralen Blutungen vergesellschaftete Mortalität um 60 % und sollten daher möglichst vermieden bzw. speziellen klinischen Situationen (z. B. mechanischer Aortenklappenersatz) vorbehalten sein. Auch der Einsatz von neuen oralen Antikoagulanzien und Thrombozytenaggregationshemmern bedarf einer strengen Risiko-Nutzen-Abwägung, da auch diese Substanzen das zerebrale Blutungsrisiko erhöhen. Insbesondere bei Patienten mit einer absoluten Arrhyhtmie bei Vorhofflimmern ist der interventionelle Vorhofohrverschluss eine therapeutische Alternative. Darüber hinaus sind weitere klinische Implikationen bei Patienten mit zerebraler Amyloidangiopathie Gegenstand dieser Literaturübersicht, beispielsweise Besonderheiten nach akutem ischämischem Schlaganfall und erforderlicher Sekundärprophylaxe, bei vorherigen intrazerebralen Blutungen und bei Patienten mit kognitiven Defiziten.

Impact of Left Atrial Appendage Closure on LAA Thrombus Formation and Thromboembolism After LAA Isolation.

This study sought to evaluate the safety and effectiveness of electrical isolation of the left atrial appendage (LAAEI) as well as the status of left atrial appendage closure (LAAC) in these patients. Catheter-based LAAEI is increasingly performed for treatment of symptomatic atrial fibrillation and pulmonary vein isolation nonresponders. Previous studies indicate an increased incidence of thromboembolic events after LAAEI despite effective oral anticoagulation. Interventional LAAC may prevent cardioembolic events after LAAEI but data regarding safety, feasibility, and efficacy of LAAC in this clinical setting are scarce. Consecutive patients who underwent LAAEI at 2 German tertiary care hospitals were analyzed. A total of 270 patients underwent LAAEI by radiofrequency ablation in 255 (94.4%), cryoballoon ablation in 12 (4.4%), and by a combination of both techniques in 3 cases (1.1%). Stroke or transient ischemic attack occurred in 24 of 244 (9.8%) individuals with available follow-up. LAA thrombus formation was found in 53 patients (19.6%). A total of 150 patients underwent LAAC after LAAEI. No LAA thrombus was documented in any patient who underwent LAAC. Of the patients who underwent LAAEI, 67.6% were in sinus rhythm after a mean of 682.7 ± 61.7days. LAA flow after LAAEI but not arrhythmia recurrence was identified as an independent predictor of stroke and/or transient ischemic attack or LAA thrombus (p<0.0001). Sinus rhythm was documented in about two-third of patients undergoing LAAEI as treatment of therapy refractory atrial arrhythmias. LAAC potentially prevents LAA thrombus formation and thromboembolism.

Comparison in Patients < 75 Years of Age - Versus – Those > 75 Years on One-year-Events With Atrial Fibrillation and Left Atrial Appendage Occluder (From the Prospective Multicenter German LAARGE Registry)

Left atrial appendage closure (LAAC) is an alternative to oral anticoagulation therapy in patients with non-valvular atrial fibrillation for the prevention of embolic stroke and systemic embolism. Although elderly patients (>75 years) have both higher ischemic and bleeding risk as compared with younger patients, they benefit from optimal anticoagulation. The subanalysis aimed to assess the indications, the safety, efficacy, and 1-year outcomes of interventional LAAC in elderly patients (≥ 75 years) compared with younger (< 75 years) patients in clinical practice. We analyzed data from the prospective Left-Atrium-Appendage Occluder Registry Germany. A total of 638 patients were included in the registry, 402 (63%) were aged ≥ 75 years. Compared with younger subjects, patients aged ≥75 were more likely to have higher CHA2DS2-VASC and HAS-BLED scores. Procedural success rate was high und similar in both groups (97.6%). Periprocedural adverse events were not statistically significant in groups (11.9% in <75 years vs 12.9% in ≥75 years; p = 0.80). At 1 year follow-up, all-cause mortality was higher in patients aged ≥75 compared withwith younger group (13.0% vs 7.8 %,p = 0.04), mainly due to non-cardiovascular causes (10.6% vs 6.0%). No significant differences in major bleeding, stroke, systemic embolism were observed. In conclusion, LAAC is feasible and safe in patients with AF at high stroke risk and with contraindications for OAC and should be considered as candidates for LAA closure. Elderly patients often present these characteristics and could benefit from this novel therapy.

Left atrial appendage closure in patients with chronic kidney disease: results from the German multicentre LAARGE registry

ObjectivesChronic kidney disease (CKD) is associated with an increased complication rate after cardiac interventions. Although CKD has a high prevalence among atrial fibrillation patients, the impact of CKD on periprocedural complications and the outcome after an interventional left atrial appendage closure (LAAC) is unclear. The present study, therefore, aimed to investigate whether CKD influences the procedure’s effectiveness and safety.MethodsLAARGE is a prospective, non-randomised registry. LAAC was conducted with different standard commercial devices, and the follow-up period was one year. CKD was defined by an eGFR < 60 mL/min/1.73 m2, and subgroups were further analysed (i.e. eGFR < 15, 15–29, and 30–59 mL/min/1.73 m2, respectively).ResultsTwo hundred ninety-nine of 623 patients (48.0%) revealed a CKD. The prevalence of cardiovascular comorbidity, CHA2DS2-VASc score (4.9 vs. 4.2), and HAS-BLED score (4.3 vs. 3.5) was significantly higher in CKD patients (each p < 0.001). Implantation success was similarly high across all GFR groups (97.9%). Periprocedural MACCE (0.7 vs. 0.3%), and other major complications (4.7 vs. 3.7%) were comparably infrequent. Survival free of stroke was significantly lower among CKD patients within 1 year (82.0 vs. 93.0%; p < 0.001; consistent after adjustment for confounding factors), without significant accentuation in advanced CKD (i.e. eGFR < 30 mL/min/1.73 m2; p > 0.05 vs. eGFR 30–59 mL/min/1.73 m2). Non-fatal strokes were absolutely infrequent during follow-up (0 vs. 1.1%). Severe non-fatal bleedings were observed only among CKD patients (1.4 vs. 0%; p = 0.021).ConclusionsDespite an increased cardiovascular risk profile of CKD patients, device implantation was safe, and LAAC was associated with effective stroke prevention across all CKD stages.

P3724Impact of chronic kidney disease on efficacy and safety of interventional left atrial appendage closure – results from the prospective multicenter LAARGE registry

Abstract Background The interventional left atrial appendage closure (LAAC) is an effective and safe alternative to standard oral anticoagulation (OAC) for stroke prevention in atrial fibrillation (AF) patients with contraindications for long-term OAC. Chronic kidney disease (CKD) has a high prevalence among AF patients, and was shown to increase the number of peri-procedural complications in cardiac interventions. Purpose This subanalysis of the LAARGE registry aimed to investigate CKD's impact on outcomes after LAAC. Methods This prospective, real-world LAAC registry included 625 patients with documented renal function from 37 German centers between April 2014 and January 2016. CKD was defined by an eGFR &lt;60 mL/min/1.73 m2. Procedure was conducted with different LAAC devices considering the relevant recommendations. Baseline characteristics, procedural data, intra-hospital and one-year follow-up outcome were registered for CKD and non-CKD patients stratified by the different CKD stages. Results CKD patients (n=300; 48.0%) had a more pronounced cardiovascular risk profile, a higher stroke (CHA2DS2-VASc score 4.9±1.5 vs. 4.2±1.5; p&lt;0.001) and bleeding risk (HAS-BLED score 4.3±1.0 vs. 3.5±1.0; p&lt;0.001), and had experienced more prior bleedings (83.7 vs. 76.3%; p=0.022). Implantation success was similarly high between both groups (97.9%; p=n.s.). In CKD patients, MACCE during one-year follow-up was more frequent (18.1 vs. 6.8%; p&lt;0.001) mainly being triggered by all-cause deaths, but in-hospital MACCE was not (0.3 vs. 0.3%; p=n.s.). Kaplan-Meier estimation showed a lower one-year survival among CKD patients (82.4 vs. 94.4%; p&lt;0.001) without significant accentuation in patients with advanced CKD (i.e., &lt;30 mL/min/1.73 m2; p=n.s. to other CKD patients). While annual rate of device associated complications (2.6 vs. 2.8%; p=n.s.) and strokes (0 vs. 1.0%; p=n.s.) was comparable during follow-up, annual severe bleeding rate was higher in CKD patients (2.6 vs. 0.3%; p=0.027) which was 71.4 and 94.4% less than expected from the HAS-BLED score (p&lt;0.01 for the comparison to the estimated risks, but no significant interaction between groups). Conclusions Despite an increased cardiovascular risk profile of CKD patients, device implantation was safe, and annual stroke rate was statistically indifferent to non-CKD patients across all CKD stages after LAAC. Moreover, a substantial reduction of annual stroke and major bleeding risk was observed, as compared to the estimated annual risk. Acknowledgement/Funding Stiftung Institut für Herzinfarktforschung, Ludwigshafen, Germany

P3727Left atrial appendage closure in patients with a reduced left ventricular ejection fraction: results from the prospective multicenter German LAARGE registry

Abstract Background and purpose Atrial fibrillation (AF) patients with increased thromboembolic risk and contraindications for standard oral anticoagulation (OAC) can profit from an interventional left atrial appendage closure (LAAC). While impaired left ventricular ejection fraction (LVEF) is associated with an increased thromboembolic risk in AF patients, cardiac interventions are often associated with an increase in complications in this patient population, and, therefore, the LAAC procedure's success and benefit has yet to be investigated in this subgroup. Methods This prospective, observational LAAC registry included 622 patients with documented LVEF from 37 German centers between April 2014 and January 2016. Patients were categorized into one of three groups: LVEF &gt;55% (preserved; p), LVEF 35–55% (mid-range; mr) and LVEF &lt;35% (reduced; r). Procedure was conducted in a standard fashion, and baseline characteristics, imaging as well as procedural data, intra-hospital and one-year follow-up outcome were registered for each group. Results 55.3% of patients had a pLVEF, 38.7% a mrLVEF and 5.9% a rLVEF. Patients with rLVEF were more often affected by coronary artery disease (p&lt;0.001 for trend), and had an elevated CHA2DS2-VASc (4.3±1.5 vs. 4.8±1.5 vs. 5.3±1.6; p&lt;0.001) and HAS-BLED score (3.7±1.1 vs. 4.1±1.2 vs. 4.3±0.9; p&lt;0.001). Percentage of prior cerebrovascular events and major bleedings was comparable at baseline (each p=n.s.). Procedural success was high (97.9%), while rates of intra-hospital MACCE (0.5%) and other major complications (4.2%) were low, with no significant difference between the groups (each p=n.s.). MACCE during follow-up was more frequent in rLVEF patients (11.0 vs. 11.3 vs. 27.8%; p=0.013), which was mainly driven by myocardial infarctions and all-cause deaths in this high risk collective. Likewise, Kaplan-Meier estimation showed a lower overall survival in this group (89.7 vs. 89.3 vs. 74.6%; p&lt;0.01). On the contrary, rates of stroke were extremely low across all groups and statistically similar (0.3 vs. 1.0 vs. 0%; p=n.s.). This was 93.4, 82.7 and 100.0% less in comparison to the estimated risk calculated from the CHA2DS2-VASc score Conclusions The LVEF had no influence on the procedural success as well as the intra-hospital complications after LAAC. Annual rate of stroke was low across all groups, and risk reduction was substantial especially in this high risk collective, as compared to the estimated risk. Acknowledgement/Funding Stiftung Institut für Herzinfarktforschung, Ludwigshafen, Germany

Thromboembolism after electrical isolation of the left atrial appendage: a new indication for interventional closure?

Left atrial appendage electrical isolation (LAAI) may improve the rhythm outcome in selected patients with atrial fibrillation (AF). Controversy exists if LAAI is associated with an increased rate of thromboembolic complications. We sought to assess the feasibility, efficacy, and safety of interventional left atrial appendage closure (LAAC) in comparison to oral anticoagulation (OAC) after electrical LAAI. Weeks after index LAAI using the cryoballoon or a linear maze like ablation strategy patients' left atrial appendage was invasively remapped. In case of persistent LAAI, LAAC was performed. Patients who refused invasive remapping continued OAC. The primary endpoint was composed of any stroke or systemic embolism (SE) and the occurrence of intracardiac thrombus. Secondary endpoints included stroke/SE, major bleeding, and all-cause death. Of 166 patients (51% female; mean age 70 ± 8 years; mean CHAD2S2VASc score 3.4 ± 1.8) after LAAI, 94 patients received LAAC (LAAC group) and 72 continued OAC (no LAAC). After LAAC, 83% of patients received dual antiplatelet therapy for 6 weeks and aspirin thereafter. During a mean follow-up of 778 ± 630 days, 5 and 11 primary endpoint events were observed in the LAAC and no LAAC group, respectively [hazard ratio (HR) 0.27, 95% confidence interval (CI) 0.10-0.75; P = 0.010]. The calculated annual thromboembolic event rates were 6.9% (no LAAC) and 2.3% (LAAC), respectively. Left atrial appendage closure significantly reduced the incidence of stroke and SE (HR 0.31, CI 0.1-0.98; P = 0.04). After electrical LAAI for rhythm control in AF patients, interventional LAAC was associated with fewer thromboembolic complications when compared with OAC.

Cerebrovascular events, bleeding complications and device related thrombi in atrial fibrillation patients with chronic kidney disease and left atrial appendage closure with the WATCHMAN\u2122 device

BackgroundImpaired renal function increases the bleeding risk, leading to a conservative prescription and frequent discontinuation of oral anticoagulation in atrial fibrillation patients with chronic kidney disease (CKD). Interventional left atrial appendage closure (LAAC) might be an alternative therapeutic strategy for these patients.MethodsWe aimed to prospectively assess cerebrovascular (CE) and bleeding events, as well as peri-procedural and long-term complications in a cohort of consecutive patients undergoing interventional LAAC using the WATCHMAN™ device, with focus on CKD patients.ResultsOne hundred and eighty-nine consecutive patients undergoing interventional LAAC were included in this analysis; 171 (90.5%) patients had a reduced estimated glomerular filtration rate (eGFR; patients for each CKD stage: II = 66; IIIa = 32; IIIb = 43; IV = 18; V = 12). During a follow-up of 310 patient years three (1.0%) patients suffered a CE (two strokes, one transitory ischemic attack) and five (1.6%) other ones a bleeding complication. The observed stroke rate was more than two-thirds and the bleeding risk more than half lower than expected. Device related thrombi (DRT) were detected in twelve (6.5%) patients; women had significantly more DRT than men (12.5% vs. 2.6%; p = 0.009). Patients with an eGFR< 30 ml/min/1.73m2 showed a trend to a higher DRT rate as compared to the opposite group (13.3% vs. 5.1%; p = 0.10). Thrombus resolved with temporary oral anticoagulation therapy in ten patients without sequelae; thrombus consolidation was confirmed by serial TEE controls in the remaining two patients.ConclusionsAtrial fibrillation patients with CKD have low CE and bleeding rates after LAAC with the WATCHMAN™ device. DRT risk is higher in female and patients with severe CKD. More frequent post-interventional TEE controls might be justified for early DRT detection and safe management of patients at high DRT risk.Trial registration(German Clinical Trials Register ID: DRKS00 010768; Registration Date 07.07.2016).

Interventional Left Atrial Appendage Closure in Atrial Fibrillation: 5-Year Experience from Wellington Hospital

Background: Left atrial appendage closure (LAAC) has a class IIb indication for stroke prevention in patients with atrial fibrillation (AF) and contraindications to anticoagulation. Method: Patients referred to Wellington Hospital for LAAC were enrolled in a registry since 2014. A moratorium was placed on LAAC in New Zealand in 2014; thus, patients who were shortlisted but did not get a LAAC were used for comparison. Procedural details and outcomes were retrospectively analysed. Primary end points were stroke and all-cause mortality. Secondary end points were myocardial infarction, cardiac failure, venous thromboembolism, and AF admissions. Results: A total of 27 patients were enrolled: 12 underwent LAAC and 15 were treated medically. Both groups had similar baseline demographics. Indications for closure were bleeding (n = 21), ineffective anticoagulation (n = 4), and drug intolerance (n = 2). The mean length of follow-up for LAAC and medical groups was 47.5 and 45 months/patient, respectively. At 1 year, primary end points occurred more frequently in the medically treated group (3 vs 0; hazard ratio [HR], 0.12; 95% CI, 0.02–0.87 [p = 0.034]). By 5 years there was no statistical difference in primary end points between the LAAC and medical group (4 vs 7; HR, 0.75; 95% CI 0.2–2.6 [p = 0.6]). Secondary end points were numerically less common in LAAC, as were strokes, including recurrent strokes (4 vs 12). The median event-free survival was 1563 and 607 days for the LAAC and medical groups, respectively. Conclusion: Our early experience with LAA closure appeared to favour LAAC. At 5 years there were fewer strokes and some favouring parameters in the LAAC group, but, overall, no statistical difference was seen between the two small cohorts.

Assessment of peri-device leaks after interventional left atrial appendage closure using standardized imaging by cardiac computed tomography angiography.

Cardiac computed tomography angiography(cCTA) has recently been proposed for evaluation of successful interventional left atrial appendage closure(LAA/LAAC). This prospective longitudinal observational study aims to assess this proposal by applying a standardized imaging protocol to detect and quantify peri-device leaks (PDL) after LAAC. cCTAdatasets of consecutive patients 6months after successful LAAC were acquired on a third generation dual-source computed tomography system and reconstructed with a slice thickness of 0.5mm. The standardized multi-planar reconstruction LAA occluder view for post-implantation evaluation (LOVE) algorithm was used to assess PDL in relation to LAA morphology and implanted LAAC devices. A total of 49patients (median age 80years, 24% female) were included consecutively. Overall PDL rate was 31%. Leak rates among different left atrial appendage morphologies varied largely. Windsock type had the highest incidence of PDL (47%). AMPLATZER™ AMULET™ device type revealed slightly higher PDL rates than WATCHMAN™ type and showed larger leaks. However, no statistical differences were found. PDL can be sized best in LOVE sagittal views, whereas a synopsis of LOVE sagittal, axial and coronal views allows further examination and detection of small leaks. PDL are common after successful interventional LAAC, which can be accurately detected and sized by standardized cCTA imaging protocols.

Antiplatelet effects of aspirin and clopidogrel after left atrial appendage (LAA) occluder implantation

BackgroundThe optimal antithrombotic strategy after interventional left atrial appendage closure (LAAC) is controversial. Dual antiplatelet therapy with aspirin and clopidogrel is the most frequently used regiment. However, pharmacodynamic response to antiplatelet medication differs significantly between individuals. Therefore, we aimed to analyse pharmacodynamic response to aspirin and clopidogrel after LAAC. MethodsIn this study, we included 129 patients undergoing interventional LAAC. Primary end point was pharmacodynamic response to antiplatelet medication. Platelet reactivity was measured by light transmittance aggregometry and vasodilator stimulated protein phosphorylation assay. Secondary endpoints were TIMI bleeding events and MACCE during hospital course and one-year follow-up. ResultsInsufficient pharmacodynamic response (high on-treatment platelet reactivity — HTPR) to clopidogrel occurred in 67 patients (52%); HTPR to aspirin in 15 patients (12%); low on-treatment platelet reactivity — LTPR — to clopidogrel in 13 patients (10%). No occluder thrombosis or stroke occurred during one year follow-up. Pharmacodynamic response to antiplatelet medication was not associated with MACCE. However, the incidence of TIMI minor bleeding was increased in patients with LTPR to clopidogrel. ConclusionsImpaired clopidogrel antiplatelet effects were very frequent in patients after LAAC. No stroke or occluder thrombosis occurred. Patients with LTPR to clopidogrel showed more minor bleeding events. Therefore, this hypothesis generating pilot study raises the question if clopidogrel early after LAAC is needed. This question should be addressed in large scale trials.

Safety and feasibility of interventional left atrial appendage closure without contrast agent.

Interventional left atrial appendage closure (LAAC) is routinely performed under both echocardiographic and angiographic guiding. However, adverse outcomes, e.g., kidney injury and cerebral embolism, might be associated with injections of contrast agent into the LAA. Therefore, this prospective registry investigated the safety and feasibility of LAAC without the support of angiographic images as the default approach. This single-centre registry included a total of 46 non-selected, consecutive patients. In the first 25 patients (54%), LAAC with the Amulet device was performed routinely with LAA angiography prior to implantation and after release of the device. The following 21 patients (46%) were treated without the use of contrast agent. The combination of successful implantation and lack of procedural complications was regarded as the primary endpoint. Procedure time, number of recapture manoeuvres, change of device size, compression, leakage, dose area product and late thrombosis on the device were investigated as secondary endpoints. Besides the longer fluoroscopy time and duration of the procedure in the group using angiography, no significant differences could be found. Major complications occurred equally often in both cohorts. Interventional LAAC with the Amulet device can be performed safely without the use of contrast agent. This approach might help to enhance the use of LAAC in patients at high risk of contrast-induced nephropathy and procedural stroke.

Real-world experience comparing two common left atrial appendage closure devices

BackgroundThe interventional left atrial appendage closure (LAAC) is a guideline-conform alternative to oral anticoagulation (OAC) in non-valvular atrial fibrillation patients with OAC ineligibility. It was aimed to directly compare two contemporary devices in a real-world patient population.MethodsLAAC was conducted in two centres between 2010 and 2014 as well as between 2014 and 2017, respectively, in a standard fashion based on the specific manufacturer’s recommendations. Baseline characteristics, procedural data and event rates during intra-hospital and 6 months follow-up were registered in a retrospective approach, and analysed in device-related groups.ResultsA total of 189 patients presented for LAAC device implantation. Baseline characteristics were mostly evenly distributed. In 148 patients, a Watchman™ device (Boston Scientific, Natick, MA, USA) was successfully implanted, an Amplatzer™ Amulet™ (St. Jude Medical, St. Paul, MN, USA) in 34 patients (96.1 and 97.1%, respectively; p = 1.00). Major access site bleedings were more frequent in the Amplatzer™ Amulet™ group (8.9 versus 1.4%; p = 0.046). No intra-hospital thromboembolic event was present. During 6 months follow-up, peri-device leaks > 5 mm and thromboembolic events were uncommon (each p = n.s.).ConclusionsWhile procedural success was equally high with both contemporary devices, complications during follow-up were rare, and evenly distributed.

Impact of left atrial appendage morphology on indication and procedural outcome after interventional occlusion: results from the prospective multicentre German LAARGE registry.

Interventional left atrial appendage closure (LAAC) is an emerging alternative to oral anticoagulation (OAC) for stroke prevention in atrial fibrillation (AF) in concomitance with a contraindication for standard OAC. This sub-analysis of the LAARGE registry aimed to investigate differences between different LAA morphologies in a real-world setting. This prospective, multicentre, observational registry included 562 patients from 37 centres with ineligibility for long-term OAC between April 2014 and January 2016. Baseline characteristics, indications, procedural data and complications were registered according to each LAA morphology (i.e., chicken wing, cauliflower, windsock, cactus and atypical morphologies). Implantation success was high across the four typical anatomies (≥97.5%, p=n.s.); only atypical anatomies exhibited a lower success rate (94%). The cactus-shaped LAA was linked to a trend indicating a shorter fluoroscopy time, while the atypical LAA was linked to a significantly prolonged fluoroscopy time (p=0.089 and p=0.025 versus the overall mean, respectively). Periprocedural and intra-hospital complications were generally rare, with no differences among the different morphologies (p=n.s.). Procedural success as well as the complication rates of LAAC were not different among the four typical LAA morphologies. A lower implantation success rate was only obvious in patients with atypical LAA morphologies.

Interventional left atrial appendage closure may affect metabolism of essential amino acids and bioenergetic efficacy

BackgroundInterventional closure of left atrial appendage (LAAC) represents an alternative for stroke prevention in patients with non-valvular atrial fibrillation. Whether LAAC may affect metabolomic pathways has not been investigated yet. This study evaluates the impact of LAAC on the metabolism of essential amino acids, kynurenine and creatinine. MethodsPeripheral blood samples of prospectively enrolled patients undergoing successful LAAC were taken before (T0) and 6 months after (T1, mid-term follow-up). Targeted metabolomic profiling was performed using electrospray ionization liquid chromatography–mass spectrometry (ESI-LC-MS/MS) and MS/MS measurements focusing on metabolism of essential amino acids. Results44 patients with non-valvular AF (mean CHA2DS2-VASc score 4, mean HAS-BLED score 4) were enrolled. Changes in metabolites of essential amino acids, myocardial contraction and bioenergetic efficacy, such as phenylalanine (percentage change 8.2%, p = 0.006), tryptophan (percentage change 20.3%, p = 0.0006), tyrosine (percentage change 20.2%, p = 0.0001), creatinine (percentage change 7.2%, p > 0.05) and kynurenine (percentage change 8.3%, p = 0.0239) were found at mid-term follow-up. ConclusionsLAAC may affect the metabolism of essential amino acids and bioenergetic efficacy.ClinicalTrials.gov Identifier: NCT02985463

Interventional Left Atrial Appendage Closure Affects the Metabolism of Acylcarnitines.

Background: Left atrial appendage closure (LAAC) represents the interventional alternative to oral anticoagulation for stroke prevention in atrial fibrillation (AF). The metabolism of acylcarnitines was shown to affect cardiovascular diseases. This study evaluates the influence of successful LAAC on the metabolism of acylcarnitines. Methods: Patients undergoing successful LAAC were enrolled prospectively. Peripheral blood samples for metabolomics measurements were collected immediately before (i.e., index) and six months after LAAC (i.e., mid-term). A targeted metabolomics analysis based on electrospray ionization–liquid chromatography–mass spectrometry (ESI–LC–MS/MS) and MS/MS measurements was performed. Results: 44 patients with non-valvular AF (median CHA2DS2-VASc score 4, median HAS-BLED score 4) and successful LAAC were included. Significant changes in acylcarnitine levels were found in the total cohort, which were mainly attributed to patients with impaired left ventricular and renal function, elevated amino-terminal pro-brain natriuretic peptide (NT-proBNP) and diabetes mellitus. Adjusted multivariable regression models revealed significant changes of five metabolites over mid-term follow-up: C2, C14:1, C16, and C18:1 decreased significantly (each p < 0.05); short-chain C5 acylcarnitine plasma levels increased significantly (p < 0.05). Conclusion: This study demonstrates that successful LAAC affects the metabolism of acylcarnitines at mid-term follow-up. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT02985463.

Left atrial enlargement and clinical considerations in patients with or without a residual interatrial shunt after closure of the left atrial appendage with the WATCHMAN\u2122-device

BackgroundInterventional closure of the left atrial appendage (LAA) in patients with non-valvular atrial fibrillation, high thromboembolic and bleeding risk or bleeding history is an alternative therapeutic strategy to oral anticoagulation. It is not known if the exclusion of the LAA from the blood circulation affects the left atrial volume (LAV) and consequently its prognostic value or the circulatory performance of the heart in humans.MethodsWe aimed to prospectively assess potential changes in baseline LAV, left ventricular ejection fraction (LVEF), NT-proBNP-level and the covered distance in the 6-min walk-test 6 weeks and 6 months after LAA closure with the WATCHMAN™ device. We used serial 3-dimensional transthoracic and transesophageal echocardiography to assess LAV, residual interatrial shunt and device performance in 58 consecutive patients with successful LAA closure.ResultsAccurate 3D–echocardiographic data for LAV measurements were evaluable for 51 (91%) patients. Maximum LAV (LAVmax) at baseline was 102.8 ± 30.8 ml and increased significantly to 107.7 ± 32.8 ml after 6 weeks (p < 0.01) and 113.5 ± 34.2 ml after 6 months (p < 0.01). Minimal LAV (LAVmin) increased from 76.9 ± 29.5 ml at baseline to 81.8 ± 30.2 ml after 45 days (p < 0.01) and 82.1 ± 33.3 ml after 6 months (p < 0.01). Similarly, their indexes to BSA (LAVImax and LAVImin) increased significantly, as well. Patients without a residual left-to-right interatrial shunt showed a significantly higher increase in LAVmax or LAVmin. Baseline LVEF, NT-proBNP-level or the distance covered at the 6-min walk test did not significantly change 6 weeks or 6 months after LAA closure.ConclusionsLAVmax and LAVmin increase significantly after interventional LAA closure. LA enlargement does not correlate with clinical progression of heart failure. Persistent left-to-right interatrial shunt counteracts the LA enlargement. A reduced LA compliance after exclusion of the LAA from the blood circulation with consecutive increase in LA pressure may be a potential cause of LA enlargement and warrants further investigation.Trial registrationGerman Clinical Trials Register ID: DRKS00010768; Registration Date 07.07.2016.

3D printing for sizing left atrial appendage closure device: head-to-head comparison with computed tomography and transoesophageal echocardiography.

Device sizing for LAA closure using transoesophageal echocardiography (TEE) can be challenging due to complex LAA anatomy. We investigated whether the use of 3D-printed left atrial appendage (LAA) models based on preprocedural computed tomography (CT) permits accurate device sizing. Twenty-two (22) patients (73±8 years, 55% male) with atrial fibrillation requiring anticoagulation at high bleeding risk underwent LAA closure (WATCHMAN device). Preprocedurally, LAA was sized by TEE and third-generation dual-source CT. Based on CT, 3D printing models of LAA anatomy were created for simulation of device implantation. Device compression was assessed in a CT scan of the 3D model with the implanted device. Implantation was successful in all patients. Mean LAA ostium diameter based on TEE was 22±4 mm and based on CT 25±3 mm (p=0.014). Predicted device size based on simulated implantation in the 3D model was equal to the device finally implanted in 21/22 patients (95%). TEE would have undersized the device in 10/22 patients (45%). Device compression determined in the 3D-CT model corresponded closely with compression upon implantation (16±3% vs. 18±5%, r=0.622, p=0.003). Patient-specific CT-based 3D printing models may assist device selection and prediction of device compression in the context of interventional LAA closure.

Serial Assessment of Natriuretic Peptides in Patients Undergoing Interventional Closure of the Left Atrial Appendage

Closure of the left atrial appendage (LAA) to prevent cardioembolic events is an alternative therapy to oral anticoagulation in patients with non-valvular atrial fibrillation. The LAA is an important source of natriuretic peptides and its exclusion from the circulation may alter the blood level of these hormones, thereby influencing their diagnostic value and clinical effects. We aimed to prospectively assess potential changes in mid-regional pro A-type natriuretic peptide (MR-proANP) and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels 6 weeks and 6 months after interventional LAA closure using the WATCHMAN device. In 29 consecutive patients with successful LAA closure baseline MR-proANP level was 274±208pmol/l and decreased by -24.5±68 (p=0.07) and -15.0±44pmol/l (p=0.10) after 6 weeks and 6 months, respectively. The drop in the MR-proANP level after 6 weeks and 6 months was significant in patients with elevated (≥214pmol/l) baseline MR-proANP level (n=15: -54.3±78.0, p<0.01 and -31.8±45.4pmol/l, p=0.03, respectively) and those with reduced left ventricular ejection fraction (LVEF<45%, n=7: -87.4±97.3, p=0.02 and -60.3±42.6pmol/l, p=0.01, respectively). Baseline NT-proBNP level (median 1054pg/ml; IQR 621-1977pg/ml), sodium, potassium, mean systolic or diastolic blood pressure did not change significantly in the mentioned patient groups. After LAA closure, MR-proANP level decreased significantly in patients with elevated baseline MR-proANP level or reduced LVEF, whereas NT-proBNP level remained unchanged, thereby altering the correlation coefficient between the two biomarkers. Our findings should be considered when using these biomarkers for diagnostic or prognostic evaluation in patients with interventional LAA closure.