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.

Recurrence After Atrial Fibrillation Ablation and Investigational Biomarkers of Cardiac Remodeling.

BACKGROUND: Recurrence after atrial fibrillation (AF) ablation remains common. We evaluated the association between recurrence and levels of biomarkers of cardiac remodeling, and their ability to improve recurrence prediction when added to a clinical prediction model. METHODS AND RESULTS: Blood samples collected before de novo catheter ablation were analyzed. Levels of bone morphogenetic protein-10, angiopoietin-2, fibroblast growth factor-23, insulin-like growth factor-binding protein-7, myosin-binding protein C3, growth differentiation factor-15, interleukin-6, N-terminal pro-brain natriuretic peptide, and high-sensitivity troponin T were measured. Recurrence was defined as ≥30 seconds of an atrial arrhythmia 3 to 12 months postablation. Multivariable logistic regression was performed using biomarker levels along with clinical covariates: APPLE score (Age >65 years, Persistent AF, imPaired eGFR [<60 ml/min/1.73m2], LA diameter ≥43 mm, EF <50%; which includes age, left atrial diameter, left ventricular ejection fraction, persistent atrial fibrillation, and estimated glomerular filtration rate), preablation rhythm, sex, height, body mass index, presence of an implanted continuous monitor, year of ablation, and additional linear ablation. A total of 1873 participants were included. A multivariable logistic regression showed an association between recurrence and levels of angiopoietin-2 (odds ratio, 1.08 [95% CI, 1.02-1.15], P=0.007) and interleukin-6 (odds ratio, 1.02 [95% CI, 1.003-1.03]; P=0.02). The area under the receiver operating characteristic curve of a model that only contained clinical predictors was 0.711. The addition of any of the 9 studied biomarkers to the predictive model did not result in a statistically significant improvement in the area under the receiver operating characteristic curve. CONCLUSIONS: Higher angiopoietin-2 and interleukin-6 levels were associated with recurrence after atrial fibrillation ablation in multivariable modeling. However, the addition of biomarkers to a clinical prediction model did not significantly improve recurrence prediction.

First Experience With Amulet in the United States: Early Insights From EMERGE LAA Postapproval Study.

BACKGROUND: The Food and Drug Administration approved the Amulet occluder (Abbott) after demonstrating safety and effectiveness in the Amulet IDE (AMPLATZER Amulet LAA Occluder) trial. OBJECTIVES: The aim of the EMERGE Left Atrial Appendage study is to evaluate early postapproval outcomes of the Amulet occluder in the United States using data from the National Cardiovascular Data Registry Left Atrial Appendage Occlusion Registry. METHODS: Patients with a commercial Amulet occluder implant attempt between Food and Drug Administration approval (August 14, 2021) and December 31, 2022, were included. The safety composite endpoint included all-cause death, ischemic stroke, systemic embolism, or device/procedure-related events requiring open cardiac surgery or endovascular intervention between device implantation and 7 days or hospital discharge (whichever is later). Major adverse events through 45 days were also reported and stratified by operator experience (early [<10 cases], moderate [10-29 cases], and high [30+ cases]). RESULTS: A total of 5,499 patients underwent attempted Amulet occluder implantation. Implant success was 95.8%, and complete closure was 97.2% post-left atrial appendage occlusion and 87.1% at 45 days. A safety composite endpoint event occurred in 0.76% patients. Any major adverse event occurred in 2.9% and 5.7% of patients in-hospital and through 45 days, respectively, driven by major bleeding and pericardial effusion (PE) requiring intervention. PE requiring surgery or percutaneous intervention decreased significantly with increasing experience both in-hospital (early vs high operator experience 1.8% vs 1.1%; P = 0.006) and at 45 days (2.3% vs 1.5%; P = 0.012). CONCLUSIONS: The EMERGE Left Atrial Appendage study demonstrates favorable safety and effectiveness of the Amulet occluder in the real-world setting. More experienced operators had improved implant success and fewer PEs, suggesting a learning curve effect implanting this dual occlusive mechanism device.

L-cysteine methyl ester overcomes the deleterious effects of morphine on ventilatory parameters and arterial blood-gas chemistry in unanesthetized rats.

We are developing a series of thiolesters that produce an immediate and sustained reversal of the deleterious effects of opioids, such as morphine and fentanyl, on ventilation without diminishing the antinociceptive effects of these opioids. We report here the effects of systemic injections of L-cysteine methyl ester (L-CYSme) on morphine-induced changes in ventilatory parameters, arterial-blood gas (ABG) chemistry (pH, pCO2, pO2, sO2), Alveolar-arterial (A-a) gradient (i.e., the index of alveolar gas-exchange within the lungs), and antinociception in unanesthetized Sprague Dawley rats. The administration of morphine (10 mg/kg, IV) produced a series of deleterious effects on ventilatory parameters, including sustained decreases in tidal volume, minute ventilation, inspiratory drive and peak inspiratory flow that were accompanied by a sustained increase in end inspiratory pause. A single injection of L-CYSme (500 µmol/kg, IV) produced a rapid and long-lasting reversal of the deleterious effects of morphine on ventilatory parameters, and a second injection of L-CYSme (500 µmol/kg, IV) elicited pronounced increases in ventilatory parameters, such as minute ventilation, to values well above pre-morphine levels. L-CYSme (250 or 500 µmol/kg, IV) also produced an immediate and sustained reversal of the deleterious effects of morphine (10 mg/kg, IV) on arterial blood pH, pCO2, pO2, sO2 and A-a gradient, whereas L-cysteine (500 µmol/kg, IV) itself was inactive. L-CYSme (500 µmol/kg, IV) did not appear to modulate the sedative effects of morphine as measured by righting reflex times, but did diminish the duration, however, not the magnitude of the antinociceptive actions of morphine (5 or 10 mg/kg, IV) as determined in tail-flick latency and hindpaw-withdrawal latency assays. These findings provide evidence that L-CYSme can powerfully overcome the deleterious effects of morphine on breathing and gas-exchange in Sprague Dawley rats while not affecting the sedative or early stage antinociceptive effects of the opioid. The mechanisms by which L-CYSme interferes with the OR-induced signaling pathways that mediate the deleterious effects of morphine on ventilatory performance, and by which L-CYSme diminishes the late stage antinociceptive action of morphine remain to be determined.

Conduction Recovery After Cavotricuspid Isthmus Ablation When Performed With or Without Concomitant Atrial Fibrillation Ablation.

OBJECTIVES: This study sought to define the association between conduction recovery across the cavotricuspid isthmus (CTI) and typical atrial flutter (AFL) recurrence when CTI ablation is performed with pulmonary vein isolation (PVI) compared with a stand-alone procedure. BACKGROUND: CTI ablation is commonly performed at the same time as PVI to treat AFL or as an empiric therapy. Conduction recovery is a recognized problem after linear ablation in the left atrium (e.g., mitral isthmus ablation) and is proarrhythmic. Less is known about conduction recovery after CTI ablation and possible differences in outcomes when performed at the time of PVI compared with at the time of a stand-alone procedure. METHODS: Eligible participants who underwent stand-alone CTI ablation were compared with those who underwent a combined (CTI+PVI) procedure. CTI conduction recovery was assessed at the time of a second ablation. Conduction recovery across the CTI (primary outcome) and recurrence of typical AFL (secondary outcome) were studied using multivariable logistic regression. RESULTS: Among 295 eligible participants (median age: 64 years [interquartile range: 55 to 69 years]; 33% women), recovery was assessed in 232 and was more common after combined versus stand-alone CTI ablation (52% [72 of 139] vs. 13% [12 of 93]; p < 0.001). In multivariable analysis, CTI ablation performed as a combined procedure increased odds of CTI conduction recovery 7.8-fold (odds ratio: 7.8; 95% confidence interval: 3.3 to 18.3; p < 0.001) and clinical AFL recurrence 4.1-fold (odds ratio: 4.1; 95% confidence interval: 1.0 to 16.9; p = 0.049). CONCLUSIONS: CTI ablation performed at the time of atrial fibrillation ablation is associated with higher rates of conduction recovery and typical flutter recurrence.

Percutaneous approaches for retrieval of an embolized or malpositioned left atrial appendage closure device: A multicenter experience.

BACKGROUND: Experience with retrieval of a Watchman left atrial (LA) appendage (LAA) closure device (WD) is limited. An embolized or grossly malpositioned WD warrants retrieval to minimize the risk of thromboembolic complications and vascular occlusion. OBJECTIVE: The purpose of this study was to report approaches for percutaneous retrieval of a WD from multicenter experience. METHODS: Data on successful WD retrievals were obtained from high-volume operators. Data included clinical characteristics; structural characteristics of the LA and LAA; and procedural details of the deployment and retrieval procedure, type of retrieval (immediate: during the same procedure; delayed: during a separate procedure after the successful deployment), equipment used, complications, and postretrieval management. RESULTS: Ten successful percutaneous and 1 surgical retrievals comprised this study. Seven patients had immediate retrieval, while 4 had delayed retrieval. The median duration before delayed retrieval was 45 days (range 1-45 days). The median LAA diameter and size of a successfully deployed WD was 16 mm (range 14-24 mm) and 21 mm (range 21-30 mm), respectively. A WD was retrieved from the LA (n = 1), LAA (n = 2), left ventricle (n = 2), and aorta (n = 6). The reason for retrieval from the LAA was inadequate deployment, resulting in a significant peri-device leak. Retrieval from the LA or LAA was successfully performed using snares (n = 2) and a Raptor grasping device (n = 1). Retrieval from the left ventricle was achieved with a snare (n = 1) and surgery (n = 1). Retrieval from the aorta required snares (n = 5) and retrieval forceps (n = 1). Five patients were successfully reimplanted with a larger size WD. The only complication during percutaneous retrieval was a pseudoaneurysm. CONCLUSION: Retrieval of an embolized or malpositioned WD is feasible, and familiarity with snares and grasping tools can facilitate a successful removal.

To retrieve, or not to retrieve: System revisions with the Micra transcatheter pacemaker.

BACKGROUND: Early experience with leadless pacemakers has shown a low rate of complications. However, little is known about system revision in patients with these devices. OBJECTIVE: The purpose of this study was to describe the system revision experience with the Micra Transcatheter Pacing System (TPS). METHODS: Patients with implants from the Pre-market Micra Transcatheter Pacing Study and the Micra Transcatheter Pacing System Continued Access Study (N = 989) were analyzed and compared with 2667 patients with transvenous pacemakers (TVPs). Revisions included TPS retrieval/explant, repositioning, replacement, or electrical deactivation (with or without prior attempt at retrieval, generally followed by TVP implant) for any reason. Kaplan-Meier revision rates were calculated to account for varying follow-up duration and were compared using a Fine-Gray competing risk model. RESULTS: The actuarial rate for revision at 24 months postimplant was 1.4% for the TPS group (11 revisions in 10 patients), 75% (95% confidence interval 53%-87%; P < .001) lower than the 5.3% for the TVP group (123 revisions in 117 patients). TPS revisions occurred 5-430 days postimplant for elevated pacing thresholds, need for alternate therapy, pacemaker syndrome, and prosthetic valve endocarditis; none were due to device dislodgment or device-related infection. TPS was disabled and left in situ in 7 cases, 3 were retrieved percutaneously (range 9-406 days postimplant), and 1 was surgically removed during aortic valve surgery. CONCLUSION: The overall system revision rate for patients with TPS at 24 months was 1.4%, 75% lower than that for patients with TVPs. TPS was disabled and left in situ in 64% of revisions, and percutaneous retrieval was successful as late as 14 months postimplant.

Angiographic Efficacy of the Atriclip Left Atrial Appendage Exclusion Device Placed by Minimally Invasive Thoracoscopic Approach.

OBJECTIVES: This study sought to assess long-term left atrial appendage (LAA) closure efficacy of the Atriclip applied via totally thoracoscopic (TT) approach with computed tomographic angiography. BACKGROUND: LAA closure is associated with a low risk for atrial fibrillation-related embolic stroke. The Atriclip exclusion device allows epicardial LAA closure, avoiding the need for post-operative oral anticoagulation. Previous data with Atriclip during open chest procedures show a high efficacy rate of closure >95%. METHODS: Three-dimensional volumetric 2-phase computed tomographic angiography ≥90 days post-implantation was independently assessed by chest radiology for complete LAA closure on all consented subjects identified retrospectively as having had a TT-placed Atriclip at Vanderbilt University Medical Center from June 13, 2011, to October 6, 2015. RESULTS: Complete LAA closure (defined by complete exclusion of the LAA with no exposed trabeculations, and clip within 1 cm from the left circumflex artery) was found in 61 of 65 subjects (93.9%). Four cases had incomplete closure (6.2%). Two clips were placed too distally, leaving a large stump with exposed trabeculae. Two clips failed to address a secondary LAA lobe. No major complications were associated with TT placement of the Atriclip. Follow-up over 183 patient-years revealed 1 stroke in a patient with complete LAA closure and no thrombus (hypertensive cerebrovascular accident). CONCLUSIONS: Angiographic LAA closure efficacy with a TT-placed Atriclip is high (93.9%). The clinical significance of a remnant stump is unknown. Confirmation of complete LAA occlusion should be made before cessation of systemic anticoagulation.

Staged versus Simultaneous Thoracoscopic Hybrid Ablation for Persistent Atrial Fibrillation Does Not Affect Time to Recurrence of Atrial Arrhythmia.

INTRODUCTION: Totally thoracoscopic (TT) epicardial ablation combined with endocardial catheter ablation is an emerging treatment for persistent AF. The effects of timing of the TT and endocardial portion on AT/AF recurrence are not known. METHODS: We retrospectively analyzed patients undergoing TT staged versus simultaneous hybrid AF ablation at our institution. Arrhythmia-free outcome was compared using time to recurrence (AF or AT greater than 30 seconds after a 3-month blanking period from endocardial ablation) at 12 months. All subjects had continuous ILR or PM monitoring. RESULTS: Eighty-three patients (52 same-day, 31 staged) underwent TT hybrid AF ablation. Recurrence was observed in 23 (29%) patients at a median time of 147 days (IQR 91,238). In univariate analysis, a staged approach significantly increased the likelihood of detecting incomplete PVI (OR 6 [95% CI 2-17] P = 0.001). However, only longstanding persistent AF (LSP-AF) status predicted recurrence (HR 4 [95% CI 1.4-12] P = 0.01). Neither a staged approach (HR 1.0 [95% CI 0.4-2.4] P = 0.9), nor detection of incomplete PVI (HR 0.9 [95% CI 0.4-2.3] P = 0.8) predicted time to first AF/AT recurrence. CONCLUSIONS: Staged hybrid ablation of AF significantly increases the likelihood of discovering incomplete PVI at the time of endocardial mapping versus a same-day procedure. However, the staged approach did not improve time to first AT/AF recurrence.

The APPLE score: a novel and simple score for the prediction of rhythm outcomes after catheter ablation of atrial fibrillation.

BACKGROUND: Recurrent atrial fibrillation (AF) occurs in up to 50 % of patients within 1 year after catheter ablation, and a clinical risk score to predict recurrence remains a critical unmet need. The aim of this study was to (1) develop a simple score for the prediction of rhythm outcome following catheter ablation; (2) compare it with the CHADS2 and CHA2DS2-VASc scores, and (3) validate it in an external cohort. METHODS: Rhythm outcome between 3 and 12 months after AF catheter ablation were documented. The APPLE score [one point for age >65 years, persistent AF, impaired eGFR (<60 ml/min/1.73 m(2)), LA diameter ≥43 mm, EF < 50 %] was associated with AF recurrence and was validated in an external cohort in 261 patients with comparable ablation and follow-up. RESULTS: In 1145 patients (60 ± 10 years, 65 % male, 62 % paroxysmal AF) the APPLE score showed better prediction of AF recurrences (AUC 0.634, 95 % CI 0.600-0.668, p < 0.001) than CHADS2 (AUC 0.538) and CHA2DS2-VASc (AUC 0.542). Compared to patients with an APPLE score of 0, the odds ratio for AF recurrences was 1.73, 2.79 and 4.70 for APPLE scores 1, 2, or ≥3, respectively (all p < 0.05). In the external validation cohort, the APPLE score showed similar results (AUC 0.624, 95 % CI 0.562-0.687, p < 0.001). CONCLUSIONS: The novel APPLE score is superior to the CHADS2 and CHA2DS2-VASc scores for prediction of rhythm outcome after catheter ablation. It holds promise as a useful tool to identify patients with low, intermediate, and high risk for AF recurrence.

Deciphering the glycosylation code.

Asparagine-linked carbohydrates profoundly impact glycoprotein folding, stability, and structure. However, the "glycosylation code" that relates these effects to protein sequence remains unsolved. We report atomically detailed replica exchange molecular dynamics simulations in explicit solvent that systematically investigate the impact of glycosylation upon peptides with the central sequon Pro-Asn-Gly/Ala-Thr-Trp/Ala. These simulations suggest that the effects of glycosylation may be quite sensitive to steric crowding by the side chain immediately following the glycosylation site but less sensitive to stacking interactions with the aromatic Trp residue. In addition, we compare our simulated ensembles with the known structures for full length glycoproteins. These structures corroborate the simulations and also suggest a remarkable consistency between the intraprotein and protein-glycan interactions of natural glycoproteins. Moreover, our analysis highlights the significance of left-handed conformations for compact ß-hairpins at glycosylation sites. In summary, these studies elucidate basic biophysical principles for the glycosylation code.

High-risk lead removal by planned sequential transvenous laser extraction and minimally invasive right thoracotomy.

INTRODUCTION: Transvenous pacemaker or implantable cardioverter defibrillator (ICD) lead extraction via mechanical or excimer laser sheath is typically safe and effective. Longer duration from implant, presence of large vegetations or thrombi, fractured leads, and prior failed extraction are risk factors predicting higher complication rates or incomplete or failed lead removal. Techniques developed for minimally invasive valve surgery were used in conjunction with laser extraction to refine a "hybrid" technique for lead extraction. We assessed the outcomes of high-risk lead extraction using this hybrid lead extraction technique. METHODS AND RESULTS: Retrospective assessment of clinical parameters and procedural outcomes in patients undergoing planned hybrid lead extraction from February 2008 to September 2012 was performed. We report 8 cases of hybrid lead extraction performed at our institution. We extracted 21 leads with average lead age of 13.8 years since implant. All leads were removed with complete clinical and radiographic success. There were no intraprocedure complications. One patient died of continued sepsis and 1 other had symptoms consistent with pulmonary embolism. CONCLUSIONS: Hybrid lead extraction using this technique is a safe and effective approach for removal of high-risk chronic pacemaker or ICD leads. This method extends the range of approachable leads resulting in complete removal without median sternotomy. Hybrid lead extraction can be scheduled electively facilitating complete lead removal with a low complication rate and short postoperative recovery time, mitigating the risks inherent in midline sternotomy or emergent cardiac surgical rescue.

Myocarditis: basic and clinical aspects.

Myocarditis represents a heterogeneous final common pathway for myocardial inflammation of diverse etiologies and accounts for up to one-third of cases of dilated cardiomyopathy. The pathophysiology of viral myocarditis can be disaggregated into the effects of direct viral mediated injury, triggered acute and chronic autoimmune responses, and subsequent adverse remodeling. Recent research highlights the pathogenic role of persistent viral genome expression, Fas-ligand, tumor necrosis factor-alpha receptor 1, and antimyosin autoantibodies in the evolution of chronic systolic and diastolic heart failure. Recent refinements in endomyocardial biopsy evaluation, cardiac magnetic resonance imaging, and cytokine assays augment existing diagnostic modalities. Novel specific immunosuppressive targets aimed at interrupting myocyte injury and apoptosis, including interferon-beta seem promising to date in small clinical studies performed on selected patients.