Atrial Fibrillation After Patent Foramen Ovale Closure: Incidence, Pathophysiology, and Management.

This comprehensive review explores the incidence, pathophysiology, and management of atrial fibrillation (AF) following percutaneous closure of patent foramen ovale (PFO). Although AF is considered a common adverse event post PFO closure, its incidence, estimated at <5%, varies based on monitoring methods. The review delves into the challenging task of precisely estimating AF incidence, given subclinical AF and diverse diagnostic approaches. Notably, a temporal pattern emerges, with peak incidence around the 14th day after closure and a subsequent decline after the 45th day, mimicking general population AF trends. The pathophysiological mechanisms behind post PFO closure AF remain elusive, with proposed factors including local irritation, device-related interference, tissue stretch, and nickel hypersensitivity. Management considerations encompass rhythm control, with flecainide showing promise, and anticoagulation tailored to individual risk profiles. The authors advocate for a personalized approach, weighing factors like age, comorbidities, and device characteristics. Notably, postclosure AF is generally considered benign, often resolving spontaneously within 45 days, minimizing thromboembolic risks. Further studies are required to refine understanding and provide evidence-based guidelines.

Two- and three-dimensional transesophageal echocardiographic assessment and successful occlusion of a window-like patent ductus arteriosus in two dogs.

A 16-month-old Labrador-Poodle cross (case 1) and a 3-month-old German shorthaired pointer (case 2) were referred for patent ductus arteriosus (PDA) occlusion. Two-dimensional transthoracic and two- and three-dimensional transesophageal echocardiography revealed a window-like PDA characterized by a wide and short ductus. Due to the atypical PDA morphology with no ampulla in case 1, ductal occlusion was attempted with non-canine-specific Amplatzer occluder devices. However, these were too small and failed to remain stable. Amplatz Canine Duct Occluder (ACDO) devices were used with success in both cases. Due to the defects' morphology, the proximal ACDO disc protruded into the aorta but there were no signs of obstruction to aortic blood flow 16 months (case 1) and 1 month (case 2) post-occlusion. We describe two cases of a window-like type PDA that were successfully occluded with an ACDO.

Assessment of degradability and endothelialization of modified poly L-lactic acid (PLLA) atrial septal defect (ASD) occluders over time in vivo.

OBJECTIVE: To evaluate the fiber-degradation and endothelialization of a modified poly L-lactic acid (PLLA) atrial septal defect (ASD) occluder for a long time in vivo. METHODS: A total of 57 New Zealand rabbits were selected to establish the vasculature implantation model, which would be used to characterize the mechanical properties and pathological reaction of PLLA filaments (a raw polymer of ASD occluder). In total, 27 Experimental piglets were used to create the ASD model for the catheter implantation of PLLA ASD occluders. Then, X-ray imaging, transthoracic echocardiography, histopathology, and scanning electron microscope (SEM) were performed in the experimental animals at 3, 6, 12, and 24 months after implantation. RESULTS: In the rabbit models, the fibrocystic grade was 0 and the inflammatory response was grade 2 at 6 months after vasculature implantation of the PLLA filaments. The mass loss of PLLA filaments increased appreciably with the increasing duration of implantation, but their mechanical strength was decreased without broken. In the porcine models, the cardiac gross anatomy showed that all PLLA ASD occluders were stable in the interatrial septum without any vegetation or thrombus formation. At 24 months, the occluders had been embedded into endogenous host tissue nearly. Pathological observations suggested that the occluders degraded gradually without complications at different periods. SEM showed that the occluders were endothelialized completely and essentially became an integral part of the body over time. CONCLUSION: In the animal model, the modified PLLA ASD occluders exhibited good degradability and endothelialization in this long-term follow-up study.

Assessment of atrial septal defects using 3-dimensional transthoracic echocardiography prior to percutaneous device closure: first report from Bangladesh.

BACKGROUND: Secundum atrial septal defect (ASD) is treated following trans-catheter closure in alternative to surgical treatment. Per-intervention selection of device size with balloon occlusive diameter (BOD) often cause tearing or enlarging, causing arrhythmias and hypotension. We assessed the suitability of percutaneous device closure for ASD using 3-dimensional transthoracic echocardiography (3DTTE). OBJECTIVES: This study was conducted to investigate if 3DTTE could be an alternative of balloon sizing for selection of device size in atrial septal defect device closure. DESIGN: It was a cross-sectional comparative study. METHODS: This study was conducted at the department of Pediatric Cardiology, Bangabandhu Sheikh Mujib Medical University for a period of 2 years. Thirty-three purposively selected secundum ASD patients suitable for device closure were included in the study. Ethical permission was taken from the Institutional Review Board and written consent was taken from each patient's guardian. In this study, 3DTTE derived ASD diameter and BOD were compared with that of deployed device size using correlation analysis. RESULTS: Out of 33 patients, 63.6% were female and 36.4% were males had a mean age of 18.07 ± 14.58 years (range 2-55 years). Mean diameter of ASD measured by 2-dimensional (2D) and 3-dimensional (3D) echocardiography were 17.09 ± 6.08 mm and 21.30 ± 6.56 mm, respectively, yielding a significant difference (p < 0.001). 3D echocardiography derived ASDs diameter were highly correlated with device size than BOD and 2D echocardiography derived diameter (2D echocardiography: r = 0.796, p = <0.001, 3D echocardiography: r = 0.960, p = <0.001, BOD: r = 0.840, p = <0.001). CONCLUSION: 3DTTE can accurately measure ASD diameter and can be used as an alternate, effective, and safe method to select device size.

Assessment of Nit-Occlud atrial septal defect occluder device healing process using micro-computed tomography imaging.

After percutaneous implantation of a cardiac occluder, a complex healing process leads to the device coverage within several months. An incomplete device coverage increases the risk of device related complications such as thrombosis or endocarditis. We aimed to assess the device coverage process of atrial septal defect (ASD) occluders in a chronic sheep model using micro-computed tomography (micro-CT). After percutaneous creation of an ASD, 8 ewes were implanted with a 16-mm Nit-Occlud ASD-R occluder (PFM medical, Cologne, Germany) and were followed for 1 month (N = 3) and 3 months (N = 5). After heart explant, the device coverage was assessed using micro-CT (resolution of 41.7 µm) and was compared to histological analysis. The micro-CT image reconstruction was performed in 2D and 3D allowing measurement of the coverage thickness and surface for each device. Macroscopic assessment of devices showed that the coverage was complete for the left-side disk in all cases. Yet incomplete coverage of the right-side disk was observed in 5 of the 8 cases. 2D and 3D micro-CT analysis allowed an accurate evaluation of device coverage of each disk and was overall well correlated to histology sections. Surface calculation from micro-CT images of the 8 cases showed that the median surface of coverage was 93±8% for the left-side disk and 55±31% for the right-side disk. The assessment of tissue reactions, including endothelialisation, after implantation of an ASD occluder can rely on in vitro micro-CT analysis. The translation to clinical practice is challenging but the potential for individual follow-up is shown, to avoid thrombotic or infective complications.

Comparison between Cardiac CTA and Echocardiography for Assessment of Ventricular Septal Rupture Diameter and Its Effect on Transcatheter Closure.

Objective: This study is aimed at comparing cardiac computed tomographic angiography (CTA) with echocardiography in the assessment of ventricular septal perforation diameter. Methods: A total of 44 ventricular septal rupture (VSR) patients undertaking transcatheter occlusion were included and randomly divided into the CTA group and echocardiography group with a 1 : 1 ratio. Clinical data, operation-related data, and 30 d follow-up data were collected and analyzed. Results: Incidence of closure failure, occluder displacement, poor occluder molding, and occluder waist diameter shrinkage between the two groups were not statistically different. The mean residual shunt volume in the echocardiography group (4.2 (3.1, 5.9) mm) was significantly higher than that in the CTA group (2.1 (0, 4.0) mm) with a p value of 0.005. However, no significant differences were found in all-cause mortality and incidence of operative complications within 30 days after surgery. Within the CTA group, the correlation was strongest between postoperative occluder diameter and long diameter measured by CTA with a correlation coefficient of 0.799 and p < 0.001, followed by the correlation between postoperative occluder diameter and mean diameter measured by CTA with a correlation coefficient of 0.740 and p < 0.001. The diameter measured by echocardiography was not correlated to postoperative occlude diameter. Conclusion: Assessment of VSR diameter by cardiac CTA is more accurate than by echocardiography.

Tailored endoscopic treatment of tracheo-oesophageal fistula using preoperative holographic assessment and a cardiac septal occluder.

Devices originally designed for closure of cardiac septal defects have also been proposed for the treatment of acquired tracheo-oesophageal fistula (TOF). Choosing the right occluder device to match TOF size and shape is essential for a tailored treatment. We report the successful endoscopic closure of a post-radiotherapy TOF using preprocedural CT scan with holographic three-dimensional reconstruction and an Amplatzer atrial septal device. Complete TOF sealing was achieved with resolution of respiratory symptoms, and the patient was maintaining his ability to eat at 4-month follow-up.

Cardiac Computed Tomography Angiography for Device-Related Thrombus Assessment After WATCHMAN FLX™ Occluder Device Implantation: A Single-Center Retrospective Observational Study.

BACKGROUND/PURPOSE: Device-related thrombosis (DRT) is one of the greatest challenges of transcatheter left atrial appendage device occlusion. Due to the invasive nature of transesophageal echocardiography (TEE), cardiac computed tomography angiography (CCTA) is being increasingly utilized in several centers for assessing adequate left atrial appendage closure and monitoring for DRT. There is a paucity of data regarding the standardized definition of DRT on CCTA for the WATCHMAN FLX™ device. METHODS/MATERIALS: A retrospective review was conducted on 43 patients receiving WATCHMAN FLX™ device implantation with CCTA performed at the first follow-up at our institution. A comparative review of DRT predictors was performed on 10 patients who had both CCTA and TEE at the time of follow-up. RESULTS: Hypoattenuated thickening (HAT) was a common finding on CCTA and was noted to be present in 95.35% of the patients. The combination of a large device size, peridevice gap >4 mm, and HAT located on the device gutter and 1 shoulder were characteristics present on CCTA observed in 2 patients with confirmed DRT on TEE. CONCLUSION: CCTA is a noninvasive imaging modality for DRT monitoring, with guidelines still in development. We report potential predictors of DRT on CCTA. Additional studies are needed to further determine standardized parameters for DRT detection on CCTA and the significance of HAT with multimodality correlation.

Endothelialization of Amplatzer PFO Occluder Device 12 Months After Implantation: First-in-Human Angioscopic Assessment.

The current guidelines recommend at least 6 months of antithrombotic and antibiotic prophylaxis following atrial septal occluding device placement using the phrase "until endothelialization." However, neo-endothelialization has not been assessed in vivo in humans. Considering the atrial septal defect occluding device, several autopsy cases and device extraction cases only demonstrated insufficient endothelialization beyond 6 months after implantation caused endocarditis and thrombosis. Accordingly, we have successfully developed a method for determining device endothelialization using angioscopy. This method helped us evaluate the endothelialization of a 25 mm Amplatzer PFO occluder device (Abbott) in a 40-year-old man 12 months after implantation. This is the first report evaluating the PFO occluder device in vivo.

Cost-effectiveness analysis of patent foramen ovale closure with Amplatzer plus medical therapy compared to medical therapy in patients with a history of stroke in France.

BACKGROUND: A patent foramen ovale (PFO) is formed when the ovale foramen does not close spontaneously or re-opens leaving the right and left atrium connected. The present study was conducted to analyze the cost-effectiveness of PFO closure with Amplatzer device plus medical therapy (MT) compared to MT alone in the French reimbursement system for PFO patients with a prior history of stroke, using the RESPECT study data. METHODS: A multi-state Markov model was used. The analysis was conducted from a collective perspective over a 10-year time horizon with 4% discount applied for costs and health effects. The simulated population included adult patients with PFO. Sub-group analysis was limited to patients with atrial septal aneurysm and/or a large-shunt. Clinical inputs were derived from the RESPECT study and literature. Costs associated with the device, drugs, and management were sourced from literature and national databases. The outcomes of analyses included life-years (LYs), quality-adjusted LYs (QALYs), incremental cost-effectiveness ratio (ICER), and number of recurrent strokes avoided. Scenario and sensitivity analyses were conducted to assess the robustness of the results. RESULTS: The use of Amplatzer plus MT provided additional QALYs (0.16) at an incremental cost of 7301€, generating an ICER of 46,288€/QALY for Amplatzer vs. MT alone. In the sub-group analysis, Amplatzer plus MT provided additional QALYs (0.20) at an incremental cost of 5818€, generating an ICER of 28,624€/QALY for Amplatzer plus MT vs. MT alone. Amplatzer plus MT led to lower number of recurrent strokes in comparison to MT alone in both populations. Scenario and sensitivity analyses confirmed the robustness of the results. CONCLUSION: Amplatzer plus MT represents a cost-effective treatment option and is associated with lower stroke recurrence compared to MT alone for PFO patients with a prior history of stroke.

Preclinical Assessment of a Novel Conformable Foam-Based Left Atrial Appendage Closure Device.

BACKGROUND: Left atrial appendage (LAA) occlusion has been established as an alternative to systemic anticoagulation for stroke prevention in patients with atrial fibrillation; however, limitations of current devices have slowed adoption. We present preclinical evaluations of a novel device, the Conformal Left Atrial Appendage Seal (CLAAS). METHODS: An in vitro assessment of conformability was conducted to evaluate the two CLAAS devices (regular 27 mm and large 35 mm) and a Watchman 2.5 (27 mm). Devices were placed within silicone tubes and compressed in a vise submerged in a water bath at 37°C. Changes in device diameter and visual seal were noted. Acute (n = 1) and chronic 60-day (n = 6) canine studies with gross and histologic assessment were performed. RESULTS: Conformability bench tests demonstrated that the regular CLAAS implant was able to seal oval orifices from 20 × 30 mm to 15 × 33 mm and the large from 30 × 35 mm to 20 × 40 mm. As the CLAAS implant was compressed in the minor diameter, it increased in the major diameter, thereby filling the oval space, whereas the Watchman 2.5 showed gaps and maintained its round configuration when compressed in one direction. Seven devices were successfully implanted in the canine model with complete seal without thrombus. Histologic examination showed complete neointima covering with minimal inflammation at 60 days. CONCLUSIONS: Preclinical testing demonstrated the conformability of the CLAAS implant and its ability to seal the LAA. Clinical studies are ongoing to characterize the utility of the CLAAS implant in the treatment of patients with atrial fibrillation.

Cost-Effectiveness Analysis of Percutaneous Patent Foramen Ovale Closure Preventing Secondary Ischemic Stroke in Japan.

OBJECTIVES: Patent foramen ovale is a hemodynamically insignificant interatrial communication that may cause ischemic stroke. Percutaneous patent foramen ovale closure reduces the risk for recurrent ischemic stroke in patients with a history of cryptogenic ischemic stroke. This study evaluated the cost-effectiveness of patent foramen ovale closure against medical therapy in patients after their first cryptogenic ischemic stroke in Japan. MATERIALS AND METHODS: The cost-effectiveness of patent foramen ovale closure compared with medical therapy was evaluated using the Markov model. The target patients started with patent foramen ovale closure or medical therapy for preventing secondary ischemic stroke under a stable state. Quality-adjusted life year was used as the outcome of effectiveness, and the analysis was conducted with a discount rate of 2% applied to both cost and effectiveness. The results of a multicenter open-label randomized controlled trial (RESPECT trial) evaluating patent foramen ovale closure using the Amplatzer™ PFO Occluder were used as clinical evidence. Cost-effectiveness was evaluated using the incremental cost-effectiveness ratio. It was evaluated as cost-effective if it was lower than 5 million JPY/ quality-adjusted life year. RESULTS: Patent foramen ovale closure was dominant over medical therapy by 2.53 quality-adjusted life years and an estimated cost reduction of 2,353,926 JPY. The probability of patent foramen ovale closure being dominant was 82.9%. CONCLUSIONS: Patent foramen ovale closure was dominant over medical therapy for preventing secondary ischemic stroke in patients with cryptogenic ischemic stroke.

Racial Disparities in In-Hospital Adverse Events Among Patients With Atrial Fibrillation Implanted With a Watchman Left Atrial Appendage Occlusion Device: A US National Perspective.

[Figure: see text].

Preclinical assessment of a modified Occlutech left atrial appendage closure device in a porcine model.

Left atrial appendage (LAA) closure is being developed as an alternative for stroke prevention in patients with atrial fibrillation that cannot tolerate long-term oral anticoagulation. To assess the feasibility, safety, and performance of a novel modified Occlutech LAA closure device in a preclinical porcine model, the modified Occlutech modified Occlutech Plus LAA closure device was implanted in 12 female pigs (25-39 kg body weight) under fluoroscopic and transesophageal echocardiography (TEE) guidance. Procedural and technical success, as well as safety of LAA closure, were evaluated peri-procedurally and after 4, 8, and 12 weeks. Moreover, after 4, 8 and, 12 weeks animals were sacrificed for pathological analysis (e.g., thrombus formation, device ingrowth, endothelialization, and inflammation). All LAA closure devices were successfully implanted. On follow-up, no serious adverse events such as device-associated thrombus or translocalization/embolization were observed. A clinically non-significant pericarditis was observed in 4 animals at the time of autopsy. Endothelialization of the device was visible after 4 weeks, advanced after 8 weeks and completed after 12 weeks. Immunohistochemistry showed low amounts of inflammatory infiltration on the edges of the device. The results of this study indicate that implantation of a modified Occlutech LAA closure device is feasible with rapid endothelialization and low inflammatory infiltration in a porcine model. Human data are needed to further characterize safety and efficacy.

Patent foramen ovale closure in the management of cryptogenic stroke: a review of current literature and guideline statements.

OBJECTIVE: The management recommendations for patent foramen ovale (PFO) closure in cryptogenic stroke are rapidly evolving. The data has expanded recently with four major trials demonstrating superiority of percutaneous device closure over medical management in preventing cryptogenic stroke recurrence. This paper aims to review the current literature for referring physicians who may encounter patients with patent foramen ovale before referring these patients to stroke specialists and/or interventional cardiologists. METHOD: For this Narrative review, we conducted a broad literature search with expert selection of relevant data. Our search included a review of the currently available trials, guideline statements, position papers, cost-effectiveness of device closure data, as well as the impact of device closure on quality of life. RESULTS: Most European societies are now in favor of evaluating all patients aged 60 years or younger with recent cryptogenic stroke in the setting of a PFO after careful consideration of the patient's echocardiographic and clinical risk factors. On the other hand, American societies, except for the American Academy of Neurology, have not yet passed official updated recommendations. CONCLUSION: PFO closure can be considered for the prevention of recurrent cryptogenic stroke in patients aged ≤60 years after a thorough evaluation and discussion about benefits and potential risks (including but not limited to atrial fibrillation) of the procedure. Accumulating evidence supports prognostic, quality of life, and economic benefit from percutaneous PFO closure with newer generation closure devices in the right subset of patients. HIGHLIGHTS: Data from 4 major trials (RESPECT, CLOSE, DEFENSE-PFO, REDUCE) demonstrates the superiority of PFO closure over medical management alone in preventing cryptogenic stroke recurrence. Trials investigated mostly patients ≤60 years old, and therefore results may not be generalizable to the entire population. Further randomized trials evaluating the safety and efficacy of PFO closure in patients older than 60 years are warranted.Atrial fibrillation is one of the most common "occult" causes of cryptogenic stroke and should be excluded by ambulatory electrocardiographic monitoring. It is important to also rule out other causes of stroke, including hypercoagulable states, atherosclerotic lesions, other cardioembolic sources, and arterial dissection.Complications of PFO procedure include new-onset AF, development of scar tissue, risk of aortic root dilation and subsequent erosions, and potential thrombi formation on the device.PFO closure with medical therapy is more cost-effective than medical therapy alone.Patients who underwent PFO closure had lower rates of depression, anxiety, and stress compared to those who did undergo closure.Development of the RoPE score has helped clinicians identify patients with cryptogenic stroke and PFO who might be a candidate for PFO closure. A score of 7, 8, and 9-10 corresponds to a causal risk of 72%, 84%, and 88%, respectively, and defines a subset of patients who may benefit from PFO closure.Current guidelines recommend determining the need for PFO closure on a case-by-case basis, depending on risk factors, in patients age 60 or less with recent cryptogenic stroke in the setting of PFO.

Synthesis of systematic reviews of percutaneous device closure of patent foramen ovale (PFO) for prevention of recurrent cryptogenic stroke: Redundant publications and methodological deficiencies.

Critical assessments of systemic reviews and meta-analyses have found them to often be redundant, lacking in novel perspectives, of poor methodological quality, and written by authors with potential conflicts of interest. We sought to investigate these issues as they relate to systemic reviews and meta-analyses of percutaneous patent foramen ovale closure for the prevention of recurrent cryptogenic stroke.

The role of device closure of patent foramen ovale in patients with cryptogenic stroke.

One of the most frequent causes of cardiac embolism in cryptogenic stroke is a paradoxical embolus, which originate from systemic venous source though an unidentified patent foramen ovale (PFO). PFO is a common finding in the general population with a prevalence of 25% to 30%. Transcatheter PFO device closure is known to be feasible and safety treatment for such patients. In recent years, several randomized controlled trials (RCTs) have been conducted to address the superiority of PFO closure over medical therapy alone in the prevention of stroke recurrence in patients with PFO. In contrast to findings from early 3 RCTs, recent 4 RCTs could successfully show the benefits of PFO device closure compared with medical therapy, with less peri- and postprocedural complication. Based on these data, PFO device closure is recommended to carefully select cryptogenic stroke patients aged from 18 to 65 years, with a high probability of a causal role of the PFO in stroke events. However, it is still uncertain whether PFO closure is superior to oral anticoagulants therapy in these patients. Therefore, further prospective randomized trials are needed to address the efficacy of PFO device closure to oral anticoagulants therapy.

Left Atrial Appendage Occlusion: Past, Present and Future.

There are several situations whereby oral anticoagulation may be unsuitable for stroke prevention in patients with atrial fibrillation (AF). Percutaneous left atrial appendage (LAA) occlusion has received much attention in this area. Various devices have already been developed and tested for this purpose. Data from registries and cohort studies have indicated favourable short- and long-term outcomes with LAA occlusion, and several international guidelines recommend its use in AF patients with contraindications to oral anticoagulation. However, prospective controlled trials in this very population are lacking. Furthermore, while modelling studies on cost analyses have suggested that LAA occlusion may be a cost-effective strategy compared with standard medical therapy, these have not been performed in high-risk patients who may have limited survival in the medium to long term. Thus, while LAA occlusion offers promise, there is a strong need for additional research to investigate its exact role, its long-term outcomes and cost efficacy.

Percutaneous Device Closure of Congenital Isolated Ventricular Septal Defects: A Single-Center Retrospective Database Study Amongst 412 Cases.

To identify suitable cases and reduce failure/complication rates for percutaneous ventricular septal defect (VSD) closure, we aimed to (1) study causes of device failure and (2) compare outcomes with different VSD types and devices in a high-volume single center with limited resources. Retrospective data of 412 elective percutaneous VSD closure of isolated congenital VSDs between 2003 and 2017 were analyzed. Out of 412, 363 were successfully implanted, in 30 device implantation failed, and in 19 the procedure was abandoned. Outcome was assessed using echocardiography, electrocardiography, and catheterization data (before procedure, immediately after and during follow-up). Logistic regression analyses were performed to assess effects of age, VSD type, and device type and size on procedural outcome. Median [interquartile range] age and body surface area were 6.6 [4.1-10.9] years and 0.7 [0.5-1.0] m2, respectively. Device failure was not associated with age (p = 0.08), type of VSD (p = 0.5), device type (p = 0.2), or device size (p = 0.1). Device failure occurred in 7.6% of patients. As device type is not related to failure rate and device failure and complication risk was not associated with age, it is justifiable to use financially beneficial ductal devices in VSD position and to consider closure of VSD with device in clinically indicated children.