Vacuum-Assisted Catheter-Based Inversion of the Left Atrial Appendage: First- in-Animal Feasibility in a Swine Model

Vacuum-Assisted Catheter-Based Inversion of the Left Atrial Appendage: First- in-Animal Feasibility in a Swine Model | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Vacuum-Assisted Catheter-Based Inversion of the Left Atrial Appendage: First- in-Animal Feasibility in a Swine Model Muhammad Ali, Jessica Amilcar, Caroline Stolz², Rick Rockar, Kyya Copeland², and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8222461/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background The left atrial appendage (LAA) is the primary source of thrombus formation in atrial fibrillation. Mechanical exclusion of the LAA using occlusion devices can prevent embolic stroke but requires permanent implants and may lead to device-related complications. Mechanical inversion of the LAA represents a potential non-implant alternative, but whether this can be achieved using a fully percutaneous, catheter-based approach is unknown. Objectives To evaluate the feasibility of catheter-based, vacuum-assisted LAA inversion using a transseptal aspiration system in a large-animal model. Methods A 59-kg domestic swine underwent transseptal access via the right femoral vein under fluoroscopy, transesophageal echocardiography (TEE), and intracardiac echocardiography (ICE). A 22-F aspiration catheter was advanced into the left atrium and positioned at the LAA apex. Negative pressure was generated manually with a 60-mL syringe attached to the aspiration port, and sequential suction–traction maneuvers were performed to induce LAA inversion. Procedural feasibility, hemodynamic stability, imaging changes, and gross pathology were assessed. Results Transseptal access, catheter positioning, and suction delivery were feasible. Complete LAA inversion into the left atrium was achieved after four suction attempts and confirmed by TEE. A mild pericardial effusion developed, likely related to contact between the stiff catheter tip and the thin appendage wall, but it was not hemodynamically significant. Necropsy demonstrated a discolored ring consistent with localized tissue injury and a small perforation at the LAA apex. Conclusions This first-in-animal feasibility study demonstrates that vacuum-assisted catheter-based inversion of the LAA is technically achievable using current-generation aspiration systems. Although preliminary safety limitations were identified, the findings support further refinement of dedicated, atraumatic aspiration catheters and justify chronic survival and design-optimization studies. A catheter-based, non-implant LAA inversion strategy may represent a future alternative for stroke prevention in patients with atrial fibrillation. atrial fibrillation left atrial appendage stroke prevention catheter-based intervention vacuum-assisted inversion Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction The left atrial appendage (LAA) is a small, muscular outpouching of the left atrium and the predominant site of thrombus formation in patients with non-valvular atrial fibrillation ( 1 , 2 ). Loss of coordinated atrial contraction leads to blood stasis within the LAA and predisposes to thrombus, accounting for more than 90% of thrombi in this setting ( 3 ). Percutaneous or surgical LAA occlusion provides an alternative to long-term oral anticoagulation but depends on permanent implants and may be complicated by device-related thrombus, migration, incomplete sealing, or pericardial effusion ( 4 – 6 ). Mechanical inversion of the LAA has recently been introduced as a novel non-implant strategy for stroke prevention. In a proof-of-concept study in swine, Wang and colleagues demonstrated that direct mechanical inversion of the LAA results in anatomic exclusion of the appendage and predictable healing and fibrosis during chronic follow-up ( 7 ). However, their technique required direct manipulation of the appendage wall through surgical or minimally invasive access and did not test any fully catheter-based approach. We hypothesized that negative pressure delivered through a transseptal aspiration catheter could generate inward traction sufficient to invert the LAA apex without surgical manipulation or implants. In this pilot study, we sought to evaluate the feasibility of vacuum-assisted, catheter-based LAA inversion in a large-animal model and to describe the procedural characteristics and immediate safety profile of this approach. Methods Animal preparation A 59-kg domestic Yorkshire swine underwent general anesthesia, endotracheal intubation, and mechanical ventilation according to institutional laboratory animal protocols for acute procedures. Continuous electrocardiographic and hemodynamic monitoring was maintained throughout the experiment. All procedures were approved by the Institutional Animal Care and Use Committee (IACUC). Baseline imaging Prior to catheterization, a comprehensive TEE examination was performed to evaluate global cardiac function, confirm normal atrial anatomy, and exclude baseline LAA thrombus or other anomalies (Fig. 1 ). Standard mid-esophageal views were obtained at multiple angles, including approximately 55° and 145°, to visualize the LAA. Vascular access and transseptal puncture Right femoral venous access was obtained via surgical cutdown, and a large-bore vascular introducer sheath was inserted. A steerable transseptal sheath (Agilis, Abbott, USA) was advanced into the right atrium. Under combined ICE and fluoroscopic guidance, a transseptal puncture was performed at the fossa ovalis using standard techniques. The dilator and sheath were advanced into the left atrium, and an extra-stiff 0.035-inch guidewire (Lunderquist, Cook Medical, USA) was positioned in the left atrium to facilitate subsequent device delivery. Aspiration catheter delivery and suction protocol The interatrial septal tract was predilated with the dilator from a 22-F AngioVac aspiration catheter (F1885, AngioDynamics, USA). The AngioVac aspiration guide catheter was then advanced across the septum over the extra-stiff guidewire and positioned within the left atrium under continuous fluoroscopic, ICE, and TEE guidance. The distal curve of the catheter was oriented toward the LAA cavity, and the tip was advanced to the LAA apex. (Fig. 2 , 3 , 4 ) Negative pressure for vacuum-assisted inversion was generated manually with a 60-mL catheter-tip syringe connected to the catheter’s aspiration port. After the onset of suction, gentle traction was applied to the catheter while maintaining its orientation to draw the LAA apex inward toward the left atrium. Suction–traction maneuvers were repeated as needed, up to four attempts, until sustained inversion was observed. Outcome measures and necropsy The primary endpoint was technical success, defined as complete inversion of the LAA apex into the left atrium confirmed by TEE in orthogonal views (Fig. 5 ). Secondary observations included procedural feasibility, hemodynamic stability, occurrence of pericardial effusion, and visible complications on imaging. Following completion of the procedure, the animal was euthanized, and a detailed necropsy was performed. The heart was inspected for evidence of LAA inversion, tissue injury, perforation, or pericardial hemorrhage. Results Baseline TEE confirmed normal cardiac anatomy and a smooth-contoured LAA without evidence of thrombus. Transseptal puncture and advancement of the 22-F aspiration catheter into the left atrium were successfully performed over the extra-stiff guidewire. During the initial suction attempts, inward deformation of the LAA wall was observed on TEE and ICE, but the appendage returned to its native configuration once suction was released. On the fourth attempt, sustained inward displacement of the appendage apex was achieved. Multiplane TEE imaging demonstrated a smooth, homogeneous tissue mound protruding into the left atrial cavity, consistent with complete inversion of the LAA. Contrast injection through the aspiration catheter during the later stages of the procedure revealed a mild pericardial effusion, which was confirmed by ICE and TEE. Despite this finding, arterial pressure, heart rate, and oxygen saturation remained stable, and there were no signs of tamponade or hemodynamic compromise. At necropsy, the LAA was identified and exhibited a discolored purple ring, most likely reflecting localized bruising and hemorrhage from suction and catheter contact. A small perforation was present in the appendage wall, corresponding to the region of maximal catheter interaction. No large pericardial clot or hemothorax was observed. Discussion In this first-in-animal feasibility study, we demonstrated that vacuum-assisted inversion of the LAA can be achieved using a fully catheter-based, transseptal approach. The technique aims to mechanically exclude the appendage by inverting its apex into the left atrium without the need for clips, sutures, or occluder implants ( 5 , 6 ). The ability to invert the LAA using negative pressure has important translational implications. Existing LAA occlusion strategies rely on permanent devices that may be associated with device-related thrombus, peri-device leaks, and the need for post-procedural antithrombotic therapy. A successful non-implant approach could potentially mitigate these limitations while preserving the minimally invasive nature of contemporary structural heart procedures. The present work complements the study by Wang et al. ( 7 ), which established the anatomical and biological feasibility of LAA inversion in swine using direct mechanical manipulation. Whereas their study focused on the healing response and long-term remodeling of an inverted appendage, our experiment introduces a purely intravascular method capable of generating inversion using tools and workflows familiar to interventional cardiologists. Together, these studies outline a potential pathway from concept to catheter-based therapy. Several limitations emerged. The aspiration catheter used in this feasibility experiment was not designed specifically for LAA inversion. Its stiff distal tip likely contributed to the observed tissue injury, including local bruising and the small perforation identified at necropsy. Manual generation of negative pressure with a large syringe also limited control over the magnitude and rate of suction, which may have increased mechanical stress on the thin atrial wall. Future device iterations should incorporate softer, atraumatic distal segments, pressure-limited suction control, and shapes tailored to conform to LAA anatomy. Chronic survival studies in large animals will be essential to determine the durability of inversion, the extent of fibrosis and endothelialization, the impact on atrial function, and the potential for thrombus formation at the inverted stump. Computational modeling of suction forces and wall stress may further inform safe operating parameters. Despite these limitations, the current study provides an important proof of concept: catheter-based vacuum-assisted LAA inversion is technically achievable. For selected patients with atrial fibrillation who are unsuitable for device-based occlusion or long-term anticoagulation ( 8 – 10 ), a refined non-implant inversion strategy could ultimately expand therapeutic options. Conclusion Vacuum-assisted inversion of the LAA using a 22-F aspiration catheter delivered through a transseptal approach is technically feasible in a swine model. While a mild, hemodynamically insignificant pericardial effusion and a small appendage perforation were observed, these findings highlight opportunities for refinement of catheter design and suction control rather than limitations of the underlying concept. Dedicated treatment-specific aspiration catheters and larger, chronic animal studies are warranted to confirm safety, durability, and translational potential of this non-implant strategy for stroke prevention in atrial fibrillation. Declarations Author Contribution Muhammad Ali: Conceptualization, procedure design, manuscript writing.Jessica Amilcar, Caroline Stolz: Animal procedure execution, imaging acquisition.Rick Rockar, Kyya Copeland, Dexter Curtis, Ashiya Chisolm: Animal handling and support procedures.Michael Sweet: Technical assistance with imaging systems.Khaldoun Ali: Assistance with drafting sections of the manuscript.Brad Farrell: Study oversight, data interpretation.All authors reviewed and approved the final manuscript. References Ho SY, Anderson RH (2005) Anatomy of the left atrial appendage. Heart 91:987–995 Yamamoto K et al (1993) Atrial natriuretic peptide secretion from the left atrial appendage. J Am Coll Cardiol 22:1464–1469 Al-Saady NM et al (1999) Left atrial appendage: structure, function, and role in thromboembolism. Heart 82:547–554 Blackshear JL, Odell JA (1996) Appendage obliteration during cardiac surgery. Ann Thorac Surg 61:755–759 Holmes DR Jr et al (2009) Prospective randomized evaluation of the Watchman left atrial appendage closure device in patients with atrial fibrillation (PROTECT AF). Lancet 374:534–542 Emmert MY et al (2014) Safe, effective and durable epicardial left atrial appendage clip occlusion: long-term results. Eur J Cardiothorac Surg 45:126–131 Wang Y, Wang M, Guo X, Han L, Kassab G (2023) Safety and feasibility of left atrial appendage inversion in swine: A proof-of-concept study for potential therapy to prevent embolic stroke. Front Bioeng Biotechnol 11:1011121 Di Biase L et al (2010) Left atrial appendage as a trigger site for atrial fibrillation. Circulation 122:109–118 Beinart R et al (2011) Left atrial appendage physiology and stroke prevention. J Am Coll Cardiol 58:2237–2245 Hindricks G et al (2021) 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation. Eur Heart J 42:373–498 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8222461","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":557208706,"identity":"925ac48a-ee3b-483d-9cd9-9c93106123d0","order_by":0,"name":"Muhammad Ali","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAx0lEQVRIiWNgGAWjYDCCA0D8wOC/HD8zAyOQzUyklgQDZmPJZjCbaC0MzIkbDhCrhe/26cQPCQVsxsbHmR8c+NhmzcDf3p2AV4vkudzNEgkGPHJmh9kMDs5sS2eQOHN2A14tBmd4NwC1SBibHeZhOMzbdpjBQCKXoJbNPxIMDBI3N5OgZRvQloTEDczEapEEarFIMDhgLAHyy4xz6TwE/cIHdNiND38OyPH3H3744EOZtRx/ey9+LRiAhzTlo2AUjIJRMAqwAgBTr0mCBdqn9wAAAABJRU5ErkJggg==","orcid":"","institution":"Clinic of Cardiology Salzgitter","correspondingAuthor":true,"prefix":"","firstName":"Muhammad","middleName":"","lastName":"Ali","suffix":""},{"id":557208707,"identity":"67f6c892-329d-4834-a5f2-841c51b45998","order_by":1,"name":"Jessica Amilcar","email":"","orcid":"","institution":"Veranex Preclinical Services","correspondingAuthor":false,"prefix":"","firstName":"Jessica","middleName":"","lastName":"Amilcar","suffix":""},{"id":557208708,"identity":"846658b7-2400-4d71-ba56-d6855af1a25f","order_by":2,"name":"Caroline Stolz²","email":"","orcid":"","institution":"Veranex Preclinical Services","correspondingAuthor":false,"prefix":"","firstName":"Caroline","middleName":"","lastName":"Stolz²","suffix":""},{"id":557208709,"identity":"bbfe35dd-b133-4603-8583-a926edd60f59","order_by":3,"name":"Rick Rockar","email":"","orcid":"","institution":"Veranex Preclinical Services","correspondingAuthor":false,"prefix":"","firstName":"Rick","middleName":"","lastName":"Rockar","suffix":""},{"id":557208710,"identity":"ec7594c0-e2d6-4db1-addd-bea70a6eb01b","order_by":4,"name":"Kyya Copeland²","email":"","orcid":"","institution":"Veranex Preclinical Services","correspondingAuthor":false,"prefix":"","firstName":"Kyya","middleName":"","lastName":"Copeland²","suffix":""},{"id":557208711,"identity":"839161fe-6f35-454c-9053-9e1102bd70ae","order_by":5,"name":"Dexter Curtis²","email":"","orcid":"","institution":"Veranex Preclinical Services","correspondingAuthor":false,"prefix":"","firstName":"Dexter","middleName":"","lastName":"Curtis²","suffix":""},{"id":557208712,"identity":"5e71f96e-88cb-49f3-b125-23198fc64e40","order_by":6,"name":"Ashiya Chisolm²","email":"","orcid":"","institution":"Veranex Preclinical Services","correspondingAuthor":false,"prefix":"","firstName":"Ashiya","middleName":"","lastName":"Chisolm²","suffix":""},{"id":557208713,"identity":"b824a99e-1a38-4b62-9f68-662a29c55aa1","order_by":7,"name":"Michael Sweet","email":"","orcid":"","institution":"Veranex Preclinical Services","correspondingAuthor":false,"prefix":"","firstName":"Michael","middleName":"","lastName":"Sweet","suffix":""},{"id":557208714,"identity":"8a814bc8-1460-4dc1-829a-39f522521db6","order_by":8,"name":"Khaldoun Ali","email":"","orcid":"","institution":"Hospital Braunschweig","correspondingAuthor":false,"prefix":"","firstName":"Khaldoun","middleName":"","lastName":"Ali","suffix":""},{"id":557208715,"identity":"3e59a6d6-60b8-49a2-ade5-83ad0f1bfff7","order_by":9,"name":"Brad Farrell","email":"","orcid":"","institution":"Veranex Preclinical Services","correspondingAuthor":false,"prefix":"","firstName":"Brad","middleName":"","lastName":"Farrell","suffix":""}],"badges":[],"createdAt":"2025-11-27 13:23:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8222461/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8222461/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":97870535,"identity":"a38bf1ae-00a9-435d-8c25-6a288c2d401c","added_by":"auto","created_at":"2025-12-10 10:13:00","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":94926,"visible":true,"origin":"","legend":"\u003cp\u003eBaseline TEE views of the left atrial appendage. Mid-esophageal two-dimensional views at approximately 55° and 145° show smooth LAA contours without thrombus, confirming suitability for interventional manipulation.\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8222461/v1/5ef9c5c05ac8122878a805f3.jpg"},{"id":97898440,"identity":"ba1a8af1-2b95-4344-9bcb-a8ee162c63a7","added_by":"auto","created_at":"2025-12-10 15:39:10","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":99627,"visible":true,"origin":"","legend":"\u003cp\u003eTEE-guided positioning of the aspiration catheter within the LAA. Mid-esophageal views at approximately 56° and 146° demonstrate the catheter tip in the appendage cavity (arrows). At the onset of suction, partial inward deformation of the LAA wall is observed.\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8222461/v1/e8e34818e3493022bc5180b6.jpg"},{"id":97870533,"identity":"16771fa9-37a2-4222-aea2-3671a09622cf","added_by":"auto","created_at":"2025-12-10 10:13:00","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":90642,"visible":true,"origin":"","legend":"\u003cp\u003eFluoroscopic guidance of catheter positioning. The distal curve of the aspiration catheter is directed toward the LAA cavity (arrow), confirming appropriate orientation for vacuum-assisted inversion.\u003c/p\u003e","description":"","filename":"Picture3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8222461/v1/98701c452c79f7668b669e83.jpg"},{"id":97900264,"identity":"5022548d-18be-4976-b168-02b5c2f8d7ee","added_by":"auto","created_at":"2025-12-10 15:45:21","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":51285,"visible":true,"origin":"","legend":"\u003cp\u003eA simplified anatomical schematic demonstrating catheter-based vacuum-assisted inversion of the left atrial appendage (LAA). After femoral venous access, a delivery catheter is advanced through the inferior vena cava, right atrium, and across the interatrial septum into the left atrium. A funnel-shaped aspiration catheter is positioned at the LAA orifice and directed toward the appendage cavity.\u003c/p\u003e","description":"","filename":"Picture4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8222461/v1/0ba0735a68056ab74114e208.jpg"},{"id":97870537,"identity":"a9bcff3a-b824-453b-bcb1-ca4886691db5","added_by":"auto","created_at":"2025-12-10 10:13:00","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":99613,"visible":true,"origin":"","legend":"\u003cp\u003eEchocardiographic confirmation of complete LAA inversion. With continued suction, TEE views at approximately 56° and 146° show complete inversion of the LAA into the left atrium (arrows), forming a smooth tissue mound consistent with mechanical inversion from negative pressure.\u003c/p\u003e","description":"","filename":"Picture5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8222461/v1/99620fc9518bc16eeeec1498.jpg"},{"id":97903411,"identity":"c664c2e2-ac58-4d0d-ae3b-607c494d4e20","added_by":"auto","created_at":"2025-12-10 15:55:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":866925,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8222461/v1/cc39176e-7606-45c9-a0ca-e0db40eb19e9.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Vacuum-Assisted Catheter-Based Inversion of the Left Atrial Appendage: First- in-Animal Feasibility in a Swine Model","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe left atrial appendage (LAA) is a small, muscular outpouching of the left atrium and the predominant site of thrombus formation in patients with non-valvular atrial fibrillation (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Loss of coordinated atrial contraction leads to blood stasis within the LAA and predisposes to thrombus, accounting for more than 90% of thrombi in this setting (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Percutaneous or surgical LAA occlusion provides an alternative to long-term oral anticoagulation but depends on permanent implants and may be complicated by device-related thrombus, migration, incomplete sealing, or pericardial effusion (\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eMechanical inversion of the LAA has recently been introduced as a novel non-implant strategy for stroke prevention. In a proof-of-concept study in swine, Wang and colleagues demonstrated that direct mechanical inversion of the LAA results in anatomic exclusion of the appendage and predictable healing and fibrosis during chronic follow-up (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). However, their technique required direct manipulation of the appendage wall through surgical or minimally invasive access and did not test any fully catheter-based approach.\u003c/p\u003e\u003cp\u003eWe hypothesized that negative pressure delivered through a transseptal aspiration catheter could generate inward traction sufficient to invert the LAA apex without surgical manipulation or implants. In this pilot study, we sought to evaluate the feasibility of vacuum-assisted, catheter-based LAA inversion in a large-animal model and to describe the procedural characteristics and immediate safety profile of this approach.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eAnimal preparation\u003c/h2\u003e\u003cp\u003eA 59-kg domestic Yorkshire swine underwent general anesthesia, endotracheal intubation, and mechanical ventilation according to institutional laboratory animal protocols for acute procedures. Continuous electrocardiographic and hemodynamic monitoring was maintained throughout the experiment. All procedures were approved by the Institutional Animal Care and Use Committee (IACUC).\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eBaseline imaging\u003c/h3\u003e\n\u003cp\u003ePrior to catheterization, a comprehensive TEE examination was performed to evaluate global cardiac function, confirm normal atrial anatomy, and exclude baseline LAA thrombus or other anomalies (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Standard mid-esophageal views were obtained at multiple angles, including approximately 55\u0026deg; and 145\u0026deg;, to visualize the LAA.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\n\u003ch3\u003eVascular access and transseptal puncture\u003c/h3\u003e\n\u003cp\u003eRight femoral venous access was obtained via surgical cutdown, and a large-bore vascular introducer sheath was inserted. A steerable transseptal sheath (Agilis, Abbott, USA) was advanced into the right atrium. Under combined ICE and fluoroscopic guidance, a transseptal puncture was performed at the fossa ovalis using standard techniques. The dilator and sheath were advanced into the left atrium, and an extra-stiff 0.035-inch guidewire (Lunderquist, Cook Medical, USA) was positioned in the left atrium to facilitate subsequent device delivery.\u003c/p\u003e\n\u003ch3\u003eAspiration catheter delivery and suction protocol\u003c/h3\u003e\n\u003cp\u003eThe interatrial septal tract was predilated with the dilator from a 22-F AngioVac aspiration catheter (F1885, AngioDynamics, USA). The AngioVac aspiration guide catheter was then advanced across the septum over the extra-stiff guidewire and positioned within the left atrium under continuous fluoroscopic, ICE, and TEE guidance. The distal curve of the catheter was oriented toward the LAA cavity, and the tip was advanced to the LAA apex. (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e,\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eNegative pressure for vacuum-assisted inversion was generated manually with a 60-mL catheter-tip syringe connected to the catheter\u0026rsquo;s aspiration port. After the onset of suction, gentle traction was applied to the catheter while maintaining its orientation to draw the LAA apex inward toward the left atrium. Suction\u0026ndash;traction maneuvers were repeated as needed, up to four attempts, until sustained inversion was observed.\u003c/p\u003e\n\u003ch3\u003eOutcome measures and necropsy\u003c/h3\u003e\n\u003cp\u003eThe primary endpoint was technical success, defined as complete inversion of the LAA apex into the left atrium confirmed by TEE in orthogonal views (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). Secondary observations included procedural feasibility, hemodynamic stability, occurrence of pericardial effusion, and visible complications on imaging. Following completion of the procedure, the animal was euthanized, and a detailed necropsy was performed. The heart was inspected for evidence of LAA inversion, tissue injury, perforation, or pericardial hemorrhage.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eBaseline TEE confirmed normal cardiac anatomy and a smooth-contoured LAA without evidence of thrombus. Transseptal puncture and advancement of the 22-F aspiration catheter into the left atrium were successfully performed over the extra-stiff guidewire.\u003c/p\u003e\u003cp\u003eDuring the initial suction attempts, inward deformation of the LAA wall was observed on TEE and ICE, but the appendage returned to its native configuration once suction was released. On the fourth attempt, sustained inward displacement of the appendage apex was achieved. Multiplane TEE imaging demonstrated a smooth, homogeneous tissue mound protruding into the left atrial cavity, consistent with complete inversion of the LAA.\u003c/p\u003e\u003cp\u003eContrast injection through the aspiration catheter during the later stages of the procedure revealed a mild pericardial effusion, which was confirmed by ICE and TEE. Despite this finding, arterial pressure, heart rate, and oxygen saturation remained stable, and there were no signs of tamponade or hemodynamic compromise.\u003c/p\u003e\u003cp\u003eAt necropsy, the LAA was identified and exhibited a discolored purple ring, most likely reflecting localized bruising and hemorrhage from suction and catheter contact. A small perforation was present in the appendage wall, corresponding to the region of maximal catheter interaction. No large pericardial clot or hemothorax was observed.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this first-in-animal feasibility study, we demonstrated that vacuum-assisted inversion of the LAA can be achieved using a fully catheter-based, transseptal approach. The technique aims to mechanically exclude the appendage by inverting its apex into the left atrium without the need for clips, sutures, or occluder implants (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe ability to invert the LAA using negative pressure has important translational implications. Existing LAA occlusion strategies rely on permanent devices that may be associated with device-related thrombus, peri-device leaks, and the need for post-procedural antithrombotic therapy. A successful non-implant approach could potentially mitigate these limitations while preserving the minimally invasive nature of contemporary structural heart procedures.\u003c/p\u003e\u003cp\u003eThe present work complements the study by Wang et al. (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e), which established the anatomical and biological feasibility of LAA inversion in swine using direct mechanical manipulation. Whereas their study focused on the healing response and long-term remodeling of an inverted appendage, our experiment introduces a purely intravascular method capable of generating inversion using tools and workflows familiar to interventional cardiologists. Together, these studies outline a potential pathway from concept to catheter-based therapy.\u003c/p\u003e\u003cp\u003eSeveral limitations emerged. The aspiration catheter used in this feasibility experiment was not designed specifically for LAA inversion. Its stiff distal tip likely contributed to the observed tissue injury, including local bruising and the small perforation identified at necropsy. Manual generation of negative pressure with a large syringe also limited control over the magnitude and rate of suction, which may have increased mechanical stress on the thin atrial wall.\u003c/p\u003e\u003cp\u003eFuture device iterations should incorporate softer, atraumatic distal segments, pressure-limited suction control, and shapes tailored to conform to LAA anatomy. Chronic survival studies in large animals will be essential to determine the durability of inversion, the extent of fibrosis and endothelialization, the impact on atrial function, and the potential for thrombus formation at the inverted stump. Computational modeling of suction forces and wall stress may further inform safe operating parameters.\u003c/p\u003e\u003cp\u003eDespite these limitations, the current study provides an important proof of concept: catheter-based vacuum-assisted LAA inversion is technically achievable. For selected patients with atrial fibrillation who are unsuitable for device-based occlusion or long-term anticoagulation (\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e), a refined non-implant inversion strategy could ultimately expand therapeutic options.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eVacuum-assisted inversion of the LAA using a 22-F aspiration catheter delivered through a transseptal approach is technically feasible in a swine model. While a mild, hemodynamically insignificant pericardial effusion and a small appendage perforation were observed, these findings highlight opportunities for refinement of catheter design and suction control rather than limitations of the underlying concept. Dedicated treatment-specific aspiration catheters and larger, chronic animal studies are warranted to confirm safety, durability, and translational potential of this non-implant strategy for stroke prevention in atrial fibrillation.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eMuhammad Ali: Conceptualization, procedure design, manuscript writing.Jessica Amilcar, Caroline Stolz: Animal procedure execution, imaging acquisition.Rick Rockar, Kyya Copeland, Dexter Curtis, Ashiya Chisolm: Animal handling and support procedures.Michael Sweet: Technical assistance with imaging systems.Khaldoun Ali: Assistance with drafting sections of the manuscript.Brad Farrell: Study oversight, data interpretation.All authors reviewed and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHo SY, Anderson RH (2005) Anatomy of the left atrial appendage. Heart 91:987\u0026ndash;995\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYamamoto K et al (1993) Atrial natriuretic peptide secretion from the left atrial appendage. J Am Coll Cardiol 22:1464\u0026ndash;1469\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAl-Saady NM et al (1999) Left atrial appendage: structure, function, and role in thromboembolism. Heart 82:547\u0026ndash;554\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBlackshear JL, Odell JA (1996) Appendage obliteration during cardiac surgery. Ann Thorac Surg 61:755\u0026ndash;759\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHolmes DR Jr et al (2009) Prospective randomized evaluation of the Watchman left atrial appendage closure device in patients with atrial fibrillation (PROTECT AF). Lancet 374:534\u0026ndash;542\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEmmert MY et al (2014) Safe, effective and durable epicardial left atrial appendage clip occlusion: long-term results. Eur J Cardiothorac Surg 45:126\u0026ndash;131\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang Y, Wang M, Guo X, Han L, Kassab G (2023) Safety and feasibility of left atrial appendage inversion in swine: A proof-of-concept study for potential therapy to prevent embolic stroke. Front Bioeng Biotechnol 11:1011121\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDi Biase L et al (2010) Left atrial appendage as a trigger site for atrial fibrillation. Circulation 122:109\u0026ndash;118\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBeinart R et al (2011) Left atrial appendage physiology and stroke prevention. J Am Coll Cardiol 58:2237\u0026ndash;2245\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHindricks G et al (2021) 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation. Eur Heart J 42:373\u0026ndash;498\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"atrial fibrillation, left atrial appendage, stroke prevention, catheter-based intervention, vacuum-assisted inversion","lastPublishedDoi":"10.21203/rs.3.rs-8222461/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8222461/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eThe left atrial appendage (LAA) is the primary source of thrombus formation in atrial fibrillation. Mechanical exclusion of the LAA using occlusion devices can prevent embolic stroke but requires permanent implants and may lead to device-related complications. Mechanical inversion of the LAA represents a potential non-implant alternative, but whether this can be achieved using a fully percutaneous, catheter-based approach is unknown.\u003c/p\u003e\u003ch2\u003eObjectives\u003c/h2\u003e\u003cp\u003eTo evaluate the feasibility of catheter-based, vacuum-assisted LAA inversion using a transseptal aspiration system in a large-animal model.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eA 59-kg domestic swine underwent transseptal access via the right femoral vein under fluoroscopy, transesophageal echocardiography (TEE), and intracardiac echocardiography (ICE). A 22-F aspiration catheter was advanced into the left atrium and positioned at the LAA apex. Negative pressure was generated manually with a 60-mL syringe attached to the aspiration port, and sequential suction\u0026ndash;traction maneuvers were performed to induce LAA inversion. Procedural feasibility, hemodynamic stability, imaging changes, and gross pathology were assessed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eTransseptal access, catheter positioning, and suction delivery were feasible. Complete LAA inversion into the left atrium was achieved after four suction attempts and confirmed by TEE. A mild pericardial effusion developed, likely related to contact between the stiff catheter tip and the thin appendage wall, but it was not hemodynamically significant. Necropsy demonstrated a discolored ring consistent with localized tissue injury and a small perforation at the LAA apex.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eThis first-in-animal feasibility study demonstrates that vacuum-assisted catheter-based inversion of the LAA is technically achievable using current-generation aspiration systems. Although preliminary safety limitations were identified, the findings support further refinement of dedicated, atraumatic aspiration catheters and justify chronic survival and design-optimization studies. A catheter-based, non-implant LAA inversion strategy may represent a future alternative for stroke prevention in patients with atrial fibrillation.\u003c/p\u003e","manuscriptTitle":"Vacuum-Assisted Catheter-Based Inversion of the Left Atrial Appendage: First- in-Animal Feasibility in a Swine Model","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-10 10:12:56","doi":"10.21203/rs.3.rs-8222461/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"bf172dba-3791-45c3-beea-b3b4122cfaf3","owner":[],"postedDate":"December 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-12-10T10:12:56+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-10 10:12:56","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8222461","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8222461","identity":"rs-8222461","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}