{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T12:59:07Z","timestamp":1762001947744},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T00:00:00Z","timestamp":1612396800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T00:00:00Z","timestamp":1612396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Occlutech Jena Germany"},{"name":"Helmholtz Association through programme-oriented funding"},{"name":"Projekt DEAL"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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\u201339\u00a0kg 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\u00a0weeks. Moreover, after 4, 8 and, 12\u00a0weeks 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\u00a0weeks, advanced after 8\u00a0weeks and completed after 12\u00a0weeks. 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.<\/jats:p>","DOI":"10.1038\/s41598-021-82359-1","type":"journal-article","created":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T11:08:10Z","timestamp":1612436890000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Preclinical assessment of a modified Occlutech left atrial appendage closure device in a porcine model"],"prefix":"10.1038","volume":"11","author":[{"given":"Markus","family":"Reinthaler","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Grosshauser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanja","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliane","family":"Unger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ross","family":"Morgan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Friederike","family":"Zimmermann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Hartung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Seppelt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denitsa","family":"Meteva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfram","family":"Haider","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulf","family":"Landmesser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carsten","family":"Skurk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,2,4]]},"reference":[{"key":"82359_CR1","doi-asserted-by":"publisher","first-page":"2893","DOI":"10.1093\/eurheartj\/ehw210","volume":"37","author":"P Kirchhof","year":"2016","unstructured":"Kirchhof, P. et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur. Heart J. 37, 2893\u20132962. https:\/\/doi.org\/10.1093\/eurheartj\/ehw210 (2016).","journal-title":"Eur. Heart J."},{"key":"82359_CR2","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1056\/NEJMoa0905561","volume":"361","author":"SJ Connolly","year":"2009","unstructured":"Connolly, S. J. et al. Dabigatran versus warfarin in patients with atrial fibrillation. N. Engl. J. Med. 361, 1139\u20131151. https:\/\/doi.org\/10.1056\/NEJMoa0905561 (2009).","journal-title":"N. Engl. J. Med."},{"key":"82359_CR3","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1056\/NEJMoa1107039","volume":"365","author":"CB Granger","year":"2011","unstructured":"Granger, C. B. et al. Apixaban versus warfarin in patients with atrial fibrillation. N. Engl. J. Med. 365, 981\u2013992. https:\/\/doi.org\/10.1056\/NEJMoa1107039 (2011).","journal-title":"N. Engl. J. Med."},{"key":"82359_CR4","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1056\/NEJMoa1009638","volume":"365","author":"MR Patel","year":"2011","unstructured":"Patel, M. R. et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N. Engl. J. Med. 365, 883\u2013891. https:\/\/doi.org\/10.1056\/NEJMoa1009638 (2011).","journal-title":"N. Engl. J. Med."},{"key":"82359_CR5","doi-asserted-by":"publisher","first-page":"2882","DOI":"10.1093\/eurheartj\/ehw233","volume":"37","author":"JP Bassand","year":"2016","unstructured":"Bassand, J. P. et al. Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF. Eur. Heart J. 37, 2882\u20132889. https:\/\/doi.org\/10.1093\/eurheartj\/ehw233 (2016).","journal-title":"Eur. Heart J."},{"key":"82359_CR6","doi-asserted-by":"publisher","first-page":"3365","DOI":"10.1093\/eurheartj\/ehu374","volume":"35","author":"GY Lip","year":"2014","unstructured":"Lip, G. Y. et al. Prognosis and treatment of atrial fibrillation patients by European cardiologists: one year follow-up of the EURObservational Research Programme-Atrial Fibrillation General Registry Pilot Phase (EORP-AF Pilot registry). Eur. Heart J. 35, 3365\u20133376. https:\/\/doi.org\/10.1093\/eurheartj\/ehu374 (2014).","journal-title":"Eur. Heart J."},{"key":"82359_CR7","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1093\/europace\/eut263","volume":"16","author":"P Kirchhof","year":"2014","unstructured":"Kirchhof, P. et al. Management of atrial fibrillation in seven European countries after the publication of the 2010 ESC Guidelines on atrial fibrillation: primary results of the PREvention oF thromboemolic events\u2013European Registry in Atrial Fibrillation (PREFER in AF). Europace 16, 6\u201314. https:\/\/doi.org\/10.1093\/europace\/eut263 (2014).","journal-title":"Europace"},{"key":"82359_CR8","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1016\/0003-4975(95)00887-X","volume":"61","author":"JL Blackshear","year":"1996","unstructured":"Blackshear, J. L. & Odell, J. A. Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation. Ann. Thorac. Surg. 61, 755\u2013759. https:\/\/doi.org\/10.1016\/0003-4975(95)00887-X (1996).","journal-title":"Ann. Thorac. Surg."},{"key":"82359_CR9","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1016\/S0140-6736(09)61343-X","volume":"374","author":"DR Holmes","year":"2009","unstructured":"Holmes, D. R. et al. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: A randomised non-inferiority trial. Lancet 374, 534\u2013542. https:\/\/doi.org\/10.1016\/S0140-6736(09)61343-X (2009).","journal-title":"Lancet"},{"key":"82359_CR10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jacc.2014.04.029","volume":"64","author":"DR Holmes Jr","year":"2014","unstructured":"Holmes, D. R. Jr. et al. Prospective randomized evaluation of the Watchman Left Atrial Appendage Closure device in patients with atrial fibrillation versus long-term warfarin therapy: The PREVAIL trial. J. Am. Coll. Cardiol. 64, 1\u201312. https:\/\/doi.org\/10.1016\/j.jacc.2014.04.029 (2014).","journal-title":"J. Am. Coll. Cardiol."},{"key":"82359_CR11","doi-asserted-by":"publisher","first-page":"2964","DOI":"10.1016\/j.jacc.2017.10.021","volume":"70","author":"VY Reddy","year":"2017","unstructured":"Reddy, V. Y. et al. 5-Year outcomes after left atrial appendage closure: From the PREVAIL and PROTECT AF trials. J. Am. Coll. Cardiol. 70, 2964\u20132975. https:\/\/doi.org\/10.1016\/j.jacc.2017.10.021 (2017).","journal-title":"J. Am. Coll. Cardiol."},{"key":"82359_CR12","doi-asserted-by":"publisher","DOI":"10.4244\/EIJY19M08_01","author":"M Glikson","year":"2019","unstructured":"Glikson, M. et al. EHRA\/EAPCI expert consensus statement on catheter-based left atrial appendage occlusion: An update. EuroIntervention https:\/\/doi.org\/10.4244\/EIJY19M08_01 (2019).","journal-title":"EuroIntervention"},{"key":"82359_CR13","doi-asserted-by":"publisher","first-page":"e590","DOI":"10.4244\/EIJ-D-18-00344","volume":"14","author":"U Landmesser","year":"2018","unstructured":"Landmesser, U. et al. Left atrial appendage occlusion with the AMPLATZER Amulet device: One-year follow-up from the prospective global Amulet observational registry. EuroIntervention 14, e590\u2013e597. https:\/\/doi.org\/10.4244\/EIJ-D-18-00344 (2018).","journal-title":"EuroIntervention"},{"key":"82359_CR14","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1016\/j.hrthm.2017.05.038","volume":"14","author":"LV Boersma","year":"2017","unstructured":"Boersma, L. V. et al. Efficacy and safety of left atrial appendage closure with WATCHMAN in patients with or without contraindication to oral anticoagulation: 1-Year follow-up outcome data of the EWOLUTION trial. Heart Rhythm 14, 1302\u20131308. https:\/\/doi.org\/10.1016\/j.hrthm.2017.05.038 (2017).","journal-title":"Heart Rhythm"},{"key":"82359_CR15","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1111\/jce.13141","volume":"28","author":"B Bellmann","year":"2017","unstructured":"Bellmann, B. et al. Left atrial appendage closure with the new Occlutech(R) device: First in man experience and neurological outcome. J. Cardiovasc. Electrophysiol. 28, 315\u2013320. https:\/\/doi.org\/10.1111\/jce.13141 (2017).","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"82359_CR16","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1016\/j.ijcard.2014.09.194","volume":"177","author":"JW Park","year":"2014","unstructured":"Park, J. W. et al. Percutaneous left atrial appendage closure with a novel self-modelizing device: A pre-clinical feasibility study. Int. J. Cardiol. 177, 957\u2013963. https:\/\/doi.org\/10.1016\/j.ijcard.2014.09.194 (2014).","journal-title":"Int. J. Cardiol."},{"key":"82359_CR17","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1002\/ccd.22536","volume":"76","author":"JL Bass","year":"2010","unstructured":"Bass, J. L. Transcatheter occlusion of the left atrial appendage\u2013experimental testing of a new Amplatzer device. Catheter. Cardiovasc. Interv. 76, 181\u2013185. https:\/\/doi.org\/10.1002\/ccd.22536 (2010).","journal-title":"Catheter. Cardiovasc. Interv."},{"key":"82359_CR18","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1007\/BF03043007","volume":"23","author":"MP Heintzen","year":"1998","unstructured":"Heintzen, M. P. & Strauer, B. E. Peripheral arterial complications after heart catheterization. Herz 23, 4\u201320. https:\/\/doi.org\/10.1007\/BF03043007 (1998).","journal-title":"Herz"},{"key":"82359_CR19","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1002\/ccd.28335","volume":"95","author":"D Ueshima","year":"2020","unstructured":"Ueshima, D. et al. The impact of pre-existing peripheral artery disease on transcatheter aortic valve implantation outcomes: A systematic review and meta-analysis. Catheter. Cardiovasc. Interv. 95, 993\u20131000. https:\/\/doi.org\/10.1002\/ccd.28335 (2020).","journal-title":"Catheter. Cardiovasc. Interv."},{"key":"82359_CR20","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.ijcard.2016.12.141","volume":"234","author":"B Bellmann","year":"2017","unstructured":"Bellmann, B. et al. Left atrial appendage closure in a patient with left atrial appendage thrombus using a novel fish ball technique. Int. J. Cardiol. 234, 146\u2013149. https:\/\/doi.org\/10.1016\/j.ijcard.2016.12.141 (2017).","journal-title":"Int. J. Cardiol."},{"key":"82359_CR21","doi-asserted-by":"publisher","first-page":"894","DOI":"10.4244\/EIJ-D-18-00419","volume":"14","author":"P Scislo","year":"2018","unstructured":"Scislo, P., Wilimski, R., Zbronski, K. & Huczek, Z. Main pulmonary artery perforations after left atrial appendage occluder implantation. EuroIntervention 14, 894\u2013895. https:\/\/doi.org\/10.4244\/EIJ-D-18-00419 (2018).","journal-title":"EuroIntervention"},{"key":"82359_CR22","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.ijcard.2016.07.048","volume":"221","author":"JS Kim","year":"2016","unstructured":"Kim, J. S. et al. Preclinical assessment of a modified Occlutech left atrial appendage closure device in a canine model. Int. J. Cardiol. 221, 413\u2013418. https:\/\/doi.org\/10.1016\/j.ijcard.2016.07.048 (2016).","journal-title":"Int. J. Cardiol."},{"key":"82359_CR23","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1016\/j.jcin.2010.04.017","volume":"3","author":"RS Schwartz","year":"2010","unstructured":"Schwartz, R. S. et al. Left atrial appendage obliteration: mechanisms of healing and intracardiac integration. JACC Cardiovasc. Interv. 3, 870\u2013877. https:\/\/doi.org\/10.1016\/j.jcin.2010.04.017 (2010).","journal-title":"JACC Cardiovasc. Interv."},{"key":"82359_CR24","doi-asserted-by":"publisher","first-page":"3996","DOI":"10.1016\/j.ijcard.2013.06.083","volume":"168","author":"YY Lam","year":"2013","unstructured":"Lam, Y. Y. et al. Preclinical evaluation of a new left atrial appendage occluder (Lifetech LAmbre device) in a canine model. Int. J. Cardiol. 168, 3996\u20134001. https:\/\/doi.org\/10.1016\/j.ijcard.2013.06.083 (2013).","journal-title":"Int. J. Cardiol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-82359-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-82359-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-82359-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T03:02:15Z","timestamp":1670036535000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-82359-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,4]]},"references-count":24,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["82359"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-82359-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,4]]},"assertion":[{"value":"9 October 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 January 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 February 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study was supported by a grant from Occlutech Jena Germany and by the Helmholtz Association through program-oriented funding to M.R.. J.G. and R.M. work at Occlutech Jena Germany. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"2988"}}