{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T17:50:18Z","timestamp":1788285018320,"version":"build-2803163510"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T00:00:00Z","timestamp":1635465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000046","name":"Abbott","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000046","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002996","name":"Dutch Heart Foundation","doi-asserted-by":"crossref","award":["2015T082"],"award-info":[{"award-number":["2015T082"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"crossref"}]},{"name":"French Government Agence National de la Recherche","award":["ANR-10-IAHU-04"],"award-info":[{"award-number":["ANR-10-IAHU-04"]}]},{"DOI":"10.13039\/501100003246","name":"Netherlands Organisation for Scientific Research","doi-asserted-by":"publisher","award":["016.176.340"],"award-info":[{"award-number":["016.176.340"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union\u2019s Horizon 2020 Research and Innovation"},{"name":"Marie Sklodowska-Curie","award":["860745"],"award-info":[{"award-number":["860745"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Investigate haemodynamic effects, and their mechanisms, of restoring atrioventricular (AV)-coupling using pacemaker therapy in normal and failing hearts in a combined computational\u2013experimental\u2013clinical study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>Computer simulations were performed in the CircAdapt model of the normal and failing human heart and circulation. Experiments were performed in a porcine model of AV dromotropathy. In a proof-of-principle clinical study, left ventricular (LV) pressure and volume were measured in 22 heart failure (HF) patients (LV ejection fraction &amp;lt;35%) with prolonged PR interval (&amp;gt;230\u2009ms) and narrow or non-left bundle branch block QRS complex. Computer simulations and animal studies in normal hearts showed that restoring of AV-coupling with unchanged ventricular activation sequence significantly increased LV filling, mean arterial pressure, and cardiac output by 10\u201315%. In computer simulations of failing hearts and in HF patients, reducing PR interval by biventricular (BiV) pacing (patients: from 300\u2009\u00b1\u200961 to 137\u2009\u00b1\u200930\u2009ms) resulted in significant increases in LV stroke volume and stroke work (patients: 34\u2009\u00b1\u200940% and 26\u2009\u00b1\u200931%, respectively). However, worsening of ventricular dyssynchrony by using right ventricular (RV) pacing abrogated the benefit of restoring AV-coupling. In model simulations, animals and patients, the increase of LV filling and associated improvement of LV pump function coincided with both larger mitral inflow (E- and A-wave area) and reduction of diastolic mitral regurgitation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Restoration of AV-coupling by BiV pacing in normal and failing hearts with prolonged AV conduction leads to considerable haemodynamic improvement. These results indicate that BiV or physiological pacing, but not RV pacing, may improve cardiac function in patients with HF and prolonged PR interval.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/europace\/euab248","type":"journal-article","created":{"date-parts":[[2021,9,11]],"date-time":"2021-09-11T11:08:53Z","timestamp":1631358533000},"page":"784-795","source":"Crossref","is-referenced-by-count":22,"title":["Pacing therapy for atrioventricular dromotropathy: a combined computational\u2013experimental\u2013clinical study"],"prefix":"10.1093","volume":"24","author":[{"given":"Floor C W M","family":"Salden","sequence":"first","affiliation":[{"name":"Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre+ (MUMC+), Maastricht, The Netherlands"},{"name":"Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1845-6837","authenticated-orcid":false,"given":"Peter R","family":"Huntjens","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands"},{"name":"Department of Cardiology, Washington University in Saint Louis, Saint Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4799-5132","authenticated-orcid":false,"given":"Rick","family":"Schreurs","sequence":"additional","affiliation":[{"name":"Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands"},{"name":"Department of Cardiothoracic Surgery, Maastricht University Medical Centre+ (MUMC+), Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Willemen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Kuiper","sequence":"additional","affiliation":[{"name":"Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3406-4083","authenticated-orcid":false,"given":"Philippe","family":"Wouters","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Centre Utrecht (UMC Utrecht), Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos G","family":"Maessen","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Maastricht University Medical Centre+ (MUMC+), Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Bordachar","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Electrophysiology and Heart Modeling Institute (LIRYC), Bordeaux University, Pessac, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammo","family":"Delhaas","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Luermans","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre+ (MUMC+), Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1102-2155","authenticated-orcid":false,"given":"Mathias","family":"Meine","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Centre Utrecht (UMC Utrecht), Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0506-9512","authenticated-orcid":false,"given":"Cornelis P","family":"Allaart","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Amsterdam University Medical Centre (Amsterdam UMC), Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonius M W","family":"van Stipdonk","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre+ (MUMC+), Maastricht, The 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