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Conduction system disease impairs cardiac function, which can reduce exercise capacity, cause symptoms such as breathlessness and fatigue, and, if severe, result in syncope and death. Pacemakers were originally developed to treat profound bradycardia caused by complete heart block. However, pacing the right ventricle leads to non-physiological activation of the ventricular myocardium, reducing global cardiac performance. Early developments in physiological pacing focused on promoting intrinsic activation, delivering more physiological heart rate responses during exercise, and co-ordinating atrial and ventricular activation. More recently, the focus has shifted to delivering pacing which preserves or restores normal ventricular activation patterns, including atrio-biventricular pacing, conduction system pacing by His-bundle pacing, left bundle branch pacing, left septal pacing, and Bachmann\u2019s bundle pacing. Adoption of these more physiological approaches might reduce the adverse effects of pacing, as well as expanding pacing indications to treatment of other forms of conduction system disease. This paper reviews the evolving field of physiological pacing.<\/jats:p>","DOI":"10.1093\/eurheartj\/ehaf440","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T15:06:56Z","timestamp":1752851216000},"page":"3407-3419","source":"Crossref","is-referenced-by-count":25,"title":["Physiological pacing: mechanisms, clinical indications, and perspectives"],"prefix":"10.1093","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2775-5126","authenticated-orcid":false,"given":"Zachary","family":"Whinnett","sequence":"first","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London , Du Cane Road, London W12 0NN ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1681-2981","authenticated-orcid":false,"given":"Akriti","family":"Naraen","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London , Du Cane Road, London W12 0NN ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2230-100X","authenticated-orcid":false,"given":"Pugazhendhi","family":"Vijayaraman","sequence":"additional","affiliation":[{"name":"Geisinger Heart Institute , Wilkes Barre, PA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1471-7016","authenticated-orcid":false,"given":"John G F","family":"Cleland","sequence":"additional","affiliation":[{"name":"School of Cardiovascular and Metabolic Health, Glasgow Cardiovascular Research Centre, University of Glasgow, British Heart Foundation , Glasgow ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7472-7358","authenticated-orcid":false,"given":"Daniel","family":"Keene","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London , Du Cane Road, London W12 0NN ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,7,18]]},"reference":[{"key":"2025091915500140800_ehaf440-B1","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1083\/jcb.102.5.1758","article-title":"Myosin types and fiber types in cardiac muscle. 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