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In individuals at risk for cardiomyopathy, non-invasive estimation of normal ventricular activation may provide valuable information to aid risk stratification to prevent sudden cardiac death. However, multiple simultaneous activation wavefronts initiated by the His-Purkinje system, severely complicate<jats:italic>i<\/jats:italic>ECG. To improve the estimation of normal ventricular activation, the<jats:italic>i<\/jats:italic>ECG method should accurately mimic the effect of the His-Purkinje system, which is not taken into account in the previously published multi-focal<jats:italic>i<\/jats:italic>ECG. Therefore, we introduce the novel multi-wave<jats:italic>i<\/jats:italic>ECG method and report on its performance. Multi-wave<jats:italic>i<\/jats:italic>ECG and multi-focal<jats:italic>i<\/jats:italic>ECG were tested in four patients undergoing invasive electro-anatomical mapping during normal ventricular activation. In each subject, 67-electrode BSPM were recorded and used as input for both<jats:italic>i<\/jats:italic>ECG methods. The<jats:italic>i<\/jats:italic>ECG and invasive local activation timing (LAT) maps were compared. Median epicardial inter-map correlation coefficient (CC) between invasive LAT maps and estimated multi-wave<jats:italic>i<\/jats:italic>ECG versus multi-focal<jats:italic>i<\/jats:italic>ECG was 0.61 versus 0.31. Endocardial inter-map CC was 0.54 respectively 0.22. Modeling the His-Purkinje system resulted in a physiologically realistic and robust non-invasive estimation of normal ventricular activation, which might enable the early detection of cardiac disease during normal sinus rhythm.<\/jats:p>","DOI":"10.1007\/s10439-022-02905-4","type":"journal-article","created":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T14:02:49Z","timestamp":1643032969000},"page":"343-359","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Modeling the His-Purkinje Effect in Non-invasive Estimation of Endocardial and Epicardial Ventricular Activation"],"prefix":"10.1007","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7550-0489","authenticated-orcid":false,"given":"Machteld J.","family":"Boonstra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob W.","family":"Roudijk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"Brummel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wil","family":"Kassenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lennart J.","family":"Blom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thom F.","family":"Oostendorp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneline S. 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