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Targeting regions identified by different substrate mapping approaches for ablation resulted in ambiguous outcomes. With the effective refractory period being a fundamental prerequisite for the maintenance of fibrillatory conduction, this study aims at estimating the effective refractory period with clinically available measurements.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>A set of 240 simulations in a spherical model of the left atrium with varying model initialization, combination of cellular refractory properties, and size of a region of lowered effective refractory period was implemented to analyse the capabilities and limitations of cycle length mapping. The minimum observed cycle length and the 25% quantile were compared to the underlying effective refractory period. The density of phase singularities was used as a measure for the complexity of the excitation pattern. Finally, we employed the method in a clinical test of concept including five patients. Areas of lowered effective refractory period could be distinguished from their surroundings in simulated scenarios with successfully induced multi-wavelet re-entry. Larger areas and higher gradients in effective refractory period as well as complex activation patterns favour the method. The 25% quantile of cycle lengths in patients with persistent atrial fibrillation was found to range from 85 to 190\u2009ms.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Cycle length mapping is capable of highlighting regions of pathologic refractory properties. In combination with complementary substrate mapping approaches, the method fosters confidence to enhance the treatment of atrial fibrillation beyond pulmonary vein isolation particularly in patients with complex activation patterns.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/europace\/euaa404","type":"journal-article","created":{"date-parts":[[2020,12,5]],"date-time":"2020-12-05T04:48:39Z","timestamp":1607143719000},"page":"i133-i142","source":"Crossref","is-referenced-by-count":10,"title":["Cycle length statistics during human atrial fibrillation reveal refractory properties of the underlying substrate: a combined <i>in silico<\/i> and clinical test of concept study"],"prefix":"10.1093","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5614-1983","authenticated-orcid":false,"given":"Laura A","family":"Unger","sequence":"first","affiliation":[{"name":"Department of Electrical Engineering and Information Technology, Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), Kaiserstr. 12, 76131 Karlsruhe, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Azzolin","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering and Information Technology, Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), Kaiserstr. 12, 76131 Karlsruhe, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Nothstein","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering and Information Technology, Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), Kaiserstr. 12, 76131 Karlsruhe, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering and Information Technology, Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), Kaiserstr. 12, 76131 Karlsruhe, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Armin","family":"Luik","sequence":"additional","affiliation":[{"name":"Medizinische Klinik IV, St\u00e4dtisches Klinikum Karlsruhe, Karlsruhe 76133, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7111-7992","authenticated-orcid":false,"given":"Gunnar","family":"Seemann","sequence":"additional","affiliation":[{"name":"Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg Bad Krozingen, Medical Center, University of Freiburg, Freiburg 79110, Germany"},{"name":"Faculty of Medicine, University of Freiburg, Freiburg 79110, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7485-6210","authenticated-orcid":false,"given":"Srinath","family":"Yeshwant","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, College of Medicine, University of Vermont, Burlington, Colchester, VT 05446, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1495-4927","authenticated-orcid":false,"given":"Tobias","family":"Oesterlein","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering and Information Technology, Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), Kaiserstr. 12, 76131 Karlsruhe, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olaf","family":"D\u00f6ssel","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering and Information Technology, Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), Kaiserstr. 12, 76131 Karlsruhe, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claus","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Medizinische Klinik IV, St\u00e4dtisches Klinikum 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