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However, the relationship between <jats:sup>123<\/jats:sup>I<jats:italic>-m<\/jats:italic>IBG activity and lethal arrhythmic events (ArE) is not well defined. This study aimed to determine this relationship in Japanese and European cohorts.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We calculated heart-to-mediastinum (H\/M) count ratios and washout rates (WRs) of 827 patients using planar <jats:sup>123<\/jats:sup>I-<jats:italic>m<\/jats:italic>IBG imaging. We defined ArEs as sudden cardiac death, arrhythmic death, and potentially lethal events such as sustained ventricular tachycardia, cardiac arrest with resuscitation, and appropriate implantable cardioverter defibrillator (ICD) discharge, either from a single ICD or as part of a cardiac resynchronization therapy device (CRTD). We analyzed the incidence of ArE with respect to H\/M ratios, WRs and New York Heart Association (NYHA) functional classes among Japanese (J; <jats:italic>n<\/jats:italic>\u2009=\u2009581) and European (E; <jats:italic>n<\/jats:italic>\u2009=\u2009246) cohorts. We also simulated ArE rates <jats:italic>versus<\/jats:italic> H\/M ratios under specific conditions using a machine-learning model incorporating 13 clinical variables. Consecutive patients with CHF were selected in group J, whereas group E comprised candidates for cardiac electronic devices. Groups J and E mostly comprised patients with NYHA functional classes I\/II (95%) and II\/III (91%), respectively, and 21% and 72% were respectively implanted with ICD\/CRTD devices. The ArE rate increased with lower H\/M ratios in group J, but the relationship was bell-shaped, with a high ArE rate within the intermediate H\/M range, in group E. This bell-shaped curve was also evident in patients with NYHA classes II\/III in the combined J and E groups, particularly in those with a high (&gt;\u200915%) <jats:italic>m<\/jats:italic>IBG WR and with ischemic, but not in those with non-ischemic etiologies. Machine learning-based prediction of ArE risk aligned with these findings, indicating a bell-shaped curve in NYHA class II\/III but not in class I.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The relationship between cardiac <jats:sup>123<\/jats:sup>I-<jats:italic>m<\/jats:italic>IBG activity and lethal arrhythmic events is influenced by the background of patients. The bell-shaped relationship in NYHA classes II\/III, high WR, and ischemic etiology likely aids in identifying patients at high risk for ArEs.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13550-024-01131-4","type":"journal-article","created":{"date-parts":[[2024,7,21]],"date-time":"2024-07-21T03:18:02Z","timestamp":1721531882000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cardiac sympathetic activity and lethal arrhythmic events: insight into bell-shaped relationship between 123I-meta-iodobenzylguanidine activity and event rates"],"prefix":"10.1186","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7188-8746","authenticated-orcid":false,"given":"Kenichi","family":"Nakajima","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoaki","family":"Nakata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Doi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derk O.","family":"Verschure","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viviana","family":"Frantellizzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Silvia","family":"De Feo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hayato","family":"Tada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hein J.","family":"Verberne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,7,21]]},"reference":[{"key":"1131_CR1","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1002\/ehf2.12005","volume":"1","author":"P Ponikowski","year":"2014","unstructured":"Ponikowski P, Anker SD, AlHabib KF, Cowie MR, Force TL, Hu S, et al. 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The Ethics Committee at Kanazawa University approved this retrospective study (2018\u2009\u2212\u2009269 [3020]), and waived the need for patient consent to participate.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"K. Nakajima has a collaborative research agreement with PDRadiopharma (Tokyo, Japan), which markets <sup>123<\/sup>I-MIBG in Japan and belongs to a department endowed by PDRadiopharma, Nihon Medi-Physics (Tokyo, Japan), and Siemens Healthcare (Tokyo, Japan).","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"67"}}