{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T08:57:31Z","timestamp":1774515451433,"version":"3.50.1"},"reference-count":19,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T00:00:00Z","timestamp":1756252800000},"content-version":"unspecified","delay-in-days":57,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Open Heart"],"accepted":{"date-parts":[[2025,8,14]]},"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Truncating variants in the Filamin C (\n                      <jats:italic>FLNCtv<\/jats:italic>\n                      ) gene are causative of highly arrhythmogenic cardiomyopathies. Guidelines remain controversial concerning competitive and high-intensity sports for\n                      <jats:italic>FLNCtv<\/jats:italic>\n                      carriers. Indeed, the impact of high-intensity exercise on individuals carrying these variants remains poorly understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      This retrospective study analysed 45 probands and relatives carrying\n                      <jats:italic>FLNCtv<\/jats:italic>\n                      , collecting data on previous physical activity. Over a mean follow-up of 4.9\u00b10.6 years, 9 individuals (20%) experienced life-threatening arrhythmias (LTA). No significant association was found between history of higher-intensity exercise and increased LTA risk (OR 1.442; 95%\u2009CI 0.321 to 6.467; p=0.633), left ventricular systolic dysfunction (OR 0.505; 95%\u2009CI 0.143 to 1.791; p=0.290) or right ventricular dysfunction (OR 3.333; 95%\u2009CI 0.263 to 42.212; p=0.353). However, three phenotype-positive subjects (7%), mostly with dilated cardiomyopathy, experienced LTA during intense exercise.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Over a mean follow-up of 5 years, high-intensity exercise did not appear to be associated with an increased risk of LTA or structural cardiac disease in\n                      <jats:italic>FLNCtv<\/jats:italic>\n                      carriers. However, we report LTA in already affected subjects during intense exercise. These findings indicate that further investigations may lead to a re-evaluation of exercise recommendations for phenotype-negative carriers and highlight the importance of larger population-based studies on this topic.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/openhrt-2025-003502","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T17:15:23Z","timestamp":1756314923000},"page":"e003502","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Prognostic role of exercise intensity in familial Filamin C truncating variants"],"prefix":"10.1136","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6324-9821","authenticated-orcid":false,"given":"Giulio","family":"Savonitto","sequence":"first","affiliation":[{"name":"Cardiothoracovascular Department, Center for Diagnosis and Treatment of Cardiomyopathies, Azienda Sanitaria Universitaria Giuliano-Isontina, University of Trieste; European Reference Network for Rare, Low-Prevalence, and Complex Diseases of the Heart (ERN GUARD-Heart), Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5823-3777","authenticated-orcid":false,"given":"Alessia","family":"Paldino","sequence":"additional","affiliation":[{"name":"Cardiothoracovascular Department, Center for Diagnosis and Treatment of Cardiomyopathies, Azienda Sanitaria Universitaria Giuliano-Isontina, University of Trieste; European Reference Network for Rare, Low-Prevalence, and Complex Diseases of the Heart (ERN GUARD-Heart), Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Setti","sequence":"additional","affiliation":[{"name":"Cardiothoracovascular Department, Center for Diagnosis and Treatment of Cardiomyopathies, Azienda Sanitaria Universitaria Giuliano-Isontina, University of Trieste; European Reference Network for Rare, Low-Prevalence, and Complex Diseases of the Heart (ERN GUARD-Heart), Trieste, Italy"},{"name":"Division of Cardiology, University of Verona Faculty of Medicine and Surgery, Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Furlan","sequence":"additional","affiliation":[{"name":"Cardiothoracovascular Department, Center for Diagnosis and Treatment of Cardiomyopathies, Azienda Sanitaria Universitaria Giuliano-Isontina, University of Trieste; European Reference Network for Rare, Low-Prevalence, and Complex Diseases of the Heart (ERN GUARD-Heart), Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irena","family":"Tavcar","sequence":"additional","affiliation":[{"name":"Cardiothoracovascular Department, Center for Diagnosis and Treatment of Cardiomyopathies, Azienda Sanitaria Universitaria Giuliano-Isontina, University of Trieste; European Reference Network for Rare, Low-Prevalence, and Complex Diseases of the Heart (ERN GUARD-Heart), Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavio Luciano","family":"Ribichini","sequence":"additional","affiliation":[{"name":"Division of Cardiology, University of Verona Faculty of Medicine and Surgery, Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Perotto","sequence":"additional","affiliation":[{"name":"Cardiothoracovascular Department, Center for Diagnosis and Treatment of Cardiomyopathies, Azienda Sanitaria Universitaria Giuliano-Isontina, University of Trieste; European Reference Network for Rare, Low-Prevalence, and Complex Diseases of the Heart (ERN GUARD-Heart), Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Gigli","sequence":"additional","affiliation":[{"name":"Cardiothoracovascular Department, Center for Diagnosis and Treatment of Cardiomyopathies, Azienda Sanitaria Universitaria Giuliano-Isontina, University of Trieste; European Reference Network for Rare, Low-Prevalence, and Complex Diseases of the Heart (ERN GUARD-Heart), Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa","family":"Mestroni","sequence":"additional","affiliation":[{"name":"Molecular Genetics, Cardiovascular Institute and Adult Medical Genetics Program, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Dal Ferro","sequence":"additional","affiliation":[{"name":"Cardiothoracovascular Department, Center for Diagnosis and Treatment of Cardiomyopathies, Azienda Sanitaria Universitaria Giuliano-Isontina, University of Trieste; European Reference Network for Rare, Low-Prevalence, and Complex Diseases of the Heart (ERN GUARD-Heart), Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1022-3131","authenticated-orcid":false,"given":"Marco","family":"Merlo","sequence":"additional","affiliation":[{"name":"Cardiothoracovascular Department, Center for Diagnosis and Treatment of Cardiomyopathies, Azienda Sanitaria Universitaria Giuliano-Isontina, University of Trieste; European Reference Network for Rare, Low-Prevalence, and Complex Diseases of the Heart (ERN GUARD-Heart), Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianfranco","family":"Sinagra","sequence":"additional","affiliation":[{"name":"Cardiothoracovascular Department, Center for Diagnosis and Treatment of Cardiomyopathies, Azienda Sanitaria Universitaria Giuliano-Isontina, University of Trieste; European Reference Network for Rare, Low-Prevalence, and Complex Diseases of the Heart (ERN GUARD-Heart), Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,8,27]]},"reference":[{"key":"2026010701104301000_12.2.e003502.1","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ijcard.2019.09.048","article-title":"Filamin C variants are associated with a distinctive clinical and immunohistochemical arrhythmogenic cardiomyopathy phenotype","volume":"307","author":"Hall","year":"2020","journal-title":"Int J Cardiol"},{"key":"2026010701104301000_12.2.e003502.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.09.927"},{"key":"2026010701104301000_12.2.e003502.3","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.abk0052","article-title":"Activation of PDGFRA signaling contributes to filamin C-related arrhythmogenic cardiomyopathy","volume":"8","author":"Chen","year":"2022","journal-title":"Sci Adv"},{"key":"2026010701104301000_12.2.e003502.4","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.120.317076"},{"key":"2026010701104301000_12.2.e003502.5","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.119.012937","article-title":"Exercise is Associated With Impaired Left Ventricular Systolic Function in Patients With Lamin A\/C Genotype","volume":"9","author":"Skj\u00f8lsvik","year":"2020","journal-title":"J Am Heart Assoc"},{"key":"2026010701104301000_12.2.e003502.6","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.181"},{"key":"2026010701104301000_12.2.e003502.7","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.938282"},{"key":"2026010701104301000_12.2.e003502.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.06.033"},{"key":"2026010701104301000_12.2.e003502.9","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1093\/eurjpc\/zwad079","article-title":"Sport and exercise in genotype positive (+) phenotype negative (-) individuals: current dilemmas and future perspectives","volume":"30","author":"Paldino","year":"2023","journal-title":"Eur J Prev Cardiol"},{"key":"2026010701104301000_12.2.e003502.10","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1093\/eurheartj\/ehaa605","article-title":"ESC Guidelines on Sports Cardiology and Exercise in Patients with Cardiovascular Disease","volume":"42","author":"Pelliccia","year":"2020","journal-title":"Eur Heart J"},{"key":"2026010701104301000_12.2.e003502.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2024.12.025"},{"key":"2026010701104301000_12.2.e003502.12","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"2026010701104301000_12.2.e003502.13","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehad194"},{"key":"2026010701104301000_12.2.e003502.14","doi-asserted-by":"publisher","DOI":"10.1093\/ehjci\/jev014"},{"key":"2026010701104301000_12.2.e003502.15","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0b013e31821ece12"},{"key":"2026010701104301000_12.2.e003502.16","doi-asserted-by":"crossref","unstructured":"Savonitto G , Paldino A , Setti M , et al . Exercise Intensity and Cardiac Disease Development in carriers of Titin variants. Eur J Prev Cardiol 2025.:zwaf094. doi:10.1093\/eurjpc\/zwaf094","DOI":"10.1093\/eurjpc\/zwaf236.100"},{"key":"2026010701104301000_12.2.e003502.17","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1161\/CIRCULATIONAHA.121.053521","article-title":"Phenotypic Expression, Natural History, and Risk Stratification of Cardiomyopathy Caused by Filamin C Truncating Variants","volume":"144","author":"Gigli","year":"2021","journal-title":"Circulation"},{"key":"2026010701104301000_12.2.e003502.18","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1001\/jamacardio.2024.5543","article-title":"Arrhythmic Risk Stratification of Carriers of Filamin C Truncating Variants","volume":"10","author":"Gigli","year":"2025","journal-title":"JAMA Cardiol"},{"key":"2026010701104301000_12.2.e003502.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.06.044"}],"container-title":["Open Heart"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/openhrt-2025-003502","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T09:11:02Z","timestamp":1767777062000},"score":1,"resource":{"primary":{"URL":"https:\/\/openheart.bmj.com\/lookup\/doi\/10.1136\/openhrt-2025-003502"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":19,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,8,27]]},"published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1136\/openhrt-2025-003502"],"URL":"https:\/\/doi.org\/10.1136\/openhrt-2025-003502","relation":{},"ISSN":["2053-3624"],"issn-type":[{"value":"2053-3624","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7]]}}}