{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T17:14:33Z","timestamp":1769102073671,"version":"3.49.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,5,3]]},"abstract":"<jats:sec xml:lang=\"en\"><jats:title>Background<\/jats:title><jats:p xml:lang=\"en\">The cause of atrioventricular block (AVB) remains unknown in approximately half of young patients with the diagnosis. Although variants in several genes associated with cardiac conduction diseases have been identified, the contribution of genetic variants in younger patients with AVB is unknown.<\/jats:p><\/jats:sec><jats:sec xml:lang=\"en\"><jats:title>Methods and Results<\/jats:title><jats:p xml:lang=\"en\">Using the Danish Pacemaker and Implantable Cardioverter Defibrillator (ICD) Registry, we identified all patients younger than 50\u00a0years receiving a pacemaker because of AVB in Denmark in the period from January 1, 1996 to December 31, 2015. From medical records, we identified patients with unknown cause of AVB at time of pacemaker implantation. These patients were invited to a genetic screening using a panel of 102 genes associated with inherited cardiac diseases. We identified 471 living patients with AVB of unknown cause, of whom 226 (48%) accepted participation. Median age at the time of pacemaker implantation was 39\u00a0years (interquartile range, 32\u201345\u00a0years), and 123 (54%) were men. We found pathogenic or likely pathogenic variants in genes associated with or possibly associated with AVB in 12 patients (5%). Most variants were found in the<jats:italic>LMNA<\/jats:italic>gene (n=5).<jats:italic>LMNA<\/jats:italic>variant carriers all had a family history of either AVB and\/or sudden cardiac death.<\/jats:p><\/jats:sec><jats:sec xml:lang=\"en\"><jats:title>Conclusions<\/jats:title><jats:p xml:lang=\"en\">In young patients with AVB of unknown cause, we found a possible genetic cause in 1 out of 20 participating patients. Variants in the<jats:italic>LMNA<\/jats:italic>gene were most common and associated with a family history of AVB and\/or sudden cardiac death, suggesting that genetic testing should be a part of the diagnostic workup in these patients to stratify risk and screen family members.<\/jats:p><\/jats:sec>","DOI":"10.1161\/jaha.121.025643","type":"journal-article","created":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T09:44:58Z","timestamp":1650966298000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["Diagnostic Yield of Genetic Testing in Young Patients With Atrioventricular Block of Unknown Cause"],"prefix":"10.1161","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4979-2566","authenticated-orcid":false,"given":"Johnni","family":"Resdal Dyssekilde","sequence":"first","affiliation":[{"name":"Department of Cardiology Aarhus University Hospital Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3338-9297","authenticated-orcid":false,"given":"Tanja Charlotte","family":"Frederiksen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Aarhus University Hospital Aarhus Denmark"},{"name":"Department of Clinical Medicine Health Aarhus University Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3894-888X","authenticated-orcid":false,"given":"Morten Krogh","family":"Christiansen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Aarhus University Hospital Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4158-5212","authenticated-orcid":false,"given":"Rikke","family":"Hasle S\u00f8rensen","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Aarhus University Hospital Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisbeth N\u00f8rum","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Aarhus University Hospital Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1405-5136","authenticated-orcid":false,"given":"Peter","family":"Loof M\u00f8ller","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Health Aarhus University Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lene Svendstrup","family":"Christensen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Hospital of Southern Jutland Aabenraa Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0574-2076","authenticated-orcid":false,"given":"Jacob Moesgaard","family":"Larsen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Aalborg University Hospital Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristian Korsgaard","family":"Thomsen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Hospital South West Jutland Esbjerg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tommi Bo","family":"Lindhardt","sequence":"additional","affiliation":[{"name":"Department of Cardiology Copenhagen University HospitalHerlev and Gentofte Hospital Hellerup Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2116-2370","authenticated-orcid":false,"given":"Morten","family":"B\u00f6ttcher","sequence":"additional","affiliation":[{"name":"Department of Cardiology Regional Hospital Herning Herning Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stig","family":"Molsted","sequence":"additional","affiliation":[{"name":"Department of Clinical Research North Zealand Hospital Hiller\u00f8d Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ole","family":"Havndrup","sequence":"additional","affiliation":[{"name":"Department of Cardiology Zealand University Hospital Roskilde Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1360-376X","authenticated-orcid":false,"given":"Thomas","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department of Cardiology Vejle Hospital Vejle Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorthe Svenstrup","family":"M\u00f8ller","sequence":"additional","affiliation":[{"name":"Department of Cardiology Regional Hospital Central Jutland Viborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1192-532X","authenticated-orcid":false,"given":"Finn Lund","family":"Henriksen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Odense University Hospital Odense Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens Brock","family":"Johansen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Odense University Hospital Odense Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9414-1653","authenticated-orcid":false,"given":"Jens Cosedis","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Aarhus University Hospital Aarhus Denmark"},{"name":"Department of Clinical Medicine Health Aarhus University Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0563-7049","authenticated-orcid":false,"given":"Henning","family":"Bundgaard","sequence":"additional","affiliation":[{"name":"Department of Cardiology The Heart Center Rigshospitalet Copenhagen Denmark"},{"name":"Department of Clinical Medicine University of Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4973-8543","authenticated-orcid":false,"given":"Mette","family":"Nygaard","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Health Aarhus University Aarhus Denmark"},{"name":"Department of Health Science and Technology Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1802-4302","authenticated-orcid":false,"given":"Henrik Kj\u00e6rulf","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Aarhus University Hospital Aarhus Denmark"},{"name":"Department of Clinical Medicine Health Aarhus University Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/euz206"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab060"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/HCG.0000000000000067"},{"key":"e_1_3_2_5_2","first-page":"1","article-title":"A novel mutation in LAMIN A\/C is associated with isolated early\u2010 onset atrial fibrillation and progressive atrioventricular block followed by cardiomyopathy and sudden cardiac death","volume":"23","author":"Loscalzo DEHRCJ","year":"2011","unstructured":"Loscalzo DEHRCJ. A novel mutation in LAMIN A\/C is associated with isolated early\u2010 onset atrial fibrillation and progressive atrioventricular block followed by cardiomyopathy and sudden cardiac death. Bone. 2011;23:1\u20137. doi: 10.1016\/j.hrthm.2009.01.037","journal-title":"Bone"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/3684965"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10840-015-9998-z"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.119.007150"},{"key":"e_1_3_2_9_2","unstructured":"Danish pacemaker and ICD register. Danish pacemaker and ICD register\u2014annual report 2019."},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccep.2017.02.002"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/chd.12595"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/jce.12401"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.108.798660"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2012.06.038"},{"key":"e_1_3_2_15_2","first-page":"58","article-title":"2013 ESC guidelines on cardiac pacing and cardiac resynchronization therapy","volume":"67","author":"Brignole M","year":"2014","unstructured":"Brignole M, Auricchio A, Baron\u2010Esquivias G, Bordachar P, Boriani G, Breithardt O\u2010A, Cleland J, Deharo J\u2010C, Delgado V, M. Elliott P, et al. 2013 ESC guidelines on cardiac pacing and cardiac resynchronization therapy. Rev Esp Cardiol (Engl Ed). 2014;67:58. doi: 10.15829\/1560\u20104071\u20102014\u20104\u20105\u201063","journal-title":"Rev Esp Cardiol (Engl Ed)"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/sdata.2017.115"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.37"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2006.00677.x"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2013.08.024"},{"key":"e_1_3_2_20_2","doi-asserted-by":"crossref","first-page":"2732","DOI":"10.1242\/jcs.184150","article-title":"Deleterious assembly of the lamin A\/C mutant p. S143P causes ER stress in familial dilated cardiomyopathy","volume":"129","author":"West G","year":"2016","unstructured":"West G, Gullmets J, Virtanen L, Li S\u2010P, Kein\u00e4nen A, Shimi T, Mauermann M, Heli\u00f6 T, Kaartinen M, Ollila L, et al. Deleterious assembly of the lamin A\/C mutant p. S143P causes ER stress in familial dilated cardiomyopathy. J Cell Sci. 2016;129:2732\u20132743. doi: 10.1242\/jcs.184150","journal-title":"J Cell Sci"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11596-010-0119-z"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.03.149"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.8.560"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehx596"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-004-0589-1"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv316"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1136\/openhrt-2021-001622"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lpm.2018.11.012"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/anec.12687"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.113.000486"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.673"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000007387"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2019-315933"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2014.04.005"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2007.01.029"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.033943"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-016-2748-0"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.121.025643","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,22]],"date-time":"2024-09-22T23:44:04Z","timestamp":1727048644000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.121.025643"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,3]]},"references-count":36,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2022,5,3]]}},"alternative-id":["10.1161\/JAHA.121.025643"],"URL":"https:\/\/doi.org\/10.1161\/jaha.121.025643","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,3]]},"assertion":[{"value":"2022-02-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e025643"}}