{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T06:55:21Z","timestamp":1793084121272,"version":"4.5.0"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Arrhythmia and Electrophysiology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Current guidelines recommend regular screening for first-degree relatives of gene-elusive arrhythmogenic right ventricular cardiomyopathy (ARVC) patients using a similar regimen as for genotype-positive\/phenotype-negative relatives. However, the multifactorial nature of gene-elusive ARVC may necessitate a different approach. This study aimed to determine the yield of cardiac screening in first-degree relatives of ARVC probands without a validated genetic cause.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>We included all first-degree relatives of probands who (1) met the 2010 Task Force Criteria, (2) underwent next-generation sequencing that included all genes with at least moderate evidence for ARVC causation per Clinical Genome Resource appraisal (validated ARVC genes), and (3) had no pathogenic\/likely pathogenic (P\/LP) variants identified in these genes. The primary and secondary end points were definite ARVC by the 2010 Task Force Criteria and ventricular arrhythmia, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      We included 44 relatives (39.0 [22.3\u201345.8] years; 36% male) from 24 families. In 4 (17%) families, a P\/LP variant was identified in a different cardiomyopathy\/arrhythmia gene (\n                      <jats:italic toggle=\"yes\">SCN5A<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">LMNA<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">CDH2<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">FLNC<\/jats:italic>\n                      ). Overall, 10 (23%) relatives had definite ARVC at baseline evaluation. Of the 20 relatives without definite ARVC who had follow-up available, 8\/20 (40%) relatives progressed to definite ARVC during 9.0 (5.8\u201314.4) years of follow-up. No statistical difference in the yield of baseline screening or serial evaluation between relatives from families with a P\/LP variant and relatives from families without a P\/LP variant was observed. Of the 27 relatives who had follow-up available, ventricular arrhythmia was observed in 2\/27 (7%) relatives and occurred 6.3 and 13.8 years after definite ARVC diagnosis. Both of those relatives were from families without a P\/LP variant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>These findings highlight the importance of managing first-degree relatives of ARVC probands without a validated genetic cause similarly to genotype-positive ARVC relatives. Furthermore, using a broad cardiomyopathy and arrhythmia gene panel in ARVC probands, rather than limiting testing to validated ARVC genes alone, is warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circep.125.014420","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T09:00:24Z","timestamp":1782982824000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Yield of Family Screening in Arrhythmogenic Right Ventricular Cardiomyopathy Without a Validated Genetic Cause"],"prefix":"10.1161","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2674-8709","authenticated-orcid":true,"given":"Steven A.","family":"Muller","sequence":"first","affiliation":[{"name":"Department of Cardiology, University Medical Center Utrecht, the Netherlands (S.A.M., A.S., P.L., P.v.d.H., M.J.C., M.I.F.J.O., A.S.J.M.t.R.)."},{"name":"Member of the European Reference Network for rare, low prevalence and complex diseases of the heart: ERN GUARD-Heart (S.A.M., A.S., P.L., P.v.d.H., M.J.C., M.I.F.J.O., J.P.v.T., A.S.J.M.t.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittney","family":"Murray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crystal","family":"Tichnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5557-0023","authenticated-orcid":true,"given":"Arman","family":"Salavati","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Utrecht, the Netherlands (S.A.M., A.S., P.L., P.v.d.H., M.J.C., M.I.F.J.O., A.S.J.M.t.R.)."},{"name":"Member of the European Reference Network for rare, low prevalence and complex diseases of the heart: ERN GUARD-Heart (S.A.M., A.S., P.L., P.v.d.H., M.J.C., M.I.F.J.O., J.P.v.T., A.S.J.M.t.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3263-9007","authenticated-orcid":true,"given":"Peter","family":"Loh","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Utrecht, the Netherlands (S.A.M., A.S., P.L., P.v.d.H., M.J.C., M.I.F.J.O., A.S.J.M.t.R.)."},{"name":"Member of the European Reference Network for rare, low prevalence and complex diseases of the heart: ERN GUARD-Heart (S.A.M., A.S., P.L., P.v.d.H., M.J.C., M.I.F.J.O., J.P.v.T., A.S.J.M.t.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5589-1216","authenticated-orcid":true,"given":"Richard T.","family":"Carrick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2825-8428","authenticated-orcid":true,"given":"Moniek G.P.J.","family":"Cox","sequence":"additional","affiliation":[{"name":"Heart Center, University Medical Center Groningen, Department of Cardiology, University of Groningen, the Netherlands (M.G.P.J.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2713-686X","authenticated-orcid":true,"given":"Pim","family":"van der Harst","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Utrecht, the Netherlands (S.A.M., A.S., P.L., P.v.d.H., M.J.C., M.I.F.J.O., A.S.J.M.t.R.)."},{"name":"Member of the European Reference Network for rare, low prevalence and complex diseases of the heart: ERN GUARD-Heart (S.A.M., A.S., P.L., P.v.d.H., M.J.C., M.I.F.J.O., J.P.v.T., A.S.J.M.t.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6041-6759","authenticated-orcid":true,"given":"Maarten J.","family":"Cramer","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Utrecht, the Netherlands (S.A.M., A.S., P.L., P.v.d.H., M.J.C., M.I.F.J.O., A.S.J.M.t.R.)."},{"name":"Member of the European Reference Network for rare, low prevalence and complex diseases of the heart: ERN GUARD-Heart (S.A.M., A.S., P.L., P.v.d.H., M.J.C., M.I.F.J.O., J.P.v.T., A.S.J.M.t.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3166-518X","authenticated-orcid":true,"given":"Marish I.F.J.","family":"Oerlemans","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Utrecht, the Netherlands (S.A.M., A.S., P.L., P.v.d.H., M.J.C., M.I.F.J.O., A.S.J.M.t.R.)."},{"name":"Member of the European Reference Network for rare, low prevalence and complex diseases of the heart: ERN GUARD-Heart (S.A.M., A.S., P.L., P.v.d.H., M.J.C., M.I.F.J.O., J.P.v.T., 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