{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T20:39:37Z","timestamp":1783024777667,"version":"3.54.6"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Arrhythmia and Electrophysiology"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Population genomic screening for desmosome variants associated with arrhythmogenic right ventricular cardiomyopathy (ARVC) may facilitate early disease detection and protective intervention. The validated ARVC risk calculator offers a novel means to risk stratify individuals with diagnosed ARVC, but predicted risk in the context of genomic screening identification has not been explored.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              Individuals harboring a pathogenic\/likely pathogenic variant in a desmosome gene (\n              <jats:italic>PKP2<\/jats:italic>\n              ,\n              <jats:italic>DSP<\/jats:italic>\n              ,\n              <jats:italic>DSG2<\/jats:italic>\n              , or\n              <jats:italic>DSC2<\/jats:italic>\n              ) were identified through the Geisinger MyCode Genomic Screening and Counseling program. The ARVC risk calculator was applied to patients with a subsequent evaluation of right ventricular function. This predicted risk was compared with outcomes in the first 5 years (range, 0.3\u20135.0 years) after genetic result return.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              Of 254 individuals with a clinically confirmed pathogenic\/likely pathogenic desmosome variant, 113 (median age, 56 [interquartile range, 42\u201366]; 71% female) had cardiac imaging in follow-up and no prior sustained ventricular arrhythmia (VA). Eighty-two (73%) had no ARVC task force criteria (TFC) besides the variant (possible diagnosis), 22 (19%) had a single additional minor criterion (borderline diagnosis), and 9 (8%) met criteria for definite diagnosis. The median 5-year predicted VA risk was 3.9% (2.3%\u20136.6%), notably lower than that of the calculator derivation cohort (20.6%). The risk of fast VA was 1.6% (1.0%\u20132.9%). The predicted VA risk was higher in individuals with any nongenetic ARVC task force criteria (6.3% [2.5\u201313.2%]) versus those without (3.7% [2.2\u20135.6%];\n              <jats:italic>P<\/jats:italic>\n              =0.01), and in individuals with\n              <jats:italic>DSP<\/jats:italic>\n              variants (6.1% [3.9\u20137.8%] versus\n              <jats:italic>PKP2<\/jats:italic>\n              3.4% [2.2\u20135.3%];\n              <jats:italic>P<\/jats:italic>\n              =0.01). Over a median 3.0 years of follow-up (\u22645 years only), no sustained VA events were observed in this cohort.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>The predicted 5-year risk of VA in individuals ascertained via population genomic screening for desmosome variants is low (3.9%; 1.6% for fast VA) but may vary by affected gene and ARVC task force criteria burden.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circep.124.013231","type":"journal-article","created":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T10:01:52Z","timestamp":1740391312000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Predicted Risk of Ventricular Arrhythmias in a Genome-First Population With Genetic Risk for Arrhythmogenic Right Ventricular Cardiomyopathy"],"prefix":"10.1161","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8184-8676","authenticated-orcid":true,"given":"Eric D.","family":"Carruth","sequence":"first","affiliation":[{"name":"Department of Genomic Health (E.D.C.), Geisinger, Danville, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7870-8584","authenticated-orcid":true,"given":"Brittney","family":"Murray","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Johns Hopkins Medical Center, Baltimore, MD (B.M., C.T., H.C., C.A.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3465-294X","authenticated-orcid":true,"given":"Crystal","family":"Tichnell","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Johns Hopkins Medical Center, Baltimore, MD (B.M., C.T., H.C., C.A.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9624-3191","authenticated-orcid":true,"given":"Katelyn","family":"Young","sequence":"additional","affiliation":[{"name":"Heart and Vascular Institute (K.Y.), Geisinger, Danville, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9262-9433","authenticated-orcid":true,"given":"Hugh","family":"Calkins","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Johns Hopkins Medical Center, Baltimore, MD (B.M., C.T., H.C., C.A.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8040-4600","authenticated-orcid":true,"given":"Cynthia A.","family":"James","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Johns Hopkins Medical Center, Baltimore, MD (B.M., C.T., H.C., C.A.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3227-4490","authenticated-orcid":true,"given":"Christopher M.","family":"Haggerty","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY 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