{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:41:47Z","timestamp":1791315707797,"version":"4.3.1"},"reference-count":106,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>\n                      Pathogenic\/likely pathogenic (LP) desmin (\n                      <jats:italic toggle=\"yes\">DES<\/jats:italic>\n                      ) variants cause heterogeneous cardiomyopathy and skeletal myopathy phenotypes. Limited data suggest a high incidence of major adverse cardiac events (MACEs), including cardiac conduction disease, sustained ventricular arrhythmias (VA), and heart failure (HF) events (HF hospitalization, left ventricular assist device\/cardiac transplant, HF-related death) in patients with pathogenic\/LP\n                      <jats:italic toggle=\"yes\">DES<\/jats:italic>\n                      variants. However, pleiotropic presentation and small cohort sizes have limited clinical phenotype and outcome characterization. We aimed to describe the natural history, phenotype spectrum, familial penetrance and outcomes in patients with pathogenic\/LP\n                      <jats:italic toggle=\"yes\">DES<\/jats:italic>\n                      variants through a systematic review and individual patient data meta-analysis using published reports.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      We searched Medline (PubMed) and Embase for studies that evaluated cardiac phenotypes in patients with pathogenic\/LP\n                      <jats:italic toggle=\"yes\">DES<\/jats:italic>\n                      variants. Cardiomyopathy diagnosis or occurrence of MACE was considered evidence of cardiac involvement\/penetrance. Lifetime event-free survival from cardiac conduction disease, sustained VA, HF events, and composite MACE was assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Of the 4212 screened publications, 71 met the inclusion criteria. A total of 230 patients were included (52.6% men, 52.2% probands, median age: 31 years [22.0\u201342.8] at first evaluation, median follow-up: 3 years [0\u201311.0]). Overall, 124 (53.9%) patients were diagnosed with cardiomyopathy, predominantly dilated cardiomyopathy (14.8%), followed by restrictive cardiomyopathy (13.5%), whereas other forms were less common: arrhythmogenic cardiomyopathy (7.0%), hypertrophic cardiomyopathy (6.1%), arrhythmogenic right ventricular cardiomyopathy (5.2%), and other forms (7.4%). Overall, 132 (57.4%) patients developed MACE, with 96 (41.7%) having cardiac conduction disease, 36 (15.7%) sustained VA, and 43 (18.7%) HF events. Familial penetrance of cardiac disease was 63.6% among relatives with pathogenic\/LP\n                      <jats:italic toggle=\"yes\">DES<\/jats:italic>\n                      variants. Male sex was associated with an increased risk of sustained VA (hazard ratio, 2.28;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.02) and HF events (hazard ratio, 2.45;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.008).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">DES<\/jats:italic>\n                      cardiomyopathy exhibits heterogeneous phenotypes and a distinct natural history, characterized by high familial penetrance and a substantial MACE burden. Male patients face a higher risk of sustained VA events.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circgen.124.004878","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T05:00:35Z","timestamp":1739941235000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":15,"title":["Natural History, Phenotype Spectrum, and Clinical Outcomes of Desmin (\n                    <i>DES<\/i>\n                    )-Associated Cardiomyopathy"],"prefix":"10.1161","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0050-5717","authenticated-orcid":true,"given":"Babken","family":"Asatryan","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine (B.A., B.M., S.A.M., C.T., A.G., R.T.C., H.C., C.A.J., A.S.B.),"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3388-4119","authenticated-orcid":true,"given":"Marina","family":"Rieder","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland (M.R.)."}],"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 (B.A., B.M., S.A.M., C.T., A.G., R.T.C., H.C., C.A.J., A.S.B.),"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2674-8709","authenticated-orcid":true,"given":"Steven A.","family":"Muller","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine (B.A., B.M., S.A.M., C.T., A.G., R.T.C., H.C., C.A.J., A.S.B.),"},{"name":"Division of Cardiology, University Medical Centre, Utrecht, the Netherlands (S.A.M., A.S.J.M.R.)."},{"name":"European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart: ERN GUARD-Heart (S.A.M., A.S.J.M.tR)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crystal","family":"Tichnell","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine (B.A., B.M., S.A.M., C.T., A.G., R.T.C., H.C., C.A.J., A.S.B.),"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3432-070X","authenticated-orcid":true,"given":"Alessio","family":"Gasperetti","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine (B.A., B.M., S.A.M., C.T., A.G., R.T.C., H.C., C.A.J., A.S.B.),"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard T.","family":"Carrick","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine (B.A., B.M., S.A.M., C.T., A.G., R.T.C., H.C., C.A.J., A.S.B.),"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1878-5694","authenticated-orcid":true,"given":"Emily","family":"Joseph","sequence":"additional","affiliation":[{"name":"Welch Medical Library (E.J.), Johns Hopkins University School of Medicine, Baltimore, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2558-7798","authenticated-orcid":true,"given":"Doris G.","family":"Leung","sequence":"additional","affiliation":[{"name":"Kennedy Krieger Institute (D.G.L.), Johns Hopkins University School of Medicine, Baltimore, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4694-4790","authenticated-orcid":true,"given":"Anneline S.J.M.","family":"te Riele","sequence":"additional","affiliation":[{"name":"Division of Cardiology, University Medical Centre, Utrecht, the Netherlands (S.A.M., A.S.J.M.R.)."},{"name":"European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart: ERN GUARD-Heart (S.A.M., A.S.J.M.tR)"},{"name":"Netherlands Heart Institute, Utrecht, the Netherlands (A.S.J.M.tR.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9422-6742","authenticated-orcid":true,"given":"Stefan L.","family":"Zimmerman","sequence":"additional","affiliation":[{"name":"The Russell H. 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