{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T23:35:32Z","timestamp":1776900932721,"version":"3.51.2"},"posted":{"date-parts":[[2024,8,26]]},"group-title":"Cardiovascular Medicine","reference-count":48,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T00:00:00Z","timestamp":1724630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,8,26]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>\n                    Pathogenic\/likely pathogenic (P\/LP) desmin (\n                    <jats:italic>DES<\/jats:italic>\n                    ) variants cause heterogeneous cardiomyopathy and\/or skeletal myopathy phenotypes. Limited data suggest a high incidence of major adverse cardiac events (MACE), including cardiac conduction disease (CCD), sustained ventricular arrhythmias (VA), and heart failure (HF) events (HF hospitalization, LVAD\/cardiac transplant, HF-related death), in patients with P\/LP\n                    <jats:italic>DES<\/jats:italic>\n                    variants. However, pleiotropic presentation and small cohort sizes have limited clinical phenotype and outcome characterization.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>\n                    We aimed to describe the natural history, phenotype spectrum, familial penetrance and outcomes in patients with P\/LP\n                    <jats:italic>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 P\/LP\n                    <jats:italic>DES<\/jats:italic>\n                    variants. Cardiomyopathy diagnosis or occurrence of MACE were considered evidence of cardiac involvement\/penetrance. Lifetime event-free survival from CCD, 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                    Out of 4,212 screened publications, 71 met the inclusion criteria. A total of 230 patients were included (52.6% male, 52.2% probands, median age: 31 years [22.0; 42.8] at first evaluation, median follow-up: 3 years [0; 11.0]). 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 CCD, 36 [15.7%] sustained VA, and 43 [18.7%] HF events. Familial penetrance of cardiac disease was 63.6% among relatives with P\/LP\n                    <jats:italic>DES<\/jats:italic>\n                    variants. Male sex was associated with increased risk of sustained VA (HR 2.28, p=0.02) and HF events (HR 2.45, p=0.008).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>\n                    <jats:italic>DES<\/jats:italic>\n                    cardiomyopathy exhibits heterogeneous phenotypes and distinct natural history, characterized by high familial penetrance and substantial MACE burden. Male patients face higher risk of sustained VA events.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.08.24.24311904","type":"posted-content","created":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T12:20:12Z","timestamp":1724674812000},"source":"Crossref","is-referenced-by-count":1,"title":["Natural History, Phenotype Spectrum and Clinical Outcomes of Desmin (\n                  <i>DES<\/i>\n                  )-Associated Cardiomyopathy"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0050-5717","authenticated-orcid":false,"given":"Babken","family":"Asatryan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Rieder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7870-8584","authenticated-orcid":false,"given":"Brittney","family":"Murray","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2674-8709","authenticated-orcid":false,"given":"Steven A.","family":"Muller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Crystal","family":"Tichnell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3432-070X","authenticated-orcid":false,"given":"Alessio","family":"Gasperetti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard T.","family":"Carrick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"Joseph","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doris G.","family":"Leung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4694-4790","authenticated-orcid":false,"given":"Anneline S.J.M.","family":"te Riele","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9422-6742","authenticated-orcid":false,"given":"Stefan L.","family":"Zimmerman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9262-9433","authenticated-orcid":false,"given":"Hugh","family":"Calkins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8040-4600","authenticated-orcid":false,"given":"Cynthia A.","family":"James","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5275-8049","authenticated-orcid":false,"given":"Andreas S.","family":"Barth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024082814350830000_2024.08.24.24311904v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2009.11.025"},{"key":"2024082814350830000_2024.08.24.24311904v1.2","doi-asserted-by":"crossref","unstructured":"Su W , van Wijk SW , Brundel B . 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