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Prior studies have described baseline DSP cardiomyopathy genetic, inflammatory, and structural characteristics. However, cohort sizes have limited full clinical characterization and identification of clinical and demographic predictors of sustained ventricular arrhythmias (VAs), heart failure (HF) hospitalizations, and transplant\/death. In particular, the relevance of acute myocarditis-like episodes for subsequent disease course is largely unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>All patients with pathogenic\/likely pathogenic (P\/LP) DSP variants in the worldwide DSP-ERADOS Network (26 academic institutions across nine countries) were included. The primary outcomes were the development of sustained VA and HF hospitalizations during follow-up. Fine\u2013Gray regressions were used to test association between clinical and instrumental parameters and the development of outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Eight hundred patients [40.3 \u00b1 17.5 years, 47.5% probands, left ventricular ejection fraction (LVEF) 49.5 \u00b1 13.9%] were included. Over 3.7 [1.4\u20137.1] years, 139 (17.4%, 3.9%\/year) and 72 (9.0%, 1.8%\/year) patients experienced sustained VA and HF episodes, respectively. A total of 32.5% of individuals did not fulfil diagnostic criteria for ARVC, DCM, or NDLVC; their VA incidence was 0.5%\/year. In multivariable regression, risk features associated with the development of VA were female sex [adjusted hazard ratio (aHR) 1.547; P = .025], prior non-sustained ventricular tachycardia (aHR 1.721; P = .009), prior sustained VA (aHR 1.923; P = .006), and LVEF \u2264 50% (aHR: 1.645; P = .032), while for HF, they were the presence of T-wave inversion in 3+ electrocardiogram leads (aHR 2.036, P = .007) and LVEF \u2264 50% (aHR 3.879; P &amp;lt; .001). Additionally, 70 (8.8%) patients experienced a myocardial injury episode at presentation or during follow-up. These episodes were associated with an increased risk of VA and HF thereafter (HR 2.394; P &amp;lt; .001, and HR 5.064, P &amp;lt; .001, respectively).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Patients with P\/LP DSP variants experience high rates of sustained VA and HF hospitalizations. These patients demonstrate a distinct clinical phenotype (DSP cardiomyopathy), whose most prominent risk features associated with adverse clinical outcomes are the presence of prior non-sustained ventricular tachycardia or sustained VA, T-wave inversion in 3+ leads on electrocardiogram, LVEF \u2264 50%, and myocardial injury events.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehae571","type":"journal-article","created":{"date-parts":[[2024,8,18]],"date-time":"2024-08-18T18:53:28Z","timestamp":1724007208000},"page":"362-376","source":"Crossref","is-referenced-by-count":86,"title":["Clinical features and outcomes in carriers of pathogenic desmoplakin variants"],"prefix":"10.1093","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3432-070X","authenticated-orcid":false,"given":"Alessio","family":"Gasperetti","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Johns Hopkins University , 601 North Caroline St., Baltimore, MD 21287 ,","place":["USA"]},{"name":"Department of Genetics, University Medical Center Utrecht, University of Utrecht ,","place":["The Netherlands"]},{"name":"Department of Medicine, Division of Cardiology, University Medical Center Utrecht, Utrecht University , Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5589-1216","authenticated-orcid":false,"given":"Richard T","family":"Carrick","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Johns Hopkins University , 601 North Caroline St., Baltimore, MD 21287 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8595-7212","authenticated-orcid":false,"given":"Alexandros","family":"Protonotarios","sequence":"additional","affiliation":[{"name":"UCL Institute of Cardiovascular Science , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7870-8584","authenticated-orcid":false,"given":"Brittney","family":"Murray","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Johns Hopkins University , 601 North Caroline St., Baltimore, MD 21287 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7326-2656","authenticated-orcid":false,"given":"Mikael","family":"Laredo","sequence":"additional","affiliation":[{"name":"Institut de Cardiologie, Sorbonne Universit\u00e9, AP-HP, IHU-ICAN, Groupe Hospitalier Piti\u00e9-Salp\u00eatri\u00e8re , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0444-9994","authenticated-orcid":false,"given":"Iris","family":"van der Schaaf","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of 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