{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T01:38:32Z","timestamp":1790386712608,"version":"4.1.0"},"posted":{"date-parts":[[2025,6,23]]},"group-title":"Cardiovascular Medicine","reference-count":20,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"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":[[2025,6,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>\n                    Desmoplakin (DSP) cardiomyopathy, caused by variants in the gene\n                    <jats:italic>DSP<\/jats:italic>\n                    , is a unique subtype of cardiomyopathy distinct from typical dilated or arrhythmogenic right ventricular cardiomyopathies. Specific diagnostic and disease staging criteria have yet to be developed for DSP cardiomyopathy.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Utilizing a large cohort of DSP cardiomyopathy patients and their genotype-positive family members, this study aims to develop diagnostic and disease staging criteria for DSP cardiomyopathy.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    Patients from the\n                    <jats:italic>DSP<\/jats:italic>\n                    -ERADOS Network with complete rhythm monitoring, electrocardiogram and cardiac magnetic resonance imaging were enrolled. Diagnostic criteria were assessed in initially-presenting patients (probands) and their genotype-positive family members. Early disease criteria (with preserved left ventricular ejection fraction, LVEF) were integrated into standard LVEF-based classifications. Diagnostic and staging criteria were assessed by time-event analyses (major ventricular arrhythmia and heart failure events).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    A total of 605 patients with complete diagnostic testing were included (mean age 40 yr, 60% female, 40% probands). The most prevalent disease features in probands were premature ventricular contractions (PVCs) &gt;500\/24hr (66%), nonsustained ventricular tachycardia (NSVT, 29%), LV late gadolinium enhancement (LGE, 53%), and reduced LVEF (44%). The presence of any one of these features was 97% sensitive for diagnosis (along with a\n                    <jats:italic>DSP<\/jats:italic>\n                    pathogenic variant) and were therefore considered as diagnostic criteria. Using these criteria, 77% of genotype-positive family members were considered clinically affected. Isolated right ventricular (RV) involvement occurred in only 0.7%. The absence of diagnostic criteria identified a low-risk group (composite event rate 0.8%\/year, p&lt;0.001). Integration of these criteria into LVEF-based classification improved identification of composite arrhythmia\/heart failure events (early: diagnostic criteria with LVEF &gt;50%, HR 2.7, p=0.04; intermediate: LVEF 41-49%, HR 3.7, p=0.009; advanced: LVEF &lt;40% HR 10.3, p&lt;0.001). LGE was mostly subepicardial (87%). Circumferential (ring-like) LGE was more frequent in intermediate or advanced vs early disease (66% vs 48%, p&lt;0.001).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>This study identifies genotype-specific diagnostic and disease staging criteria for DSP cardiomyopathy that improve identification of risk for both heart failure and sustained ventricular arrhythmias. This work highlights how gene-specific criteria may be used to refine diagnosis and staging for cardiomyopathy subtypes \u2013 a critical step as gene-targeted treatments move toward clinical trials.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.06.16.25329734","type":"posted-content","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T23:45:15Z","timestamp":1750722315000},"source":"Crossref","is-referenced-by-count":2,"title":["Diagnostic Criteria and Disease Staging for Desmoplakin Cardiomyopathy"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5915-9492","authenticated-orcid":false,"given":"Eric","family":"Smith","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3432-070X","authenticated-orcid":false,"given":"Alessio","family":"Gasperetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard 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