{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T01:32:18Z","timestamp":1793410338730,"version":"4.5.0"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"23","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2020,6,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Mutations in desmoplakin (\n                      <jats:italic>DSP<\/jats:italic>\n                      ), the primary force transducer between cardiac desmosomes and intermediate filaments, cause an arrhythmogenic form of cardiomyopathy that has been variably associated with arrhythmogenic right ventricular cardiomyopathy. Clinical correlates of\n                      <jats:italic>DSP<\/jats:italic>\n                      cardiomyopathy have been limited to small case series.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Clinical and genetic data were collected on 107 patients with pathogenic\n                      <jats:italic>DSP<\/jats:italic>\n                      mutations and 81 patients with pathogenic plakophilin 2 (\n                      <jats:italic>PKP2<\/jats:italic>\n                      ) mutations as a comparison cohort. A composite outcome of severe ventricular arrhythmia was assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      <jats:italic>DSP<\/jats:italic>\n                      and\n                      <jats:italic>PKP2<\/jats:italic>\n                      cohorts included similar proportions of probands (41% versus 42%) and patients with truncating mutations (98% versus 100%). Left ventricular (LV) predominant cardiomyopathy was exclusively present among patients with\n                      <jats:italic>DSP<\/jats:italic>\n                      (55% versus 0% for\n                      <jats:italic>PKP2<\/jats:italic>\n                      ,\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.001), whereas right ventricular cardiomyopathy was present in only 14% of patients with\n                      <jats:italic>DSP<\/jats:italic>\n                      versus 40% for\n                      <jats:italic>PKP2<\/jats:italic>\n                      (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.001). Arrhythmogenic right ventricular cardiomyopathy diagnostic criteria had poor sensitivity for\n                      <jats:italic>DSP<\/jats:italic>\n                      cardiomyopathy. LV late gadolinium enhancement was present in a primarily subepicardial distribution in 40% of patients with\n                      <jats:italic>DSP<\/jats:italic>\n                      (23\/57 with magnetic resonance images). LV late gadolinium enhancement occurred with normal LV systolic function in 35% (8\/23) of patients with\n                      <jats:italic>DSP<\/jats:italic>\n                      . Episodes of acute myocardial injury (chest pain with troponin elevation and normal coronary angiography) occurred in 15% of patients with\n                      <jats:italic>DSP<\/jats:italic>\n                      and were strongly associated with LV late gadolinium enhancement (90%), even in cases of acute myocardial injury with normal ventricular function (4\/5, 80% with late gadolinium enhancement). In 4\n                      <jats:italic>DSP<\/jats:italic>\n                      cases with 18F-fluorodeoxyglucose positron emission tomography scans, acute LV myocardial injury was associated with myocardial inflammation misdiagnosed initially as cardiac sarcoidosis or myocarditis. Left ventricle ejection fraction &lt;55% was strongly associated with severe ventricular arrhythmias for\n                      <jats:italic>DSP<\/jats:italic>\n                      cases (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.001, sensitivity 85%, specificity 53%). Right ventricular ejection fraction &lt;45% was associated with severe arrhythmias for\n                      <jats:italic>PKP2<\/jats:italic>\n                      cases (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.001) but was poorly associated for\n                      <jats:italic>DSP<\/jats:italic>\n                      cases (\n                      <jats:italic>P<\/jats:italic>\n                      =0.8). Frequent premature ventricular contractions were common among patients with severe arrhythmias for both\n                      <jats:italic>DSP<\/jats:italic>\n                      (80%) and\n                      <jats:italic>PKP2<\/jats:italic>\n                      (91%) groups (\n                      <jats:italic>P<\/jats:italic>\n                      =non-significant).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      <jats:italic>DSP<\/jats:italic>\n                      cardiomyopathy is a distinct form of arrhythmogenic cardiomyopathy characterized by episodic myocardial injury, left ventricular fibrosis that precedes systolic dysfunction, and a high incidence of ventricular arrhythmias. A genotype-specific approach for diagnosis and risk stratification should be used.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.119.044934","type":"journal-article","created":{"date-parts":[[2020,5,6]],"date-time":"2020-05-06T05:00:21Z","timestamp":1588741221000},"page":"1872-1884","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":499,"title":["Desmoplakin Cardiomyopathy, a Fibrotic and Inflammatory Form of Cardiomyopathy Distinct From Typical Dilated or Arrhythmogenic Right Ventricular Cardiomyopathy"],"prefix":"10.1161","volume":"141","author":[{"given":"Eric D.","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Cardiovascular Medicine (E.D.S., P.A., A.S.H.), University of Michigan, Ann Arbor."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neal K.","family":"Lakdawala","sequence":"additional","affiliation":[{"name":"Cardiovascular Genetics Program, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (N.K.L., K.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Papoutsidakis","sequence":"additional","affiliation":[{"name":"Inherited Cardiomyopathy Program, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT (N.P., D.L.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Aubert","sequence":"additional","affiliation":[{"name":"Center for Genetic Medicine (G.A.), Feinberg School of Medicine, Northwestern University, Chicago, IL."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Mazzanti","sequence":"additional","affiliation":[{"name":"Department of Molecular Cardiology, Istituto di Ricovero e Cura a Carattere Scientifico Instituti Clinici Scientifici Maugeri, Pavia, Italy (A.M., S.G.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony C.","family":"McCanta","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology, University of California-Irvine and Children\u2019s Hospital of Orange County, Orange (A.C.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prachi P.","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Radiology, Department of Radiology (P.P.A.), University of Michigan, Ann Arbor."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Arscott","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Cardiovascular Medicine (E.D.S., P.A., A.S.H.), University of Michigan, Ann Arbor."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M.","family":"Dellefave-Castillo","sequence":"additional","affiliation":[{"name":"Feinberg Cardiovascular Research Institute (L.M.D.-C., L.D.W., E.M.M.), Feinberg School of Medicine, Northwestern University, Chicago, IL."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther E.","family":"Vorovich","sequence":"additional","affiliation":[{"name":"Division of Cardiology (E.E.V.), Feinberg School of Medicine, Northwestern University, Chicago, IL."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavitha","family":"Nutakki","sequence":"additional","affiliation":[{"name":"Cardiovascular Genetics Program, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (N.K.L., K.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa D.","family":"Wilsbacher","sequence":"additional","affiliation":[{"name":"Feinberg Cardiovascular Research Institute (L.M.D.-C., L.D.W., E.M.M.), Feinberg School of Medicine, Northwestern University, Chicago, IL."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia G.","family":"Priori","sequence":"additional","affiliation":[{"name":"Department of Molecular Cardiology, Istituto di Ricovero e Cura a Carattere Scientifico Instituti Clinici Scientifici Maugeri, Pavia, Italy (A.M., S.G.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel L.","family":"Jacoby","sequence":"additional","affiliation":[{"name":"Inherited Cardiomyopathy Program, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT (N.P., D.L.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M.","family":"McNally","sequence":"additional","affiliation":[{"name":"Feinberg Cardiovascular Research Institute (L.M.D.-C., L.D.W., E.M.M.), Feinberg School of Medicine, Northwestern University, Chicago, 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