{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T18:18:00Z","timestamp":1793902680767,"version":"4.8.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Many cardiovascular disorders propel the development of advanced heart failure that necessitates cardiac transplantation. When treatable causes are excluded, studies to define causes are often abandoned, resulting in a diagnosis of end-stage idiopathic cardiomyopathy. We studied whether DNA sequence analyses could identify unrecognized causes of end-stage nonischemic cardiomyopathy requiring heart transplantation and whether the prevalence of genetic causes differed from ambulatory cardiomyopathy cases.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>We performed whole exome and genome sequencing of 122 explanted hearts from 101 adult and 21 pediatric patients with idiopathic cardiomyopathy from a single center. Data were analyzed for pathogenic\/likely pathogenic variants in nuclear and mitochondrial genomes and assessed for nonhuman microbial sequences. The frequency of damaging genetic variants was compared among cardiomyopathy cohorts with different clinical severity.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              Fifty-four samples (44.3%) had pathogenic\/likely pathogenic cardiomyopathy gene variants. The frequency of pathogenic variants was similar in pediatric (42.9%) and adult (43.6%) samples, but the distribution of mutated genes differed (\n              <jats:italic>P<\/jats:italic>\n              =8.30\u00d710\n              <jats:sup>-4<\/jats:sup>\n              ). The prevalence of causal genetic variants was significantly higher in end-stage than in previously reported ambulatory adult dilated cardiomyopathy cases (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). Among remaining samples with unexplained causes, no damaging mitochondrial variants were identified, but 28 samples contained parvovirus genome sequences, including 2 samples with 6- to 9-fold higher levels than the overall mean levels in other samples.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Pathogenic variants and viral myocarditis were identified in 45.9% of patients with unexplained end-stage cardiomyopathy. Damaging gene variants are significantly more frequent among transplant compared with patients with ambulatory cardiomyopathy. Genetic analyses can help define cause of end-stage cardiomyopathy to guide management and risk stratification of patients and family members.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgen.123.004062","type":"journal-article","created":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T09:00:15Z","timestamp":1695891615000},"page":"452-461","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":21,"title":["Genetic Contribution to End-Stage Cardiomyopathy Requiring Heart Transplantation"],"prefix":"10.1161","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5978-5779","authenticated-orcid":true,"given":"Yuri","family":"Kim","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital (Y.K., B.M., C.E.S.)."},{"name":"Department of Genetics, Harvard Medical School, Boston, MA (Y.K., O.B.G., D.R., D.Q., J.A.L.W., J.J.C., J.G., S.R.D., J.G.S., C.E.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7625-0976","authenticated-orcid":true,"given":"Oddn\u00fd Brattberg","family":"Gunnarsd\u00f3ttir","sequence":"additional","affiliation":[{"name":"Department of Genetics, Harvard Medical School, Boston, MA (Y.K., O.B.G., D.R., D.Q., J.A.L.W., J.J.C., J.G., S.R.D., J.G.S., C.E.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anissa","family":"Viveiros","sequence":"additional","affiliation":[{"name":"Department of Medicine (A.V., H.Z., H.C., D.H.K., G.Y.O.), University of Alberta."},{"name":"Mazankowski Alberta Heart Institute, Edmonton, Canada (A.V., H.Z., H.C., D.H.K., G.Y.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Reichart","sequence":"additional","affiliation":[{"name":"Department of Genetics, Harvard Medical School, Boston, MA (Y.K., O.B.G., D.R., D.Q., J.A.L.W., J.J.C., J.G., S.R.D., J.G.S., C.E.S.)."},{"name":"Department of Medicine I, University Hospital, Ludwig Maximilian University of Munich, Germany (D.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4224-7277","authenticated-orcid":true,"given":"Daniel","family":"Quiat","sequence":"additional","affiliation":[{"name":"Department of Genetics, Harvard Medical School, Boston, MA (Y.K., O.B.G., D.R., D.Q., J.A.L.W., J.J.C., J.G., S.R.D., J.G.S., C.E.S.)."},{"name":"Department of Cardiology, Boston Children\u2019s Hospital, MA (D.Q.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3782-4770","authenticated-orcid":true,"given":"Jon A.L.","family":"Willcox","sequence":"additional","affiliation":[{"name":"Department of Genetics, Harvard Medical School, Boston, MA (Y.K., O.B.G., D.R., D.Q., J.A.L.W., J.J.C., J.G., S.R.D., J.G.S., 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