{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T02:54:37Z","timestamp":1790218477293,"version":"4.1.0"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,5,6]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Familial dilated cardiomyopathy (DCM) is characterized by marked variability in phenotypic penetrance. The extent to which this is determined by patient\u2010specific environmental factors is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      A retrospective longitudinal cohort study was performed in families with DCM\u2010causing genetic variants. Environmental factors were classified into 2 subsets based on evidence for a causal link to depressed myocardial contractility, termed (1) DCM\u2010promoting factors and (2) heart failure comorbidities. These factors were correlated with DCM diagnosis and disease trajectory after accounting for relevant confounders and familial relatedness. A total of 105 probands and family members were recruited: 51 genotype positive, phenotype positive, 24 genotype positive, phenotype negative, and 30 genotype negative, phenotype negative. Demographic characteristics were similar between the 3 genotype groups. DCM\u2010promoting environmental factors (eg, alcohol excess) were enriched in genotype\u2010positive, phenotype\u2010positive individuals compared with genotype\u2010positive, phenotype\u2010negative (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      &lt;0.001) and genotype\u2010negative, phenotype\u2010negative (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.003) individuals and were significantly associated with age at DCM onset (hazard ratio, 2.01;\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.014). Heart failure comorbidities (eg, diabetes) had a similar prevalence in genotype\u2010positive, phenotype\u2010positive and genotype\u2010negative, phenotype\u2010negative individuals but were significantly reduced in the genotype\u2010positive, phenotype\u2010negative group. Fluctuations in left ventricular ejection fraction during follow\u2010up were linked to changes in environmental factors in 35 of 45 (78%) of instances: 32 (91%) of these were DCM\u2010promoting factors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">We identified distinct subsets of environmental factors that affect DCM penetrance and trajectory. Our data highlight DCM\u2010promoting environmental factors as key determinants of penetrance and natural history. Collectively, these findings provide a new framework for risk factor assessment in familial DCM and have important implications for clinical management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.124.037311","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T07:59:49Z","timestamp":1746172789000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Environmental Risk Factors Are Associated With the Natural History of Familial Dilated Cardiomyopathy"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3593-3228","authenticated-orcid":false,"given":"Stacey A.","family":"Peters","sequence":"first","affiliation":[{"name":"Royal Melbourne Hospital","place":["Melbourne, Australia"]},{"name":"Royal Melbourne Hospital","place":["Melbourne, Australia"]},{"name":"University of Melbourne","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Wright","sequence":"additional","affiliation":[{"name":"University of Melbourne","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8974-4265","authenticated-orcid":false,"given":"Jess","family":"Yao","sequence":"additional","affiliation":[{"name":"Royal Melbourne Hospital","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"McCall","sequence":"additional","affiliation":[{"name":"Royal Melbourne Hospital","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9405-6595","authenticated-orcid":false,"given":"Tina","family":"Thompson","sequence":"additional","affiliation":[{"name":"Royal Melbourne Hospital","place":["Melbourne, Australia"]},{"name":"University of Melbourne","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8655-1839","authenticated-orcid":false,"given":"Bryony","family":"Thompson","sequence":"additional","affiliation":[{"name":"Royal Melbourne Hospital","place":["Melbourne, Australia"]},{"name":"Royal Melbourne Hospital","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8979-2096","authenticated-orcid":false,"given":"Renee","family":"Johnson","sequence":"additional","affiliation":[{"name":"Victor Chang Cardiac Research Institute","place":["Sydney, Australia"]},{"name":"University of New South Wales","place":["Sydney, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1368-5160","authenticated-orcid":false,"given":"Quan","family":"Huynh","sequence":"additional","affiliation":[{"name":"University of Melbourne","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celine F.","family":"Santiago","sequence":"additional","affiliation":[{"name":"Victor Chang Cardiac Research Institute","place":["Sydney, Australia"]},{"name":"University of New South Wales","place":["Sydney, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Trainer","sequence":"additional","affiliation":[{"name":"Royal Melbourne Hospital","place":["Melbourne, Australia"]},{"name":"Familial Cancer Centre, Peter MacCallum Centre","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9813-4338","authenticated-orcid":false,"given":"Mark","family":"Perrin","sequence":"additional","affiliation":[{"name":"Royal Melbourne Hospital","place":["Melbourne, Australia"]},{"name":"Royal Melbourne Hospital","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4361-4657","authenticated-orcid":false,"given":"Paul","family":"James","sequence":"additional","affiliation":[{"name":"Royal Melbourne Hospital","place":["Melbourne, Australia"]},{"name":"University of Melbourne","place":["Melbourne, Australia"]},{"name":"Familial Cancer Centre, Peter MacCallum Centre","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0437-1581","authenticated-orcid":false,"given":"Dominica","family":"Zentner","sequence":"additional","affiliation":[{"name":"Royal Melbourne Hospital","place":["Melbourne, Australia"]},{"name":"Royal Melbourne Hospital","place":["Melbourne, Australia"]},{"name":"University of Melbourne","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6618-7184","authenticated-orcid":false,"given":"Jon","family":"Kalman","sequence":"additional","affiliation":[{"name":"Royal Melbourne Hospital","place":["Melbourne, Australia"]},{"name":"University of Melbourne","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9065-0899","authenticated-orcid":false,"given":"Thomas H.","family":"Marwick","sequence":"additional","affiliation":[{"name":"University of Melbourne","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9010-9856","authenticated-orcid":false,"given":"Diane","family":"Fatkin","sequence":"additional","affiliation":[{"name":"Victor Chang Cardiac Research Institute","place":["Sydney, Australia"]},{"name":"University of New South Wales","place":["Sydney, Australia"]},{"name":"St. Vincent\u2019s Hospital","place":["Sydney, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.318157"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2021.08.039"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.10.011"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2206916"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.07.023"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehx808"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.053033"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.2333"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0b013e31829e8776"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000455"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.03.590"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31713-5"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2014.10.003"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.119.006832"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.18179"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.039573"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2004.02.057"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcad.2018.08.006"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.121.003540"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12123937"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.03.462"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hlc.2020.09.009"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2019.11.053"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2012.09.035"},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.06.054"},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.10.056"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.124.037311","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T10:57:04Z","timestamp":1784113024000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.124.037311"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,6]]},"references-count":27,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,5,6]]}},"alternative-id":["10.1161\/JAHA.124.037311"],"URL":"https:\/\/doi.org\/10.1161\/jaha.124.037311","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,6]]},"assertion":[{"value":"2024-06-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e037311"}}