{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T18:52:15Z","timestamp":1793040735182,"version":"4.5.0"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T00:00:00Z","timestamp":1665014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Guidelines recommend genetic testing and cardiovascular magnetic resonance (CMR) for the investigation of dilated cardiomyopathy (DCM). However, the incremental value is unclear. We assessed the impact of these investigations in determining etiology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sixty consecutive patients referred with DCM and recruited to our hospital biobank were selected. Six independent experts determined the etiology of each phenotype in a step-wise manner based on (1) routine clinical data, (2) clinical and genetic data and (3) clinical, genetic and CMR data. They indicated their confidence (1-3) in the classification and any changes to management at each step.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Six physicians adjudicated 60 cases. The addition of genetics and CMR resulted in 57 (15.8%) and 26 (7.2%) changes in the classification of etiology, including an increased number of genetic diagnoses and a reduction in idiopathic diagnoses. Diagnostic confidence improved at each step (<jats:italic>p<\/jats:italic> &amp;lt; 0.0005). The number of diagnoses made with low confidence reduced from 105 (29.2%) with routine clinical data to 71 (19.7%) following the addition of genetics and 37 (10.3%) with the addition of CMR. The addition of genetics and CMR led to 101 (28.1%) and 112 (31.1%) proposed changes to management, respectively. Interobserver variability showed moderate agreement with clinical data (\u03ba = 0.44) which improved following the addition of genetics (\u03ba = 0.65) and CMR (\u03ba = 0.68).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We demonstrate that genetics and CMR, frequently changed the classification of etiology in DCM, improved confidence and interobserver variability in determining the diagnosis and had an impact on proposed management.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2022.1017119","type":"journal-article","created":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T12:32:32Z","timestamp":1665059552000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["The addition of genetic testing and cardiovascular magnetic resonance to routine clinical data for stratification of etiology in dilated cardiomyopathy"],"prefix":"10.3389","volume":"9","author":[{"given":"Ravi J.","family":"Amin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Morris-Rosendahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mat","family":"Edwards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Upasana","family":"Tayal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Buchan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Hammersley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard E.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabiha","family":"Gati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zohya","family":"Khalique","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Batool","family":"Almogheer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dudley J.","family":"Pennell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun John","family":"Baksi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonis","family":"Pantazis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James S.","family":"Ware","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay K.","family":"Prasad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian P.","family":"Halliday","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1016\/j.cardfail.2022.02.009","article-title":"2022 American College of Cardiology\/American Heart Association\/Heart Failure Society of America Guideline for the management of heart failure: executive summary","volume":"28","author":"Heidenreich","year":"2022","journal-title":"J Card Fail."},{"key":"B2","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1161\/CIRCULATIONAHA.116.027134","article-title":"Personalizing risk stratification for sudden death in dilated cardiomyopathy: the past, present, and future","volume":"136","author":"Halliday","year":"2017","journal-title":"Circulation."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1850","DOI":"10.1093\/eurheartj\/ehv727","article-title":"Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice","volume":"37","author":"Pinto","year":"2016","journal-title":"Eur Heart J."},{"key":"B4","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1038\/nrcardio.2013.105","article-title":"Dilated cardiomyopathy: the complexity of a diverse genetic architecture","volume":"10","author":"Hershberger","year":"2013","journal-title":"Nat Rev Cardiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1480","DOI":"10.1016\/j.jacc.2019.06.072","article-title":"Genetic risk of arrhythmic phenotypes in patients with dilated cardiomyopathy","volume":"74","author":"Gigli","year":"2019","journal-title":"J Am Coll Cardiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1161\/CIRCULATIONAHA.110.970673","article-title":"Mitogen-activated protein kinase inhibitors improve heart function and prevent fibrosis in cardiomyopathy caused by mutation in lamin A\/C gene","volume":"123","author":"Wu","year":"2011","journal-title":"Circulation."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1649","DOI":"10.1002\/ejhf.1933","article-title":"Effects of danicamtiv, a novel cardiac myosin activator, in heart failure with reduced ejection fraction: experimental data and clinical results from a phase 2a trial","volume":"22","author":"Voors","year":"2020","journal-title":"Eur J Heart Fail."},{"key":"B8","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.cardfail.2009.01.006","article-title":"Genetic evaluation of cardiomyopathy\u2013a Heart Failure Society of America practice guideline","volume":"15","author":"Hershberger","year":"2009","journal-title":"J Card Fail."},{"key":"B9","doi-asserted-by":"publisher","first-page":"3599","DOI":"10.1093\/eurheartj\/ehab368","article-title":"2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure","volume":"42","author":"McDonagh","year":"2021","journal-title":"Eur Heart J."},{"key":"B10","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.cardfail.2018.03.004","article-title":"Genetic evaluation of cardiomyopathy-A Heart Failure Society of America practice guideline","volume":"24","author":"Hershberger","year":"2018","journal-title":"J Card Fail."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1645","DOI":"10.1016\/j.jcmg.2018.07.015","article-title":"Outcome in dilated cardiomyopathy related to the extent, location, and pattern of late gadolinium enhancement","volume":"12","author":"Halliday","year":"2018","journal-title":"JACC Cardiovasc Imaging."},{"key":"B12","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1093\/ehjci\/jez188","article-title":"Dilated cardiomyopathy and arrhythmogenic left ventricular cardiomyopathy: a comprehensive genotype-imaging phenotype study","volume":"21","author":"Augusto","year":"2020","journal-title":"Eur Heart J Cardiovasc Imaging."},{"key":"B13","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1080\/10976640600572889","article-title":"Normalized left ventricular systolic and diastolic function by steady state free precession cardiovascular magnetic resonance","volume":"8","author":"Maceira","year":"2006","journal-title":"J Cardiovasc Magn Reson."},{"key":"B14","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1161\/CIRCULATIONAHA.119.037661","article-title":"Reevaluating the genetic contribution of monogenic dilated cardiomyopathy","volume":"141","author":"Mazzarotto","year":"2020","journal-title":"Circulation."},{"key":"B15","doi-asserted-by":"publisher","first-page":"e002480","DOI":"10.1161\/CIRCGEN.119.002480","article-title":"Variant interpretation for dilated cardiomyopathy: refinement of the American College of Medical Genetics and Genomics\/ClinGen Guidelines for the DCM precision medicine study","volume":"13","author":"Morales","year":"2020","journal-title":"Circ Genom Precis Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2106","DOI":"10.1161\/CIRCULATIONAHA.116.026910","article-title":"Association Between midwall late gadolinium enhancement and sudden cardiac death in patients with dilated cardiomyopathy and mild and moderate left ventricular systolic dysfunction","volume":"135","author":"Halliday","year":"2017","journal-title":"Circulation."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1002\/ejhf.1914","article-title":"Contemporary survival trends and aetiological characterization in non-ischaemic dilated cardiomyopathy","volume":"22","author":"Merlo","year":"2020","journal-title":"Eur J Heart Fail."},{"key":"B19","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1093\/eurheartj\/ehx808","article-title":"Titin cardiomyopathy leads to altered mitochondrial energetics, increased fibrosis and long-term life-threatening arrhythmias","volume":"39","author":"Verdonschot","year":"2018","journal-title":"Eur Heart J."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2264","DOI":"10.1016\/j.jacc.2017.08.063","article-title":"Phenotype and clinical outcomes of titin cardiomyopathy","volume":"70","author":"Tayal","year":"2017","journal-title":"J Am Coll Cardiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e876","DOI":"10.1161\/CIR.0000000000001062","article-title":"2022 AHA\/ACC\/HFSA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology\/American Heart Association Joint Committee on clinical practice guidelines","volume":"145","author":"Heidenreich","year":"2022","journal-title":"Circulation."},{"key":"B22","doi-asserted-by":"publisher","first-page":"2293","DOI":"10.1016\/j.jacc.2018.03.462","article-title":"Genetic etiology for alcohol-induced cardiac toxicity","volume":"71","author":"Ware","year":"2018","journal-title":"J Am Coll Cardiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2254","DOI":"10.1038\/s41467-020-15823-7","article-title":"Analysis of cardiac magnetic resonance imaging in 36,000 individuals yields genetic insights into dilated cardiomyopathy","volume":"11","author":"Pirruccello","year":"2020","journal-title":"Nat Commun."},{"key":"B24","doi-asserted-by":"publisher","first-page":"2440","DOI":"10.1016\/j.jacc.2016.09.927","article-title":"Truncating FLNC mutations are associated with high-risk dilated and arrhythmogenic cardiomyopathies","volume":"68","author":"Ortiz-Genga","year":"2016","journal-title":"J Am Coll Cardiol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"2171","DOI":"10.1053\/euhj.2001.2822","article-title":"Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload","volume":"22","author":"Anderson","year":"2001","journal-title":"Eur Heart J."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1682","DOI":"10.1016\/j.jacc.2021.08.039","article-title":"Association of genetic variants with outcomes in patients with nonischemic dilated cardiomyopathy","volume":"78","author":"Escobar-Lopez","year":"2021","journal-title":"J Am Coll Cardiol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1872","DOI":"10.1161\/CIRCULATIONAHA.119.044934","article-title":"Desmoplakin cardiomyopathy, a fibrotic and inflammatory form of cardiomyopathy distinct from typical dilated or arrhythmogenic right ventricular cardiomyopathy","volume":"141","author":"Smith","year":"2020","journal-title":"Circulation."},{"key":"B28","doi-asserted-by":"publisher","first-page":"2466","DOI":"10.1016\/j.jacc.2017.03.530","article-title":"Truncating variants in titin independently predict early arrhythmias in patients with dilated cardiomyopathy","volume":"69","author":"Tayal","year":"2017","journal-title":"J Am Coll Cardiol."}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2022.1017119\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T12:32:35Z","timestamp":1665059555000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2022.1017119\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,6]]},"references-count":28,"alternative-id":["10.3389\/fcvm.2022.1017119"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2022.1017119","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,6]]},"article-number":"1017119"}}