{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:20:11Z","timestamp":1791566411280,"version":"4.3.4"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T00:00:00Z","timestamp":1637193600000},"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:p><jats:bold>Background:<\/jats:bold> Epidemiological characteristics and prognostic profiles of patients with newly diagnosed coronary artery disease (CAD) are heterogeneous. Therefore, providing individualized cardiovascular (CV) risk stratification and tailored prevention is crucial.<\/jats:p><jats:p><jats:bold>Objective:<\/jats:bold> Phenotypic unsupervised clustering integrating clinical, coronary computed tomography angiography (CCTA), and cardiac magnetic resonance (CMR) data were used to unveil pathophysiological differences between subgroups of patients with newly diagnosed CAD.<\/jats:p><jats:p><jats:bold>Materials and Methods:<\/jats:bold> Between 2008 and 2020, consecutive patients with newly diagnosed obstructive CAD on CCTA and further referred for vasodilator stress CMR were followed for the occurrence of major adverse cardiovascular events (MACE), defined by cardiovascular death or non-fatal myocardial infarction. For this exploratory work, a cluster analysis was performed on clinical, CCTA, and CMR variables, and associations between phenogroups and outcomes were assessed.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Among 2,210 patients who underwent both CCTA and CMR, 2,015 (46% men, mean 70 \u00b1 12 years) completed follow-up [median 6.8 (IQR 5.9\u20139.2) years], in which 277 experienced a MACE (13.7%). Three mutually exclusive and clinically distinct phenogroups (PG) were identified based upon unsupervised hierarchical clustering of principal components: (PG1) CAD in elderly patients with few traditional risk factors; (PG2) women with metabolic syndrome, calcified plaques on CCTA, and preserved left ventricular ejection fraction (LVEF); (PG3) younger men smokers with proximal non-calcified plaques on CCTA, myocardial scar, and reduced LVEF. Using survival analysis, the occurrence of MACE, cardiovascular mortality, and all-cause mortality (all <jats:italic>p<\/jats:italic> &amp;lt; 0.001) differed among the three PG, in which PG3 had the worse prognosis. In each PG, inducible ischemia was associated with MACE [PG1, Hazards Ratio (HR) = 3.09, 95% CI, 1.70\u20135.62; PG2, HR = 3.62, 95% CI, 2.31\u20135.7; PG3, HR = 3.55, 95% CI, 2.3\u20135.49; all <jats:italic>p<\/jats:italic> &amp;lt; 0.001]. The study presented some key limitations that may impact generalizability.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> Cluster analysis of clinical, CCTA, and CMR variables identified three phenogroups of patients with newly diagnosed CAD that were associated with distinct clinical and prognostic profiles. Inducible ischemia assessed by stress CMR remained associated with the occurrence of MACE within each phenogroup. Whether automated unsupervised phenogrouping of CAD patients may improve clinical decision-making should be further explored in prospective studies.<\/jats:p>","DOI":"10.3389\/fcvm.2021.760120","type":"journal-article","created":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T06:49:30Z","timestamp":1637218170000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Phenotypic Clustering of Patients With Newly Diagnosed Coronary Artery Disease Using Cardiovascular Magnetic Resonance and Coronary Computed Tomography Angiography"],"prefix":"10.3389","volume":"8","author":[{"given":"Th\u00e9o","family":"Pezel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Unterseeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Hovasse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anouk","family":"Asselin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Lef\u00e8vre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Chevalier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoinette","family":"Neylon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hakim","family":"Benamer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Champagne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Sanguineti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solenn","family":"Toupin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Garot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Garot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e56","DOI":"10.1161\/CIR.0000000000000659","article-title":"Heart disease and stroke statistics-2019 update: a report from the American Heart Association","volume":"139","author":"Benjamin","year":"2019","journal-title":"Circulation."},{"key":"B2","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1093\/eurheartj\/ehz425","article-title":"2019 ESC guidelines for the diagnosis and management of chronic coronary syndromes","volume":"41","author":"Knuuti","year":"2020","journal-title":"Eur Heart J"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2315","DOI":"10.1093\/eurheartj\/ehw106","article-title":"2016 European guidelines on cardiovascular disease prevention in clinical practice: the sixth joint task force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR)","volume":"37","author":"Piepoli","year":"2016","journal-title":"Eur Heart J"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1864","DOI":"10.1016\/j.jacc.2010.07.005","article-title":"ACCF\/SCCT\/ACR\/AHA\/ASE\/ASNC\/NASCI\/SCAI\/SCMR 2010 appropriate use criteria for cardiac computed tomography. A report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the Society of Cardiovascular Computed Tomography, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the American Society of Nuclear Cardiology, the North American Society for Cardiovascular Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society for Cardiovascular Magnetic Resonance","volume":"56","author":"Taylor","year":"2010","journal-title":"J Am Coll Cardiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1016\/j.jacc.2013.04.064","article-title":"Optimized prognostic score for coronary computed tomographic angiography: results from the CONFIRM registry (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter Registry)","volume":"62","author":"Hadamitzky","year":"2013","journal-title":"J Am Coll Cardiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"e013523","DOI":"10.1161\/JAHA.119.013523","article-title":"Long-term prognostic value of coronary computed tomography angiography in an asymptomatic elderly population","volume":"8","author":"Moon","year":"2019","journal-title":"J Am Heart Assoc."},{"key":"B7","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.jcct.2019.11.015","article-title":"Coronary atherosclerosis scoring with semiquantitative CCTA risk scores for prediction of major adverse cardiac events: propensity score-based analysis of diabetic and non-diabetic patients","volume":"14","author":"van den Hoogen","year":"2020","journal-title":"J Cardiovasc Comput Tomogr."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.1016\/j.jacc.2019.07.074","article-title":"Cardiac magnetic resonance stress perfusion imaging for evaluation of patients with chest pain","volume":"74","author":"Kwong","year":"2019","journal-title":"J Am College Cardiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1016\/j.jacc.2020.06.063","article-title":"Imaging of clinically unrecognized myocardial fibrosis in patients with suspected coronary artery disease","volume":"76","author":"Antiochos","year":"2020","journal-title":"J Am Coll Cardiol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1093\/ehjci\/jeu010","article-title":"Incremental prognostic value of sequential imaging of single-photon emission computed tomography and coronary computed tomography angiography in patients with suspected coronary artery disease","volume":"15","author":"Kim","year":"2014","journal-title":"Eur Heart J Cardiovasc Imaging."},{"key":"B11","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1093\/ehjci\/jeaa026","article-title":"Long-term prognostic value of stress myocardial perfusion echocardiography in patients with coronary artery disease: a meta-analysis","volume":"22","author":"Qian","year":"2021","journal-title":"Eur Heart J Cardiovasc Imaging."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1016\/j.jcmg.2019.12.009","article-title":"Stress-only adenosine cmr improves diagnostic yield in stable symptomatic patients with coronary artery calcium","volume":"13","author":"Rijlaarsdam-Hermsen","year":"2020","journal-title":"JACC Cardiovasc Imaging."},{"key":"B13","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1161\/CIRCULATIONAHA.114.010637","article-title":"Phenomapping for novel classification of heart failure with preserved ejection fraction","volume":"131","author":"Shah","year":"2015","journal-title":"Circulation."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1016\/j.jacc.2007.03.067","article-title":"Prognostic value of multidetector coronary computed tomographic angiography for prediction of all-cause mortality","volume":"50","author":"Min","year":"2007","journal-title":"J Am Coll Cardiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/j.jacc.2014.12.018","article-title":"2014 ACC\/AHA key data elements and definitions for cardiovascular endpoint events in clinical trials","volume":"66","author":"Hicks","year":"2015","journal-title":"J Am College Cardiol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e618","DOI":"10.1161\/CIR.0000000000000617","article-title":"Fourth universal definition of myocardial infarction","volume":"138","author":"Thygesen","year":"2018","journal-title":"Circulation."},{"key":"B17","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.jcct.2009.03.004","article-title":"SCCT guidelines for performance of coronary computed tomographic angiography: a report of the Society of Cardiovascular Computed Tomography Guidelines Committee","volume":"3","author":"Abbara","year":"2009","journal-title":"J Cardiovasc Comput Tomogr."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1016\/j.jacc.2006.07.003","article-title":"ACCF\/ACR\/SCCT\/SCMR\/ASNC\/NASCI\/SCAI\/SIR 2006 appropriateness criteria for cardiac computed tomography and cardiac magnetic resonance imaging: a report of the American College of Cardiology Foundation Quality Strategic Directions Committee Appropriateness Criteria Working Group, American College of Radiology, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, American Society of Nuclear Cardiology, North American Society for Cardiac Imaging, Society for Cardiovascular Angiography and Interventions, and Society of Interventional Radiology","volume":"48","author":"Hendel","year":"2006","journal-title":"J Am Coll Cardiol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/j.jcct.2016.10.002","article-title":"SCCT guidelines for the performance and acquisition of coronary computed tomographic angiography: a report of the society of Cardiovascular Computed Tomography Guidelines Committee: Endorsed by the North American Society for Cardiovascular Imaging (NASCI)","volume":"10","author":"Abbara","year":"2016","journal-title":"J Cardiovasc Comput Tomogr."},{"key":"B20","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1161\/01.CIR.51.4.5","article-title":"A reporting system on patients evaluated for coronary artery disease. Report of the Ad Hoc Committee for Grading of Coronary Artery Disease, Council on Cardiovascular Surgery, American Heart Association","volume":"51","author":"Austen","year":"1975","journal-title":"Circulation."},{"key":"B21","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1093\/ehjci\/jex150","article-title":"Incremental prognostic value of coronary computed tomography angiography over coronary calcium scoring for major adverse cardiac events in elderly asymptomatic individuals","volume":"19","author":"Han","year":"2018","journal-title":"Eur Heart J Cardiovasc Imaging."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1458","DOI":"10.1016\/j.jcct.2016.04.005","article-title":"CAD-RADSTM: coronary artery disease - reporting and data system: an expert consensus document of the society of cardiovascular computed tomography (SCCT), the American College of Radiology (ACR) and the North American Society for Cardiovascular Imaging (NASCI). Endorsed by the American College of Cardiology","volume":"13","author":"Cury","year":"2016","journal-title":"J Am Coll Radiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/j.jcmg.2020.07.041","article-title":"Feasibility and prognostic value of vasodilator stress perfusion cmr in patients with atrial fibrillation","volume":"14","author":"Pezel","year":"2021","journal-title":"JACC Cardiovasc Imaging."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e010599","DOI":"10.1161\/CIRCIMAGING.120.010599","article-title":"Safety and prognostic value of vasodilator stress cardiovascular magnetic resonance in patients with heart failure and reduced ejection fraction","volume":"13","author":"Pezel","year":"2020","journal-title":"Circ Cardiovasc Imaging."},{"key":"B25","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1081\/JCMR-120003946","article-title":"Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart. A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association","volume":"105","author":"Cerqueira","year":"2002","journal-title":"Circulation."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.1093\/eurheartj\/ehi258","article-title":"Delayed enhancement cardiovascular magnetic resonance assessment of non-ischaemic cardiomyopathies","volume":"26","author":"Mahrholdt","year":"2005","journal-title":"Eur Heart J."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1056\/NEJM200011163432003","article-title":"The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction","volume":"343","author":"Kim","year":"2000","journal-title":"N Engl J Med."},{"key":"B28","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":"B29","doi-asserted-by":"publisher","first-page":"2497","DOI":"10.1093\/eurheartj\/ehx518","article-title":"Fructose metabolism, cardiometabolic risk, and the epidemic of coronary artery disease","volume":"39","author":"Mirtschink","year":"2018","journal-title":"Eur Heart J."},{"key":"B30","doi-asserted-by":"publisher","first-page":"43965","DOI":"10.1038\/srep43965","article-title":"Cluster analysis: a new approach for identification of underlying risk factors for coronary artery disease in essential hypertensive patients","volume":"7","author":"Guo","year":"2017","journal-title":"Sci Rep."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1056\/NEJMoa1707914","article-title":"Antiinflammatory therapy with canakinumab for atherosclerotic disease","volume":"377","author":"Ridker","year":"2017","journal-title":"N Engl J Med."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.1056\/NEJMoa1709118","article-title":"Rivaroxaban with or without aspirin in stable cardiovascular disease","volume":"377","author":"Eikelboom","year":"2017","journal-title":"N Engl J Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"2816","DOI":"10.1016\/j.jacc.2009.11.096","article-title":"Angiographic versus functional severity of coronary artery stenoses in the FAME study fractional flow reserve versus angiography in multivessel evaluation","volume":"55","author":"Tonino","year":"2010","journal-title":"J Am Coll Cardiol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1056\/NEJMoa1915922","article-title":"Initial invasive or conservative strategy for stable coronary disease","volume":"382","author":"Maron","year":"2020","journal-title":"N Engl J Med."},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2021.3055","article-title":"Association of statin treatment with progression of coronary atherosclerotic plaque composition","author":"van Rosendael","year":"2021","journal-title":"JAMA Cardiol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1148\/radiol.15141110","article-title":"Combined assessment of high-sensitivity troponin t and noninvasive coronary plaque composition for the prediction of cardiac outcomes","volume":"276","author":"Gitsioudis","year":"2015","journal-title":"Radiology."}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2021.760120\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T06:49:33Z","timestamp":1637218173000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2021.760120\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,18]]},"references-count":36,"alternative-id":["10.3389\/fcvm.2021.760120"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2021.760120","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,18]]},"article-number":"760120"}}