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dc.contributor.authorVerdonschot, Job A.J.
dc.contributor.authorMerlo, Marco
dc.contributor.authorDomínguez, Fernando
dc.contributor.authorWang, Ping
dc.contributor.authorHenkens, Michiel T.H.M.
dc.contributor.authorAdriaens, Michiel E.
dc.contributor.authorHazebroek, Mark R.
dc.contributor.authorMase, Marco
dc.contributor.authorEscobar, Luis E.
dc.contributor.authorCobas-Paz, Rafael
dc.contributor.authorDerks, Kasper W.J.
dc.contributor.authorVan den Wijngaard, Arthur
dc.contributor.authorKrapels, Ingrid P.C.
dc.contributor.authorBrunner, Han G.
dc.contributor.authorSinagra, Gianfranco
dc.contributor.authorGarcía Pavía, Pablo 
dc.contributor.authorHeymans, Stephane R.B.
dc.date.accessioned2021-07-27T11:57:57Z
dc.date.available2021-07-27T11:57:57Z
dc.date.issued2020
dc.identifier.issn0195-668Xspa
dc.identifier.urihttp://hdl.handle.net/10641/2371
dc.description.abstractAims The dilated cardiomyopathy (DCM) phenotype is the result of combined genetic and acquired triggers. Until now, clinical decision-making in DCM has mainly been based on ejection fraction (EF) and NYHA classification, not considering the DCM heterogenicity. The present study aimed to identify patient subgroups by phenotypic clustering integrating aetiologies, comorbidities, and cardiac function along cardiac transcript levels, to unveil pathophysiological differences between DCM subgroups. Methods and results We included 795 consecutive DCM patients from the Maastricht Cardiomyopathy Registry who underwent in-depth phenotyping, comprising extensive clinical data on aetiology and comorbodities, imaging and endomyocardial biopsies. Four mutually exclusive and clinically distinct phenogroups (PG) were identified based upon unsupervised hierarchical clustering of principal components: [PG1] mild systolic dysfunction, [PG2] auto-immune, [PG3] genetic and arrhythmias, and [PG4] severe systolic dysfunction. RNA-sequencing of cardiac samples (n = 91) revealed a distinct underlying molecular profile per PG: pro-inflammatory (PG2, auto-immune), pro-fibrotic (PG3; arrhythmia), and metabolic (PG4, low EF) gene expression. Furthermore, event-free survival differed among the four phenogroups, also when corrected for well-known clinical predictors. Decision tree modelling identified four clinical parameters (auto-immune disease, EF, atrial fibrillation, and kidney function) by which every DCM patient from two independent DCM cohorts could be placed in one of the four phenogroups with corresponding outcome (n = 789; Spain, n = 352 and Italy, n = 437), showing a feasible applicability of the phenogrouping. Conclusion The present study identified four different DCM phenogroups associated with significant differences in clinical presentation, underlying molecular profiles and outcome, paving the way for a more personalized treatment approach.spa
dc.language.isoengspa
dc.publisherEuropean Heart Journalspa
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 España*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/es/*
dc.subjectMachine learningspa
dc.subjectClusteringspa
dc.subjectDilated cardiomyopathyspa
dc.subjectPathophysiologyspa
dc.titlePhenotypic clustering of dilated cardiomyopathy patients highlights important pathophysiological differences.spa
dc.typejournal articlespa
dc.type.hasVersionAMspa
dc.rights.accessRightsopen accessspa
dc.description.extent1323 KBspa
dc.identifier.doi10.1093/eurheartj/ehaa841spa
dc.relation.publisherversionhttps://academic.oup.com/eurheartj/article/42/2/162/5959816spa


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