Transcriptomic biomarkers for the accurate diagnosis of myocarditis.
Background: Lymphocytic myocarditis is a clinically important condition that is difficult to diagnose and distinguish. We hypothesized that the transcriptome obtained from an endomyocardial biopsy would yield clinically relevant and accurate molecular signatures.Methods and Results: Microarray analy...
| Published in: | Circulation Vol. 123; no. 11; pp. 1174 - 1185 |
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| Main Authors: | , , , , , , , , , , , , , , , , , , , |
| Format: | research Journal Article |
| Published: |
Lippincott Williams & Wilkins
3/22/2011
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104853109&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104853109 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00097322 1FV jtl: Circulation issn: 00097322 maglogo: N pubinfo: dt: 3/22/2011 vid: 123 iid: 11 pid: 433 pub: Lippincott Williams & Wilkins place: Baltimore, Maryland artinfo: ui: 104853109 NLM21382894 2010988656 10.1161/CIRCULATIONAHA.110.002857 NLM21382894 PMC3408077 104853109 ppf: 1174 ppct: 11 formats: tig: atl: Transcriptomic biomarkers for the accurate diagnosis of myocarditis. aug: au: Heidecker B Kittleson MM Kasper EK Wittstein IS Champion HC Russell SD Hruban RH Rodriguez ER Baughman KL Hare JM Heidecker, Bettina Kittleson, Michelle M Kasper, Edward K Wittstein, Ilan S Champion, Hunter C Russell, Stuart D Hruban, Ralph H Rodriguez, E Rene Baughman, Kenneth L Hare, Joshua M affil: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Biomedical Research Bldg, Room 824, PO Box 016960 (R-125), Miami, FL 33101, USA sug: subj: Gene Expression Profiling Myocardial Diseases Diagnosis Adult Algorithms Biological Markers Diagnosis, Differential Female Human Male Middle Age Myocardial Diseases Phenotype Reverse Transcriptase Polymerase Chain Reaction Adult: 19-44 years Middle Aged: 45-64 years Female Male ab: Background: Lymphocytic myocarditis is a clinically important condition that is difficult to diagnose and distinguish. We hypothesized that the transcriptome obtained from an endomyocardial biopsy would yield clinically relevant and accurate molecular signatures.Methods and Results: Microarray analysis was performed on samples from patients with histologically proven lymphocytic myocarditis (n=16) and idiopathic dilated cardiomyopathy (n=32) to develop accurate diagnostic transcriptome-based biomarkers using multiple classification algorithms. We identified 9878 differentially expressed genes in lymphocytic myocarditis versus idiopathic dilated cardiomyopathy (fold change >1.2; false discovery rate <5%) from which a transcriptome-based biomarker containing 62 genes was identified that distinguished myocarditis with 100% sensitivity (95% confidence interval, 46 to 100) and 100% specificity (95% confidence interval, 66 to 100) and was generalizable to a broad range of secondary cardiomyopathies associated with inflammation (n=27), ischemic cardiomyopathy (n=8), and the normal heart (n=11). Multiple classification algorithms and quantitative real-time reverse-transcription polymerase chain reaction analysis further reduced this subset to a highly robust molecular signature of 13 genes, which still performed with 100% accuracy.Conclusions: Together, these findings demonstrate that transcriptomic biomarkers from a single endomyocardial biopsy can improve the clinical detection of patients with inflammatory diseases of the heart. This approach advances the clinical management and treatment of cardiac disorders with highly variable outcome. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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