title: Blood signature of pre-heart failure: a microarrays study.
abstract: BACKGROUND
  The preclinical stage of systolic heart failure (HF), known as asymptomatic left ventricular dysfunction (ALVD), is diagnosed only by echocardiography, frequent in the general population and leads to a high risk of developing severe HF. Large scale screening for ALVD is a difficult task and represents a major unmet clinical challenge that requires the determination of ALVD biomarkers.
  
  
  RESULTS
  294 individuals were screened by echocardiography. We identified 9 ALVD cases out of 128 subjects with cardiovascular risk factors. White blood cell gene expression profiling was performed using pangenomic microarrays. Data were analyzed using principal component analysis (PCA) and Significant Analysis of Microarrays (SAM). To build an ALVD classifier model, we used the nearest centroid classification method (NCCM) with the ClaNC software package. Classification performance was determined using the leave-one-out cross-validation method. Blood transcriptome analysis provided a specific molecular signature for ALVD which defined a model based on 7 genes capable of discriminating ALVD cases. Analysis of an ALVD patients validation group demonstrated that these genes are accurate diagnostic predictors for ALVD with 87% accuracy and 100% precision. Furthermore, Receiver Operating Characteristic curves of expression levels confirmed that 6 out of 7 genes discriminate for left ventricular dysfunction classification.
  
  
  CONCLUSIONS
  These targets could serve to enhance the ability to efficiently detect ALVD by general care practitioners to facilitate preemptive initiation of medical treatment preventing the development of HF.
authors: INSERM/Universite Paul Sabatier UMR 1048, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse, France. fatima.smith-rouet@inserm.fr
authors: Fatima
authors: F
authors: Smih
authors: Franck
authors: F
authors: Desmoulin
authors: Matthieu
authors: M
authors: Berry
authors: Annie
authors: A
authors: Turkieh
authors: Romain
authors: R
authors: Harmancey
authors: Jason
authors: J
authors: Iacovoni
authors: Charlotte
authors: C
authors: Trouillet
authors: Clement
authors: C
authors: Delmas
authors: Atul
authors: A
authors: Pathak
authors: Olivier
authors: O
authors: Lairez
authors: François
authors: F
authors: Koukoui
authors: Pierre
authors: P
authors: Massabuau
authors: Jean
authors: J
authors: Ferrieres
authors: Michel
authors: M
authors: Galinier
authors: Philippe
authors: P
authors: Rouet
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006333:Heart Failure / Q000097:blood* / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008955:Models, Cardiovascular; D020097:Natriuretic Peptide, Brain / Q000097:blood; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D025341:Principal Component Analysis; D012372:ROC Curve; D015203:Reproducibility of Results; D012307:Risk Factors; D012984:Software; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000235:genetics / Q000503:physiopathology; D055815:Young Adult
chemical_list: D020097:Natriuretic Peptide, Brain