title: Midregional pro-atrial natriuretic peptide: a novel marker of myocardial fibrosis in patients with hypertrophic cardiomyopathy.
abstract: We aimed to determine the diagnostic performance of biomarkers in predicting myocardial fibrosis assessed by late gadolinium enhancement (LGE) cardiovascular magnetic resonance imaging (CMR) in patients with hypertrophic cardiomyopathy (HCM). LGE CMR was performed in 40 consecutive patients with HCM. Left and right ventricular parameters, as well as the extent of LGE were determined and correlated to the plasma levels of midregional pro-atrial natriuretic peptide (MR-proANP), midregional pro-adrenomedullin (MR-proADM), carboxy-terminal pro-endothelin-1 (CT-proET-1), carboxy-terminal pro-vasopressin (CT-proAVP), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and interleukin-8 (IL-8). Myocardial fibrosis was assumed positive, if CMR indicated LGE. LGE was present in 26 of 40 patients with HCM (65%) with variable extent (mean: 14%, range: 1.3-42%). The extent of LGE was positively associated with MR-proANP (r = 0.4; P = 0.01). No correlations were found between LGE and MR-proADM (r = 0.1; P = 0.5), CT-proET-1 (r = 0.07; P = 0.66), CT-proAVP (r = 0.16; P = 0.3), MMP-9 (r = 0.01; P = 0.9), TIMP-1 (r = 0.02; P = 0.85), and IL-8 (r = 0.02; P = 0.89). After adjustment for confounding factors, MR-proANP was the only independent predictor associated with the presence of LGE (P = 0.007) in multivariate analysis. The area under the ROC curve (AUC) indicated good predictive performance (AUC = 0.882) of MR-proANP with respect to LGE. The odds ratio was 1.268 (95% confidence interval 1.066-1.508). The sensitivity of MR-proANP at a cut-off value of 207 pmol/L was 69%, the specificity 94%, the positive predictive value 90% and the negative predictive value 80%. The results imply that MR-proANP serves as a novel marker of myocardial fibrosis assessed by LGE CMR in patients with HCM.
authors.affiliation: 1st Department of Medicine, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
authors.forename: Elif
authors.initials: E
authors.lastname: Elmas
authors.forename: Christina
authors.initials: C
authors.lastname: Doesch
authors.forename: Stephan
authors.initials: S
authors.lastname: Fluechter
authors.forename: Miriam
authors.initials: M
authors.lastname: Freundt
authors.forename: Christel
authors.initials: C
authors.lastname: Weiss
authors.forename: Siegfried
authors.initials: S
authors.lastname: Lang
authors.forename: Thorsten
authors.initials: T
authors.lastname: Kälsch
authors.forename: Dariush
authors.initials: D
authors.lastname: Haghi
authors.forename: Jana
authors.initials: J
authors.lastname: Papassotiriou
authors.forename: Jan
authors.initials: J
authors.lastname: Kunde
authors.forename: Stefan O
authors.initials: SO
authors.lastname: Schoenberg
authors.forename: Martin
authors.initials: M
authors.lastname: Borggrefe
authors.forename: Theano
authors.initials: T
authors.lastname: Papavassiliu
mesh_terms: D053607:Adrenomedullin / Q000097:blood; D000328:Adult; D000368:Aged; D009320:Atrial Natriuretic Factor / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002312:Cardiomyopathy, Hypertrophic / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D003287:Contrast Media; D019332:Endothelin-1 / Q000097:blood; D005260:Female; D005355:Fibrosis; D019786:Gadolinium DTPA; D005858:Germany; D006020:Glycopeptides / Q000097:blood; D006801:Humans; D016209:Interleukin-8 / Q000097:blood; D016015:Logistic Models; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D009206:Myocardium / Q000737:chemistry* / Q000473:pathology; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011498:Protein Precursors / Q000097:blood; D012372:ROC Curve; D013318:Stroke Volume; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D016277:Ventricular Function, Left
chemical_list: D015415:Biomarkers; C508606:CXCL8 protein, human; D003287:Contrast Media; D019332:Endothelin-1; D006020:Glycopeptides; D016209:Interleukin-8; D011498:Protein Precursors; D019715:Tissue Inhibitor of Metalloproteinase-1; C048197:copeptins; C088633:proadrenomedullin; C093240:proendothelin 1; D053607:Adrenomedullin; D009320:Atrial Natriuretic Factor; D020780:Matrix Metalloproteinase 9; D019786:Gadolinium DTPA