title: The relationship between serum fibrosis markers and restrictive ventricular filling in patients with heart failure with reduced ejection fraction: A technetium-99m radionuclide ventriculography study.
abstract: Myocardial fibrosis leads to a restrictive diastolic filling pattern of the left ventricle which is associated with a poor prognosis in patients with heart failure. We investigated the relationship between cardiac fibrosis and restrictive filling pattern of the left ventricle measured by Tc99m left ventriculography in patients with chronic symptomatic heart failure. Serum cardiac extracellular matrix markers including type I and III aminoterminal propeptide of procollagen (PINP and PIIINP), matrix metalloproteinase-2,9 (MMP-2,9), and tissue inhibitor of MMP-1 (TIMP-1) were analyzed. Fifty-one (39 males) patients were enrolled. Their median age was 51.8 years, and median left ventricular ejection fraction was 31.9%. Time to peak filling rate of the left ventricle was significantly correlated with serum levels of the three cardiac extracellular matrix markers (TIMP-1, PIIINP, and MMP-2). The patients with a restrictive diastolic filling pattern of the left ventricle (time to peak filling rate ≤ 154 ms) had significantly higher levels of these extracellular matrix markers. In receiver operating characteristic curve analysis, areas under the curve of PIIINP, TIMP-1, and MMP-2 were 0.758, 0.695, and 0.751 to predict the presence of a restrictive pattern. In C-statistics, all three cardiac extracellular matrix markers significantly increased the area under the curve after adding creatinine. In net reclassification improvement and integrated discrimination improvement models, PIIINP and MMP-2 significantly improved the predictive power of age, creatinine and brain natriuretic peptide. In conclusion, serum extracellular matrix markers are significantly correlated with restrictive diastolic filling pattern of the left ventricle in patients with heart failure.
authors.affiliation: Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan.
authors.forename: Yen-Tin
authors.initials: YT
authors.lastname: Lin
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.|Department of Medicine, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Yen-Hung
authors.initials: YH
authors.lastname: Lin
authors.affiliation: Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan.
authors.forename: Xue-Ming
authors.initials: XM
authors.lastname: Wu
authors.affiliation: Department of Nuclear Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Chi-Lun
authors.initials: CL
authors.lastname: Ko
authors.affiliation: Department of Nuclear Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Ruoh-Fang
authors.initials: RF
authors.lastname: Yen
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Ying-Hsein
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Ron-Bin
authors.initials: RB
authors.lastname: Hsu
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Lee
authors.affiliation: Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Shoei-Shen
authors.initials: SS
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.|Cardiovascular Research Laboratory, Cardiovascular Center, Clinical Outcome Research and Training Center, Big Data Center, China Medical University Hospital, China Medical University, Taichung, Taiwan.
authors.forename: Ming-Fong
authors.initials: MF
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.|Department of Nuclear Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.|Cardiology Division of Cardiovascular Medical Center, Department of Nuclear Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.|National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Yen-Wen
authors.initials: YW
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D004719:Endomyocardial Fibrosis / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D015635:Radionuclide Ventriculography / Q000379:methods*; D012680:Sensitivity and Specificity; D013318:Stroke Volume / Q000502:physiology*; D013667:Technetium / Q000737:chemistry; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D013667:Technetium
keywords: fibrosis; restrictive filling; ventriculography