Oncotarget

Research Papers:

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

Yen-Tin Lin, Yen-Hung Lin, Xue-Ming Wu, Chi-Lun Ko, Ruoh-Fang Yen, Ying-Hsein Chen, Ron-Bin Hsu, Chi-Ming Lee, Shoei-Shen Wang, Ming-Fong Chen and Yen-Wen Wu _

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Oncotarget. 2017; 8:2381-2390. https://doi.org/10.18632/oncotarget.13795

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Abstract

Yen-Tin Lin1,*, Yen-Hung Lin2,5,*, Xue-Ming Wu1, Chi-Lun Ko3, Ruoh-Fang Yen3, Ying-Hsein Chen2, Ron-Bin Hsu4, Chi-Ming Lee2, Shoei-Shen Wang4, Ming-Fong Chen2,6 and Yen-Wen Wu2,3,7,8

1 Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan

2 Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

3 Department of Nuclear Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

4 Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

5 Department of Medicine, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts, USA

6 Cardiovascular Research Laboratory, Cardiovascular Center, Clinical Outcome Research and Training Center, Big Data Center, China Medical University Hospital, China Medical University, Taichung, Taiwan

7 Cardiology Division of Cardiovascular Medical Center, Department of Nuclear Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan

8 National Yang-Ming University School of Medicine, Taipei, Taiwan

* These authors have contributed equally to this work

Correspondence to:

Yen-Wen Wu, email:

Keywords: fibrosis; restrictive filling; ventriculography

Received: October 04, 2016 Accepted: November 24, 2016 Published: December 04, 2016

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.


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