Lack of Relationship between Fibrosis-Related Biomarkers and Cardiac Magnetic Resonance-Assessed Replacement and Interstitial Fibrosis in Dilated Cardiomyopathy.

Paweł Rubiś,Jan Robak,Małgorzata Mielnik,Mateusz Winiarczyk,Monika Kaciczak,Sylwia Wiśniowska-Śmiałek,Robert Banyś,Matylda Gliniak,Piotr Podolec,Magdalena Szymańska,Arman Karapetyan,Ewa Wypasek,Małgorzata Urbańczyk-Zawadzka,Maciej Krupiński,Aleksandra Karabinowska,Ewa Dziewięcka

doi:10.3390/cells10061295

Abstract

The relationship between circulating fibrosis-related molecules and magnetic resonance-assessed cardiac fibrosis in dilated cardiomyopathy (DCM) is poorly understood. To compare circulating biomarkers between DCM patients with high and low fibrosis burdens, we performed a prospective, single-center, observational study. The study population was composed of 100 DCM patients (87 male, mean age 45.2 ± 11.8 years, mean ejection fraction 29.7% ± 10.1%). Replacement fibrosis was quantified by means of late gadolinium enhancement (LGE), whereas interstitial fibrosis was assessed via extracellular volume (ECV). Plasma concentrations of cardiotrophin-1, growth differentiation factor-15, platelet-derived growth factor, procollagen I C-terminal propeptide, procollagen III N-terminal propeptide, and C-terminal telopeptide of type I collagen were measured. There were 44% patients with LGE and the median ECV was 27.7%. None of analyzed fibrosis serum biomarkers were associated with the LGE or ECV, whereas NT-proBNP was independently associated with both LGE and ECV, and troponin T was associated with ECV. None of the circulating fibrosis markers differentiated between DCM patients with and without replacement fibrosis, or patients stratified according to median ECV. However, cardiac-specific markers, such as NT-proBNP and hs-TnT, were associated with fibrosis. Levels of circulating markers of fibrosis seem to have no utility in the diagnosis and monitoring of cardiac fibrosis in DCM.

Highlights

In healthy individuals, cardiac the extracellular matrix (ECM) stays in a state of homeostasis, i.e., anabolic processes, such as the synthesis of ECM components, are in balance with catabolism [1,2]
We reported that 12 serum markers of ECM metabolism, such as markers of collagen synthesis and controlling factors, including galectin-3, as well as the matrix metalloproteinases (MMPs)/TIMPs system, were of zero utility when it came to the prediction of EBMassessed fibrosis in dilated cardiomyopathy (DCM) [6,27]
We believe that we provide rather solid evidence regarding the lack of association between various fibrosis-linked circulating molecules with replacement and interstitial fibrosis in one of the largest DCM cohorts

Summary

Introduction

Cardiac the extracellular matrix (ECM) stays in a state of homeostasis, i.e., anabolic processes, such as the synthesis of ECM components, are in balance with catabolism (the degradation of collagens) [1,2]. Optimal cardiac morphology and function are determined solely by the quantity and quality of myocytes and the collagen and other ECM compounds surrounding them. After coronary artery disease (CAD) and hypertension, dilated cardiomyopathy (DCM) is the third most common cause of heart failure (HF) [3]. DCM typically occurs in adolescence and young adults and becomes a life-long and potentially fatal disease. During the course of DCM, the heart undergoes profound structural changes; these include left and right ventricular (LV, RV) enlargement, wall thinning, changes from an elliptical geometry towards a spherical one, the development of pulmonary hypertension, and fibrosis of the ECM [4]. Cardiac fibrosis is one of the hallmarks of DCM and is typically observed in 40–60%

Objectives

Methods

Results

Discussion

Conclusion