Stratification of heart failure using biomarkers of myocardial fibrosis

Abstract

The collagen network of the heart consists mainly of collagen type I and III fibres. This network provides the cardiac geometry, but also the tensile strength and contractility of the myocardium. However, during heart failure (HF) the cardiac structure is altered, leading to, among others, accumulation of collagen in the myocardium, hence fibrosis. Fibrosis is a major contributor to the progression of HF, sudden cardiac death, and cardiac arrhythmias. Non-invasive methods such as biomarkers might be used to require additional information about fibrosis in HF patients. Therefore, biomarkers reflecting cardiac fibrosis might be useful in clinics for diagnostic, prognostic, and preventive purposes. Currently, several biomarkers of collagen turnover are known. The N-propeptide of the procollagen type I and III and the C-propeptide of collagen I (PINP, PIIINP, and PICP respectively) might serve as markers reflecting the synthesis of collagen fibres. The telopeptide which is cleaved of collagen I during degradation (ICTP) may represent the breakdown of collagen I. The proteases which are responsible for the breakdown of the extracellular matrix, called matrix metalloproteinases, and their endogenous inhibitors, tissue inhibitors of metalloproteinases, can also be detected in blood. This thesis summarizes and discusses the current knowledge about the use of these biomarkers as a diagnostic, prognostic, or predictive tool. Studies investigating the difference in biomarker levels of HF patients and controls are included. Next to this subject, this thesis also provides information about the correlation between the different biomarkers and the amount of myocardial collagen observed with histology or histochemistry. Studies which determine the diagnostic, predictive, or prognostic value of the previously mentioned biomarkers are also discussed in this thesis. In conclusion, based on this thesis PICP, ICTP, PIIINP, and the tissue inhibitor of metalloproteinases type I seem to be very promising biomarkers as a diagnostic, prognostic, or predictive tool. However, more investigation is demanded to gain more knowledge in the specificity and sensitivity of these biomarkers, cut off values of these biomarkers, and the correlation between these biomarkers and the amount of different collagen types in the myocardium. The influence of patient characteristics such as underlying disorders, stage of HF, body mass index, age, and medication on the biomarker levels also have to be investigated more extensively.