Assessment of the association of new biomarkers (GDF15, ST2, galectin-3, TIMP-1, MMP-9, NfL) and plasma prothrombotic potential in the course of cardiac transthyretin amyloidosis.

The development of cardiac amyloidosis (ATTR) is caused by the deposition of misfolded, insoluble proteins in the extracellular matrix of tissues. An important element of the clinical presentation of the disease is the increased risk of thromboembolic complications. Currently, there is limited published data on the potential role of new heart failure biomarkers in the assessment of ATTR cardiomyopathy, particularly in the assessment of asymptomatic carriers of pathogenic transthyretin (TTR) variants.

Purpose of the study: To assess the diagnostic value of biomarkers related to heart failure (growth differentiation factor-15 (GDF15), soluble suppression of tumorigenicity-2 (ST2), galectin-3), amyloidosis ( retinol binding protein 4 (RBP4, transthyretin) , tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9, matrix metalloproteinase-9), neurofilament light chain (NfL)) and the generation potential thrombin as a marker of the prothrombotic state in the course of ATTR.

Methods: This prospective, single-center study included consecutive patients diagnosed with ATTR, asymptomatic carriers of pathogenic TTR variants, and a matched control group of healthy volunteers.   The values of these biomarkers were evaluated using the ELISA method from peripheral blood (enzyme-linked immunosorbent assay) GDF15, ST2, RBP4 (TTR), TIMP-1, MMP-9, galectin-3, NfL. Additionally, the prothrombotic potential of plasma was tested using the calibrated automatic thrombogram (CAT) method. Results are presented in Table 1. Baseline demographic, clinical and laboratory characteristics of the study population are presented in Table 2.

Conclusions: The project provides information on the value of novel biomarkers in the assessment of ATTR cardiomyopathy, especially in the assessment of asymptomatic carriers of pathogenic TTR variants. Moreover, it evaluated prothrombotic state in the course of ATTR.