Biomarkers for monitoring patients with cardiac amyloidosis during transthyretin-stabilizer therapy

Abstract Introduction Cardiac amyloidosis is characterized by deposition of amyloid fibrils in the heart, leading to structural abnormalities and functional impairments resulting in heart failure. Amyloid transthyretin amyloidosis cardiomyopathy (ATTR-CM) is the most common form with increasing incidence due to growing awareness and improved diagnosis. The ATTR stabilizer tafamidis serves as the first specific therapy approved for ATTR-CM, and many promising substances are in late-stage clinical trials. With growing numbers of patients receiving stabilizer therapy, valid tools for monitoring treatment response and detecting disease progression are currently lacking. Here, we aim to assess systemic and cardiac biomarkers in patients receiving stabilizer therapy. Method All individuals diagnosed with ATTR-CM at our university hospital, were systematically assessed for eligibility in this study. We enrolled patients who were undergoing therapy with tafamidis. Biomarkers including Hemoglobin (Hb), Creatinine, estimated glomerular filtration rate (eGFR), International Normalized Ratio (INR), C-reactive protein (CRP), Troponin and NT-proBNP were examined at baseline and during 6 and 12 months follow-up. Wilcoxon signed rank test was used for statistical analysis. The study was approved by the local ethics committee (23-11500-BO). Results 194 patients were included in the analysis with median age of 80 (76-83) years (86,6% male). Results showed an impaired renal function at baseline (all mean ± SD) with creatinine 1.24 ± 0.46 mg/dl and eGFR 58.64 ± 18.24 ml/min/kg with statistically significant increase after 6 months in creatinine (1.31 ± 0.51 mg/dl, p<0.001) and eGFR (55.06 ± 17.65 ml/min/kg, p<0.001) and after 12 months (creatinine 1.35 ± 0.54 mg/dl, p<0.001, eGFR 53.27 ± 17.68 ml/min/kg, p<0.001). Hb showed a significant increase after 6 (13.61 ± 1.78 g/dl, p<0.001) and 12 months (13.6 ± 1.79 g/dl, p<0.001), compared to baseline (13.41 ± 1.71 g/dl, p<0.001). Comparison of baseline values for CRP (0.08 ± 1.18 mg/dl), Troponin (86.33 ± 190.6 ng/l), NT-pro BNP (4703 ± 4385 pg/ml) and INR (1.25 ± 0.46) after 6 (CRP p=0.28, Troponin p=0.7, NT-pro BNP p=0.97, INR p=0.91) and 12 months (CRP p=0.12, Troponin p=0.59, NT-pro BNP p=0.78, INR p=0.28) showed no significant changes. Conclusion Although troponin and BNP are routinely used and recommended as biomarker for monitoring patients with ATTR-CM, the diagnostic value may be insufficient to assess therapy response. Results emphasize the need to identify new biomarkers to adequately reflect the specific aspects of ATTR-CM disease progression. This study reveals significant alterations in creatinine and eGFR due to a worsening of kidney function, but an increase of Hb, suggesting a potential indicator for treatment response. Future research should explore innovative approaches like proteomic analysis as promising approach for both diagnostic and prognostic biomarkers.