Abstract

Introduction: Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognised cause of heart failure. However, the role of cardiac and non-cardiac biomarkers in patients with ATTR-CA remains poorly understood. We sought to characterise a range of routinely measured blood biomarkers in ATTR-CA, and assess which biomarkers are independently associated with prognosis. Methods: Consecutive patients diagnosed with ATTR-CA between 2005 and 2023 were included. Results: We identified 2566 patients (wild-type ATTR = 1834, p.(V142I) = 425, non-p.(V142I) = 307). Anaemia (39%), uraemia (52%), hyperbilirubinemia (18%), raised alkaline phosphatase (ALP) (16%), raised c-reactive protein (CRP) (27%) and a troponin-T >56ng/L (52%) were common findings in the overall population, while hyponatraemia (6%) and hypoalbuminemia (2%) were less common. These abnormalities were most common in p.(V142I) patients, and became more prevalent as the severity of cardiac disease increased, as measured by New York Heart Association (NYHA) functional class (p<0.001 for all) and National Amyloidosis (NAC) disease stage (p<0.001 for all). Multivariable Cox regression analysis adjusting for age, NAC stage, and hereditary vs wild-type ATTR-CA demonstrated that anaemia (HR=1.19, 95%CI[1.04-1.37], P=0.013), uraemia (HR=1.23, 95%CI[1.04-1.45], P=0.011), hyperbilirubinemia (HR=1.32, 95%CI[1.13-1.57], P=0.001), raised ALP (HR=1.20, 95%CI[1.01-1.42], P=0.035), hyponatraemia (HR=1.65, 95%CI[1.28-2.11], P<0.001) and troponin-T >56ng/L (HR=1.72, 95%CI[1.46-2.03], P<0.001) were all independently associated with an increased risk of mortality. Conclusions: Blood biomarker abnormalities are common in ATTR-CA and are more prevalent in patients with advanced cardiac disease. ATTR-CA is a complex and multifaceted disease process with both cardiac and non-cardiac biomarkers being independently associated with prognosis.

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