Affiliation:
1. National Amyloidosis Centre University College London London United Kingdom
2. Center for Diagnosis and Treatment of Cardiomyopathies, Cardiovascular Department Azienda Sanitaria Universitaria Giuliano‐Isontina, University of Trieste Trieste Italy
3. Cardiology Unit, Department of Cardiac Thoracic and Vascular Istituto di Ricovero e Cura a Carattere Scientifico Azienda Ospedaliero–Universitaria di Bologna Bologna Italy
4. Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences Sapienza University of Rome Rome Italy
5. Heart Failure and Rehabilitation Unit, IRCCS MultiMedica, Sesto San Giovanni Milan Italy
6. Department for Biomedical Sciences for Health University of Milano Milan Italy
7. University College London London United Kingdom
Abstract
Background
Transthyretin cardiac amyloidosis (ATTR‐CA) is a progressive and ultimately fatal cardiomyopathy. Biomarkers reflecting multiorgan dysfunction are of increasing importance in patients with heart failure; however, their significance in ATTR‐CA remains largely unknown. The aims of this study were to characterize the multifaceted nature of ATTR‐CA using blood biomarkers and assess the association between blood biomarkers and prognosis.
Methods and Results
This is a retrospective cohort study of 2566 consecutive patients diagnosed with ATTR‐CA between 2007 and 2023. Anemia (39%), high urea (52%), hyperbilirubinemia (18%), increased alkaline phosphatase (16%), increased CRP (C‐reactive protein; 27%), and increased troponin (98.2%) were common findings in the overall population, whereas hyponatremia (6%) and hypoalbuminemia (2%) were less common. These abnormalities were most common in patients with p.(V142I) hereditary ATTR‐CA, and became more prevalent as the severity of cardiac disease increased. Multivariable Cox regression analysis demonstrated that anemia (hazard ratio [HR], 1.19 [95% CI, 1.04–1.37];
P
=0.01), high urea (HR, 1.23 [95% CI, 1.04–1.45];
P
=0.01), hyperbilirubinemia (HR, 1.32 [95% CI, 1.13–1.57;
P
=0.001), increased alkaline phosphatase (HR, 1.20 [95% CI, 1.01–1.42;
P
=0.04), hyponatremia (HR, 1.65 [95% CI, 1.28–2.11];
P
<0.001), and troponin‐T >56 ng/L (HR, 1.72 [95% CI, 1.46–2.03];
P
<0.001) were all independently associated with mortality in the overall population. The association between biomarkers and mortality varied across the spectrum of genotypes and left ventricular ejection fraction, with anemia remining independently associated with mortality in p.(V142I) hereditary ATTR‐CA (HR, 1.58 [95% CI, 1.17–2.12];
P
=0.003) and in a subgroup of the overall population with a left ventricular ejection fraction ≤40% (HR, 1.39 [95% CI, 1.08–1.81];
P
=0.01).
Conclusions
Cardiac and noncardiac biomarker abnormalities were common and reflect the complex and multifaceted nature of ATTR‐CA, with a wide range of biomarkers remaining independently associated with mortality. Clinical trials are needed to investigate whether biomarker abnormalities represent modifiable risk factors that if specifically targeted could improve outcomes.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine