Objective: Cardiac biomarkers hold promise for follow-up and management of aortic valve stenosis (AVS). When interpreting serial biomarker measurements of patients with AVS, it can be challenging to distinguish 'real changes' from 'random fluctuation'. Hence, robust estimation of the biological variation of these biomarkers is essential. In the present study we assessed biological variation of B-type natriuretic peptide (BNP), N-terminus pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin-T and high-sensitivity troponin-I (hs-TnT and hs-TnI), and ST2 in subjects with stable AVS.
Methods: Serial blood sampling was performed in 25 subjects with moderate AVS-confirmed by echocardiography-and all free from acute cardiovascular events in the past 6 months. Blood samples were taken on seven standardised occasions during 1 year. Analytical variation (CVA), within-subject biological variation (CVI), between-subject biological variation (CVG), index of individuality (II) and reference change values were calculated for all cardiac biomarkers.
Results: CVI was highest for BNP (62.0%, 95% CI 52.5 to 75.4) and lowest for hs-TnI (9.2%, 95% CI 2.8 to 13.8). CVG exceeded the CVI for all biomarkers except BNP, and ranged from 19.8% (95% CI 13.8 to 33.4) for ST2 to 57.2% (95% CI 40.4 to 97.3) for hs-TnT. NT-proBNP, hs-TnT and ST2 revealed CVA <5%, while BNP and hs-TnI showed a higher CVA (19.7 and 14.9, respectively). All biomarkers except BNP showed marked individuality, with II ranging from 0.21 to 0.67 (BNP 1.34).
Conclusion: This study provides the first biological variation estimates of cardiac biomarkers in patients with stable AVS. These estimates allow a more evidence-based interpretation of biomarker changes in the follow-up and management of patients with AVS.
Trial registration number: NCT02510482.
Keywords: aortic valve stenosis; biological variation; cardiac biomarkers; echocardiography; progression.