Cardiac biomarkers and effects of aficamten in obstructive hypertrophic cardiomyopathy: the SEQUOIA-HCM trial

• Published in: European heart journal 2024-11, Vol.45 (42), p.4464-4478
• Main Authors: Coats, Caroline J, Masri, Ahmad, Barriales-Villa, Roberto, Abraham, Theodore P, Brinkley, Douglas Marshall, Claggett, Brian L, Hagege, Albert, Hegde, Sheila M, Ho, Carolyn Y, Kulac, Ian J, Lee, Matthew M Y, Maron, Martin S, Olivotto, Iacopo, Owens, Anjali T, Solomon, Scott D, Tfelt-Hansen, Jacob, Watkins, Hugh, Jacoby, Daniel L, Heitner, Stephen B, Kupfer, Stuart, Malik, Fady I, Meng, Lisa, Wohltman, Amy, Januzzi, James L
• Format: Article
• Language: English
• Subjects: Aged; Biomarkers - blood; Biomarkers - metabolism; Cardiomyopathy, Hypertrophic - drug therapy; Double-Blind Method; Fast Track – Clinical Research; Female; Growth Differentiation Factor 15 - blood; Humans; Male; Middle Aged; Natriuretic Peptide, Brain - blood; Natriuretic Peptide, Brain - metabolism; Peptide Fragments - blood; Peptide Fragments - metabolism; Troponin I - blood
• ISSN: 0195-668X; 1522-9645; 1522-9645
• DOI: 10.1093/eurheartj/ehae590

The role of biomarker testing in the management of obstructive hypertrophic cardiomyopathy is not well defined. This pre-specified analysis of SEQUOIA-HCM (NCT05186818) sought to define the associations between clinical characteristics and baseline concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (hs-cTnI), and to evaluate the effect of treatment with aficamten on biomarker concentrations. Cardiac biomarkers were measured at baseline and serially throughout the study. Regression analyses determined predictors of baseline NT-proBNP and hs-cTnI concentrations, and evaluated whether early changes in these biomarkers relate to later changes in left ventricular outflow tract gradient (LVOT-G), other echocardiographic measures, health status, and functional capacity. Baseline concentration of NT-proBNP was associated with LVOT-G and measures of diastolic function, while hs-cTnI was associated with left ventricular thickness. Within 8 weeks of treatment with aficamten, NT-proBNP was reduced by 79% (95% confidence interval 76%-83%, P < .001) and hs-cTnI by 41% (95% confidence interval 32%-49%, P < .001); both biomarkers reverted to baseline after washout. Reductions in NT-proBNP and hs-cTnI by 24 weeks were strongly associated with a lowering of LVOT-G, improvement in health status, and increased peak oxygen uptake. N-Terminal pro-B-type natriuretic peptide reduction strongly correlated with the majority of improvements in exercise capacity. Furthermore, the change in NT-proBNP by Week 2 was associated with the 24-week change in key endpoints. N-Terminal pro-B-type natriuretic peptide and hs-cTnI concentrations are associated with key variables in obstructive hypertrophic cardiomyopathy. Serial measurement of NT-proBNP and hs-cTnI appears to reflect clinical response to aficamten therapy.