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

SEQUOIA-HCM Investigators

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Abstract

BACKGROUND AND AIMS: The role of biomarker testing in the management of obstructive hypertrophic cardiomyopathy (oHCM) 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 effect of treatment with aficamten on biomarker concentrations.

METHODS: Cardiac biomarkers were measured at baseline and serially throughout the study. Regression analyses determined predictors of baseline NT-proBNP and hs-cTnI concentrations, and to evaluate 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.

RESULTS: 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% CI 83%-76%, P < .001) and hs-cTnI by 41% (95% CI 49%-32%, 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. NT-proBNP 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.

CONCLUSIONS: NT-proBNP and hs-cTnI concentrations are associated with key variables in oHCM. Serial measurement of NT-proBNP and hs-cTnI appears to reflect clinical response to aficamten therapy.

Original languageEnglish
Article numberehae590
JournalEuropean Heart Journal
ISSN0195-668X
DOIs
Publication statusE-pub ahead of print - 2024

Bibliographical note

© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.

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