Cardiac biomarkers and effects of aficamten in obstructive hypertrophic cardiomyopathy: the SEQUOIA-HCM trial.
Journal
European heart journal
ISSN: 1522-9645
Titre abrégé: Eur Heart J
Pays: England
ID NLM: 8006263
Informations de publication
Date de publication:
01 Sep 2024
01 Sep 2024
Historique:
received:
25
07
2024
revised:
13
08
2024
accepted:
21
08
2024
medline:
1
9
2024
pubmed:
1
9
2024
entrez:
1
9
2024
Statut:
aheadofprint
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND AND AIMS
OBJECTIVE
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
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
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
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.
Identifiants
pubmed: 39217447
pii: 7745563
doi: 10.1093/eurheartj/ehae590
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Investigateurs
Yuhui Zhang
(Y)
Haibo Yang
(H)
Chunli Shao
(C)
Zuyi Yuan
(Z)
Qingchun Zeng
(Q)
Xiaodong Li
(X)
Changsheng Ma
(C)
Yushi Wang
(Y)
Yan Shu
(Y)
Mulei Chen
(M)
Ling Tao
(L)
Xinli Li
(X)
Jingfeng Wang
(J)
Zaixin Yu
(Z)
Xiang Cheng
(X)
Kui Hong
(K)
David Zemanek
(D)
Henning Bundgaard
(H)
Jens Thune
(J)
Morten Jensen
(M)
Jens Mogensen
(J)
Albert Hagege
(A)
Gilbert Habib
(G)
Philippe Charron
(P)
Thibault Lhermusier
(T)
Jean-Noël Trochu
(JN)
Patricia Reant
(P)
Damien Logeart
(D)
Veselin Mitrovic
(V)
Tarek Bekfani
(T)
Frank Edelmann
(F)
Tim Seidler
(T)
Benjamin Meder
(B)
Paul Christian Schulze
(P)
Stephan Stoerk
(S)
Tienush Rassaf
(T)
Bela Merkely
(B)
Donna Zfat-Zwas
(D)
Michael Arad
(M)
Majdi Halabi
(M)
Offir Paz
(O)
Xavier Piltz
(X)
Iacopo Olivotto
(I)
Mattia Targetti
(M)
Marco Metra
(M)
Marco Canepa
(M)
Beatrice Musumeci
(B)
Michele Emdin
(M)
Michelle Michels
(M)
Ahmad Amin
(A)
Christian Knackstedt
(C)
Artur Oreziak
(A)
Wojciech Wojakowski
(W)
Dariusz Dudek
(D)
Alexandra Toste
(A)
José Mesquita Bastos
(J)
Roberto Barriales-Villa
(R)
Pablo Garcia Pavia
(P)
Juan Ramón Gimeno Blanes
(J)
Rafael Jesus Hidalgo Urbano
(R)
Ana Garcia Alvarez
(A)
Luis Miguel Rincón Diaz
(L)
Tomas Vicente Ripoll Vera
(T)
Perry Elliott
(P)
Caroline Coats
(C)
Rob Cooper
(R)
Masliza Mahmod
(M)
William Bradlow
(W)
Antonis Pantazis
(A)
Maria Teresa Tome Esteban
(M)
Ahmad Masri
(A)
Michael Nassif
(M)
Ali Marian
(A)
David Owens
(D)
Matthew Wheeler
(M)
Frank McGrew
(F)
Richard Bach
(R)
Omar Wever-Pinzon
(O)
Elias Collado
(E)
Aslan Turer
(A)
Bashar Hannawi
(B)
Jeffrey Geske
(J)
Anjali Owens
(A)
John Symanski
(J)
Christopher Kramer
(C)
Nitasha Sarswat
(N)
Ferhaan Ahmad
(F)
Theodore Abraham
(T)
Jeremy Markowitz
(J)
Neal Lakdawala
(N)
Lubna Choudhury
(L)
Sandeep Jani
(S)
Marshall Brinkley
(M)
Ozlem Bilen
(O)
Craig Asher
(C)
Sitaramesh Emani
(S)
Abhinav Sharma
(A)
David Fermin
(D)
Melissa Lyle
(M)
David Raymer
(D)
Andrew Darlington
(A)
Martin Maron
(M)
Christopher Nielsen
(C)
Andrew Wang
(A)
Sherif Nagueh
(S)
Matthew Martinez
(M)
Milind Desai
(M)
Albree Tower-Rader
(A)
Jacob Kelly
(J)
Florian Rader
(F)
Sounok Sen
(S)
Patrick Bering
(P)
Mathew Maurer
(M)
Sumeet Mitter
(S)
Mark Sherrid
(M)
Timothy Wong
(T)
Zainal Hussain
(Z)
Sara Saberi
(S)
Srihari Naidu
(S)
Jorge Silva Enciso
(J)
Informations de copyright
© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.