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

IF 37.6 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS European Heart Journal Pub Date : 2024-11-08 DOI:10.1093/eurheartj/ehae590
Caroline J Coats, Ahmad Masri, Roberto Barriales-Villa, Theodore P Abraham, Douglas Marshall Brinkley, Brian L Claggett, Albert Hagege, Sheila M Hegde, Carolyn Y Ho, Ian J Kulac, Matthew M Y Lee, Martin S Maron, Iacopo Olivotto, Anjali T Owens, Scott D Solomon, Jacob Tfelt-Hansen, Hugh Watkins, Daniel L Jacoby, Stephen B Heitner, Stuart Kupfer, Fady I Malik, Lisa Meng, Amy Wohltman, James L Januzzi
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Abstract

Background and aims: 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.

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 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.

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% 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.

Conclusions: 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.

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阻塞性肥厚型心肌病的心脏生物标志物和阿非坎顿的作用:SEQUOIA-HCM 试验。
背景和目的:生物标志物检测在阻塞性肥厚型心肌病(oHCM)治疗中的作用尚未明确。SEQUOIA-HCM (NCT05186818)的这项预先指定分析旨在确定临床特征与N-末端前B型利钠肽(NT-proBNP)和高敏心肌肌钙蛋白I(hs-cTnI)基线浓度之间的关系,并评估阿非卡坦治疗对生物标志物浓度的影响:在基线和整个研究过程中连续测量心脏生物标志物。回归分析确定基线 NT-proBNP 和 hs-cTnI 浓度的预测因素,并评估这些生物标志物的早期变化是否与左心室流出道梯度(LVOT-G)、其他超声心动图测量指标、健康状况和功能能力的后期变化有关:结果:NT-proBNP的基线浓度与左心室流出道梯度和舒张功能相关,而hs-cTnI与左心室厚度相关。在使用阿菲康坦治疗的 8 周内,NT-proBNP 降低了 79% (95% CI 83%-76%, P < .001) ,hs-cTnI 降低了 41% (95% CI 49%-32%, P < .001) ;在冲洗后,这两种生物标志物都恢复到基线水平。24 周前 NT-proBNP 和 hs-cTnI 的降低与 LVOT-G 的降低、健康状况的改善和峰值摄氧量的增加密切相关。NT-proBNP 的降低与运动能力的大部分改善密切相关。此外,第 2 周 NT-proBNP 的变化与 24 周关键终点的变化相关:结论:NT-proBNP 和 hs-cTnI 浓度与 oHCM 的关键变量相关。结论:NT-proBNP和hs-cTnI浓度与oHCM的关键变量相关,连续测量NT-proBNP和hs-cTnI似乎能反映出对阿非坎顿治疗的临床反应。
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来源期刊
European Heart Journal
European Heart Journal 医学-心血管系统
CiteScore
39.30
自引率
6.90%
发文量
3942
审稿时长
1 months
期刊介绍: The European Heart Journal is a renowned international journal that focuses on cardiovascular medicine. It is published weekly and is the official journal of the European Society of Cardiology. This peer-reviewed journal is committed to publishing high-quality clinical and scientific material pertaining to all aspects of cardiovascular medicine. It covers a diverse range of topics including research findings, technical evaluations, and reviews. Moreover, the journal serves as a platform for the exchange of information and discussions on various aspects of cardiovascular medicine, including educational matters. In addition to original papers on cardiovascular medicine and surgery, the European Heart Journal also presents reviews, clinical perspectives, ESC Guidelines, and editorial articles that highlight recent advancements in cardiology. Additionally, the journal actively encourages readers to share their thoughts and opinions through correspondence.
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