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.

中文翻译：

---

心脏生物标志物和 aficamten 在阻塞性肥厚型心肌病中的影响：SEQUOIA-HCM 试验


背景和目的 生物标志物检测在梗阻性肥厚型心肌病管理中的作用尚不明确。这项对 SEQUOIA-HCM （NCT05186818） 的预先指定分析旨在确定临床特征与 N 末端 B 型利钠肽前体 （NT-proBNP） 和高敏心肌肌钙蛋白 I （hs-cTnI） 基线浓度之间的关联，并评估 aficamten 治疗对生物标志物浓度的影响。方法 在基线时测量心脏生物标志物，并在整个研究过程中连续测量。回归分析确定了基线 NT-proBNP 和 hs-cTnI 浓度的预测因子，并评估了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、健康状况和功能能力的后期变化有关。结果 NT-proBNP 基线浓度与 LVOT-G 和舒张功能测量相关，而 hs-cTnI 与左心室厚度相关。在 aficamten 治疗后 8 周内，NT-proBNP 降低 79% （95% 置信区间 76%–83%，P < .001） 和 hs-cTnI 降低 41% （95% 置信区间 32%–49%，P < .001）;清除后两种生物标志物都恢复到基线。到 24 周时 NT-proBNP 和 hs-cTnI 的降低与 LVOT-G 降低、健康状况改善和峰值氧摄取量增加密切相关。N 末端 B 型利钠肽前体减少与运动能力的大多数改善密切相关。此外，第 2 周 NT-proBNP 的变化与关键终点的 24 周变化相关。 结论 N 末端 B 型利钠肽前体和 hs-cTnI 浓度与阻塞性肥厚型心肌病的关键变量相关。NT-proBNP 和 hs-cTnI 的连续测量似乎反映了对 aficamten 治疗的临床反应。