TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
Eur J Heart Fail. 2023 Jun;25(6):832-841. doi: 10.1002/ejhf.2844. Epub 2023 Apr 18.
Cardiac functional and structural remodelling in patients with atrial fibrillation (AF) contributes to development of heart failure (HF) as their major cardiovascular comorbidity. Circulating biomarkers may reflect these cardiac alterations.
ENGAGE AF-TIMI 48 was a randomized trial of edoxaban versus warfarin in 21 105 patients with AF. We performed a nested biomarker study, analysing high-sensitivity troponin T (hsTnT, n = 8705), N-terminal pro-B-type natriuretic peptide (NT-proBNP, n = 8765), and growth differentiation factor-15 (GDF-15, n = 8705) at baseline and 12 months. Of the biomarker cohort, 5207 had a history of HF, among whom 3996 had known ejection fraction (EF): 926 with reduced EF (HFrEF; ≤40%), 1043 with mildly reduced EF (HFmrEF; 40-49%), and 2027 with preserved EF (HFpEF; ≥50%). Elevated baseline hsTnT, NT-proBNP, and GDF-15 were associated with higher risk of hospitalization for HF (HHF) or HF death overall and in subpopulations defined by HF history and EF (p < 0.001 for each). These associations of outcome with each biomarker were consistent regardless of a history of HF or EF (p-interaction >0.05 for each). Patients who had an increase in or had persistently elevated values in any of the three biomarkers over 12 months were at higher risk for HHF or HF death in the overall population (p < 0.001 for each biomarker and category).
Serial measurement of hsTnT, NT-proBNP, and GDF-15 revealed that higher baseline values, and increasing or persistently elevated values over 1 year are associated with higher risk of HF outcomes in patients with AF regardless of HF history or HF phenotype based on EF.
ClinicalTrials.gov unique identifier NCT00781391.
心房颤动（AF）患者的心脏功能和结构重塑导致心力衰竭（HF）的发展，这是其主要的心血管合并症。循环生物标志物可能反映这些心脏变化。
ENGAGE AF-TIMI 48 是一项在 21105 例 AF 患者中比较依度沙班与华法林的随机试验。我们进行了一项嵌套的生物标志物研究，分析了高敏肌钙蛋白 T（hsTnT，n=8705）、N 末端脑钠肽前体（NT-proBNP，n=8765）和生长分化因子 15（GDF-15，n=8705）在基线和 12 个月时的水平。在生物标志物队列中，5207 例患者有 HF 病史，其中 3996 例已知射血分数（EF）：926 例为射血分数降低（HFrEF；≤40%），1043 例为射血分数轻度降低（HFmrEF；40-49%），2027 例为射血分数保留（HFpEF；≥50%）。基线 hsTnT、NT-proBNP 和 GDF-15 升高与 HF 住院或 HF 死亡的风险增加相关（p<0.001）。这些与每个生物标志物的结局的关联在根据 HF 病史和 EF 定义的亚组中是一致的（p 交互>0.05）。在整个人群中，在 12 个月内任何一种生物标志物升高或持续升高的患者发生 HF 住院或 HF 死亡的风险更高（p<0.001，每个生物标志物和类别）。
hsTnT、NT-proBNP 和 GDF-15 的连续测量显示，基线水平较高，以及在 1 年内增加或持续升高与 AF 患者 HF 结局的风险增加相关，无论 HF 病史或基于 EF 的 HF 表型如何。
ClinicalTrials.gov 唯一标识符 NCT00781391。
