Background:Circulating high-sensitivity cardiac troponin T (hsTnT) predominantly reflects myocardial injury, and higher levels are associated with a higher risk of worsening heart failure and death in patients with heart failure with reduced ejection fraction. Less is known about the prognostic significance of changes in hsTnT over time, the effects of dapagliflozin on clinical outcomes in relation to baseline hsTnT levels, and the effect of dapagliflozin on hsTnT levels.Methods:DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) was a randomized, double-blind, placebo-controlled trial of dapagliflozin (10 mg daily) in patients with New York Heart Association class II to IV symptoms and left ventricular ejection fraction ≤40% (median follow-up, 18.2 months). hsTnT (Roche Diagnostics) was measured at baseline in 3112 patients and at 1 year in 2506 patients. The primary end point was adjudicated worsening heart failure or cardiovascular death. Clinical end points were analyzed according to baseline hsTnT and change in hsTnT from baseline to 1 year. Comparative treatment effects on clinical end points with dapagliflozin versus placebo were assessed by baseline hsTnT. The effect of dapagliflozin on hsTnT was explored.Results:Median baseline hsTnT concentration was 20.0 (25th–75th percentile, 13.7–30.2) ng/L.Over 1 year, 67.9% of patients had a ≥10% relative increase or decrease in hsTnT concentrations, and 43.5% had a ≥20% relative change. A stepwise gradient of higher risk for the primary end point was observed across increasing quartiles of baseline hsTnT concentration (adjusted hazard ratio Q4 versus Q1, 3.44 [95% CI, 2.46–4.82]). Relative and absolute increases in hsTnT over 1 year were associated with higher subsequent risk of the primary end point. The relative reduction in the primary end point with dapagliflozin was consistent across quartiles of baseline hsTnT (P-interaction=0.55), but patients in the top quartile tended to have the greatest absolute risk reduction (absolute risk difference, 7.5% [95% CI, 1.0%–14.0%]). Dapagliflozin tended to attenuate the increase in hsTnT over time compared with placebo (relative least squares mean reduction, –3% [–6% to 0%]; P=0.076).Conclusions:Higher baseline hsTnT and greater increase in hsTnT over 1 year are associated with worse clinical outcomes. Dapagliflozin consistently reduced the risk of the primary end point, irrespective of baseline hsTnT levels.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.

中文翻译：

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高灵敏度心肌肌钙蛋白的系列评估和达格列净对射血分数降低的心力衰竭患者的影响：DAPA-HF 试验的分析

背景：循环高敏心肌肌钙蛋白 T (hsTnT) 主要反映心肌损伤，在射血分数降低的心力衰竭患者中，高敏肌钙蛋白 T (hsTnT) 水平越高，心力衰竭恶化和死亡的风险越高。关于 hsTnT 随时间变化的预后意义、达格列净对与基线 hsTnT 水平相关的临床结果的影响以及达格列净对 hsTnT 水平的影响知之甚少。方法：DAPA-HF（达格列净和预防不良结局心力衰竭）是一项随机、双盲、安慰剂对照的达格列净（每天 10 毫克）试验，用于纽约心脏协会 II 至 IV 级症状和左心室射血分数≤40% 的患者（中位随访时间为 18.2 个月） ）。hsTnT（罗氏诊断）在 3112 名患者的基线和 2506 名患者的 1 年时进行了测量。主要终点被裁定为心力衰竭恶化或心血管死亡。根据基线 hsTnT 和 hsTnT 从基线到 1 年的变化分析临床终点。通过基线 hsTnT 评估达格列净与安慰剂对临床终点的比较治疗效果。探讨了达格列净对 hsTnT 的影响。结果：中位基线 hsTnT 浓度为 20.0（第 25-75 个百分位，13.7-30.2）ng/L。在 1 年内，67.9% 的患者 hsTnT 相对增加或减少 ≥10%浓度，43.5% 的相对变化≥20%。在基线 hsTnT 浓度增加的四分位数中观察到主要终点风险的逐步梯度（调整后的风险比 Q4 与 Q1，3.44 [95% CI，2.46–4.82]）。超过 1 年 hsTnT 的相对和绝对增加与主要终点的较高后续风险相关。达格列净主要终点的相对降低在基线 hsTnT 的四分位数中是一致的（P -interaction=0.55），但处于前四分之一的患者往往具有最大的绝对风险降低（绝对风险差异，7.5% [95% CI，1.0%–14.0%]）。与安慰剂相比，达格列净倾向于减弱 hsTnT 随时间的增加（相对最小二乘均值减少，–3% [–6% 至 0%]；P = 0.076）。结论：1 年内基线 hsTnT 较高且 hsTnT 增加较大与较差的临床结果相关。无论基线 hsTnT 水平如何，达格列净始终降低主要终点的风险。注册：URL：https://www.clinicaltrials.gov；唯一标识符：NCT03036124。