TIMI Study Group, 75 Francis Street, Boston, MA, USA.
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA, USA.
Eur Heart J. 2019 Oct 21;40(40):3345-3352. doi: 10.1093/eurheartj/ehz240.
Circulating high-sensitivity cardiac troponin (hsTn) and soluble ST2 (sST2) reflect myocardial stress in patients with heart failure (HF). Production of cyclic guanosine 3'5' monophosphate (cGMP) in response to activation of natriuretic peptide receptors reduces cardiac afterload and preload. We assessed the effects of sacubitril/valsartan on these biomarkers in patients with reduced ejection fraction and acute decompensated HF (ADHF).
PIONEER-HF was a randomized, double-blind trial of sacubitril/valsartan vs. enalapril in hospitalized patients with ADHF following haemodynamic stabilization. We measured circulating hsTnT, sST2, and urinary cGMP at baseline, 1, 2 (sST2, cGMP), 4, and 8 weeks (n = 694 with all baseline biomarkers). Ratios of geometric means (timepoint/baseline) were determined and compared as a ratio for sacubitril/valsartan vs. enalapril. Compared with enalapril, sacubitril/valsartan led to a significantly greater decline in hsTnT and sST2. This effect emerged as early as 1 week for sST2 and was significant for both at 4 weeks with a 16% greater reduction in hsTnT (P < 0.001) and 9% greater reduction in sST2 (P = 0.0033). Serial urinary cGMP increased with sacubitril/valsartan compared with enalapril (P < 0.001, 1 week). The significant differences between treatment groups for each biomarker were sustained at 8 weeks. In an exploratory multivariable-adjusted analysis of cardiovascular death or HF-rehospitalization, the concentrations of hsTnT, sST2 at week 1 were significantly associated with subsequent outcome.
Biomarkers of myocardial stress are elevated in patients with ADHF and associated with outcome. Compared with enalapril, sacubitril/valsartan reduces myocardial injury and haemodynamic stress as reflected by biomarkers, with an onset that is apparent within 1-4 weeks.
NCT02554890 clinical.trials.gov.
循环高敏心肌肌钙蛋白（hsTn）和可溶性 ST2（sST2）反映心力衰竭（HF）患者的心肌应激。环鸟苷酸 3'5' 一磷酸（cGMP）的产生对利钠肽受体的激活反应降低了心脏后负荷和前负荷。我们评估了沙库巴曲缬沙坦对射血分数降低和急性失代偿性 HF（ADHF）患者这些生物标志物的影响。
PIONEER-HF 是一项在血流动力学稳定后住院的 ADHF 患者中沙库巴曲缬沙坦与依那普利的随机、双盲试验。我们在基线、1、2（sST2、cGMP）、4 和 8 周时测量了循环 hsTnT、sST2 和尿 cGMP（n=694 例，所有基线生物标志物）。确定了几何平均值（时间点/基线）的比值，并比较了沙库巴曲缬沙坦与依那普利的比值。与依那普利相比，沙库巴曲缬沙坦可显著降低 hsTnT 和 sST2。这种效应早在第 1 周就出现了，第 4 周时两种标志物均有显著差异，hsTnT 降低 16%（P<0.001），sST2 降低 9%（P=0.0033）。与依那普利相比，沙库巴曲缬沙坦治疗组的尿 cGMP 水平呈持续增加趋势（P<0.001，第 1 周）。在 8 周时，各标志物的治疗组间差异仍有统计学意义。在心血管死亡或 HF 再入院的探索性多变量调整分析中，第 1 周 hsTnT 和 sST2 的浓度与随后的结果显著相关。
ADHF 患者的心肌应激生物标志物升高，与结局相关。与依那普利相比，沙库巴曲缬沙坦降低了心肌损伤和生物标志物反映的血液动力学应激，其起始作用在 1-4 周内即可显现。
NCT02554890 clinical.trials.gov。
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