Department of Cardiology, Angiology, and Pneumology, University Hospital Heidelberg, Germany.
Eur Heart J Acute Cardiovasc Care. 2020 Nov;9(4_suppl):S169-S174. doi: 10.1177/2048872618815062. Epub 2018 Nov 19.
Early risk stratification remains an unmet clinical need in patients with in out-of-hospital cardiac arrest. We hypothesised that soluble neprilysin may represent a promising biomarker in patients with out-of-hospital cardiac arrest of non-traumatic origin and provide new pathobiological insight.
This pilot study was a biomarker analysis from the Heidelberg Resuscitation Registry. Serum soluble neprilysin levels on admission were measured in 144 patients with successful return of spontaneous circulation after out-of-hospital cardiac arrest of non-traumatic origin. The primary endpoint was time to all-cause mortality. KM Event Rates are reported. Cox models were adjusted for age, bystander resuscitation, initial ECG rhythm, baseline estimated glomerular filtration rate, baseline lactate, left ventricular function at baseline, and targeted temperature management.
In total, 90 (62.5%) patients died over a follow-up of at least 30 days. Soluble neprilysin correlated weakly with high-sensitivity troponin T (=0.18, P=0.032) but did not correlate significantly with estimated glomerular filtration rate (=-0.12) or lactate (=0.11). Patients with elevated soluble neprilysin levels on admission were at significantly higher risk of all-cause mortality (Q4 69.1% vs. Q1 48.4%). After multivariable adjustment, soluble neprilysin in the top quartile (Q4) was significantly associated with all-cause mortality (Q4 vs. Q1: adjusted hazard ratio 2.48 (1.20-5.12)). In an adjusted multimarker model including high-sensitivity troponin T and high-sensitivity C-reactive protein, soluble neprilysin and high-sensitivity troponin T remained independently associated with all-cause mortality (soluble neprilysin: adjusted hazard ratio 2.27 (1.08-4.78); high-sensitivity troponin T: adjusted hazard ratio 3.40 (1.63-7.09)).
Soluble neprilysin, measured as early as on hospital admission, was independently associated with all-cause mortality in patients with out-of-hospital cardiac arrest of non-traumatic origin and may prove to be useful in the estimation of risk in these patients.
在院外心搏骤停患者中，早期风险分层仍然是未满足的临床需求。我们假设可溶性 Neprilysin 可能是一种有前途的生物标志物，可用于非创伤性院外心搏骤停患者，并提供新的病理生物学见解。
本研究为海德堡复苏登记处的一项生物标志物分析。纳入了 144 例成功复苏非创伤性院外心搏骤停后自主循环恢复的患者，入院时测量血清可溶性 Neprilysin 水平。主要终点为全因死亡率的时间。报告 KM 事件率。Cox 模型根据年龄、旁观者复苏、初始心电图节律、基线估算肾小球滤过率、基线乳酸、基线左心室功能和目标体温管理进行调整。
在至少 30 天的随访中，共有 90 例（62.5%）患者死亡。可溶性 Neprilysin 与高敏肌钙蛋白 T 呈弱相关（=0.18，P=0.032），但与估算肾小球滤过率（=-0.12）或乳酸（=-0.11）无显著相关性。入院时可溶性 Neprilysin 水平升高的患者全因死亡率显著升高（Q4 为 69.1%，Q1 为 48.4%）。多变量调整后，四分位间距（Q4）的可溶性 Neprilysin 与全因死亡率显著相关（Q4 与 Q1：调整后的危险比 2.48（1.20-5.12））。在包括高敏肌钙蛋白 T 和高敏 C 反应蛋白的调整后的多标志物模型中，可溶性 Neprilysin 和高敏肌钙蛋白 T 仍然与全因死亡率独立相关（可溶性 Neprilysin：调整后的危险比 2.27（1.08-4.78）；高敏肌钙蛋白 T：调整后的危险比 3.40（1.63-7.09））。
在非创伤性院外心搏骤停患者中，入院时即可测量的可溶性 Neprilysin 与全因死亡率独立相关，可能有助于评估这些患者的风险。
