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[可溶性致瘤性抑制因子2增加急性心力衰竭失代偿后风险分层的机会]

[Soluble Suppression of Tumorogenicity 2 Increases Opportunities for Risk Stratification After Acute Heart Failure Decompensation].

作者信息

Skvortsov A A, Protasov V N, Narusov O Yu, Koshkina D E, Nasonova S N, Masenko V P, Tereschenko S N

机构信息

Institute of Cardiology of Russian Cardiology Scientific and Production Complex, Moscow, Russia.

National Research Center for Preventive Medicine, Moscow, Russia.

出版信息

Kardiologiia. 2017 Jan(1):48-58.

Abstract

PURPOSE

to evaluate the significance of soluble ST2-receptor (sST2) concentrations in patient (pts) risk stratification in with acute decompensated heart failure (ADHF) during long-term follow-up period.

METHODS

In the prospective single-center study were included 159 pts with ADHF III-IV FC NYHA. Blood samples to determine NT-proBNP, sST2, hsTnT concentration were collected at the admission and at discharge from the hospital, and after 3, 6 and 12 months of follow-up. The combined primary end point of the trial included cardiovascular (CV) death, hospitalization due to HF, episodes of HF deterioration needed additional i/v diuretics and CV death with successful resuscitation.

RESULTS

At admission all pts had elevated biomarker concentrations: NT-proBNP - 3615.5 (1578.0; 6289.3)pg/ml, sST2 - 60,49 (41.95; 92.87) ng/ml, hsTnT - 29.95 (21.85; 49.63) pg/ml; and at discharge: NT-proBNP - 2165.5 (982.7; 4221,2) pg/ml (%=-38,27 (-49.7; -24.34)%, p<0.0001), sST2 - 38.43 (24.67; 63.72) ng/ml (%=-30,13 (-42,07; -17,64)%, p<0,0001), and hsTnT - 28,37(21.29; 46.6) pg/ml. During 1-year follow-up 56 pts (35.2 %) had 78 (49.1%) cardiovascular events. Biomarker concentrations in low risk pts (without CV events) were significantly lower compared with high risk pts (who have CV events). At the discharge NT-proBNP and sST2 concentrations had the most predictive capacity relatively the primary end point during 1-year follow-up: AUC=0.727 (95% CI 0.637-0.816), <0,0001, and AUC=0,768 (95% CI 0.682-0.854), <0.0001, respectively. Maximally sST2 values were predictive for 180 days period of follow-up: AUC=0,809 (95% CI 0.726-0.921; <0,0001). Lack of NT-proBNP and sST2 concentrations decrease below 1696 pg/ml and 37.8 ng/ml respectively were associated with the highest risk of CV events (HR 4.41 [95% CI 1.41-9.624], p<0,0001 and HR 6.755 [95% CI 3.026- 15.082], p<0.0001, respectively). Changes of sST2 concentration during the period of pts hospitalization were also prognostically important, AUC=0.696 (0.596-0.796); p<0.0001. And pts with insufficient degree of sST2 concentrations reduction during the period of hospitalization (% <-28,3%) had the worst short-term and long-term prognosis [HR 3.68 (95% CI 2.05-6.64), p<0.0001]. Values of sST2 at the discharge were the most significant independent predictor of CV events in long-term follow-up (=0.519, p<0.0001). 91,8% of pts without CV events in the study had sST2 and NT-proBNP levels below 37.8 ng/ml and 1696 pg/ml respectively after 3, 6 and 12 months of follow-up.

CONCLUSION

The values of soluble ST2-receptor over 37.8 ng/ml and NT-proBNP over 1696 pg/ml at the discharge from the hospital reflects the adverse prognosis in patients with ADHF. Serial determination of sST2 and NT-proBNP concentrations after discharge from the hospital indicates the necessity of reduction the levels of these biomarkers below the cut-off values (<37.8ng/mL and <1696pg/ml respectively) in pts with ADHF in long-term follow-up period.

摘要

目的

评估可溶性ST2受体(sST2)浓度在急性失代偿性心力衰竭(ADHF)患者长期随访期间风险分层中的意义。

方法

前瞻性单中心研究纳入159例纽约心脏协会(NYHA)心功能III-IV级的ADHF患者。在入院时、出院时以及随访3、6和12个月后采集血样,以测定N末端B型利钠肽原(NT-proBNP)、sST2、高敏肌钙蛋白T(hsTnT)浓度。试验的联合主要终点包括心血管(CV)死亡、因心力衰竭住院、需要额外静脉注射利尿剂的心力衰竭恶化发作以及成功复苏后的CV死亡。

结果

入院时所有患者的生物标志物浓度均升高:NT-proBNP为3615.5(1578.0;6289.3)pg/ml,sST2为60.49(41.95;92.87)ng/ml,hsTnT为29.95(21.85;49.63)pg/ml;出院时:NT-proBNP为2165.5(982.7;4221.2)pg/ml(%=-38.27(-49.7;-24.34)%,p<0.0001),sST2为38.43(24.67;63.72)ng/ml(%=-30.13(-42.07;-17.64)%,p<0.0001),hsTnT为28.37(21.29;46.6)pg/ml。在1年的随访期间,56例患者(35.2%)发生了78次(49.1%)心血管事件。低风险患者(无CV事件)的生物标志物浓度显著低于高风险患者(有CV事件)。出院时NT-proBNP和sST2浓度对1年随访期间的主要终点具有最强的预测能力:AUC分别为0.727(95%CI 0.637-0.816),p<0.0001,以及AUC为0.768(95%CI 0.682-0.854),p<0.0001。sST2的最大值对180天的随访期具有预测性:AUC=0.809(95%CI 0.726-0.921;p<0.0001)。NT-proBNP和sST2浓度分别未降至1696 pg/ml和37.8 ng/ml以下与CV事件的最高风险相关(HR分别为4.41[95%CI 1.41-9.624],p<0.0001和HR为6.755[95%CI 3.026-15.082],p<0.0001)。患者住院期间sST2浓度的变化在预后方面也很重要,AUC=0.696(0.596-0.796);p<0.0001。住院期间sST2浓度降低程度不足(%<-28.3%)的患者短期和长期预后最差[HR 3.68(95%CI 2.05-6.64),p<0.0001]。出院时sST2值是长期随访中CV事件最显著的独立预测因子(p=0.519,p<0.0001)。在研究中,91.8%无CV事件的患者在随访3、6和12个月后sST2和NT-proBNP水平分别低于37.8 ng/ml和1696 pg/ml。

结论

出院时可溶性ST2受体值超过37.8 ng/ml和NT-proBNP超过1696 pg/ml反映了ADHF患者的不良预后。出院后连续测定sST2和NT-proBNP浓度表明,在ADHF患者的长期随访期间,有必要将这些生物标志物水平降至临界值以下(分别为<37.8ng/mL和<1696pg/ml)。

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