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Novel Biomarkers, ST-Elevation Resolution, and Clinical Outcomes Following Primary Percutaneous Coronary Intervention.

新型生物标志物、 ST 段抬高分辨率和直接经皮冠状动脉介入治疗后的临床结局。

  • 影响因子:4.44
  • DOI:10.1161/JAHA.120.016033
  • 作者列表:"Shavadia JS","Granger CB","Alemayehu W","Westerhout CM","Povsic TJ","Van Diepen S","Defilippi C","Armstrong PW
  • 发表时间:2020-06-17

:Background Despite restoration of epicardial flow following primary percutaneous coronary intervention (PPCI), microvascular reperfusion as reflected by ST-elevation resolution (ST-ER) resolution remains variable and its pathophysiology remains unclear. Methods and Results Using principal component analyses, we explored associations between 91 serum biomarkers drawn before PPCI clustered into 14 pathobiologic processes (including NT-proBNP [N-terminal pro-B-type natriuretic peptide] as an independent cluster), and (1) ST-ER resolution ≥50% versus <50%; and (2) 90-day composite of death, shock, and heart failure. Network analyses were performed to understand interbiomarker relationships between the ST-ER groups. Among the 1160 patients studied, 861 (74%) had ST-ER ≥50% at a median 40 (interquartile range, 23-70) minutes following PPCI, yet both groups had comparable post-PPCI TIMI (Thrombolysis in Myocardial Infarction) grade 3 flow (86.6% versus 82.9%; P=0.25). ST-ER ≥50% was associated with significantly lower pre-PPCI concentrations of platelet activation cluster (particularly P-selectin, von Willebrand factor, and platelet-derived growth factor A) and NT-proBNP, including after risk adjustment. Across both ST-ER groups, strong interbiomarker relationships were noted between pathways indicative of myocardial stretch, platelet activation, and inflammation, whereas with ST-ER <50% correlations between iron homeostasis and inflammation were observed. Of all 14 biomarker clusters, only NT-proBNP was significantly associated with the 90-day clinical composite. Conclusions Suboptimal ST-ER is common despite achieving post-PPCI TIMI grade 3 flow. The cluster of platelet activation proteins and NT-proBNP were strongly correlated with suboptimal ST-ER and NT-proBNP was independently associated with 90-day outcomes. This analysis provides insights into the pathophysiology of microvascular reperfusion in ST-segment-elevation myocardial infarction and suggests novel pre-PPCI risk targets potentially amenable to enhancing tissue-level reperfusion following PPCI.


背景: 尽管直接经皮冠状动脉介入治疗 (PPCI) 后心外膜血流恢复,但 ST 段抬高分辨率 (ST-ER) 分辨率反映的微血管再灌注仍然存在差异,其病理生理学仍不清楚。使用主成分分析的方法和结果,我们探讨了 PPCI 前提取的 91 个血清生物标志物之间的相关性,聚集到 14 个病理生物学过程中 (包括 NT-proBNP [N 末端 b型利钠肽前体] 作为独立的簇)。(1) ST-ER 分辨率 ≥ 50% vs <50%; (2) 90 天死亡、休克、和心力衰竭。进行网络分析以了解 ST-ER 组之间的生物标志物间关系。在研究的 1160 例患者中,861 例 (74%) 在 PPCI 后中位 40 (四分位距,23-70) 分钟时 ST-ER ≥ 50%,然而,两组 PPCI 后 TIMI (心肌梗死溶栓) 3 级血流相当 (86.6% vs 82.9%; P = 0.25)。ST-ER ≥ 50% 与 PPCI 术前血小板活化簇浓度显著降低相关 (特别是 P-选择素、血管性血友病因子和血小板衍生生长因子 A) 和 NT-proBNP,包括风险调整后。在两个 ST-ER 组中,在指示心肌牵张、血小板活化和炎症的通路之间观察到强烈的生物标志物间关系,而 ST-ER <50% 时,观察到铁稳态与炎症之间的相关性。在所有 14 个生物标志物簇中,只有 NT-proBNP 与 90 天临床复合显著相关。结论尽管达到了 PPCI 后 TIMI 3 级血流,但次优的 ST-ER 是常见的。血小板活化蛋白和 NT-proBNP 簇与次优 ST-ER 强相关,NT-proBNP 与 90 天结局独立相关。该分析提供了对 ST 段抬高型心肌梗死微血管再灌注病理生理学的见解,并提出了可能适合增强 PPCI 术后组织水平再灌注的新型 PPCI 前风险靶点。



来源期刊:Thrombosis research
作者列表:["Palmerini T","Barozzi C","Tomasi L","Riva DD","Marengo M","Cicoria G","Bruno AG","Bacchi-Reggiani ML","Naldi M","Bartolini M","Fanti S","Galiè N","Stone GW"]

METHODS:Aims : We sought to investigate the thrombogenicity of different DES and BMS in an in vitro system of stent perfusion. Material and Methods: The experimental model consisted of a peristaltic pump connected to 4 parallel silicone tubes in which different stents were deployed. Blood was drawn from healthy volunteers and the amount of stent surfaced -induced thrombus deposition was determined using 125 I -fibrinogen. Results: Compared to Resolute, Biomatrix and Vision, Xience was associated with the lowest amount of stent surface -induced thrombus formation, with a significant difference compared to Vision (125 I -fibrinogen median value deposition [IQ range]: 50 ng [25 -98] versus 560 ng [320 - 1,520], respectively, p<0.05), but not to other DES. In the second set of experiments Fluoropolymer -coated BMS not eluting drug was associated with a significant 3 -fold reduction in 125 I -fibrinogen deposition (245 ng [80 -300]) compared to Vision (625 ng [320 -760], p<0.05), but a 7 -fold increase compared to Xience (35 ng [20 -60], p<0.05). Finally Xience was associated with a significantly greater absorption of albumin compared to BMS. Conclusions: In an in vitro system of stent perfusion, Xience was associated with the lowest amount of stent surface -induced thrombus formation compared with Resolute, Biomatrix and Vision, with a noted synergistic effect between the fluoropolymer and the drug.

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作者列表:["Jain M","Dhanesha N","Doddapattar P","Chorawala MR","Nayak MK","Cornelissen A","Guo L","Finn AV","Lentz SR","Chauhan AK"]

METHODS::Fibronectin-splice variant containing extra domain A (Fn-EDA) is associated with smooth muscle cells (SMCs) following vascular injury. The role of SMC-derived Fn-EDA in SMC phenotypic switching or its implication in neointimal hyperplasia remains unclear. Herein, using human coronary artery sections with a bare metal stent, we demonstrate the expression of Fn-EDA in the vicinity of SMC-rich neointima and peri-strut areas. In mice, Fn-EDA colocalizes with SMCs in the neointima of injured carotid arteries and promotes neointima formation in the comorbid condition of hyperlipidemia by potentiating SMC proliferation and migration. No sex-based differences were observed. Mechanistic studies suggested that Fn-EDA mediates integrin- and TLR4-dependent proliferation and migration through activation of FAK/Src and Akt1/mTOR signaling, respectively. Specific deletion of Fn-EDA in SMCs, but not in endothelial cells, reduced intimal hyperplasia and suppressed the SMC synthetic phenotype concomitant with decreased Akt1/mTOR signaling. Targeting Fn-EDA in human aortic SMCs suppressed the synthetic phenotype and downregulated Akt1/mTOR signaling. These results reveal that SMC-derived Fn-EDA potentiates phenotypic switching in human and mouse aortic SMCs and neointimal hyperplasia in the mouse. We suggest that targeting Fn-EDA could be explored as a potential therapeutic strategy to reduce neointimal hyperplasia.

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作者列表:["Lee SY","Ahn JM","Mintz GS","Hong SJ","Ahn CM","Park DW","Kim JS","Kim BK","Ko YG","Choi D","Jang Y","Park SJ","Hong MK"]

METHODS:OBJECTIVE:The goal of this study was to determine the impact of late-acquired stent malapposition (LASM) on long-term clinical outcomes in patients treated with coronary stent implantation. Approach and Results: We investigated major adverse cardiac event during 10 years after 6-month intravascular ultrasound examination using our previous studies database. A total of 732 patients treated with bare-metal stent (54 LASM versus 678 non-LASM) and 529 patients treated with first-generation drug-eluting stent (82 LASM versus 447 non-LASM), who did not have clinical event or censoring at the time of follow-up intravascular ultrasound, were included for the present analysis. major adverse cardiac event was defined as the composite of cardiac death, target vessel-related myocardial infarction, target lesion revascularization and stent thrombosis. Multivariable adjustment and inverse probability weight were performed to consider baseline differences. After multivariable adjustment, LASM was related to a greater risk of major adverse cardiac event (hazard ratio, 1.666 [95% CI, 1.041-2.665]; P=0.0333) and very-late stent thrombosis (hazard ratio, 3.529 [95% CI, 1.153-10.798]; P=0.0271) than non-LASM in patients treated with first-generation drug-eluting stent, but not in those treated with bare-metal stent. Results were consistent after inverse probability weight. Among patients with LASM of first-generation drug-eluting stent, no late stent thrombosis occurred in patients who continued to receive dual antiplatelet therapy. CONCLUSIONS:The relationship between LASM and major adverse cardiac event might depend on the type of implanted stents during the long-term follow-up, highlighting the clinical significance of polymers and drugs in drug-eluting stent system.

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