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西地那非降低了HeartMate II型低水平溶血患者发生血栓栓塞事件的风险,并显著改善了肺循环。

Sildenafil Reduces the Risk of Thromboembolic Events in HeartMate II Patients with Low-Level Hemolysis and Significantly Improves the Pulmonary Circulation.

作者信息

Zayat Rashad, Ahmad Usaama, Stoppe Christian, Khattab Mohammad Amen, Arab Fateh, Moza Ajay, Tewarie Lachmandath, Goetzenich Andreas, Autschbach Rüdiger, Schnoering Heike

机构信息

Department of Thoracic and Cardiovascular Surgery, RWTH University Hospital.

Department of Intensive Care Medicine, RWTH University Hospital.

出版信息

Int Heart J. 2018 Nov 28;59(6):1227-1236. doi: 10.1536/ihj.18-001. Epub 2018 Oct 10.

DOI:10.1536/ihj.18-001
PMID:30305587
Abstract

Low-level hemolysis (LLH) after left ventricular assist device implantation contributes to thromboembolic events (TE). Free plasma hemoglobin (fHb) scavenges nitric oxide (NO), which causes endothelial dysfunction and activates platelets. fHb also interacts with von Willebrand factor (vWF). We hypothesized that improved hemodynamic and enhanced NO signaling in HeartMate II (HMII) patients with LLH taking the phosphodiesterase-5 inhibitor sildenafil may reduce the risk of TE.From 2011 to 2015, 83 patients underwent HMII implantation. Patients with LLH as defined by elevated lactate dehydrogenase (400 < LDH ≤ 700 U/L) at hospital discharge were identified. Patients were categorized into 4 groups: 1) LLH + sildenafil, 2) LLH no sildenafil, 3) no LLH + sildenafil, and 4) no LLH no sildenafil. Adverse event-free survival was compared between the groups.Thirty-four patients (40.9%) were discharged with LLH and 22 (64.7%) of them took sildenafil. LDH and fHb remained significantly elevated in both LLH groups compared to the no LLH patients (P < 0.0001). Overall incidence of pump thrombosis (PT) was 4.8% and of ischemic stroke (IS) was 8.4%. HMII patients with LLH not on sildenafil had higher risk of TE (hazard ratio (HR): 14.4, 95%-CI: 1.8-117.1, P = 0.001). vWF activity and bleeding incidence did not differ between the LLH and no LLH patients. Mean pulmonary artery pressure and pulmonary vascular resistance decreased significantly in HMII taking sildenafil (P < 0.0001) while cardiac index increased (P < 0.0001).Sildenafil treatment among HMII patients with LLH reduced the risk of thromboembolic events and significantly improved and decompressed the pulmonary circulation during HMII support.

摘要

左心室辅助装置植入后发生的低水平溶血(LLH)会导致血栓栓塞事件(TE)。游离血浆血红蛋白(fHb)会清除一氧化氮(NO),这会导致内皮功能障碍并激活血小板。fHb还会与血管性血友病因子(vWF)相互作用。我们推测,对于发生LLH的HeartMate II(HMII)患者,服用磷酸二酯酶-5抑制剂西地那非改善血流动力学并增强NO信号传导可能会降低TE风险。

2011年至2015年,83例患者接受了HMII植入。确定出院时乳酸脱氢酶升高(400 < LDH ≤ 700 U/L)定义的LLH患者。患者分为4组:1)LLH +西地那非,2)LLH未服用西地那非,3)无LLH +西地那非,4)无LLH未服用西地那非。比较各组之间无不良事件生存情况。

34例患者(40.9%)出院时伴有LLH,其中22例(64.7%)服用西地那非。与无LLH患者相比,两个LLH组的LDH和fHb仍显著升高(P < 0.0001)。泵血栓形成(PT)的总体发生率为4.8%,缺血性卒中(IS)的发生率为8.4%。未服用西地那非的LLH的HMII患者发生TE的风险更高(风险比(HR):14.4,95%置信区间:1.8 - 117.1,P = 0.001)。LLH患者和无LLH患者之间的vWF活性和出血发生率没有差异。服用西地那非的HMII患者平均肺动脉压和肺血管阻力显著降低(P < 0.0001),而心脏指数增加(P < 0.0001)。

LLH的HMII患者接受西地那非治疗可降低血栓栓塞事件的风险,并在HMII支持期间显著改善和缓解肺循环。

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