Saeed Omar, Rangasamy Sabarivinoth, Selevany Ibrahim, Madan Shivank, Fertel Jeremy, Eisenberg Ruth, Aljoudi Mohammad, Patel Snehal R, Shin Julia, Sims Daniel B, Reyes Gil Morayma, Goldstein Daniel J, Slepian Marvin J, Billett Henny H, Jorde Ulrich P
From the Division of Cardiology, Department of Medicine, Montefiore Medical Center (O.S., S.R., I.S., S.M., J.F., M.A., S.R.P., J.S., D.B.S., U.P.J.), Department of Epidemiology and Population Health (R.E.), Department of Pathology, Montefiore Medical Center (M.R.G.) Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center (D.J.G.), and Division of Hematology, Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY (H.H.B.).; and Departments of Medicine and Biomedical Engineering, Sarver Heart Center, University of Arizona, Tucson (M.J.S.).
Circ Heart Fail. 2017 Nov;10(11). doi: 10.1161/CIRCHEARTFAILURE.117.004222.
Persistent low-level hemolysis (LLH) during continuous-flow mechanical circulatory support is associated with subsequent thrombosis. Free hemoglobin from ongoing hemolysis scavenges nitric oxide (NO) to create an NO deficiency which can augment platelet function leading to a prothrombotic state. The phosphodiesterase-5 inhibitor, sildenafil, potentiates NO signaling to inhibit platelet function. Accordingly, we investigated the association of sildenafil administration and thrombotic events in patients with LLH during Heart Mate II support.
A single-center review of all patients implanted with a Heart Mate II who survived to discharge (n=144). LLH was defined by a discharge lactate dehydrogenase level of 400 to 700 U/L. Patients were categorized as (1) LLH not on sildenafil, (2) LLH on sildenafil, (3) no LLH not on sildenafil, and (4) no LLH on sildenafil. Age, sex, platelet count, and mean platelet volume were similar between groups. Seventeen patients had either device thrombosis or ischemic stroke. Presence of LLH was associated with a greater risk of thrombosis (adjusted hazard ratio, 15; 95% confidence interval, 4.5-50; <0.001 versus no LLH, not on sildenafil). This risk was reduced in patients with LLH on sildenafil (adjusted hazard ratio, 1.7; 95% confidence interval, 0.2-16.1; =0.61). Device thrombosis and ischemic stroke were associated with an increase in mean platelet volume (9.6±0.5 to 10.9±0.8 fL, <0.001). Patients with LLH not on sildenafil had a greater increase in mean platelet volume in comparison to those with LLH on sildenafil (<0.001).
Sildenafil is associated with reduced device thrombosis and ischemic stroke during ongoing LLH on Heart Mate II support.
连续流机械循环支持期间的持续性低水平溶血（LLH）与随后的血栓形成有关。正在进行的溶血产生的游离血红蛋白会清除一氧化氮（NO），导致NO缺乏，这会增强血小板功能，从而导致血栓前状态。磷酸二酯酶-5抑制剂西地那非可增强NO信号传导以抑制血小板功能。因此，我们研究了在Heart Mate II支持期间接受西地那非治疗的LLH患者中，西地那非给药与血栓形成事件之间的关联。
对所有植入Heart Mate II并存活至出院的患者（n = 144）进行单中心回顾性研究。LLH定义为出院时乳酸脱氢酶水平为400至700 U/L。患者分为（1）未使用西地那非的LLH患者，（2）使用西地那非的LLH患者，（3）未使用西地那非且无LLH的患者，以及（4）使用西地那非且无LLH的患者。各组之间的年龄、性别、血小板计数和平均血小板体积相似。17名患者发生了装置血栓形成或缺血性卒中。LLH的存在与更高的血栓形成风险相关（调整后的风险比为15；95%置信区间为4.5 - 50；与未使用西地那非且无LLH的患者相比，P < 0.001）。使用西地那非的LLH患者的这种风险降低（调整后的风险比为1.7；95%置信区间为0.2 - 16.1；P = 0.61）。装置血栓形成和缺血性卒中与平均血小板体积增加有关（从9.6±0.5飞升增加至10.9±0.8飞升，P < 0.001）。与使用西地那非的LLH患者相比，未使用西地那非的LLH患者的平均血小板体积增加更大（P < 0.001）。
在Heart Mate II支持期间持续存在LLH的情况下，西地那非与降低装置血栓形成和缺血性卒中的发生率相关。
