Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA.
Department of Cardiovascular Medicine, Heart and Vascular Institute, Kaufman Center for Heart Failure, Cleveland Clinic, Cleveland, OH, USA.
ESC Heart Fail. 2019 Oct;6(5):1005-1014. doi: 10.1002/ehf2.12473. Epub 2019 Jul 18.
The risk of HeartMate II (HMII) left ventricular assist device (LVAD) thrombosis has been reported, and serum lactate dehydrogenase (LDH), a biomarker of haemolysis, increases secondary to LVAD thrombosis. This study evaluated longitudinal measurements of LDH post-LVAD implantation, hypothesizing that LDH trends could timely predict future LVAD thrombosis.
From October 2004 to October 2014, 350 HMIIs were implanted in 323 patients at Cleveland Clinic. Of these, patients on 339 HMIIs had at least one post-implant LDH value (7996 total measurements). A two-step joint model combining longitudinal biomarker data and pump thrombosis events was generated to assess the effect of changing LDH on thrombosis risk. Device-specific LDH trends were first smoothed using multivariate boosted trees, and then used as a time-varying covariate function in a multiphase hazard model to analyse time to thrombosis. Pre-implant variables associated with time-varying LDH values post-implant using boostmtree were also investigated. Standardized variable importance for each variable was estimated as the difference between model-based prediction error of LDH when the variable was randomly permuted and prediction error without permuting the values. The larger this difference, the more important a variable is for predicting the trajectory of post-implant LDH. Thirty-five HMIIs (10%) had either confirmed (18) or suspected (17) thrombosis, with 15 (43%) occurring within 3 months of implant. LDH was associated with thrombosis occurring both early and late after implant (P < 0.0001 for both hazard phases). The model demonstrated increased probability of HMII thrombosis as LDH trended upward, with steep changes in LDH trajectory paralleling trajectories in probability of pump thrombosis. The most important baseline variables predictive of the longitudinal pattern of LDH were higher bilirubin, higher pre-implant LDH, and older age. The effect of some pre-implant variables such as sodium on the post-implant LDH longitudinal pattern differed across time.
Longitudinal trends in surveillance LDH for patients on HMII support are useful for dynamic prediction of pump thrombosis, both early after implant and late. Incorporating upward and downward trends in LDH that dynamically update a model of LVAD thrombosis risk provides a useful tool for clinical management and decisions.
已有研究报道 HeartMate II（HMII）左心室辅助装置（LVAD）血栓形成的风险，而乳酸脱氢酶（LDH）作为溶血的生物标志物，在 LVAD 血栓形成后会升高。本研究评估了 LVAD 植入后 LDH 的纵向测量值，假设 LDH 趋势可以及时预测未来的 LVAD 血栓形成。
2004 年 10 月至 2014 年 10 月，克利夫兰诊所共植入 350 例 HMII，其中 323 例患者植入 339 例 HMII，至少有一次植入后 LDH 值（共 7996 次测量）。采用两步联合模型，将纵向生物标志物数据与泵血栓事件相结合，评估 LDH 变化对血栓形成风险的影响。首先使用多元提升树对设备特异性 LDH 趋势进行平滑处理，然后将其用作多阶段风险模型中的时变协变量函数，以分析血栓形成时间。还研究了使用 boostmtree 对植入后随时间变化的 LDH 值进行预测的预植入变量。使用随机置换和不置换变量值时的 LDH 模型预测误差之间的差异来估计每个变量的标准化变量重要性。该差异越大，该变量对预测植入后 LDH 轨迹的重要性就越大。35 例（10%）患者发生明确（18 例）或疑似（17 例）血栓形成，其中 15 例（43%）发生在植入后 3 个月内。植入后早期和晚期 LDH 均与血栓形成相关（两个危险阶段均 P<0.0001）。该模型表明，随着 LDH 呈上升趋势，HMII 血栓形成的可能性增加，LDH 轨迹的急剧变化与泵血栓形成的轨迹平行。预测 LDH 纵向模式的最重要的基线变量是胆红素较高、植入前 LDH 较高和年龄较大。一些术前变量（如钠）对植入后 LDH 纵向模式的影响在时间上有所不同。
对 HMII 支持患者进行纵向 LDH 监测趋势有助于对植入后早期和晚期的泵血栓形成进行动态预测。纳入 LDH 的上升和下降趋势，动态更新 LVAD 血栓形成风险模型，为临床管理和决策提供了有用的工具。
