Division of Cardiovascular Medicine, University of Michigan Health System, Ann Arbor, Michigan.
Department of Cardiac Surgery, University of Michigan Health System, Ann Arbor, Michigan.
J Heart Lung Transplant. 2014 Jan;33(1):35-43. doi: 10.1016/j.healun.2013.08.021. Epub 2013 Nov 28.
The clinical relevance of elevated serum markers of hemolysis during left ventricular assist device (LVAD) support has not been fully ascertained.
Lactate dehydrogenase (LDH) and serum free hemoglobin (sfHg) values were tallied monthly in 182 patients on HeartMate II (Thoratec, Pleasanton, CA) LVAD support. Peak values for each marker were identified, and 2 hemolysis definitions were applied to the cohort: Hemolysis according to Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) criteria (sfHg > 40 mg/dl with signs/symptoms) and/or hemolysis defined by an LDH ≥ 600 IU/liter (2.5-times the upper limit of laboratory normal). Kaplan-Meier survival free from death, urgent United Network of Organ Sharing 1A transplant for thrombosis, device exchange for thrombosis, and stroke/peripheral embolism was estimated, and Cox hazard ratios (HR) with the 95% confidence interval (95% CI) were calculated. Areas under the receiver-operating characteristic curves (AUCs) for predicting 1-year event-free survival were calculated.
Hemolysis occurred in 32 patients (18%) by INTERMACS criteria and in 68 (37%) patients by LDH criteria. Over a median (25(th), 75(th)) support of 427 days (245, 793 days), there were 78 events. One year event-free survival after the onset of INTERMACS-defined hemolysis was 16% ± 8.3% compared with 85% ± 3.2% in non-hemolyzers (HR, 14.7; 95% CI, 7.9-27; AUC 0.70 ± 0.05; p < 0.001; ). One year event-free survival after the onset of LDH-defined hemolysis was 32% ± 7.2% compared with 89% ± 3.2% in those with persistent LDH values < 600 IU/liter (HR, 8.0; 95% CI, 4.4-14; AUC 0.87 ± 0.04; p < 0.001). Patients who met the LDH hemolysis definition had longer times from hemolysis onset to clinical events and larger magnitudes of risk for embolism and device exchange for thrombosis than those with INTERMACS hemolysis.
Serum hemolysis marker elevations are associated with increased events in LVAD patients. LDH monitoring provides an earlier diagnosis of adverse events than sfHg, supporting need for a new INTERMACS definition of VAD-associated hemolysis.
左心室辅助装置（LVAD）支持期间血清溶血标志物升高的临床相关性尚未完全确定。
182 例接受 HeartMate II（Thoratec，Pleasanton，CA）LVAD 支持的患者每月记录乳酸脱氢酶（LDH）和血清游离血红蛋白（sfHg）值。确定每个标志物的峰值，并将两种溶血定义应用于该队列：根据 INTERMACS 标准（sfHg > 40mg/dl 伴有体征/症状）的溶血和/或 LDH≥600IU/L（实验室正常值上限的 2.5 倍）的溶血。通过 Kaplan-Meier 生存分析估计无死亡、紧急 United Network of Organ Sharing 1A 移植血栓形成、因血栓形成而更换设备以及卒中/外周栓塞的事件，计算 Cox 风险比（HR）及其 95%置信区间（95%CI）。计算预测 1 年无事件生存的受试者工作特征曲线（ROC）下面积（AUC）。
根据 INTERMACS 标准，32 例患者（18%）发生溶血，根据 LDH 标准，68 例患者（37%）发生溶血。中位（25%，75%）支持时间为 427 天（245 天，793 天），发生 78 例事件。与非溶血患者（HR，14.7；95%CI，7.9-27；AUC 0.70 ± 0.05；p < 0.001）相比，发生 INTERMACS 定义的溶血后 1 年无事件生存率为 16%±8.3%。与持续 LDH 值<600IU/L 的患者（HR，8.0；95%CI，4.4-14；AUC 0.87 ± 0.04；p < 0.001）相比，发生 LDH 定义的溶血后 1 年无事件生存率为 32%±7.2%。与 INTERMACS 溶血相比，符合 LDH 溶血定义的患者从溶血发生到临床事件的时间更长，发生栓塞和因血栓形成更换设备的风险更大。
血清溶血标志物升高与 LVAD 患者事件增加相关。LDH 监测比 sfHg 更早诊断不良事件，支持需要新的 INTERMACS 定义来描述与 VAD 相关的溶血。
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