Division of Cardiology, Department of Medicine (S.V., P.P.V., S.R.P., S.G.S., O.S., D.B.S., T.C., J.J.S., U.P.J.).
Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY (X.X.).
Circ Heart Fail. 2018 Aug;11(8):e004899. doi: 10.1161/CIRCHEARTFAILURE.118.004899.
Gastrointestinal bleeding (GIB) is one of the principal adverse events affecting patients with continuous-flow left ventricular assist devices (CF-LVADs). Despite the early recognition that GIB is commonly because of gastrointestinal angiodysplasia (GIAD), the exact pathophysiology of this process remains elusive. It has been postulated that the abnormal hemodynamic profile in CF-LVAD patients may activate the angiogenesis signaling cascade via the HIF (hypoxia-inducible factor)-1α/angiopoietin-2 pathway leading to formation of GIADs. Digoxin is a potent inhibitor of HIF-1α synthesis, and we hypothesized that its use reduces the incidence of GIAD and GIB in patients with CF-LVAD.
Charts of all adult patients implanted with CF-LVAD between February 2006 and February 2017 were reviewed with particular emphasis on occurrence and cause of GIB. Fifty-four of 199 patients (27%) experienced a GIB. Overall frequency of GIB was lower in the 64 patients receiving digoxin compared with the 135 patients not receiving digoxin (16% versus 33%, P=0.01). Multivariable-adjusted Cox regression analysis confirmed that digoxin use was independently associated with a reduced risk for overall GIB (hazard ratio, 0.49; 95% CI, 0.24-0.98; P=0.045). GIBs were then categorized as non-GIAD, GIAD, or likely GIAD. Although the incidence of non-GIAD was similar in both groups (11% versus 7%, P=0.41), the frequency of GIAD/likely GIAD bleeding was significantly reduced in the digoxin group (5% versus 25%, P=0.0003). Multivariable-adjusted analysis confirmed that digoxin use was independently associated with a reduced risk for GIAD/likely GIAD bleeding (hazard ratio, 0.18; 95% CI, 0.06-0.6; P=0.005). However, digoxin use was not associated with reduced risk for non-GIAD GIB (hazard ratio, 1.54; 95% CI, 0.58-4.08; P=0.39).
Use of digoxin was associated with a significant reduction in GIAD-related GIB in patients with CF-LVAD.
胃肠道出血（GIB）是影响连续血流左心室辅助装置（CF-LVAD）患者的主要不良事件之一。尽管早期认识到 GIB 通常是由于胃肠道血管扩张症（GIAD）引起的，但这一过程的确切病理生理学仍然难以捉摸。据推测，CF-LVAD 患者异常的血液动力学特征可能通过 HIF（缺氧诱导因子）-1α/血管生成素-2 途径激活血管生成信号级联反应，导致 GIAD 的形成。地高辛是 HIF-1α 合成的有效抑制剂，我们假设其使用可降低 CF-LVAD 患者 GIAD 和 GIB 的发生率。
回顾了 2006 年 2 月至 2017 年 2 月期间植入 CF-LVAD 的所有成年患者的图表，特别强调了 GIB 的发生和原因。199 例患者中有 54 例（27%）经历了 GIB。与未使用地高辛的 135 例患者相比，使用地高辛的 64 例患者总体 GIB 发生率较低（16%比 33%，P=0.01）。多变量调整的 Cox 回归分析证实，地高辛的使用与总体 GIB 的风险降低独立相关（风险比，0.49；95%CI，0.24-0.98；P=0.045）。然后将 GIB 分为非-GIAD、GIAD 或可能的 GIAD。虽然两组非-GIAD 的发生率相似（11%比 7%，P=0.41），但地高辛组 GIAD/可能的 GIAD 出血的频率明显降低（5%比 25%，P=0.0003）。多变量调整分析证实，地高辛的使用与 GIAD/可能的 GIAD 出血的风险降低独立相关（风险比，0.18；95%CI，0.06-0.6；P=0.005）。然而，地高辛的使用与非-GIAD GIB 的风险降低无关（风险比，1.54；95%CI，0.58-4.08；P=0.39）。
在 CF-LVAD 患者中，地高辛的使用与 GIAD 相关的 GIB 发生率显著降低有关。
