Digoxin Is Associated With a Decreased Incidence of Angiodysplasia-Related Gastrointestinal Bleeding in Patients With Continuous-Flow Left Ventricular Assist Devices

Abstract

Background: 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. Methods and Results: 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). Conclusions: Use of digoxin was associated with a significant reduction in GIAD-related GIB in patients with CF-LVAD.

Questionable utility of digoxin in left-ventricular assist device recipients: A multicenter, retrospective analysis

“…An additional circumstance in which digoxin utilization in LVAD patients may be those who have angiodysplasia-related gastrointestinal bleeding. This was recently described in a single center, retrospective analysis wherein digoxin use was associated with a reduction in angiodysplasia-related gastrointestinal bleeding [19]. Although our data collection pre-dates the publication of this analysis, it is unclear if the proposed mechanism of digoxin’s effect on neoangiogenesis, reduction in the stimulation of angiopoeietin-2 via inhibition of hypoxia-induced factor 1α, may have influenced providers in starting digoxin in the PostD group.…”

Left Ventricular Assist Devices (LVADS): History, Clinical Application and Complications

“…Thalidomide has also been used to treat angiodysplasias in LVAD patients because of its anti-angiogenic effects 39). Another option for medical therapy is digoxin which inhibits HIF-1α synthesis 40). Although the incidence of GI bleeding is higher in recipients of second and third generation LVADs compare to the first generation pulsatile LVADs, mortality from GI bleeds is actually lower in recipients of the newer, CF LVADs compared to the pulsatile LVADs (20.9% vs. 43.7%, respectively) 35).…”

Response to: Prevention of thrombus formation following transcatheter aortic valve replacement in patients with durable left ventricular assist device

“…With regard to prevention of gastrointestinal (GI) bleeding with omega-3 fatty acid and digoxin, the authors raise two studies showing alternate methods of preventing GI bleeding. 3,4 However, these are single-center nonrandomized studies and as we eagerly await prospective randomized studies demonstrating its efficacy, the use with these agents cannot be recommended on routine bases for prevention of GI bleeding in LVAD patients. In addition, the most concerning feature of our case was the development of TAVR thrombosis whilst on therapeutic vitamin K antagonism, which would be considered more than adequate for prevention of thrombosis formation based on current literature.…”