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.

Fibrinogen is a clotting factor and a major determinant of platelet aggregation. Albumin, on the other hand, inhibits platelet function and thrombus formation. Taken together, an elevated fibrinogen albumin ratio (FAR) has been described as a marker of disease severity during prothrombotic conditions. We evaluated the association of FAR and ischemic stroke during venoarterial extracorporeal membrane oxygenation (VA ECMO) support. A single center, retrospective study was performed including all adult patients placed on VA ECMO. FAR was calculated from fibrinogen and albumin measurements in the first 24 hours of VA-ECMO initiation. Patients were categorized into high (≥125) and low (<125) FAR groups and the risk of eventual ischemic stroke was determined. There were 201 patients who underwent VA ECMO placement and 157 had a FAR. They were 56 ± 14 years old and 66 (42%) had a high FAR. Patients with a high FAR had lower survival free from an ischemic stroke during VA ECMO (log rank p < 0.001; adjusted hazard ratio 5.51; 95% CI: 1.8–16.5). In tertile analysis, the level of FAR was associated with an incrementally higher likelihood of eventual ischemic stroke (log rank p = 0.004). Those with a high FAR had greater mean platelet volume (10.8[10.4–12] vs. 10.5[10.2–11.9]fl, p = 0.004). An elevated FAR during the first 24 hours of VA ECMO placement is associated with a greater risk of a subsequent ischemic stroke. Our findings suggest that assessment of FAR soon after VA ECMO placement may assist with early stratification of patients at risk for an ischemic stroke.

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