Left ventricular assist devices (LVADs) offer a therapeutic strategy for patients with end-stage heart failure. Increased device utilization has also increased the incidence of device-related complications including gastrointestinal bleeding (GIB). Multiple mechanisms have been proposed in the pathophysiology of continuous-flow LVAD-associated GIB including physiologic changes associated with high shear and nonpulsatile flow such as gastrointestinal arteriovenous malformations and acquired von Willebrand syndrome. Strategies to minimize the morbidity and mortality of LVAD-associated GIB are needed. Octreotide, a somatostatin analogue, has been described as an adjunct to current therapies and interventions. Factors that contribute to LVAD-associated GIB may be targeted by the pharmacologic effects of octreotide, including improved platelet aggregation, increased vascular resistance, and decreased splanchnic circulation. Octreotide has demonstrated clinical benefit in several case series and clinical trials for the treatment of LVAD-associated GIB. The focus of this article will be to review the pathophysiology of LVAD-associated GIB, discuss pharmacologic and nonpharmacologic treatment modalities, and review available literature on the role of octreotide in the management of LVAD-associated GIB.

Endpoints were compared between genotype groups with independent t-tests. Results: The study included 78% men, 65% Caucasian, 17% African American, and mean age at HTx= 49 ± 13 yrs. The mean time to achieve first TAC trough level within the goal range of 10-15 ng/ml was 7 ± 3 days. Mean TAC TDD at HTx discharge was 1.85 times higher in CYP3A5 expressors compared with non-expressors (15.0 ± 6.8 vs 8.1 ± 3.2 mg per day, p= 0.008). Similarly, TAC L/D at HTx discharge was 2-fold lower in CYP3A5 expressors compared with non-expressors (0.9 ± 0.3 vs 1.8 ± 0.9 ng/ml per mg/day, p= 0.004). Mean time to achieve TAC trough level within goal range was longer in CYP3A5 expressors vs non-expressors (8.6 ± 3.5 vs 6.1 ± 2.5 days, p= 0.07). No significant differences in TAC exposure were found between CYP3A4 genotype groups. Conclusion: Our findings in HTx are consistent with general CPIC recommendations for TAC dosing in relation to CYP3A5 genotype, i.e., CYP3A5 expressors require 1.5-2 times higher TAC doses than non-expressors. Prospective studies are needed to determine if CYP3A5 genotype-guided TAC dosing influences clinical outcomes (e.g., cardiac allograft rejection or nephrotoxicity) in HTx recipients.

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