A reappraisal of the pharmacologic management of gastrointestinal bleeding in patients with continuous flow left ventricular assist devices

Heart Failure Reviews - Tập 26 - Trang 277-288 - 2020
Audrey J. Littlefield1, Gregory Jones1, Alana M. Ciolek2, Melana Yuzefpolskaya3, Douglas L. Jennings2,4
1NewYork-Presbyterian Hospital, Weill Cornell Medical Center, New York, USA
2Columbia University Medical Center, New York, USA
3Columbia University, New York, USA
4Department of Pharmacy Practice, Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, New York, USA

Tóm tắt

Advancements in the design and functionality of continuous flow left ventricular assist devices (CF-LVADs), as well as a limited number of donor hearts, have resulted in an increased utilization of this therapy among advanced heart failure (HF) patients. Despite these advancements, gastrointestinal bleeding (GIB) remains a common complication after CF-LVAD implantation. The mechanism of GIB in these patients is complex and includes a combination of angiodysplasia, platelet dysfunction, acquired von Willebrand disease, and a variety of patient-specific factors including advanced age and history of GIB. Several pharmacotherapy options have been reported in the literature, though studies supporting the use of these agents are often small, retrospective reports. Within this review, we discuss the various pharmacologic agents, their proposed mechanisms of action, and the available literature pertaining to their effectiveness and tolerability. Additionally, we propose an evidence-based treatment algorithm, encompassing the updated literature, cost of therapy, medication side effects, and ease of administration.

Tài liệu tham khảo

Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, de Ferranti SD, Floyd J, Fornage M, Gillespie C, Isasi CR, Jiménez MC, Jordan LC, Judd SE, Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Mackey RH, Matsushita K, Mozaffarian D, Mussolino ME, Nasir K, Neumar RW, Palaniappan L, Pandey DK, Thiagarajan RR, Reeves MJ, Ritchey M, Rodriguez CJ, Roth GA, Rosamond WD, Sasson C, Towfighi A, Tsao CW, Turner MB, Virani SS, Voeks JH, Willey JZ, Wilkins JT, Wu JH, Alger HM, Wong SS, Muntner P, American Heart Association Statistics Committee and Stroke Statistics Subcommittee (2017) Heart disease and stroke statistics-2017 update: a report from the American Heart Association. Circulation. 135(10):e146–e603 U.S. Department of Health & Human Services, Health Resources and Services Administration, Organ Procurement and Transplantation Network (accessed 6/20/19) Kirklin JK, Pagani FD, Kormos RL, Stevenson LW, Blume ED, Myers SL, Miller MA, Baldwin JT, Young JB, Naftel DC (2017) Eighth annual INTERMACS report: special focus on framing the impact of adverse events. J Heart Lung Transplant 36(10):1080–1086 Aggarwal A, Pant R, Kumar S, Sharma P, Gallagher C, Tatooles AJ, Pappas PS, Bhat G (2012) Incidence and management of gastrointestinal bleeding with continuous flow assist devices. Ann Thorac Surg 93(5):1534–1540 Draper KV, Huang RJ, Gerson LB (2014) GI bleeding in patients with continuous-flow left ventricular assist devices: a systematic review and meta-analysis. Gastrointest Endosc 80(3):435–446 e431 Mehra MR, Uriel N, Naka Y, Cleveland JC Jr, Yuzefpolskaya M, Salerno CT, Walsh MN, Milano CA, Patel CB, Hutchins SW, Ransom J, Ewald GA, Itoh A, Raval NY, Silvestry SC, Cogswell R, John R, Bhimaraj A, Bruckner BA, Lowes BD, Um JY, Jeevanandam V, Sayer G, Mangi AA, Molina EJ, Sheikh F, Aaronson K, Pagani FD, Cotts WG, Tatooles AJ, Babu A, Chomsky D, Katz JN, Tessmann PB, Dean D, Krishnamoorthy A, Chuang J, Topuria I, Sood P, Goldstein DJ (2019) A fully magnetically levitated left ventricular assist device - final report. N Engl J Med 380(17):1618–1627 Forest SJ, Bello R, Friedmann P, Casazza D, Nucci C, Shin JJ, D'Alessandro D, Stevens G, Goldstein DJ (2013) Readmissions after ventricular assist device: etiologies, patterns, and days out of hospital. Ann Thorac Surg 95(4):1276–1281 Gurvits GE, Fradkov E (2017) Bleeding with the artificial heart: gastrointestinal hemorrhage in LVAD-LVAD patients. World J Gastroenterol 23(22):3945–3953 Goldstein DJ, Aaronson KD, Tatooles AJ, Silvestry SC, Jeevanandam V, Gordon R, Hathaway DR, Najarian KB, Slaughter MS, ADVANCE Investigators (2015) Gastrointestinal bleeding in recipients of the HeartWare ventricular assist system. JACC Heart Fail 3(4):303–313 Axelrad JE, Pinsino A, Trinh PN, Thanataveerat A, Brooks C, Demmer RT, Effner L, Parkis G, Cagliostro B, Han J, Garan AR, Topkara V, Takeda K, Takayama H, Naka Y, Ramirez I, Garcia-Carrasquillo R, Colombo PC, Gonda T, Yuzefpolskaya M (2018) Limited usefulness of endoscopic evaluation in patients with continuous-flow left ventricular assist devices and gastrointestinal bleeding. J Heart Lung Transplant 37(6):723–732 Joy PS, Kumar G, Guddati AK, Bhama JK, Cadaret LM (2016) Risk factors and outcomes of gastrointestinal bleeding in left ventricular assist device recipients. Am J Cardiol 117(2):240–244 Jiang HY, Chen HZ, Hu XJ, Yu ZH, Yang W, Deng M, Zhang YH, Ruan B (2015) Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal bleeding: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 13(1):42–50 e43 Patel SR, Madan S, Saeed O, Algodi M, Luke A, Gibber M, Goldstein DJ, Jorde UP (2016) Association of nasal mucosal vascular alterations, gastrointestinal arteriovenous malformations, and bleeding in patients with continuous-flow left ventricular assist devices. JACC Heart Fail 4(12):962–970 Kim GSG, Ransom J, Keebler M, Katz J, Kilic A et al (2018) Increased bleeding risk in LVAD patients with elevated angiopoietin-2 and TNF-alpha: analysis of the PREVENT multicenter study [abstract]. J Heart Lung Transplant 37 Kataria R, Jorde UP (2019) Gastrointestinal bleeding during continuous-flow left ventricular assist device support: state of the field. Cardiol Rev 27(1):8–13 Tabit CE, Chen P, Kim GH, Fedson SE, Sayer G, Coplan MJ, Jeevanandam V, Uriel N, Liao JK (2016) Elevated angiopoietin-2 level in patients with continuous-flow left ventricular assist devices leads to altered angiogenesis and is associated with higher nonsurgical bleeding. Circulation. 134(2):141–152 Yamakawa M, Liu LX, Date T, Belanger AJ, Vincent KA, Akita GY, Kuriyama T, Cheng SH, Gregory RJ, Jiang C (2003) Hypoxia-inducible factor-1 mediates activation of cultured vascular endothelial cells by inducing multiple angiogenic factors. Circ Res 93(7):664–673 Simon MP, Tournaire R, Pouyssegur J (2008) The angiopoietin-2 gene of endothelial cells is up-regulated in hypoxia by a HIF binding site located in its first intron and by the central factors GATA-2 and Ets-1. J Cell Physiol 217(3):809–818 Converse MP, Sobhanian M, Taber DJ, Houston BA, Meadows HB, Uber WE (2019) Effect of angiotensin II inhibitors on gastrointestinal bleeding in patients with left ventricular assist devices. J Am Coll Cardiol 73(14):1769–1778 Chen Z, Mondal NK, Zheng S, Koenig SC, Slaughter MS, Griffith BP, Wu ZJ (2019) High shear induces platelet dysfunction leading to enhanced thrombotic propensity and diminished hemostatic capacity. Platelets. 30(1):112–119 Uriel N, Pak SW, Jorde UP, Jude B, Susen S, Vincentelli A, Ennezat PV, Cappleman S, Naka Y, Mancini D (2010) Acquired von Willebrand syndrome after continuous-flow mechanical device support contributes to a high prevalence of bleeding during long-term support and at the time of transplantation. J Am Coll Cardiol 56(15):1207–1213 Suarez J, Patel CB, Felker GM, Becker R, Hernandez AF, Rogers JG (2011) Mechanisms of bleeding and approach to patients with axial-flow left ventricular assist devices. Circ Heart Fail 4(6):779–784 Jilma-Stohlawetz P, Quehenberger P, Schima H, Stoiber M, Knöbl P, Steinlechner B, Felli A, Jilma B (2016) Acquired von Willebrand factor deficiency caused by LVAD is ADAMTS-13 and platelet dependent. Thromb Res 137:196–201 Lopilato AC, Doligalski CT, Caldeira C (2015) Incidence and risk factor analysis for gastrointestinal bleeding and pump thrombosis in left ventricular assist device recipients. Artif Organs 39(11):939–944 Katz JN, Adamson RM, John R, Tatooles A, Sundareswaran K, Kallel F, Farrar DJ, Jorde UP, TRACE study (2015) Safety of reduced anti-thrombotic strategies in HeartMate II patients: a one-year analysis of the US-TRACE study. J Heart Lung Transplant 34(12):1542–1548 Netuka I, Litzler PY, Berchtold-Herz M, Flecher E, Zimpfer D, Damme L, Sundareswaran KS, Farrar DJ, Schmitto JD, EU TRACE Investigators (2017) Outcomes in HeartMate II patients with no antiplatelet therapy: 2-year results from the European TRACE study. Ann Thorac Surg 103(4):1262–1268 Najjar SS, Slaughter MS, Pagani FD, Starling RC, McGee E, Eckman P, Tatooles AJ, Moazami N, Kormos RL, Hathaway DR, Najarian KB, Bhat G, Aaronson KD, Boyce SW, HVAD Bridge to Transplant ADVANCE Trial Investigators (2014) An analysis of pump thrombus events in patients in the HeartWare ADVANCE bridge to transplant and continued access protocol trial. J Heart Lung Transplant 33(1):23–34 Netuka I, Ivak P, Tucanova Z et al (2018) Evaluation of low-intensity anti-coagulation with a fully magnetically levitated centrifugal-flow circulatory pump-the MAGENTUM 1 study. J Heart Lung Transplant 37(5):579–586 Saeed O, Colombo PC, Mehra MR, Uriel N (2020) Effect of aspirin dose on hemocompatibility related outcomes with a magnetically levitated left ventricular assist device: an analysis from the MOMENTUM 3 study [in press]. J Heart Lung Transplant Antiplatelet Removal and HemocompatIbility EventS With the HeartMate 3 Pump IDE Study. ClinicalTrialsgov.Identifier: NCT04069156 Harris J, Heil JS (2013) Managing depression in patients with advanced heart failure awaiting transplantation. Am J Health Syst Pharm 70(10):867–873 Mawardi G MT, Muslem R, et al (2018) SSRI/SNRI Therapy is associated with a higher risk of GI bleed in LVAD patients [abstract]. J Heart Lung Transplant 37 Schultz J, Bream-Rouwenhorst H, Hobbs R, McDanel D, Goerbig-Campbell J (2016) Serotonergic agents increase the incidence of gastrointestinal bleeds in patients with continuous-flow left ventricular assist devices. J Heart Lung Transplant 35(6):823–824 Houston BA, Schneider AL, Vaishnav J et al (2017) Angiotensin II antagonism is associated with reduced risk for gastrointestinal bleeding caused by arteriovenous malformations in patients with left ventricular assist devices. J Heart Lung Transplant 36(4):380–385 Schultz J, John R, Alexy T, Thenappan T, Cogswell R (2019) Association between angiotensin II antagonism and gastrointestinal bleeding on left ventricular assist device support. J Heart Lung Transplant 38(4):469–471 Jennings DL, Truby L, Fried J (2020) Impact of heart failure drug therapy on GI bleeding rates in LVAD patients: an INTERMACS analysis [abstract]. J Heart Lung Transplant 39:S26 Group CTS (1987) Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med 316(23):1429–1435 Yusuf S, Pitt B, Davis CE, Hood WB, Cohn JN (1991) Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 325(5):293–302 Yousefzai R, Brambatti M, Tran HA, et al (2019) Benefits of neurohormonal therapy in patients with continuous-flow left ventricular assist devices. ASAIO J Wang W, Zhu J, Lyu F et al (2014) Omega-3 polyunsaturated fatty acids-derived lipid metabolites on angiogenesis, inflammation and cancer. Prostaglandins Lipid Mediat 113-115:13–20 Zhang G, Kodani S, Hammock BD (2014) Stabilized epoxygenated fatty acids regulate inflammation, pain, angiogenesis and cancer. Prog Lipid Res 53:108–123 Imamura T, Nguyen A, Rodgers D, Kim G, Raikhelkar J, Sarswat N, Kalantari S, Smith B, Chung B, Narang N, Juricek C, Burkhoff D, Song T, Ota T, Jeevanandam V, Sayer G, Uriel N (2018) Omega-3 therapy is associated with reduced gastrointestinal bleeding in patients with continuous-flow left ventricular assist device. Circ Heart Fail 11(10):e005082 Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT Jr, Juliano RA, Jiao L, Granowitz C, Tardif JC, Ballantyne CM, REDUCE-IT Investigators (2019) Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med 380(1):11–22 Ganda OP, Bhatt DL, Mason RP, Miller M, Boden WE (2018) Unmet need for adjunctive dyslipidemia therapy in hypertriglyceridemia management. J Am Coll Cardiol 72(3):330–343 Molina TL, Krisl JC, Donahue KR, Varnado S (2018) Gastrointestinal bleeding in left ventricular assist device: octreotide and other treatment modalities. ASAIO J 64(4):433–439 Rennyson SL, Shah KB, Tang DG, Kasirajan V, Pedram S, Cahoon W, Malhotra R (2013) Octreotide for left ventricular assist device-related gastrointestinal hemorrhage: can we stop the bleeding? ASAIO J 59(4):450–451 Dang G, Grayburn R, Lamb G, Umpierrez De Reguero A, Gaglianello N (2014) Octreotide for the management of gastrointestinal bleeding in a patient with a HeartWare left ventricular assist device. Case Rep Cardiol 2014:826453 Loyaga-Rendon RY, Hashim T, Tallaj JA, Acharya D, Holman W, Kirklin J, Pamboukian SV (2015) Octreotide in the management of recurrent gastrointestinal bleed in patients supported by continuous flow left ventricular assist devices. ASAIO J 61(1):107–109 Shah KB, Gunda S, Emani S, et al (2017) Multicenter evaluation of octreotide as secondary prophylaxis in patients with left ventricular assist devices and gastrointestinal bleeding. Circ Heart Fail 10(11) Smallfield GB GS, Emani S, et al (2016) A multicenter evaluation of octreotide for ventricular assist device related gastrointestinal bleeding [abstract]. J Heart Lung Transplant 35(4) Malhotra R, Shah KB, Chawla R, Pedram S, Smallfield MC, Priday AG, DeWilde CT, Brophy DF (2017) Tolerability and biological effects of long-acting octreotide in patients with continuous flow left ventricular assist devices. ASAIO J 63(3):367–370 (2012) Sandostatin (octreotide solution) [prescribing information]. Novartis, East Hanover Sandostatin LAR (2016) Depot (octreotide suspension) [prescribing information]. Novartis, East Hanover Zhang H, Qian DZ, Tan YS, Lee K, Gao P, Ren YR, Rey S, Hammers H, Chang D, Pili R, Dang CV, Liu JO, Semenza GL (2008) Digoxin and other cardiac glycosides inhibit HIF-1alpha synthesis and block tumor growth. Proc Natl Acad Sci U S A 105(50):19579–19586 Vukelic S, Vlismas PP, Patel SR, Xue X, Shitole SG, Saeed O, Sims DB, Chinnadurai T, Shin JJ, Forest SJ, Goldstein DJ, Jorde UP (2018) Digoxin is associated with a decreased incidence of angiodysplasia-related gastrointestinal bleeding in patients with continuous-flow left ventricular assist devices. Circ Heart Fail 11(8):e004899 Lopes RD, Rordorf R, De Ferrari GM et al (2018) Digoxin and mortality in patients with atrial fibrillation. J Am Coll Cardiol 71(10):1063–1074 See I, Shehab N, Kegler SR, Laskar SR, Budnitz DS (2014) Emergency department visits and hospitalizations for digoxin toxicity: United States, 2005 to 2010. Circ Heart Fail 7(1):28–34 Schettle S, Bawardy BA, Asleh R, Sherazi S, Rajan E, Stulak J, Pereira N (2018) Danazol treatment of gastrointestinal bleeding in left ventricular assist device-supported patients. J Heart Lung Transplant 37(8):1035–1037 Kenyon BM, Browne F, D'Amato RJ (1997) Effects of thalidomide and related metabolites in a mouse corneal model of neovascularization. Exp Eye Res 64(6):971–978 Feng N, Chen HY, Fu SW, et al (2016) HIF-1 alpha and HIF-2 alpha induced angiogenesis in gastrointestinal vascular malformation and reversed by thalidomide. Sci Rep-Uk 6 Chan LL, Lim CP, Lim CH, Tan TE, Sim D, Sivathasan C (2017) Novel use of thalidomide in recurrent gastrointestinal tract bleeding in patients with left ventricular assist devices: a case series. Heart Lung Circ 26(10):1101–1104 Draper K, Kale P, Martin B, Cordero K, Ha R, Banerjee D (2015) Thalidomide for treatment of gastrointestinal angiodysplasia in patients with left ventricular assist devices: case series and treatment protocol. J Heart Lung Transplant 34(1):132–134 Ray R, Kale PP, Ha R, Banerjee D (2014) Treatment of left ventricular assist device-associated arteriovenous malformations with thalidomide. ASAIO J 60(4):482–483 Namdaran P, Zikos TA, Pan JY, Banerjee D (2019) Thalidomide use reduces risk of refractory gastrointestinal bleeding in patients with continuous flow left ventricular assist devices. ASAIO J (2016) Thalomid (thalidomide) [product monograph]. Celgene Inc., Mississauga (2018) DDAVP (desmopressin) [product monograph]. Hospira Inc., Lake Forest Hollis IB, Chen SL, Chang PP, Katz JN (2017) Inhaled desmopressin for refractory gastrointestinal bleeding in a patient with a HeartMate II left ventricular assist device. ASAIO J 63(4):e47–e49 Bartoli CR, Kang J, Restle DJ, Zhang DM, Shabahang C, Acker MA, Atluri P (2015) Inhibition of ADAMTS-13 by doxycycline reduces von Willebrand factor degradation during supraphysiological shear stress: therapeutic implications for left ventricular assist device-associated bleeding. JACC Heart Fail 3(11):860–869 Keebler M, Haglund N, Zalawadiya S et al (2017) Standard dose doxycycline does not alter von Willebrand factor degradation in patients with CF LVAD [abstract]. J Heart Lung Transplant 36(4):S11 Asleh R, Albitar HAH, Schettle SD, Kushwaha SS, Pereira NL, Behfar A, Stulak JM, Rodeheffer RJ, Iyer VN (2020) Intravenous bevacizumab as a novel treatment for refractory left ventricular assist device-related gastrointestinal bleeding. J Heart Lung Transplant 39(5):492–495 Baldeo CM, Rivera CE, Tun HW, Vishnu P (2018) Pharmacokinetics-based clinical management of acquired von Willebrand syndrome: a case report. J Blood Med 9:9–13 Franchini M, Mannucci PM (2013) Von Willebrand disease-associated angiodysplasia: a few answers, still many questions. Br J Haematol 161(2):177–182 Cushing M, Kawaguchi K, Friedman KD, Mark T (2012) Factor VIII/von Willebrand factor concentrate therapy for ventricular assist device-associated acquired von Willebrand disease. Transfusion. 52(7):1535–1541