Clin J Gastroenterol (2015) 8:63–67 DOI 10.1007/s12328-015-0551-5
CLINICAL REVIEW
Gastrointestinal bleeding with continuous-flow left ventricular assist devices Syed Amer • Parth Shah • Syed Hassan
Received: 20 November 2014 / Accepted: 25 December 2014 / Published online: 24 January 2015 Ó Springer Japan 2015
Abstract Continuous-flow left ventricular assist device (CF-LVAD) insertion is a life-saving procedure that is being increasingly used in patients with advanced heart failure. However, patients with CF-LVADs are at an increased risk of gastrointestinal bleeding (GIB). Bleeding can occur anywhere in the GI tract with lesions being more prevalent in the upper GI tract than in the lower GI tract. The pathophysiology of GIB in patients with CF-LVADs is unique and likely involves three synergistic mechanisms— coagulopathy, acquired von Willebrand disease and continuous non-pulsatile blood flow. Management strategies vary depending on the presentation and site of bleeding. Prevention strategies to prevent GIB in these patients include low pump speed, close hemodynamic monitoring and a low threshold for endoscopy. We aim to review in detail the pathophysiology, management, complications and preventive strategies in patients with CF-LVAD who present with GIB. Keywords CF-LVAD Gastrointestinal bleeding Management
Introduction In the United States, over five million people have congestive heart failure [1]. Of those, approximately 25 % eventually develop end-stage heart failure. Since mechanical circulatory support has rapidly evolved over the past S. Amer (&) P. Shah Mayo Clinic, Phoenix, AZ 85054, USA e-mail: [email protected] S. Hassan Duke University, Durham, NC 27708, USA
two decades [2, 3], left ventricular assist devices (LVADs) are now being inserted into an increasing number of patients with advanced heart failure. The patient outcomes have been positive as exemplified through an overall survival rate as high as 72 % after 1 year of LVAD support. The RE-MATCH trial showed 1- and 2-year survival that was more than twice the optimal medical therapy [4]. LVADs were originally used for decompensated patients who needed a temporary bridge to recovery. They were then used as a bridge to heart transplant. However, a vast disparity exists between supply and demand with only 2,200 organs available for [1 million patients with endstage heart disease. Furthermore, the majority of patients with end-stage heart disease are elderly with multiple comorbid conditions that make them ineligible for transplant. For these reasons, LVADs are being increasingly used as destination therapy, i.e., a permanent device for improved survival. There is also strong evidence that with LVAD unloading, particularly when combined with pharmacological treatment, a patient’s myocardial function can also recover. This recovery allows for device removal and avoids the need for transplantation, immunosuppression and the associated complications of an LVAD; this new and expanding indication is known as ‘bridge to recovery’. LVAD technology is progressing quickly, survival is improving, the incidence of complications is decreasing and durability of the devices is advancing. The two main types of LVADs have different flow patterns—pulsatile and non-pulsatile. The earliest LVAD was a pulsatile device that mimicked the natural physiology of the heart; however, due to various limitations, they have been replaced with newer, non-pulsatile devices which are continuous-flow LVADs (CF-LVADs). These CF-LVADs have been shown to have an improved overall survival [5]. However, CF-LVADs are associated with significant
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complications that include infection [6], neurological complications [7] renal dysfunction [8, 9] and gastrointestinal bleeding (GIB) [10]. GIB is becoming a common occurrence in post-LVAD implantation patients, and has been found to be an increasingly important cause of morbidity in patients with CFLVADs. Several studies performed on CF-LVADs have shown varying rates of GIB, ranging from 15-50 % [11, 12]. Location Bleeding can occur throughout the GI tract. In some patients, no bleeding site can be identified despite extensive investigations [13]. However, in cases where the source was found it could extend anywhere from the esophagus to the stomach [14–16]. Upper GI tract lesions include vascular ectasias, hemorrhagic gastritis, Cameron’s ulcers and erosive gastropathy, peptic ulcer disease, Mallory-Weiss, and driveline erosion. Lower GI tract lesions include vascular ectasia, diverticulosis, ischemic colitis, polyps, and hemorrhoids. Lesions found on small bowel endoscopy include vascular lesions like Dieulafoy and arteriovenous malformations. Most studies indicate a predominance of upper GI lesions over lower GI lesions. Furthermore, patients with CF-LVADs who present with GIB may also present with recurrent bleeding from the same site.
Clin J Gastroenterol (2015) 8:63–67
GIB in patients with aortic stenosis. Warkentin et al. [20] postulated that aortic stenosis predisposed patients to the development of acquired von Willebrand (AvW) syndrome. This could contribute to higher bleeding events from gastrointestinal angiodysplasia, which is a common finding in patients with aortic stenosis. Recently, it has been found that aortic stenosis and GIB are associated with type 2 AvW syndrome, which is characterized by the loss of high-molecular-weight (HMW) vWF multimers [21]. HMW vWF multimers are believed to be essential for platelet-mediated hemostasis and prevention of bleeding in high-shear areas. High-shear forces induce structural changes in the shape of the vWF molecule, leading to exposure of the bond between amino acids 842 and 843. This results in proteolysis of the HMW multimers of vWF, which are the most effective in platelet-mediated hemostasis under conditions of high-shear stress [22, 23]. This hematological syndrome is reversed by aortic valve replacement [24]. CF-LVADs may cause a similar syndrome as they lead to a relatively high non-physiological shear stress imparted on blood components when they move through the device. The continuous impeller mechanism of the non-pulsatile LVAD pump may result in vWF deformation, proteolysis, and ultimately deficiency. It is likely that the three proposed mechanisms—coagulopathy, AvW disease and lack of pulsatility—act synergistically in the pathophysiology of GIB with CF-LVADs.
Risk factors Management Risk factors [17] for increased risk of bleeding in patients with CF-LVAD include a prior history of GIB (before LVAD implantation), lower body mass index, old age, smoking, elevated international normalized ratio (INR), and a low platelet count.
Management of a CF-LVAD patient with GIB encompasses a multidisciplinary approach. The main steps involved in the management of these patients are [25, 26]: 1.
Temporarily discontinuing anticoagulation until bleeding ceased. Reducing LVAD speed to lowest possible safe speed. Endoscopic evaluation.
Pathophysiology
2. 3.
Patients with non-pulsatile devices receive anticoagulation with warfarin [target range INR 1.5–3] due to the high risk of thrombosis, whereas pulsatile-device recipients do not receive anticoagulation. Both non-pulsatile and pulsatile device recipients take aspirin daily. Crow et al. [18] noted that when comparing GIB rates in patients with CF-LVADs who received anticoagulation and present with GIB, the propensity for GI bleeding could not be attributed to the anticoagulation alone. Patients with CF-LVADs have states physiologically similar to aortic stenosis because of the narrow pulse pressure. Heyde et al. [19] reported a higher incidence of
Upper and lower endoscopies are initially performed to localize the source of the bleeding. If this fails, small bowel capsule endoscopy is performed. Balloon enteroscopy is used in the case of challenging small bowel lesions. The endoscopic and interventional techniques include cauterization, injection, clipping of a visible vessel, and mesenteric angiography with coil embolization. Rarely, when other non-surgical treatment options fail, surgical intervention in the form of partial gastrectomy or bowel resection is required. The management GIB in patients with LVAD is summarized in Fig 1.
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65
Fig. 1 Management of GIB in patients with CF-LVAD
Octreotide, a synthetic somatostatin analog, is often used in treatment for GIB irrespective of the etiology. The mechanisms involved in the pharmacological effect of octreotide include decreased splanchnic blood flow, increased vascular resistance, improved platelet aggregation, and inhibition of angiogenesis [27] via inhibition of vascular endothelial growth factor [28]. Octreotide use in the management of GIB in patients with LVAD is controversial as one study has shown positive results [29], while another showed no benefits [17]. Additionally, thalidomide, due to its angiogenic properties, has shown therapeutic promise in non-LVAD patients with GIB [30, 31]. As such, it may also be potentially effective for GIB in patients with LVADs. Factor VIII concentrates that contain both factor VIII and vWF have also been used in a few cases with moderate success [32].
Complications from GIB in patients with LVADs There have been reports of increased mortality post-transplant among patients with LVADs who had GIB. This is likely related to an increased use of blood products, which leads to an increase in allosensitization [10, 33].
Prevention Preventive steps need to be taken in patients with LVADs to minimize GIB. A few suggested preventive strategies include: 1.
Resumption of anticoagulation post GIB
2.
Aspirin is usually restarted after cessation of GIB and once hemodynamic stability is ensured. The target INR for those anticoagulated with warfarin post GIB is aimed at the lower end of the therapeutic range (1.5–2).
3. 4.
Maintain LVAD pump speed at the lowest possible safe range (ensuring adequate unloading of the left ventricle) under echocardiographic guidance, decrease flow, and gain relative pulsatility. Maintain INR at the lower end of the recommended range (1.5–2) in those at high risk of GIB. Frequent monitoring of hematological parameters like INR, hemoglobin, and platelets. Low threshold for endoscopy in those suspected of having GIB.
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Interestingly, several studies have shown that after orthotopic heart transplantation, none of the patients with GIB had recurrent bleeding [11, 13, 25].
Conclusion GIB from CF-LVADs is a growing concern with the increasing use of CF-LVADs as destination therapy, bridge to transplant and bridge to recovery. The mechanism of bleeding, although unclear, is probably multifactorial involving anticoagulation, AvW disease and non-pulsatile flow. Endoscopy seems to be a safe and effective tool for diagnosing, risk stratifying, and treating LVAD patients with GIB. Additional evaluation of the small bowel with video capsule endoscopy and double-balloon enteroscopy is helpful in patients with non-diagnostic esophagogastroduodenoscopy and colonoscopy. Further prospective studies are needed in this patient population to determine the mechanisms leading to GIB and to evaluate novel therapeutic approaches. Disclosures Conflict of Interest: Syed Amer, Parth Shah and Syed Hassan declare that they have no conflict of interest. Human/Animal rights: All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008(5) Informed consent: Informed consent was obtained from all patients for being included in the study.
References 1. Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics—2013 update: a report from the American heart association. Circulation. 2013;127:e6–245. 2. Miller LW, Pagani FD, Russell SD, et al. HeartMate II Clinical Investigators. Frazier OH use of a continuous-flow device in patients awaiting heart transplantation. N Engl J Med. 2007;357:885–96. 3. Slaughter MS, Rogers JG, Milano CA, et al. Advanced heart failure treated with continuous-flow left ventricular assist device. N Engl J Med. 2009;361:2241–51. 4. Rose EA, Gelijns AC, Moskowitz AJ, et al. Long-term use of a left ventricular assist device for end-stage heart failure. N Engl J Med. 2001;345:1435–43. 5. John R, Kamdar F, Liao K, et al. Low thromboembolic risk for patients with the Heartmate II left ventricular assist device. J Thorac Cardiovasc Surg. 2008;136:1318–23. 6. Holman WL, Rayburn BK, McGiffin DC, et al. Infection in ventricular assist devices: prevention and treatment. Ann Thorac Surg. 2003;75(suppl):S48–57. 7. Hagan K. LVADs help mend a broken heart. Nurse Pract. 2010;35:28–37.
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Clin J Gastroenterol (2015) 8:63–67 8. Miller LW, Pagani FD, Russell SD, et al. Use of a continuousflow device in patients awaiting heart transplantation. N Engl J Med. 2007;357:885–96. 9. Kamdar F, Boyle A, Liao K, et al. Effects of centrifugal, axial and pulsatile left ventricular assist device support on end organ function in heart failure patients. J Heart Lung Transplant. 2009;28:352–9. 10. Uriel N, Pak SW, Jorde UP, et al. 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. 2010;56:1207–13. 11. Morgan JA, Paone G, Nemeh HW, et al. Gastrointestinal bleeding with the HeartMate II left ventricular assist device. J Heart Lung Transplant. 2012;31:715–8. 12. John R. Lessons learned from experience with over 100 consecutive HeartMate II leftventricular assist devices. Ann Thorac Surg. 2011;92:1593–9. 13. Stern DR, Kazam J, Edwards P, et al. Increased incidence of gastrointestinal bleeding following implantation of the HeartMate II LVAD. J Card Surg. 2010;25:352–6. 14. Daas AY, Small MB, Pinkas H, et al. Safety of conventional and wireless capsule endoscopy in patients supported with nonpulsatile axial flow heart-mate II left ventricular assist device. Gastrointest Endosc. 2008;68:379–82. 15. Letsou GV, Shah N, Gregoric ID, et al. Gastrointestinal bleeding from arteriovenous malformations in patients supported by the Jarvik 2000 axial-flow left ventricular assist device. J Heart Lung Transplant. 2005;24:105–9. 16. Islam S, Cevik C, Madonna R, et al. Left ventricular assist devices and gastrointestinal bleeding: a narrative review of case reports and case series. Clin Cardiol. 2013;36:190–200. 17. Aggarwal A, Pant R, Kumar S, et al. Incidence and management of gastrointestinal bleeding with continuous flow assist devices. Ann Thorac Surg. 2012;93:1534–40. 18. Crow S, John R, Boyle A, et al. Gastrointestinal bleeding rates in recipients of nonpulsatile and pulsatile left ventricular assist devices. J Thorac Cardiovasc Surg. 2009;137:208–15. 19. Heyde E. Gastrointestinal bleeding in aortic stenosis. N Engl J Med. 1958;259:196–200. 20. Warkentin TE, Moore JC, Morgan DG. Aortic stenosis and bleeding gastrointestinal angiodysplasia: is acquired von Willebrand’s disease the link? Lancet. 1992;340:35–7. 21. Federici AB, Rand JH, Bucciarelli P. Acquired von Willebrand syndrome: data from an international registry. Thromb Haemost. 2000;84:345–9. 22. Tsai HM, Sussman II, Nagel RL. Shear stress enhances the proteolysis of von Willebrand factor in normal plasma. Blood. 1994;83:2171–9. 23. Siedlecki CA, Lestini BJ, Kottke-Marchant KK, et al. Sheardependent changes in the three-dimensional structure of human von Willebrand factor. Blood. 1996;88:2939–50. 24. Vincentelli A, Susen S, Le Tourneau T. Acquired von Willebrand syndrome in aortic stenosis. N Engl J Med. 2003;349:343–9. 25. Demirozu ZT, Radovancevic R, Hochman LF, et al. Arteriovenous malformation and gastrointestinal bleeding in patients with the Heart-Mate II left ventricular assist device. J Heart Lung Transplant. 2011;30:849–53. 26. Hayes HM, Dembo LG, Larbalestier R, et al. Management options to treat gastrointestinal bleeding in patients supported on rotary left ventricular assist devices: a single-center experience. Artif Organs. 2010;34:703–6. 27. Lamberts SW, van der Lely AJ, de Herder WW, Hofland LJ. Octreotide. N Eng J Med. 1996;334:246–54. 28. Kurosaki M, Saegert W, Abe T, et al. Expression of vascular endothelial growth factor in growth hormone-secreting pituitary
Clin J Gastroenterol (2015) 8:63–67 adenomas: special reference to the octreotide treatment. Neurol Res. 2008;30:518–22. 29. Rennyson SL, Shah KB, Tang DG, et al. Octreotide for left ventricular assist device-related gastrointestinal hemorrhage: can we stop the bleeding? ASAIO J. 2013;59:450–1. 30. Ge ZZ, Chen HM, Gao YJ, et al. Efficacy of thalidomide for refractory gastrointestinal bleeding from vascular malformation. Gastroenterology. 2011;141(1629–37):e1–4. 31. Garrido A, Sayago M, Lopez J, et al. Thalidomide in refractory bleeding due to gastrointestinal angiodysplasias. Rev Esp Enferm Dig. 2012;104:69–71.
67 32. Cushing M. Factor VIII/von Willebrand factor concentrate therapy for ventricular-assist device associated acquired von Willebrand Disease. Transfusion. 2012;52:1535–41. 33. Patlolla V, Patten RD, Denofrio D, et al. The effect of ventricular assist devices on post-transplant mortality an analysis of the united network for organ sharing thoracic registry. J Am Coll Cardiol. 2009;53:264–71.
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CLINICAL REVIEW
Gastrointestinal bleeding with continuous-flow left ventricular assist devices Syed Amer • Parth Shah • Syed Hassan
Received: 20 November 2014 / Accepted: 25 December 2014 / Published online: 24 January 2015 Ó Springer Japan 2015
Abstract Continuous-flow left ventricular assist device (CF-LVAD) insertion is a life-saving procedure that is being increasingly used in patients with advanced heart failure. However, patients with CF-LVADs are at an increased risk of gastrointestinal bleeding (GIB). Bleeding can occur anywhere in the GI tract with lesions being more prevalent in the upper GI tract than in the lower GI tract. The pathophysiology of GIB in patients with CF-LVADs is unique and likely involves three synergistic mechanisms— coagulopathy, acquired von Willebrand disease and continuous non-pulsatile blood flow. Management strategies vary depending on the presentation and site of bleeding. Prevention strategies to prevent GIB in these patients include low pump speed, close hemodynamic monitoring and a low threshold for endoscopy. We aim to review in detail the pathophysiology, management, complications and preventive strategies in patients with CF-LVAD who present with GIB. Keywords CF-LVAD Gastrointestinal bleeding Management
Introduction In the United States, over five million people have congestive heart failure [1]. Of those, approximately 25 % eventually develop end-stage heart failure. Since mechanical circulatory support has rapidly evolved over the past S. Amer (&) P. Shah Mayo Clinic, Phoenix, AZ 85054, USA e-mail: [email protected] S. Hassan Duke University, Durham, NC 27708, USA
two decades [2, 3], left ventricular assist devices (LVADs) are now being inserted into an increasing number of patients with advanced heart failure. The patient outcomes have been positive as exemplified through an overall survival rate as high as 72 % after 1 year of LVAD support. The RE-MATCH trial showed 1- and 2-year survival that was more than twice the optimal medical therapy [4]. LVADs were originally used for decompensated patients who needed a temporary bridge to recovery. They were then used as a bridge to heart transplant. However, a vast disparity exists between supply and demand with only 2,200 organs available for [1 million patients with endstage heart disease. Furthermore, the majority of patients with end-stage heart disease are elderly with multiple comorbid conditions that make them ineligible for transplant. For these reasons, LVADs are being increasingly used as destination therapy, i.e., a permanent device for improved survival. There is also strong evidence that with LVAD unloading, particularly when combined with pharmacological treatment, a patient’s myocardial function can also recover. This recovery allows for device removal and avoids the need for transplantation, immunosuppression and the associated complications of an LVAD; this new and expanding indication is known as ‘bridge to recovery’. LVAD technology is progressing quickly, survival is improving, the incidence of complications is decreasing and durability of the devices is advancing. The two main types of LVADs have different flow patterns—pulsatile and non-pulsatile. The earliest LVAD was a pulsatile device that mimicked the natural physiology of the heart; however, due to various limitations, they have been replaced with newer, non-pulsatile devices which are continuous-flow LVADs (CF-LVADs). These CF-LVADs have been shown to have an improved overall survival [5]. However, CF-LVADs are associated with significant
123
64
complications that include infection [6], neurological complications [7] renal dysfunction [8, 9] and gastrointestinal bleeding (GIB) [10]. GIB is becoming a common occurrence in post-LVAD implantation patients, and has been found to be an increasingly important cause of morbidity in patients with CFLVADs. Several studies performed on CF-LVADs have shown varying rates of GIB, ranging from 15-50 % [11, 12]. Location Bleeding can occur throughout the GI tract. In some patients, no bleeding site can be identified despite extensive investigations [13]. However, in cases where the source was found it could extend anywhere from the esophagus to the stomach [14–16]. Upper GI tract lesions include vascular ectasias, hemorrhagic gastritis, Cameron’s ulcers and erosive gastropathy, peptic ulcer disease, Mallory-Weiss, and driveline erosion. Lower GI tract lesions include vascular ectasia, diverticulosis, ischemic colitis, polyps, and hemorrhoids. Lesions found on small bowel endoscopy include vascular lesions like Dieulafoy and arteriovenous malformations. Most studies indicate a predominance of upper GI lesions over lower GI lesions. Furthermore, patients with CF-LVADs who present with GIB may also present with recurrent bleeding from the same site.
Clin J Gastroenterol (2015) 8:63–67
GIB in patients with aortic stenosis. Warkentin et al. [20] postulated that aortic stenosis predisposed patients to the development of acquired von Willebrand (AvW) syndrome. This could contribute to higher bleeding events from gastrointestinal angiodysplasia, which is a common finding in patients with aortic stenosis. Recently, it has been found that aortic stenosis and GIB are associated with type 2 AvW syndrome, which is characterized by the loss of high-molecular-weight (HMW) vWF multimers [21]. HMW vWF multimers are believed to be essential for platelet-mediated hemostasis and prevention of bleeding in high-shear areas. High-shear forces induce structural changes in the shape of the vWF molecule, leading to exposure of the bond between amino acids 842 and 843. This results in proteolysis of the HMW multimers of vWF, which are the most effective in platelet-mediated hemostasis under conditions of high-shear stress [22, 23]. This hematological syndrome is reversed by aortic valve replacement [24]. CF-LVADs may cause a similar syndrome as they lead to a relatively high non-physiological shear stress imparted on blood components when they move through the device. The continuous impeller mechanism of the non-pulsatile LVAD pump may result in vWF deformation, proteolysis, and ultimately deficiency. It is likely that the three proposed mechanisms—coagulopathy, AvW disease and lack of pulsatility—act synergistically in the pathophysiology of GIB with CF-LVADs.
Risk factors Management Risk factors [17] for increased risk of bleeding in patients with CF-LVAD include a prior history of GIB (before LVAD implantation), lower body mass index, old age, smoking, elevated international normalized ratio (INR), and a low platelet count.
Management of a CF-LVAD patient with GIB encompasses a multidisciplinary approach. The main steps involved in the management of these patients are [25, 26]: 1.
Temporarily discontinuing anticoagulation until bleeding ceased. Reducing LVAD speed to lowest possible safe speed. Endoscopic evaluation.
Pathophysiology
2. 3.
Patients with non-pulsatile devices receive anticoagulation with warfarin [target range INR 1.5–3] due to the high risk of thrombosis, whereas pulsatile-device recipients do not receive anticoagulation. Both non-pulsatile and pulsatile device recipients take aspirin daily. Crow et al. [18] noted that when comparing GIB rates in patients with CF-LVADs who received anticoagulation and present with GIB, the propensity for GI bleeding could not be attributed to the anticoagulation alone. Patients with CF-LVADs have states physiologically similar to aortic stenosis because of the narrow pulse pressure. Heyde et al. [19] reported a higher incidence of
Upper and lower endoscopies are initially performed to localize the source of the bleeding. If this fails, small bowel capsule endoscopy is performed. Balloon enteroscopy is used in the case of challenging small bowel lesions. The endoscopic and interventional techniques include cauterization, injection, clipping of a visible vessel, and mesenteric angiography with coil embolization. Rarely, when other non-surgical treatment options fail, surgical intervention in the form of partial gastrectomy or bowel resection is required. The management GIB in patients with LVAD is summarized in Fig 1.
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Clin J Gastroenterol (2015) 8:63–67
65
Fig. 1 Management of GIB in patients with CF-LVAD
Octreotide, a synthetic somatostatin analog, is often used in treatment for GIB irrespective of the etiology. The mechanisms involved in the pharmacological effect of octreotide include decreased splanchnic blood flow, increased vascular resistance, improved platelet aggregation, and inhibition of angiogenesis [27] via inhibition of vascular endothelial growth factor [28]. Octreotide use in the management of GIB in patients with LVAD is controversial as one study has shown positive results [29], while another showed no benefits [17]. Additionally, thalidomide, due to its angiogenic properties, has shown therapeutic promise in non-LVAD patients with GIB [30, 31]. As such, it may also be potentially effective for GIB in patients with LVADs. Factor VIII concentrates that contain both factor VIII and vWF have also been used in a few cases with moderate success [32].
Complications from GIB in patients with LVADs There have been reports of increased mortality post-transplant among patients with LVADs who had GIB. This is likely related to an increased use of blood products, which leads to an increase in allosensitization [10, 33].
Prevention Preventive steps need to be taken in patients with LVADs to minimize GIB. A few suggested preventive strategies include: 1.
Resumption of anticoagulation post GIB
2.
Aspirin is usually restarted after cessation of GIB and once hemodynamic stability is ensured. The target INR for those anticoagulated with warfarin post GIB is aimed at the lower end of the therapeutic range (1.5–2).
3. 4.
Maintain LVAD pump speed at the lowest possible safe range (ensuring adequate unloading of the left ventricle) under echocardiographic guidance, decrease flow, and gain relative pulsatility. Maintain INR at the lower end of the recommended range (1.5–2) in those at high risk of GIB. Frequent monitoring of hematological parameters like INR, hemoglobin, and platelets. Low threshold for endoscopy in those suspected of having GIB.
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Interestingly, several studies have shown that after orthotopic heart transplantation, none of the patients with GIB had recurrent bleeding [11, 13, 25].
Conclusion GIB from CF-LVADs is a growing concern with the increasing use of CF-LVADs as destination therapy, bridge to transplant and bridge to recovery. The mechanism of bleeding, although unclear, is probably multifactorial involving anticoagulation, AvW disease and non-pulsatile flow. Endoscopy seems to be a safe and effective tool for diagnosing, risk stratifying, and treating LVAD patients with GIB. Additional evaluation of the small bowel with video capsule endoscopy and double-balloon enteroscopy is helpful in patients with non-diagnostic esophagogastroduodenoscopy and colonoscopy. Further prospective studies are needed in this patient population to determine the mechanisms leading to GIB and to evaluate novel therapeutic approaches. Disclosures Conflict of Interest: Syed Amer, Parth Shah and Syed Hassan declare that they have no conflict of interest. Human/Animal rights: All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008(5) Informed consent: Informed consent was obtained from all patients for being included in the study.
References 1. Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics—2013 update: a report from the American heart association. Circulation. 2013;127:e6–245. 2. Miller LW, Pagani FD, Russell SD, et al. HeartMate II Clinical Investigators. Frazier OH use of a continuous-flow device in patients awaiting heart transplantation. N Engl J Med. 2007;357:885–96. 3. Slaughter MS, Rogers JG, Milano CA, et al. Advanced heart failure treated with continuous-flow left ventricular assist device. N Engl J Med. 2009;361:2241–51. 4. Rose EA, Gelijns AC, Moskowitz AJ, et al. Long-term use of a left ventricular assist device for end-stage heart failure. N Engl J Med. 2001;345:1435–43. 5. John R, Kamdar F, Liao K, et al. Low thromboembolic risk for patients with the Heartmate II left ventricular assist device. J Thorac Cardiovasc Surg. 2008;136:1318–23. 6. Holman WL, Rayburn BK, McGiffin DC, et al. Infection in ventricular assist devices: prevention and treatment. Ann Thorac Surg. 2003;75(suppl):S48–57. 7. Hagan K. LVADs help mend a broken heart. Nurse Pract. 2010;35:28–37.
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Clin J Gastroenterol (2015) 8:63–67 8. Miller LW, Pagani FD, Russell SD, et al. Use of a continuousflow device in patients awaiting heart transplantation. N Engl J Med. 2007;357:885–96. 9. Kamdar F, Boyle A, Liao K, et al. Effects of centrifugal, axial and pulsatile left ventricular assist device support on end organ function in heart failure patients. J Heart Lung Transplant. 2009;28:352–9. 10. Uriel N, Pak SW, Jorde UP, et al. 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. 2010;56:1207–13. 11. Morgan JA, Paone G, Nemeh HW, et al. Gastrointestinal bleeding with the HeartMate II left ventricular assist device. J Heart Lung Transplant. 2012;31:715–8. 12. John R. Lessons learned from experience with over 100 consecutive HeartMate II leftventricular assist devices. Ann Thorac Surg. 2011;92:1593–9. 13. Stern DR, Kazam J, Edwards P, et al. Increased incidence of gastrointestinal bleeding following implantation of the HeartMate II LVAD. J Card Surg. 2010;25:352–6. 14. Daas AY, Small MB, Pinkas H, et al. Safety of conventional and wireless capsule endoscopy in patients supported with nonpulsatile axial flow heart-mate II left ventricular assist device. Gastrointest Endosc. 2008;68:379–82. 15. Letsou GV, Shah N, Gregoric ID, et al. Gastrointestinal bleeding from arteriovenous malformations in patients supported by the Jarvik 2000 axial-flow left ventricular assist device. J Heart Lung Transplant. 2005;24:105–9. 16. Islam S, Cevik C, Madonna R, et al. Left ventricular assist devices and gastrointestinal bleeding: a narrative review of case reports and case series. Clin Cardiol. 2013;36:190–200. 17. Aggarwal A, Pant R, Kumar S, et al. Incidence and management of gastrointestinal bleeding with continuous flow assist devices. Ann Thorac Surg. 2012;93:1534–40. 18. Crow S, John R, Boyle A, et al. Gastrointestinal bleeding rates in recipients of nonpulsatile and pulsatile left ventricular assist devices. J Thorac Cardiovasc Surg. 2009;137:208–15. 19. Heyde E. Gastrointestinal bleeding in aortic stenosis. N Engl J Med. 1958;259:196–200. 20. Warkentin TE, Moore JC, Morgan DG. Aortic stenosis and bleeding gastrointestinal angiodysplasia: is acquired von Willebrand’s disease the link? Lancet. 1992;340:35–7. 21. Federici AB, Rand JH, Bucciarelli P. Acquired von Willebrand syndrome: data from an international registry. Thromb Haemost. 2000;84:345–9. 22. Tsai HM, Sussman II, Nagel RL. Shear stress enhances the proteolysis of von Willebrand factor in normal plasma. Blood. 1994;83:2171–9. 23. Siedlecki CA, Lestini BJ, Kottke-Marchant KK, et al. Sheardependent changes in the three-dimensional structure of human von Willebrand factor. Blood. 1996;88:2939–50. 24. Vincentelli A, Susen S, Le Tourneau T. Acquired von Willebrand syndrome in aortic stenosis. N Engl J Med. 2003;349:343–9. 25. Demirozu ZT, Radovancevic R, Hochman LF, et al. Arteriovenous malformation and gastrointestinal bleeding in patients with the Heart-Mate II left ventricular assist device. J Heart Lung Transplant. 2011;30:849–53. 26. Hayes HM, Dembo LG, Larbalestier R, et al. Management options to treat gastrointestinal bleeding in patients supported on rotary left ventricular assist devices: a single-center experience. Artif Organs. 2010;34:703–6. 27. Lamberts SW, van der Lely AJ, de Herder WW, Hofland LJ. Octreotide. N Eng J Med. 1996;334:246–54. 28. Kurosaki M, Saegert W, Abe T, et al. Expression of vascular endothelial growth factor in growth hormone-secreting pituitary
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