Propranolol for gastrointestinal bleeding in two patients with continuous flow left ventricle assist device

Propranolol for gastrointestinal bleeding in two patients with continuous flow left ventricle... Abstract Patients with continuous-flow left ventricle assist devices are at risk for gastrointestinal bleeding from angiodysplastic bowel lesions. Neoangiogenesis secondary to von Willebrand factor degradation and increased vascular endothelial growth factor (VEGF) signalling is likely related to their pathophysiology. We speculated that propranolol, known to downregulate VEGF signalling, could be beneficial in patients with recurrent bleeding episodes and anaemia. In this case report, we present a short-term outcome of 2 patients treated with propranolol. Continuous-flow left ventricle assist devices, Propranolol, Gastrointestinal bleeding INTRODUCTION Gastrointestinal bleeding occurs in 17–40% of patients with continuous-flow left ventricle assist devices (cf-LVADs). Angiodysplastic lesions are dilated thin-walled vessels combining capillaries and veins and are often the source of bleeding. The source of bleeding is confirmed in approximately 75% of patients, which is identified as arteriovenous malformations in 19–61% of cases, whereas recurrent bleeding is observed in 35–45% of patients [1, 2]. Degradation products of the von Willebrand factor are likely involved in the pathogenesis by increasing VEGF-mediated angiogenesis. Pharmacological treatment relies on ACE/ATIIR inhibitor, somatostatin analogue, thalidomide or androgen analogue therapy. Adverse side effects, cost and route of administration are some of the issues limiting their use [1]. Profound bleeding often requires temporary or permanent discontinuation of antiplatelet and anticoagulant therapy, which increases the risk for pump thrombosis. The role of novel oral anticoagulants in cf-LVAD patient management has also been proposed in the recent literature [2]. Propranolol, a non-selective beta-blocker, indicated in coronary artery disease and arrhythmia is also used in patients with hepatic cirrhosis and portal hypertension, where the reduced portal pressure is likely due to decreased cardiac output and splanchnic vasoconstriction [3]. Recently it has been successfully used for treating infantile haemangiomas that are vascular malformations characterized by endothelial proliferation and ectatic vessel lesions. The therapeutic mechanism might be related to vasoconstriction, inhibition of angiogenesis signalling, decreased renin production or increased apoptosis [4]. In a previous case report, it was stated that propranolol was effective for gastrointestinal bleeding in a patient with subaortic stenosis and Heyde’s syndrome [5]. We hypothesized that propranolol therapy could be effective in cf-LVAD patients with recurrent gastrointestinal bleeding and anaemia possibly by limiting splanchnic blood flow and reducing angiogenesis. We herein present the short-term outcome of 2 patients treated with warfarin (INR target 2–3) and aspirin 100 mg daily. CASES Patient 1: A 62-year-old man with ischaemic heart failure received a HeartWare® HVAD in January 2016. The patient suffered from anaemia and recurrent episodes of gastrointestinal bleeding and melaena. Gastroscopy, colonoscopy and capsule endoscopy did not reveal any source of bleeding in February 2017. Faecal samples were positive for haemoglobin, and gastrointestinal bleeding was considered the cause of anaemia. Aspirin was discontinued, and bisoprolol treatment was successfully replaced by propranolol. The patient’s haemoglobin levels improved. Mean haemoglobin was 105 g/l during 5 months before treatment and increased to 123 g/l during a 5-month follow-up period. The patient had no further signs of gastrointestinal bleeding. During bleeding episodes, warfarin was briefly discontinued, and the patient had several INR values below target. Time within the therapeutic range was 58% prior to propranolol therapy and 93% afterwards. Patient 2: A 63-year-old woman with ischaemic heart failure received a HeartWare® HVAD in August 2016 and was discharged after a prolonged hospital stay. The patient was examined for anaemia in April 2017. Gastroscopy, colonoscopy and capsule endoscopy were normal. Faecal content of blood was positive, and the anaemia was considered secondary to chronic gastrointestinal bleeding. Aspirin was stopped, and propranolol therapy was initiated. Aspirin therapy commenced 1 month later. Haemoglobin improved with no further episodes of melaena. Mean haemoglobin was 101 g/l during 4 months prior to treatment and increased to 119 g/l during a 4-month follow-up. The patient was on continuous warfarin therapy. Therapeutic range before propranolol therapy was 86% and 80% later. Both the patients suffered from iron deficiency that was corrected with intravenous iron infusions at least 1 month prior to propranolol therapy. Propranolol was started at 40 mg 3 times daily. Both the patients had received several units of red blood cells during the previous months before propranolol therapy but required none during later follow-up. PATIENT CONSENT Written informed consent was acquired from both patients who participated in this study. CONCLUSIONS Propranolol might be a safe and affordable alternative to other treatments in recurrent gastrointestinal bleeding in cf-LVAD patients. We aim to determine the possible underlying mechanisms in future studies. ACKNOWLEDGEMENTS Catharina Yesil is acknowledged for coordinating the LVAD patients. Conflict of interest: Karl Lemström and Jan Kiss have received educational grants from Medtronic, Finland. All other authors declare no conflict of interest. REFERENCES 1 Sieg A , Moretz J , Horn W , Jennings D. Pharmacotherapeutic management of gastrointestinal bleeding in patients with continuous-flow left-ventricular assist devices . Pharmacotherapy 2017 ; doi:10.1002/phar.2016. 2 Pollari F , Fischlein T , Fittkau M , Santarpino G. Anticoagulation with apixaban in a patient with a left ventricular assist device and gastrointestinal bleeding: a viable alternative to warfarin? J Thorac Cardiovasc Surg 2016 ; 151 : e79 – 81 . Google Scholar CrossRef Search ADS PubMed 3 Hobolth L , Bendtsen F , Hansen E , Møller S. Effects of carvedilol and propranolol on circulatory regulation and oxygenation in cirrhosis: a randomised study . Dig Liver Dis 2014 ; 46 : 251 – 6 . Google Scholar CrossRef Search ADS PubMed 4 Ji Y , Chen S , Xu C , Li L , Xiang B. The use of propranolol in the treatment of infantile haemangiomas: an update on potential mechanisms of action . Br J Dermatol 2015 ; 172 : 24 – 32 . Google Scholar CrossRef Search ADS PubMed 5 Schwartz J , Rozenfeld V , Habot B. Cessation of recurrent bleeding from gastrointestinal angiodysplasia, after beta blocker treatment in a patient with hypertrophic subaortic stenosis—a case history . Angiology 1992 ; 43 : 244 – 8 . Google Scholar CrossRef Search ADS PubMed © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Cardio-Thoracic Surgery Oxford University Press

Propranolol for gastrointestinal bleeding in two patients with continuous flow left ventricle assist device

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Publisher
Oxford University Press
Copyright
© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
ISSN
1010-7940
eISSN
1873-734X
D.O.I.
10.1093/ejcts/ezx455
Publisher site
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Abstract

Abstract Patients with continuous-flow left ventricle assist devices are at risk for gastrointestinal bleeding from angiodysplastic bowel lesions. Neoangiogenesis secondary to von Willebrand factor degradation and increased vascular endothelial growth factor (VEGF) signalling is likely related to their pathophysiology. We speculated that propranolol, known to downregulate VEGF signalling, could be beneficial in patients with recurrent bleeding episodes and anaemia. In this case report, we present a short-term outcome of 2 patients treated with propranolol. Continuous-flow left ventricle assist devices, Propranolol, Gastrointestinal bleeding INTRODUCTION Gastrointestinal bleeding occurs in 17–40% of patients with continuous-flow left ventricle assist devices (cf-LVADs). Angiodysplastic lesions are dilated thin-walled vessels combining capillaries and veins and are often the source of bleeding. The source of bleeding is confirmed in approximately 75% of patients, which is identified as arteriovenous malformations in 19–61% of cases, whereas recurrent bleeding is observed in 35–45% of patients [1, 2]. Degradation products of the von Willebrand factor are likely involved in the pathogenesis by increasing VEGF-mediated angiogenesis. Pharmacological treatment relies on ACE/ATIIR inhibitor, somatostatin analogue, thalidomide or androgen analogue therapy. Adverse side effects, cost and route of administration are some of the issues limiting their use [1]. Profound bleeding often requires temporary or permanent discontinuation of antiplatelet and anticoagulant therapy, which increases the risk for pump thrombosis. The role of novel oral anticoagulants in cf-LVAD patient management has also been proposed in the recent literature [2]. Propranolol, a non-selective beta-blocker, indicated in coronary artery disease and arrhythmia is also used in patients with hepatic cirrhosis and portal hypertension, where the reduced portal pressure is likely due to decreased cardiac output and splanchnic vasoconstriction [3]. Recently it has been successfully used for treating infantile haemangiomas that are vascular malformations characterized by endothelial proliferation and ectatic vessel lesions. The therapeutic mechanism might be related to vasoconstriction, inhibition of angiogenesis signalling, decreased renin production or increased apoptosis [4]. In a previous case report, it was stated that propranolol was effective for gastrointestinal bleeding in a patient with subaortic stenosis and Heyde’s syndrome [5]. We hypothesized that propranolol therapy could be effective in cf-LVAD patients with recurrent gastrointestinal bleeding and anaemia possibly by limiting splanchnic blood flow and reducing angiogenesis. We herein present the short-term outcome of 2 patients treated with warfarin (INR target 2–3) and aspirin 100 mg daily. CASES Patient 1: A 62-year-old man with ischaemic heart failure received a HeartWare® HVAD in January 2016. The patient suffered from anaemia and recurrent episodes of gastrointestinal bleeding and melaena. Gastroscopy, colonoscopy and capsule endoscopy did not reveal any source of bleeding in February 2017. Faecal samples were positive for haemoglobin, and gastrointestinal bleeding was considered the cause of anaemia. Aspirin was discontinued, and bisoprolol treatment was successfully replaced by propranolol. The patient’s haemoglobin levels improved. Mean haemoglobin was 105 g/l during 5 months before treatment and increased to 123 g/l during a 5-month follow-up period. The patient had no further signs of gastrointestinal bleeding. During bleeding episodes, warfarin was briefly discontinued, and the patient had several INR values below target. Time within the therapeutic range was 58% prior to propranolol therapy and 93% afterwards. Patient 2: A 63-year-old woman with ischaemic heart failure received a HeartWare® HVAD in August 2016 and was discharged after a prolonged hospital stay. The patient was examined for anaemia in April 2017. Gastroscopy, colonoscopy and capsule endoscopy were normal. Faecal content of blood was positive, and the anaemia was considered secondary to chronic gastrointestinal bleeding. Aspirin was stopped, and propranolol therapy was initiated. Aspirin therapy commenced 1 month later. Haemoglobin improved with no further episodes of melaena. Mean haemoglobin was 101 g/l during 4 months prior to treatment and increased to 119 g/l during a 4-month follow-up. The patient was on continuous warfarin therapy. Therapeutic range before propranolol therapy was 86% and 80% later. Both the patients suffered from iron deficiency that was corrected with intravenous iron infusions at least 1 month prior to propranolol therapy. Propranolol was started at 40 mg 3 times daily. Both the patients had received several units of red blood cells during the previous months before propranolol therapy but required none during later follow-up. PATIENT CONSENT Written informed consent was acquired from both patients who participated in this study. CONCLUSIONS Propranolol might be a safe and affordable alternative to other treatments in recurrent gastrointestinal bleeding in cf-LVAD patients. We aim to determine the possible underlying mechanisms in future studies. ACKNOWLEDGEMENTS Catharina Yesil is acknowledged for coordinating the LVAD patients. Conflict of interest: Karl Lemström and Jan Kiss have received educational grants from Medtronic, Finland. All other authors declare no conflict of interest. REFERENCES 1 Sieg A , Moretz J , Horn W , Jennings D. Pharmacotherapeutic management of gastrointestinal bleeding in patients with continuous-flow left-ventricular assist devices . Pharmacotherapy 2017 ; doi:10.1002/phar.2016. 2 Pollari F , Fischlein T , Fittkau M , Santarpino G. Anticoagulation with apixaban in a patient with a left ventricular assist device and gastrointestinal bleeding: a viable alternative to warfarin? J Thorac Cardiovasc Surg 2016 ; 151 : e79 – 81 . Google Scholar CrossRef Search ADS PubMed 3 Hobolth L , Bendtsen F , Hansen E , Møller S. Effects of carvedilol and propranolol on circulatory regulation and oxygenation in cirrhosis: a randomised study . Dig Liver Dis 2014 ; 46 : 251 – 6 . Google Scholar CrossRef Search ADS PubMed 4 Ji Y , Chen S , Xu C , Li L , Xiang B. The use of propranolol in the treatment of infantile haemangiomas: an update on potential mechanisms of action . Br J Dermatol 2015 ; 172 : 24 – 32 . Google Scholar CrossRef Search ADS PubMed 5 Schwartz J , Rozenfeld V , Habot B. Cessation of recurrent bleeding from gastrointestinal angiodysplasia, after beta blocker treatment in a patient with hypertrophic subaortic stenosis—a case history . Angiology 1992 ; 43 : 244 – 8 . Google Scholar CrossRef Search ADS PubMed © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

Journal

European Journal of Cardio-Thoracic SurgeryOxford University Press

Published: Dec 12, 2017

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