Novel Use of Low-dose Thalidomide in Refractory Gastrointestinal Bleeding in Left Ventricular Assist Device Patients

Seng, Jun Jie Benjamin; Teo, Livia; Chan, Laura; Sim, David; Kerk, Ka Lee; Soon, Jia-Lin; Tan, Teing Ee; Sivathasan, Cumaraswamy; Lim, Choon Pin

doi:10.5301/ijao.5000620

Cited by 25 publications

(15 citation statements)

References 16 publications

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“…Prospective, randomized, and larger studies are underway to confirm these results (NCT01707225). Thalidomide and danazol also seem to decrease recurrent bleeding, 25–28 to be confirmed by prospective and larger studies. Recently, a pilot study reported a significant reduction of blood transfusions, bleeding‐related hospitalizations, and endoscopy procedures in LVAD's patients with refractory GI angiodysplasia related bleeding after intravenous infusion of a humanized monoclonal antibody against VEGF (bevacizumab Avastin) 29 .…”

Section: Discussionmentioning

confidence: 76%

Prevalence, management, and outcomes of haemorrhagic events in left ventricular assist device recipients

et al. 2022

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Aims Left ventricular assist devices (LVADs) have reduced the mortality of patients with advanced heart failure both as bridge-to-transplant and as destination therapy. However, LVADs are associated with various complications, including bleedings, which affect the prognosis. The aim of the study was to explore the prevalence, management, and outcomes of haemorrhagic adverse events in LVAD recipients. Methods and resultsWe conducted a retrospective, single-centre, cohort study including all patients who received an LVAD from January 2008 to December 2019 in our tertiary centre (Rangueil University Hospital, Toulouse, France). Bleeding events, death, and heart transplantation were collected from electronic medical files. Eighty-eight patients were included, and 43 (49%) presented at least one bleeding event. Gastrointestinal (GI) bleeding was the most frequent (n = 21, 24%), followed by epistaxis (n = 12, 14%) and intracranial haemorrhage (n = 9, 10%). Bleeding events were associated with increased mortality [hazard ratio (HR) 3.8, 95% confidence interval (CI) 1.5-9.3, P < 0.01], particularly in case of intracranial haemorrhage (HR 14.6, 95% CI 4.2-51.1, P < 0.0001). GI bleedings were associated with a trend towards increased mortality (HR 3.0, 95% CI 0.9-9.3, P = 0.05). Each bleeding episode multiplied the risk of death by 1.8 (95% CI 1.2-2.7, P < 0.01). Finally, only early bleedings (<9 months post-implantation) had an impact on mortality (HR 4.2, 95% CI 1.6-11.1, P < 0.01). Therapeutic management was mainly based on temporary interruption of anticoagulation and permanent interruption of antiplatelet therapy. Invasive management was rarely performed. Conclusions Haemorrhagic events in LVAD recipients are frequent and associated with increased mortality. GI bleedings are the most frequent, and intracranial haemorrhages the most associated with mortality. Management remains empirical requiring more research.

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Section: Discussionmentioning

confidence: 76%

Prevalence, management, and outcomes of haemorrhagic events in left ventricular assist device recipients

et al. 2022

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“…Both somatostatin and octreotide inhibit GI bleeding by increasing platelet aggregation, decreasing splanchnic blood flow, downregulating the formation of vascular endothelial growth factor and increasing GI vascular bed resistance 38). Thalidomide has also been used to treat angiodysplasias in LVAD patients because of its anti-angiogenic effects 39). Another option for medical therapy is digoxin which inhibits HIF-1α synthesis 40).…”

Section: Complications Of Lvadsmentioning

confidence: 99%

Left Ventricular Assist Devices (LVADS): History, Clinical Application and Complications

Eisen

2019

Korean Circ J

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Congestive heart failure is a major cause of morbidity and mortality as well as a major health care cost in the developed world. Despite the introduction of highly effective heart failure medical therapies and simple devices such as cardiac resynchronization therapy that reduce mortality, improve cardiac function and quality of life, there remains a large number of patients who do not respond to these therapies or whose heart failure progresses despite optimal therapy. For these patients, cardiac transplantation is an option but is limited by donor availability as well as co-morbidities which may limit survival post-transplant. For these patients, left ventricular assist devices (LVADs) offer an alternative that can improve survival as well as exercise tolerance and quality of life. These devices have continued to improve as technology has improved with substantially improved durability of the devices and fewer post-implant complications. Pump thrombosis, stroke, gastrointestinal bleeding and arrhythmias post-implant have become less common with the newest devices, making destination therapy where ventricular assist device are implanted permanently in patients with advanced heart failure, a reality and an appropriate option for many patients. This may offer an opportunity for long term survival in many patients. As the first of the totally implantable devices are introduced and go to clinical trials, LVADs may be introduced that may truly be alternatives to cardiac transplantation in selected patients. Post-implant right ventricular failure remains a significant complication and better ways to identify patients at risk as well as to manage this complication must be developed.

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“…In patients with refractory or recurrent GI-bleeding or in whom a lesion cannot be localized or treated by endoscopy, others approaches might be discussed according to the “2-hit model: these aiming to prevent or eradicate angiodysplasias and/or those aiming to reduce or prevent HMW-multimers defect. Data supporting the use of antiangiogenic drugs, mostly octreotide (52, 70–73) and thalidomide (74–76), are sparse and mostly limited to case reports and retrospective single-center studies. In constitutional VWD, recurrent GI-bleeding is an indication to start prophylaxis with intravenous infusion of VWF concentrates.…”

Section: Therapeutic Options For Bleeding Management Of Vad-patients:mentioning

confidence: 99%

Acquired von Willebrand Syndrome in Patients With Ventricular Assist Device

2019

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During the last decade the use of ventricular assist devices (VADs) for patients with severe heart failure has increased tremendously. However, flow disturbances, mainly high shear induced by the device is associated with bleeding complications. Shear stress-induced changes in VWF conformation are associated with a loss of high molecular weight multimers (HMW) of VWF and an increased risk of bleeding. This phenomenon and its cause will be elaborated and reviewed in the following.

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Novel Use of Low-dose Thalidomide in Refractory Gastrointestinal Bleeding in Left Ventricular Assist Device Patients

Abstract: Thalidomide appears to be a safe and effective option for management of refractory LVAD-related GIB. Monitoring for recurrent GIB should be performed closely following cessation of thalidomide therapy.

Cited by 25 publications

References 16 publications

Prevalence, management, and outcomes of haemorrhagic events in left ventricular assist device recipients

Prevalence, management, and outcomes of haemorrhagic events in left ventricular assist device recipients

Left Ventricular Assist Devices (LVADS): History, Clinical Application and Complications

Acquired von Willebrand Syndrome in Patients With Ventricular Assist Device

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