Gastrointestinal bleeding in patients with continuous-flow left ventricular assist devices: A comprehensive review.

BACKGROUND: Gastrointestinal bleeding is a major cause of morbidity that plagues the quality of life of patients supported on contemporary continuous-flow left ventricular assist devices (CF-LVADs). Despite benefits in survival and the nearly 50% reduction in complications provided by CF-LVADs, bleeding remains one of the most frequent adverse events with CF-LVAD implants. The CF-LVADs cause an increased risk of bleeding mainly due to the activation of the coagulation cascade. METHODS: A literature search was done using PubMed and Google Scholar from Inception to February 2022. Qualitative analyses of the articles retrieved were used to construct this review. This review attempts to provide a comprehensive summary of the epidemiology, pathophysiology, risk stratification, and management of gastrointestinal bleeding as a complication of CF-LVAD as well as propose an algorithm for diagnosis and treatment. RESULTS: Bleeding can occur at different sites in the gastrointestinal tract, the most common underlying pathology being arteriovenous malformations located in the upper gastrointestinal tract The increased prevalence of gastrointestinal (GI) bleeding in CF-LVAD patients has been attributed to the physiology of the LVAD itself, the use of anticoagulants, as well as patient comorbidities. Management involves pharmacologic and nonpharmacologic strategies. CONCLUSIONS: CF-LVAD-supported patients have a significant risk of GI bleeding that is mainly caused by arteriovenous malformations located in the upper GI tract. The increased prevalence of GI bleeding in CF-LVAD patients is attributed to several etiologies that include factors attributed to the device itself and extrinsic factors such as the use of anticoagulation.

Arteriovenous malformation in the adult mouse brain resembling the human disease.

OBJECTIVE: Brain arteriovenous malformations (bAVMs) are an important cause of hemorrhagic stroke. The underlying mechanisms are not clear. No animal model for adult bAVM is available for mechanistic exploration. Patients with hereditary hemorrhagic telangiectasia type 2 (HHT2) with activin receptor-like kinase 1 (ALK1; ACVRL1) mutations have a higher incidence of bAVM than the general population. We tested the hypothesis that vascular endothelial growth factor (VEGF) stimulation with regional homozygous deletion of Alk1 induces severe dysplasia in the adult mouse brain, akin to human bAVM. METHODS: Alk1(2f/2f) (exons 4-6 flanked by loxP sites) and wild-type (WT) mice (8-10 weeks old) were injected with adenoviral vector expressing Cre recombinase (Ad-Cre; 2 × 10(7) plaque forming units [PFU]) and adeno-associated viral vectors expressing VEGF (AAV-VEGF; 2 × 10(9) genome copies) into the basal ganglia. At 8 weeks, blood vessels were analyzed. RESULTS: Gross vascular irregularities were seen in Alk1(2f/2f) mouse brain injected with Ad-Cre and AAV-VEGF. The vessels were markedly enlarged with abnormal patterning resembling aspects of the human bAVM phenotype, displayed altered expression of the arterial and venous markers (EphB4 and Jagged-1), and showed evidence of arteriovenous shunting. Vascular irregularities were not seen in similarly treated WT mice. INTERPRETATION: Our data indicate that postnatal, adult formation of the human disease, bAVM, is possible, and that both genetic mutation and angiogenic stimulation are necessary for lesion development. Our work not only provides a testable adult mouse bAVM model for the first time, but also suggests that specific medical therapy can be developed to slow bAVM growth and potentially stabilize the rupture-prone abnormal vasculature.

Extensive Osler-Rendu disease in a breast cancer patient: increasing hepatic arteriovenous malformations under endocrine therapy mimicking liver metastases.

BACKGROUND: Undefined, increasing hepatic lesions are a common issue in the follow-up care of breast cancer patients and frequently result in invasive diagnostic procedures. CASE REPORT: This case report describes the diagnostic approach in the case of a 58-year-old breast cancer patient with a previously unknown visceral involvement of Osler-Rendu disease. The patient was admitted to our institution because of newly diagnosed, increasing hepatic lesions occurring during endocrine treatment with aromatase inhibitors. On the basis of ultrasound findings, secondary liver metastases were suspected. After a thorough clinical and imaging examination, we reviewed the literature on typical radiological findings of visceral involvement of Osler-Rendu disease, and the impact of endocrine treatment on arteriovenous malformations. Multislice computed tomography scan identified the hepatic lesions as arteriovenous malformations. In the current literature, there are no reports available on the interaction between aromatase inhibitors and arteriovenous malformations. However, some data do show an effect of endocrine therapy with estrogen/progesterone, or tamoxifen on arteriovenous malformations, although some of the results are partially contradictory. CONCLUSION: This case report demonstrates that for undefined hepatic lesions in breast cancer patients, extensive Osler-Rendu disease should be considered as a potential differential diagnosis. Furthermore, we discuss the possible influence of aromatase inhibitors on arteriovenous malformations.

Cervical vascular malformation as a cause of antepartum and intrapartum bleeding in three diethylstilbestrol-exposed progeny.

Adverse pregnancy outcome in diethylstilbestrol-exposed progeny has been described by many authors. These three cases demonstrate many of the features discussed in the literature as well as a previously unreported cause of antepartum and intrapartum bleeding: a cervical vascular malformation.