Heyde's syndrome: a challenging case of severe aortic stenosis and gastrointestinal bleeding.

We present the case of an elderly man with a history of diastolic congestive heart failure, severe aortic stenosis and atrial fibrillation, who presented with fatigue, weakness, coffee ground emesis and black tarry stool. Haemoglobin was 68 g/L. Lactate dehydrogenase was elevated at 1038. Evaluation by cardiology and gastroenterology specialists revealed reflux oesophagitis and a mild hiatal hernia on oesophagogastroduodenoscopy, normal colonoscopy and small bowel series without obstruction. Capsule endoscopy identified angiodysplasia in the small intestine.The patient was diagnosed with Heyde's syndrome based on the triad of severe aortic stenosis, gastrointestinal bleeding from angiodysplasia and acquired von Willebrand syndrome. The patient underwent transcatheter aortic valve replacement, resulting in the resolution of symptoms.Heyde's syndrome represents a challenging clinical entity requiring a multidisciplinary approach for accurate diagnosis and management. Early recognition, prompt intervention and interdisciplinary collaboration are crucial in optimising patient outcomes.

Standard of Care Versus Octreotide in Angiodysplasia-Related Bleeding (the OCEAN Study): A Multicenter Randomized Controlled Trial.

BACKGROUND & AIMS: Gastrointestinal angiodysplasias are vascular anomalies that may result in transfusion-dependent anemia despite endoscopic therapy. An individual patient data meta-analysis of cohort studies suggests that octreotide decreases rebleeding rates, but component studies possessed a high risk of bias. We investigated the efficacy of octreotide in reducing the transfusion requirements of patients with angiodysplasia-related anemia in a clinical trial setting. METHODS: The study was designed as a multicenter, open-label, randomized controlled trial. Patients with angiodysplasia bleeding were required to have had at least 4 red blood cell (RBC) units or parental iron infusions, or both, in the year preceding randomization. Patients were allocated (1:1) to 40-mg octreotide long-acting release intramuscular every 28 days or standard of care, including endoscopic therapy. The treatment duration was 1 year. The primary outcome was the mean difference in the number of transfusion units (RBC + parental iron) between the octreotide and standard of care groups. Patients who received at least 1 octreotide injection or followed standard of care for at least 1 month were included in the intention-to-treat analyses. Analyses of covariance were used to adjust for baseline transfusion requirements and incomplete follow-up. RESULTS: We enrolled 62 patients (mean age, 72 years; 32 men) from 17 Dutch hospitals in the octreotide (n = 31) and standard of care (n = 31) groups. Patients required a mean number of 20.3 (standard deviation, 15.6) transfusion units and 2.4 (standard deviation, 2.0) endoscopic procedures in the year before enrollment. The total number of transfusions was lower with octreotide (11.0; 95% confidence interval [CI], 5.5-16.5) compared with standard of care (21.2; 95% CI, 15.7-26.7). Octreotide reduced the mean number of transfusion units by 10.2 (95% CI, 2.4-18.1; P = .012). Octreotide reduced the annual volume of endoscopic procedures by 0.9 (95% CI, 0.3-1.5). CONCLUSIONS: Octreotide effectively reduces transfusion requirements and the need for endoscopic therapy in patients with angiodysplasia-related anemia. CLINICALTRIALS: gov, NCT02384122.

Angiodysplasia of the appendix: a diagnostic challenge and the importance of colonoscopy.

The case report discusses the challenges in diagnosing gastrointestinal bleeding of unknown origin, with angiodysplasia (AD) of the appendix being a rare cause. The report presents a case of a man in his late 60s who presented with vomiting, diarrhoea and rectal bleeding. As a result of the bleeding, the patient developed a type II myocardial infarction (MI), which had to be simultaneously managed further complicating the diagnostic process. Despite a normal CT angiogram, ongoing bleeding led to suspicion of AD, which was diagnosed using colonoscopy with limited bowel preparation. The patient underwent an open appendicectomy and was found to have AD of the tip of the appendix as the cause of the bleeding. The case highlights the limitations of CT angiography in haemodynamically unstable patients and subsequent importance of colonoscopy with bowel preparation in diagnosing rare causes of bleeding, even with limited bowel preparation, and the potential life-threatening consequences of untreated AD.

Gastrointestinal Angiodysplasia in Patients with Severe Aortic Stenosis: The Endoscopic Features of Heyde's Syndrome.

INTRODUCTION: Aortic stenosis (AS) is sometimes associated with gastrointestinal bleeding, and this phenomenon is known as Heyde's syndrome. Such bleeding is most often considered to originate from gastrointestinal angiodysplasias, but the frequency and endoscopic features of such bleeding remain unclear. This study aimed to determine the frequency and endoscopic features of gastrointestinal angiodysplasia in patients with severe AS. PATIENTS AND METHODS: In this multicenter, retrospective study, we evaluated consecutive patients who underwent transcatheter aortic valve implantation (TAVI) with severe AS from May 2016 to December 2019. We extracted the data on the clinicopathological features according to the status of anemia, the proportion of patients who underwent gastrointestinal endoscopic examinations and demonstrated gastrointestinal angiodysplasia, and identified the endoscopic features associated with such patients. RESULTS: In 325 patients, the rates of moderate/severe anemia (hemoglobin < 11 g/dL) were 52%. Regarding medicine, there were no significant differences between the patients with and without moderate/severe anemia. Patients were examined by esophagogastroduodenoscopy (21%), colonoscopy (12%), and balloon-assisted enteroscopy or small bowel capsule endoscopy (1.5%). Patients with moderate/severe anemia had significantly more angiodysplasia (38.3% vs. 7.7%; p < 0.0001) and active bleeding (23.4% vs. 0%; p < 0.01). Angiodysplasia was detected in 21 patients (stomach, n = 9; small intestine, n = 5, and colon, n = 10). CONCLUSIONS: The results suggest, for the first time, that patients with severe AS who underwent TAVI and moderate/severe anemia frequently had gastrointestinal angiodysplasia and active bleeding throughout the entire gastrointestinal tract.

Diagnostic accuracy of artificial intelligence-aided capsule endoscopy (TOP100) in overt small bowel bleeding.

BACKGROUND: Capsule endoscopy (CE) is the first-choice exploration in case of overt small bowel bleeding (SBB). An early CE is known to increase diagnostic yield, but long reading times may delay therapeutics. The study evaluates the diagnostic performance of the artificial intelligence tool TOP100 in patients with overt SBB undergoing early CE with Pillcam SB3. METHODS: Patients who underwent early CE (up to 14 days from the bleeding episode) for suspected overt SBB were included. One experienced endoscopist prospectively performed standard reading (SR) and a second blind experienced endoscopist performed a TOP100-based reading (TR). The primary endpoint was TR diagnostic accuracy for lesions with high bleeding potential (P2). RESULTS: A total of 111 patients were analyzed. The most common clinical presentation was melena (64%). CE showed angiodysplasias in 40.5% of patients (45/111). In per-patient analysis, TR showed a sensitivity of 90.48% (95% CI 82.09-95.80), specificity of 100% (95% CI 87.23-100) with a PPV of 100% (95% CI 94.01-100), NPV of 77.14% (95% CI 63.58-86.71) and diagnostic accuracy of 92.79 (86.29-96.84). At multivariate analysis, adequate intestinal cleansing was the only independent predictor of concordance between TR and SR (OR 2.909, p = 0.019). The median reading time for SR and TR was 23 min (18.0-26.8) and 1.9 min (range 1.7-2.1), respectively (p < 0.001). CONCLUSIONS: TOP100 provides a fast-reading mode for early CE in case of overt small bowel bleeding. It identifies most patients with active bleeding and angiodysplasias, aiding in the prioritization of therapeutic procedures. However, its accuracy in detecting ulcers, varices and P1 lesions seems insufficient.

Did angiodysplasia associated with heyde's syndrome disappear spontaneously?: a case report.

BACKGROUND: Heyde's syndrome can be easily overlooked or misjudged in clinical practice because it shares common clinical manifestations with multiple diseases as well as limited accuracy of several corresponding examinations for diagnosing Heyde's triad. Moreover, aortic valve replacement is often delayed in these patients due to the contradiction between anticoagulation and hemostasis. Herein, we present a rare case of atypical Heyde's syndrome. The patient's severe intermittent gastrointestinal bleeding was not completely cured even through a local enterectomy. In the absence of direct evidence of acquired von Willebrand syndrome (AVWS) or angiodysplasia, her long-standing gastrointestinal bleeding was finally stopped after receiving transcatheter aortic valve implantation (TAVI). CASE PRESENTATION: A 64-year-old female suffered from refractory gastrointestinal bleeding and exertional dyspnoea. A local enterectomy was performed owing to persistent hemorrhage and repeated transfusions; subsequently, histological examination revealed angiodysplasia. Heyde's syndrome was not suspected until 3 years later, at which time the patient started bleeding again and was also found to have severe aortic valve stenosis upon echocardiography. TAVI was consequently performed when the patient was in a relatively stable condition even though the predisposition to bleed, but there was no evidence of angiodysplasia and AVWS during angiography at that time. The patient's above symptoms were significantly relieved after TAVI and followed up for 2 years without any significant ischemic or bleeding events. CONCLUSIONS: The visible characteristics of angiodysplasia or a shortage of HMWM-vWFs should not be indispensable for the clinical diagnosis of Heyde's syndrome. Enterectomy could be a bridging therapy for aortic valve replacement in patients with severe hemorrhage, and TAVI may be beneficial for moderate to high surgical-risk patients even if they have a potential risk of bleeding.

Gastrointestinal bleeding in von Willebrand patients: special diagnostic and management considerations.

INTRODUCTION: Severe and recurrent gastrointestinal (GI) bleeding caused by angiodysplasia is a significant problem in patients with von Willebrand disease (VWD) and in those with acquired von Willebrand syndrome (AVWS). At present, angiodysplasia-related GI bleeding is often refractory to standard treatment including replacement therapy with von Willebrand factor (VWF) concentrates and continues to remain a major challenge and cause of significant morbidity in patients despite advances in diagnostics and therapeutics. AREAS COVERED: This paper reviews the available literature on GI bleeding in VWD patients, examines the molecular mechanisms implicated in angiodysplasia-related GI bleeding, and summarizes existing strategies in the management of bleeding GI angiodysplasia in patients with VWF abnormalities. Suggestions are made for further research directions. EXPERT OPINION: Bleeding from angiodysplasia poses a significant challenge for individuals with abnormal VWF. Diagnosis remains a challenge and may require multiple radiologic and endoscopic investigations. Additionally, there is a need for enhanced understanding at a molecular level to identify effective therapies. Future studies of VWF replacement therapies using newer formulations as well as other adjunctive treatments to prevent and treat bleeding will hopefully improve care.

Von Willebrand disease (VWD) is the most common inherited bleeding disorder. It is caused by problems with von Willebrand factor (VWF), a protein in blood that helps stop bleeding. People with VWD either have low levels of VWF or VWF that does not work properly. The disease causes bleeding symptoms in 1 in 1000 individuals. Three main types of VWD exist. Depending on the type, people can have minimal symptoms or serious bleeding that needs hospital care.Patients with severe VWD may often experience repeated bleeding from the gastrointestinal tract. This is usually due to the formation of abnormal fragile vessels (malformations) called angiodysplasia, which have been linked to the absence or abnormal function of VWF. These fragile vessels are very difficult to find and diagnose. At present, available treatments for angiodysplasia, including long-term VWF replacement therapy, are not very effective. As a result, VWD patients with angiodysplasia have a poor quality of life.More research is needed to better evaluate current treatments and explore the contribution of abnormal VWF in the development of angiogenesis and angiodysplasia in VWD which may reveal new targets for treatment.

Colonoscopic and Clinical Features of Colonic Angiodysplasia: A Study in 54 Patients.

OBJECTIVES: Colonic angiodysplasia is a rare disease, it is nevertheless a common cause of lower gastrointestinal (GI) bleeding in older adults. The study summarized the colonoscopic and clinical features of colonic angiodysplasia to raise awareness among endoscopists regarding this disease. MATERIALS AND METHODS: We performed a retrospective study of enrolled patients diagnosed with colonic angiodysplasia between September 2013 and April 2022. Clinical and colonoscopic features of the patients with active bleeding were analyzed and compared with those of patients without bleeding. The comparisons were also conducted between the patients with active lower GI bleeding caused by colonic angiodysplasia and those by other diseases. RESULTS: In total, 54 eligible patients were included in this study; 55.55% of the participants were aged over 60 years. Ten patients (3 men and 7 women) with colonic angiodysplasia suffered from active lower GI bleeding, which was mainly located in the left and total colon. The patients with type 2 diabetes mellitus, radiotherapy history, antiplatelet drug use, and multiple lesions were more likely to endure lower GI bleeding. The duration between bleeding and admission was longer in the colonic angiodysplasia group than in the other diseases group ( P = 0.043). In the colonic angiodysplasia group, bleeding relapsed in 3 patients, and the recurrence rate was higher than in the other diseases group ( P < 0.001). CONCLUSION: Endoscopists should perform colonoscopy scrupulously and consider colonic angiodysplasia as a differential diagnosis in patients with lower GI bleeding, especially for older women and adults with chronic diseases, such as type 2 diabetes mellitus.

Tranexamic acid may be a useful pharmacotherapy for endoscopically resistant small bowel angiodysplasia.

Small bowel angiodysplasia (SBAD) is reported to account for nearly 50% of cases of small bowel bleeding. When SBAD occurs frequently, it is difficult to treat all the angiodysplasias endoscopically, and gastrointestinal bleeding often recurs. Hormone therapy, somatostatin analogs, thalidomide and vascular endothelial growth factor (VEGF)-neutralizing antibodies have been reported to reduce gastrointestinal angiodysplasia (GIAD) bleeding. However, there is no strong evidence to recommend them. Also, there are no guidelines for their use. Hereditary hemorrhagic telangiectasia (HHT) is a hereditary disease caused by abnormalities in VEGF, resulting in multiple GIADs. A treatment guideline has been created for GIAD in HHT, and the use of tranexamic acid, an antifibrinolytic agent, is the first recommendation pharmacotherapy for GIAD with gastrointestinal bleeding that is difficult to treat endoscopically. It has been reported that fibrinolysis is accelerated in GIAD patients who are not HHT, similar to HHT patients. The use of tranexamic acid for gastric antral vascular ectasia in GIAD has been reported to be useful. However, there are very few reports of its use for SBAD. There are concerns with tranexamic acid use regarding the development of thrombosis/embolism, but there are few reports of such side effects. Future clinical trials including tranexamic acid for SBAD are desired.

Gastrointestinal angiodysplasias diagnosed using video capsule endoscopy in 15 dogs.

BACKGROUND: Angiodysplasia (AGD) is rarely diagnosed in dogs with gastrointestinal bleeding (GIB) and is reported in case reports in dogs. OBJECTIVE: Describe signalment, clinical and diagnostic features of dogs with gastrointestinal (GI) AGD diagnosed by video capsule endoscopy (VCE). ANIMALS: Dogs with overt or suspected GIB which underwent VCE. METHODS: Dogs for which a VCE was submitted for overt or suspected GIB from 2016 to 2021 were selected retrospectively. Medical records and full-length VCE recordings where AGDs were initially detected, were reviewed by 2 trained internists. AGD was considered definitive if 2 readers detected it. Signalment, clinical signs, blood work, medications, concurrent diseases, findings of previous conventional endoscopy, and surgical exploration (if applicable) of dogs with AGD were recorded. RESULTS: Definitive AGD was diagnosed in 15 of 291 (5%) dogs (12 males, 3 females). Twelve (80%) had overt GIB, 11 (73%) had hematochezia, and 6 (40%) had microcytic and hypochromic anemia. AGD was missed by conventional endoscopy in 9/9 dogs and exploratory surgery in 3/3 dogs. Thirteen capsules were administered by mouth (1 incomplete study), and 2 via endoscopy directly into the duodenum. AGD was visualized in the stomach of 3 dogs, in the small intestine of 4, and in the colon of 13 dogs. CONCLUSION AND CLINICAL IMPORTANCE: Although rare, AGD should be considered in dogs with suspected GIB after a negative conventional endoscopy or surgical exporation. Video capsuel endoscopy appears to be a sensitive test to identify AGD within the GI tract.

Convolutional neural network-based segmentation network applied to image recognition of angiodysplasias lesion under capsule endoscopy.

BACKGROUND: Small intestinal vascular malformations (angiodysplasias) are common causes of small intestinal bleeding. While capsule endoscopy has become the primary diagnostic method for angiodysplasia, manual reading of the entire gastrointestinal tract is time-consuming and requires a heavy workload, which affects the accuracy of diagnosis. AIM: To evaluate whether artificial intelligence can assist the diagnosis and increase the detection rate of angiodysplasias in the small intestine, achieve automatic disease detection, and shorten the capsule endoscopy (CE) reading time. METHODS: A convolutional neural network semantic segmentation model with a feature fusion method, which automatically recognizes the category of vascular dysplasia under CE and draws the lesion contour, thus improving the efficiency and accuracy of identifying small intestinal vascular malformation lesions, was proposed. Resnet-50 was used as the skeleton network to design the fusion mechanism, fuse the shallow and depth features, and classify the images at the pixel level to achieve the segmentation and recognition of vascular dysplasia. The training set and test set were constructed and compared with PSPNet, Deeplab3+, and UperNet. RESULTS: The test set constructed in the study achieved satisfactory results, where pixel accuracy was 99%, mean intersection over union was 0.69, negative predictive value was 98.74%, and positive predictive value was 94.27%. The model parameter was 46.38 M, the float calculation was 467.2 G, and the time length to segment and recognize a picture was 0.6 s. CONCLUSION: Constructing a segmentation network based on deep learning to segment and recognize angiodysplasias lesions is an effective and feasible method for diagnosing angiodysplasias lesions.

Jejunal Angiodysplasia in an Elderly Patient with Aortic Stenosis: Significance of Von Willebrand Factor as an Etiologic Factor.

Heyde's syndrome is a disease in which patients with aortic stenosis (AS) bleed from angiodysplasia. An 80-year-old woman with a history of severe AS was referred to our hospital with melena and anemia. The patient underwent jejunal resection after repeated blood transfusions. A pathological examination revealed angiodysplasia, and the patient's plasma lacked high-molecular-weight von Willebrand factor (VWF) multimers, leading to the diagnosis of Heyde's syndrome. The patient underwent transcatheter aortic valve implantation (TAVI) one year after the diagnosis, and the VWF index recovered. This is a valuable case in which the pathological analysis of angiodysplasia associated with Heyde's syndrome was possible.

Special considerations in GI bleeding in VWD patients.

Gastrointestinal (GI) bleeding is an important cause of morbidity and mortality in von Willebrand disease (VWD). It has been noted that GI bleeding caused by angiodysplasia is overrepresented in VWD patients compared to other causes. The bleeding from angiodysplasia is notoriously difficult to treat; recurrences and rebleeds are common. A growing body of basic science evidence demonstrates that von Willebrand factor negatively regulates angiogenesis through multiple pathways. VWD is clinically highly associated with angiodysplasia. The predisposition to angiodysplasia likely accounts for many of the clinical difficulties related to managing GI bleeding in VWD patients. Diagnosis and treatment are challenging with the current tools available, and much further research is needed to further optimize care for these patients with regard to acute treatment, prophylaxis, and adjunctive therapies. In this review we provide an overview of the available literature on GI bleeding in VWD and explore the molecular underpinnings of angiodysplasia-related GI bleeding. Considerations for diagnostic effectiveness are discussed, as well as the natural history and recurrence of these lesions and which therapeutic options are available for acute and prophylactic management.

How to manage lower gastrointestinal bleeding in 2022?

Lower gastrointestinal bleeding (LGIB), originating mainly in the colon, rectum and anus, occurs most often in older patients (7th decade) with co-morbidity, half of whom have coagulation abnormalities due to anti-coagulant or anti-aggregant therapy. In three cases out of four, bleeding regresses spontaneously but can recur in up to one third of patients. The main causes are diverticular disease, vascular disorders (hemorrhoids, angiodysplasia) and colitis. Ten to 15% of patients present in hypovolemic shock. The main problem is to determine the precise location and etiology of bleeding. First-line steps include correction of hemodynamics, correction of coagulation disorders and transfusion, as necessary. Rectal digital examination allows differentiation between melena and hematochezia. In patients with severe LGIB, upper endoscopy can eliminate upper gastro-intestinal bleeding (UGIB). Computerized tomography (CT) angiography can pinpoint the source. If contrast material extravasates, the therapeutic strategy depends on the cause of bleeding and the general status of the patient: therapeutic colonoscopy, arterial embolization and/or surgery. In the absence of severity criteria (Oakland score≤10), ambulatory colonoscopy should be performed within 14 days. Discontinuation of anticoagulant and/or antiplatet therapy should be discussed case by case according to the original indications.

Efficacy of pharmacologic treatment for treating gastrointestinal angiodysplasias-related bleeding: a systematic review and meta-analysis.

INTRODUCTION: We evaluated the efficacy of pharmacologic treatments for patients with overt or occult bleeding due to gastrointestinal angiodysplasias (GIADs). METHODS: A systematic computer-aided literature search across Medline, Cochrane, Scopus and Embase databases was performed. Studies evaluating pharmacologic treatments for patients presenting with GIADs-related overt or occult bleeding were included. Post-treatment rebleeding was the primary outcome. Need for red blood cells (RBC) transfusion, post-treatment hemoglobin levels and adverse events rate comprised secondary outcomes. Results are presented as odds ratio (OR), mean difference (MD) or pooled rates (%) with 95% confidence intervals (95%CI). RESULTS: Four types of pharmacologic treatment were identified (25 studies): somatostatin analogs, hormonal therapy, thalidomide and angiogenesis inhibitors. Pharmacologic treatment of any kind led to significantly reduced bleeding episodes [OR (95% CI), 0.08 (0.04-0.18)]. No pharmacologic treatment was superior to others ( P = 0.46). Overall, pooled rebleeding rate post-treatment was 34% (26-43%). Similarly, significantly fewer patients required RBC transfusion during the post-treatment period [0.03 (0.03-0.07)], with no differences among various treatments ( P = 0.83), yielding an overall pooled transfusion rate of 33% (19-46%). Administration of pharmacological treatment led to significant improvement in terms of hemoglobin levels [MD (95% CI), 3.21 g/dL (2.42-3.99)]. The pooled rate of adverse events was 32% (22-42%). CONCLUSION: In patients with GIADs administration of any pharmacologic treatment significantly decreases rebleeding episodes and transfusions leading to higher hemoglobin values. One-third of them experience at least one adverse event related to the treatment.

Heyde's syndrome: a systematic review of case reports.

OBJECTIVE: Heyde's syndrome (HS), a rare condition characterised by a unique relationship between severe aortic stenosis and angiodysplasia, is often diagnosed late increasing the risk for a prolonged hospital course and mortality in the elderly. The leading hypothesis explaining the aetiology of HS is acquired von Willebrand syndrome (AVWS) but not all studies support this claim. While individual cases of HS have been reported, here we present the first systematic review of case reports and focus on the prevalence of AVWS. DESIGN: A systematic search was conducted through PubMed/MEDLINE, CINAHL-EBSCO, Web of Science and Google Scholar since inception. The resulting articles were screened by two independent reviewers based on inclusion criteria that the article must be a case report/series or a letter to the editor in English describing HS in an adult patient. RESULTS: Seventy-four articles encompassing 77 cases met the inclusion criteria. The average age was 74.3±9.3 years old with a slight female predominance. The small intestine, especially the jejunum, was the most common location for bleeding origin. Capsule endoscopy and double balloon enteroscopy were superior at identifying bleeding sources than colonoscopy (p=0.0027 and p=0.0095, respectively) and oesophagogastroduodenoscopy (p=0.0006 and p=0.0036, respectively). The mean duration from symptom onset to diagnosis/treatment of HS was 23.8±39 months. Only 27/77 cases provided evidence for AVWS. Surgical and transcutaneous aortic valve replacement (AVR) were superior at preventing rebleeding than non-AVR modalities (p<0.0001). CONCLUSION: Further research is warranted for a stronger understanding and increased awareness of HS, which may hasten diagnosis and optimal management.