• Heyde syndrome
• acquired von Willebrand syndrome
• aortic stenosis
• semiautomatic von Willebrand factor multimer analysis

• Humans
• Male
• Transcatheter Aortic Valve Replacement/methods
• Aged
• Aortic Valve Stenosis/surgery
• Aortic Valve Stenosis/complications
• von Willebrand Diseases/diagnosis
• von Willebrand Diseases/complications
• Angiodysplasia/diagnosis
• von Willebrand Factor/analysis
• Syndrome

• Nationwide Readmissions Database
• aortic stenosis
• noncardiac surgery
• transcatheter aortic valve replacement

• Humans
• Transcatheter Aortic Valve Replacement/adverse effects
• Female
• Aortic Valve Stenosis/surgery
• Aortic Valve Stenosis/diagnostic imaging
• Aortic Valve Stenosis/physiopathology
• Time Factors
• Male
• Risk Factors
• Aged
• Aged, 80 and over
• Risk Assessment
• Databases, Factual
• Treatment Outcome
• United States/epidemiology
• Postoperative Complications/epidemiology
• Postoperative Complications/etiology
• Time-to-Treatment
• Retrospective Studies
• Patient Readmission
• Aortic Valve/surgery
• Aortic Valve/diagnostic imaging
• Aortic Valve/physiopathology
• Surgical Procedures, Operative/adverse effects

• aortic stenosis
• noncardiac surgery
• transcatheter aortic valve replacement

• Humans
• Aged
• Transcatheter Aortic Valve Replacement/adverse effects
• Retrospective Studies
• Prevalence
• Risk Factors
• Aortic Valve Stenosis/epidemiology
• Aortic Valve Stenosis/surgery
• Aortic Valve Stenosis/complications
• Treatment Outcome
• Aortic Valve/surgery
• Heart Valve Prosthesis Implantation/adverse effects

• Anaemia
• Aortic stenosis
• Case report
• Gastrointestinal bleeding
• Heyde’s syndrome
• Transcatheter aortic valve implantation

• Aortic valvuloplasty
• bilateral transradial access
• severe aortic stenosis
• transradial access
• valvular disease in the elderly

• GI bleed management in CF-LVADs
• arteriovenous malformations
• continuous-flow left ventricular assist devices
• gastrointestinal bleeds
• octreotide

• Aged, 80 and over
• Aortic Valve Stenosis/surgery
• Child
• Cohort Studies
• Female
• Humans
• Male
• Prospective Studies
• Transcatheter Aortic Valve Replacement/adverse effects
• Transcatheter Aortic Valve Replacement/methods
• Treatment Outcome

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.

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.

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).

Further research is warranted for a stronger understanding and increased awareness of HS, which may hasten diagnosis and optimal management.

• angiodysplasia
• diagnostic and therapeutic endoscopy
• gastrointestinal bleeding
• small bowel enteroscopy

•

Vascular and bleeding events remain frequent after balloon aortic valvuloplasty.

Vascular and bleeding events remain the main complications after balloon aortic valvuloplasty (BAV). While BAV is usually performed with per procedural heparin injection, BAV performed without heparin may reduce hemorrhagic events. We aimed to determine whether vascular and bleeding complications may be reduced with BAV performed without heparin.

This randomized, double-blind, placebo-controlled study was conducted from January 2013 to September 2016. Patients were randomly assigned to placebo or intravenous unfractionated heparin (UH) 50 IU/kg bolus during the procedure. The primary endpoint included major vascular, bleeding and ischemic complications (stroke, transient ischemic attack, myocardial infarction) according to VARC-2 criteria.

Among 89 randomized patients, 82 completed the study (n = 39 in the UH group and n = 43 in the placebo group). At baseline, diabetes, sex male and renal failure were more frequent in the UH group and peripheral artery disease was more frequent in the placebo group. The primary endpoint was achieved in 7 patients (8.5%), 1 in the placebo group (2.3%) versus 6 in the UH group (15.4%). After adjustment on diabetes, sex, renal failure, peripheral artery disease, percutaneous closure device and chronic obstructive pulmonary disease, UH utilization was associated with a significant risk of major vascular, bleeding and ischemic complications (primary endpoint) (_adjOR: 11.9; 95%CI: 1.2–117.2; p = 0.03). Hospitalization length was lower in the placebo group compared to the UH group (p = 0.03).

BAV without per procedural UH was associated with a reduction of major VC and bleeding events without increasing the ischemic risk and with a shorter hospitalization length.

Heyde syndrome is the association between gastrointestinal (GI) bleeding from intestinal angiodysplasia (IA) and aortic stenosis (AS). Although the course of disease progression that links AS and GI bleeding has not been determined, overlaps among AS, intestinal dysplasia, and acquired von Willebrand's syndrome is thought to result in GI bleeding. Proper repair of the aortic valve can result in significant improvement of GI bleeding and its recurrence. Herein, we are reporting this rare case, in which a patient with moderate AS on echocardiogram presents with recurrent GI bleeding from multiple IA in the setting of elevated factor VIII levels, to propose a theory that angiodysplasia could potentially develop due to intermittent, recurrent low-grade obstruction of submucosal veins at the level of the muscularis propria secondary to venous thrombosis related to elevated factor VIII levels.

• Angiodysplasia
• aortic stenosis
• case report
• hemorrhage
• heyde syndrome

von Willebrand factor (VWF) is an adhesive protein involved in primary hemostasis and facilitates platelet adhesion to sites of vascular injury, thereby promoting thrombus formation. VWF exists in plasma as multimers of increasing size, with the largest (high molecular weight; HMW) expressing the greatest functional activity. A deficiency of VWF is associated with a bleeding disorder called von Willebrand disease (VWD), whereas an excess of VWF, in particular the HMW forms, is associated with thrombosis. ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif-13), also known as VWF-cleaving protease, functions to moderate the activity of VWF by cleaving multimers of VWF and limiting the expression of the largest multimers of VWF. A deficiency of ADAMTS13 is therefore associated with an excess of (HMW forms of) VWF, and thus thrombosis. Indeed, any disturbance of the VWF/ADAMTS13 ratio or ‘axis’ may be associated with pathophysiological processes, including prothrombotic tendency. However, both thrombosis or bleeding may be associated with such disturbances, depending on the presenting events. This review evaluates the relationship of VWF and ADAMTS13 with cardiac disease, including cardiac failure, and associated pathophysiology.

• ADAMTS13
• cardiac failure
• endothelium
• von Willebrand factor

• Anemia
• Bleeding
• Hematologic malignancy
• Hemorrhage
• Platelet transfusion
• Primary hemostasis
• Thrombocytopenia

Heyde syndrome is a multisystem disorder characterized by the classical triad of aortic stenosis, gastrointestinal (GI) angiodysplasias, and acquired von Willebrand syndrome. GI angiodysplasias, common in older patients, are tortuous, thin-walled blood vessels seen in the mucosa or submucosa of the GI tract and are highly prone to rupture resulting in GI bleeds. In this case report, we describe an elderly female with a past medical history of end-stage renal disease and chronic anemia who presented to the emergency department (ED) with complaints of dark-tarry stools and associated abdominal cramping. Patient reported a history of dark-tarry stools and multiple blood transfusions in the past, secondary to severe anemia. An inpatient echocardiogram was performed, revealing severe aortic stenosis. Additionally, gastroenterology was consulted for esophagogastroduodenoscopy and colonoscopy, which were negative for active bleeding. About a year ago, the patient underwent capsule endoscopy at an outlying facility, which was positive for angiodysplasia. Therefore, due to high clinical suspicion, presence of aortic stenosis, and GI angiodysplasia, a platelet function assay was ordered. It was found to be abnormal, pointing to the presence of acquired von Willebrand syndrome. Hence, a diagnosis of Heyde syndrome was established. The patient gradually improved and was discharged with a follow-up appointment with the cardiologist for a possible transcatheter aortic valve replacement procedure. The patient underwent the procedure without complications, after which she did not report episodes of GI bleeding. In this case report, we discuss the presentation, pathophysiology, diagnostic approach, and management of patients with Heyde syndrome.

• aortic stenosis
• gastrointestinal bleeding
• von Willebrand disorder

• Cardiovascular Diseases/diagnosis
• Cardiovascular Diseases/epidemiology
• Cardiovascular Diseases/therapy
• Gastrointestinal Diseases/diagnosis
• Gastrointestinal Diseases/epidemiology
• Gastrointestinal Diseases/therapy
• Humans
• Inflammation

Heyde syndrome is a triad of bleeding colonic angiodysplasia, aortic stenosis, and acquired coagulopathy. It is most commonly seen in the elderly between 60-80 years of age. We present a case of Heyde syndrome presenting with severe anemia secondary to bleeding angiodysplasia or arteriovenous malformations (AVM) in the lower gastrointestinal (GI) tract.

• acquired coagulopathy
• acquired vwf factor deficiency
• anemia
• aortic stenosis
• arteriovenous malformations
• colonic angiodysplasia
• heyde syndrome

• Angiodysplasia
• Aortic stenosis
• Cardiac surgery
• Gastrointestinal bleeding
• Heyde’s syndrome
• von willebrand

• Heyde syndrome
• acquired Von Willebrand disease
• aortic stenosis
• perioperative
• von Willebrand factor

• Aortic valve stenosis
• Cerebral ischemia
• Embolism

Heyde syndrome is characterized by an association between gastrointestinal (GI) bleeding and calcific aortic stenosis (AS). Although the course of disease progression that links AS and GI bleeding has not been determined, overlaps among AS, intestinal dysplasia, and acquired von Willebrand's syndrome are thought to result in GI bleeding. Aortic valve repair in some patients has been reported to result in marked improvement or the complete resolution of signs and symptoms of Heyde syndrome. The prevalence of Heyde syndrome is higher among elderly persons than among other age groups, suggesting that a degenerative process may be a significant factor in the disease progression. This report describes a patient with Heyde syndrome, as well as a review of the current literature. 

• aortic stenosis
• gastrointestinal bleeding
• heyde syndrome

• angiodysplasia
• angiopoietin-2
• aortic valve stenosis
• endothelial cells
• von Willebrand factor

• Angiodysplasia
• Aortic Valve Stenosis/surgery
• Cell Proliferation
• Humans
• von Willebrand Diseases
• von Willebrand Factor

• Acquired Von Willebrand Syndrome
• Von Willebrand Factor

Heyde syndrome manifests as aortic stenosis associated with gastrointestinal bleeding. We describe the case of a 64-year-old man who came to the emergency room due to acute heart failure and intermittent gastrointestinal bleeding. Treatment involves initial correction of anemia and heart failure followed by aortic valve replacement. The prosthesis used depends on the characteristics of each patient and valve replacement allows the resolution of bleeding in most cases. Gastrointestinal bleeding in patients with aortic stenosis is associated with severity of the valve obstruction. A mechanical prosthesis was used with no recurrent bleeding even with the need for lifelong anticoagulation therapy.

• Anemia
• Aortic Valve Stenosis
• Gastrointestinal Hemorrhage
• Heart Failure
• Heart Valve Prosthesis

• Heyde Syndrome
• TAVI
• aortic valve stenosis
• von Willebrand disease

• Aged
• Angiodysplasia/complications
• Angiodysplasia/etiology
• Aortic Valve/surgery
• Aortic Valve Stenosis/complications
• Aortic Valve Stenosis/etiology
• Aortic Valve Stenosis/surgery
• Calcinosis/complications
• Calcinosis/surgery
• Female
• Gastrointestinal Hemorrhage/etiology
• Humans
• Transcatheter Aortic Valve Replacement
• von Willebrand Diseases/etiology

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Angiodysplasia/complications
• Angiodysplasia/epidemiology
• Aortic Valve Stenosis/complications
• Aortic Valve Stenosis/surgery
• Cause of Death/trends
• Databases, Factual
• Female
• Gastrointestinal Hemorrhage/complications
• Gastrointestinal Hemorrhage/epidemiology
• Hospital Mortality/trends
• Humans
• Incidence
• Inpatients
• Male
• Middle Aged
• Postoperative Complications/epidemiology
• Propensity Score
• Registries
• Retrospective Studies
• Risk Factors
• Survival Rate/trends
• Syndrome
• Time Factors
• Transcatheter Aortic Valve Replacement
• United States/epidemiology
• Young Adult

• Aged
• Aged, 80 and over
• Anemia/diagnosis
• Anemia/drug therapy
• Anemia/etiology
• Angiodysplasia/complications
• Angiodysplasia/diagnosis
• Angiodysplasia/drug therapy
• Blood Transfusion
• Drug Combinations
• Ethinyl Estradiol/administration & dosage
• Ethinyl Estradiol/adverse effects
• Female
• Gastrointestinal Agents/administration & dosage
• Gastrointestinal Agents/adverse effects
• Gastrointestinal Hemorrhage/diagnosis
• Gastrointestinal Hemorrhage/drug therapy
• Gastrointestinal Hemorrhage/etiology
• Hemoglobins/metabolism
• Humans
• Length of Stay
• Levonorgestrel/administration & dosage
• Levonorgestrel/adverse effects
• Male
• Patient Admission
• Recurrence
• Severity of Illness Index
• Time Factors
• Treatment Outcome

Heyde’s syndrome is a well-documented entity in the medical literature that can result in life-threatening gastrointestinal (GI) bleeding. It is a syndrome that is characterized by the combination of GI angioectasias and aortic stenosis. In most cases, the GI angioectasias resolve entirely with correction of the stenotic valve by way of total aortic valve replacement (TAVR). Rarely will cases recur after TAVR. Our case consists of an 84-year-old woman who presented with three new gastric angioectasias several months after undergoing TAVR. This is an exceedingly rare presentation of Heyde’s syndrome. To our knowledge this is the first such case reported in the medical literature.

Heyde’s syndrome describes an association between aortic stenosis and a predisposition to bleeding from intestinal angiodysplasia resulting from acquired von Willebrand disease.

We present the case of an 82-year-old woman with recurrent intestinal bleeding, severe anaemia and secondary myocardial infarction. Investigation identified ileal angiectasia as the source of haemorrhage. As echocardiography revealed severe aortic stenosis the patient underwent surgical valve replacement. At her 3-month follow-up, the patient reported no new bleeding episodes and her functional status had improved.

This case highlights Heyde’s syndrome, an entity probably underdiagnosed despite the high prevalence of aortic stenosis and intestinal angiodysplasia in elderly patients.

• Aortic stenosis
• Heyde’s syndrome
• acquired von Willebrand disease
• intestinal angiodysplasia

The aim of this study was to evaluate the prevalence and prognostic implication of iron deficiency (ID) and anaemia in patients with severe aortic stenosis (AS).

In an observational study of consecutive patients referred for aortic valve replacement (AVR), we assessed a wide range of biomarkers of iron status, including the definition of ID commonly applied in patients with chronic heart failure (ferritin <100 µg/L or ferritin 100–299 µg/L with a transferrin saturation <20%). The endpoints were short-term (one-year) and long-term (median 4.7 years, IQR: 3.8–5.5) mortality and major adverse cardiovascular events (MACE) within the first year after inclusion.

464 patients were included in this substudy. 91 patients (20%) received conservative treatment and 373 patients (80%) received AVR. ID was detected in 246 patients (53%). 94 patients (20%) had anaemia. Patients with ID had an overall worse clinical profile than patients without ID. During follow-up, 129 patients (28%) died. Neither ID as defined above, soluble transferrin receptor nor hepcidin were associated with short-term or long-term mortality or MACE independent on treatment allocation. Anaemia was associated with one-year mortality in conservatively treated patients.

ID and anaemia are prevalent in patients with severe AS. In our cohort, ID did not provide independent prognostic information on top of conventional risk factors. More studies are required to determine how to correctly diagnose ID in patients with AS.

NCT01794832.

• anaemia
• aortic valve disease
• epidemiology
• iron deficiency
• prosthetic heart valves

• cardiac surgery
• thrombotic microangiopathy
• von Willebrand factor multimers

• Angiodysplasia/drug therapy
• Angiodysplasia/genetics
• Angiodysplasia/metabolism
• Animals
• Biomarkers
• Blood Vessels/metabolism
• Endothelial Cells/metabolism
• Endothelium, Vascular/metabolism
• Gene Expression Regulation
• Humans
• Neovascularization, Pathologic/drug therapy
• Neovascularization, Pathologic/genetics
• Neovascularization, Pathologic/metabolism
• Neovascularization, Physiologic
• Signal Transduction
• von Willebrand Diseases/blood
• von Willebrand Diseases/genetics
• von Willebrand Diseases/metabolism
• von Willebrand Factor/chemistry
• von Willebrand Factor/genetics
• von Willebrand Factor/metabolism
• von Willebrand Factor/therapeutic use

• PG/16/91/32515 British Heart Foundation

• Anaemia
• TAVI
• TAVR
• anaemic
• aortic valve replacement
• aortic valve stenosis

Heyde syndrome is known as a triad of calcific aortic stenosis, anemia due to gastrointestinal bleeding from angiodysplasia, and acquired type 2A von Willebrand disease. This acquired hemorrhagic disorder is characterized by the loss of the large von Willebrand factor multimers due to the shear stress across the diseased aortic valve. The most frequently observed type of bleeding in these patients is mucosal or skin bleeding, such as epistaxis, followed by gastrointestinal bleeding. On the other hand, intracranial hemorrhage complicating Heyde syndrome is extremely rare.

A 77-year-old woman presented to our hospital with severe aortic stenosis and severe anemia due to gastrointestinal bleeding and was diagnosed with Heyde syndrome. Although aortic valve replacement was performed without recurrent gastrointestinal bleeding, postoperative life-threatening acute subdural hematoma occurred with a marked midline shift. Despite prompt surgical evacuation of the hematoma, she did not recover consciousness and she died 1 month after the operation.

Postoperative subdural hematoma is rare, but it should be kept in mind as a devastating hemorrhagic complication, especially in patients with Heyde syndrome.

• Aortic valve replacement
• Case report
• Heyde syndrome
• Subdural hematoma

• Blood Coagulation Tests/methods
• Factor VIII/metabolism
• Humans
• von Willebrand Diseases/blood
• von Willebrand Diseases/diagnosis
• von Willebrand Diseases/epidemiology
• von Willebrand Factor/metabolism

• R01 HL112614 NHLBI NIH HHS
• P01 HL144457 NHLBI NIH HHS
• R01 HL126810 NHLBI NIH HHS
• P01 HL081588 NHLBI NIH HHS
• R01 HL139847 NHLBI NIH HHS

• Bariatric surgery
• Celiac disease
• Chronic hepatitis
• Gastritis
• Gastrointestinal bleeding
• Gastrointestinal neoplasm
• Infection
• Iron deficiency anemia
• Non-alcoholic fatty liver disease
• Nonsteroidal anti-inflammatory drugs

• Anemia/complications
• Anemia, Iron-Deficiency/complications
• Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
• Bariatric Surgery
• Celiac Disease/microbiology
• Feces
• Gastritis/microbiology
• Gastrointestinal Diseases/complications
• Gastrointestinal Hemorrhage/complications
• Gastrointestinal Neoplasms/complications
• Helicobacter Infections/diagnosis
• Helicobacter pylori
• Hepatitis, Chronic/complications
• Hernia, Hiatal/pathology
• Humans
• Iron/chemistry
• Liver Diseases/complications
• Non-alcoholic Fatty Liver Disease/complications
• Prevalence
• Quality of Life

Gastrointestinal bleeding (GB) due to angiodysplasias can cause severe, recurrent bleeding, especially in elderly patients. Angiodysplastic bleedings in the gastrointestinal tract have been associated with aortic stenosis and, more recently, hypertrophic obstructive cardiomyopathy, caused by an acquired coagulopathy known as Heyde’s syndrome. Multiple factors are involved in the pathogenesis of angiodysplastic bleeding including genetic factors and increased levels of vascular intestinal growth factor at tissue levels. Endoscopic coagulation therapy is the primary treatment but often fails to resolve bleeding, especially in patients with large numbers of angiodysplasias. In patients with aortic stenosis and GB, the main treatment is aortic valve replacement but the patients may be unfit to undergo surgery due to the complicating anemia. In this case story, we present a patient with severe, GB due to hypertrophic subvalvular obstructive cardiomyopathy. Endoscopic procedures with argon beaming were performed without effect on bleeding. The patient was treated with a combination of both thalidomide and octreotide. Within 3 months, the patient recovered from the anemia and was able to undergo transcoronary ethanol ablation. No further bleeding episodes occurred, and thalidomide and octreotide were arrested. To our knowledge, this case report is the first to describe how this new drug combination therapy is an effective treatment of GB from angiodysplasias and can be used to bridge to surgical or endovascular treatment.

• Angiodysplasia
• Gastrointestinal bleeding
• Heyde’s syndrome
• Hypertrophic cardiomyopathy
• Sandostatin
• Subvalvular aortic obstruction
• Thalidomide

• Angiodisplasias
• Angiodysplasia
• Estenose aórtica grave
• Gastrointestinal bleeding
• Hemorragia gastrointestinal
• Heyde syndrome
• Hipertensão pulmonar
• Pulmonary hypertension
• Severe aortic stenosis
• Síndrome de Heyde

• Aged
• Anemia/diagnosis
• Anemia/etiology
• Angiodysplasia/complications
• Aortic Valve Stenosis/complications
• Heart Failure/complications
• Humans
• Hypertension, Pulmonary/complications
• Intestines/blood supply
• Male
• Syndrome