Heyde syndrome: prevalence and outcomes in patients undergoing transcatheter aortic valve implantation.

BACKGROUND: Heyde syndrome (HS) is known as the association of severe aortic stenosis (AS) and recurrent gastrointestinal bleeding (GIB) from angiodysplasia. Data on the prevalence of HS and results after TAVI remain scarce. METHODS: 2548 consecutive patients who underwent TAVI for the treatment of AS from 2008 to 2017 were evaluated for a history of GIB and the presence of HS. The diagnosis of HS was defined as a clinical triad of severe AS, a history of recurrent GIB, and an endoscopic diagnosis of angiodysplasia. These patients (Heyde) were followed to investigate clinical outcomes, bleeding complications and the recurrence of GIB and were compared to patients with GIB unrelated to HS (Non-Heyde). RESULTS: A history of GIB prior to TAVI was detected in 190 patients (7.5%). Among them, 47 patients were diagnosed with HS (1.8%). Heyde patients required blood transfusions more frequently compared to Non-Heyde patients during index hospitalization (50.0% vs. 31.9%, p = 0.03). Recurrent GIB was detected in 39.8% of Heyde compared to 21.2% of Non-Heyde patients one year after TAVI (p = 0.03). In patients diagnosed with HS and recurrent GIB after TAVI, the rate of residual ≥ mild paravalvular leakage (PVL) was higher compared to those without recurrent bleeding (73.3% vs. 38.1%, p = 0.05). CONCLUSION: A relevant number of patients undergoing TAVI were diagnosed with HS. Recurrent GIB was detected in a significant number of Heyde patients during follow-up. A possible association with residual PVL requires further investigation to improve treatment options and outcomes in patients with HS.

Risk factors for bleeding from gastrointestinal angiodysplasia: a case-control study in patients with bleeding and non-bleeding angiodysplasia.

OBJECTIVES: Angiodysplasia (AD) is a common source of gastrointestinal bleeding. Yet, little is known about factors forwarding bleeding in these vascular malformations. The presented study aims to determine risk factors for bleeding that occurs only in patients with symptomatic, but not with asymptomatic, AD. METHODS: Case-control study in patients with AD and either a positive or a negative history of gastrointestinal bleeding in Munich, Germany. Groups were compared by clinical, laboratory, and endoscopic features. RESULTS: 80 patients with (58, f 31, med. age 72) or without bleeding AD (22, f 12, med. age 61) were included. Bleeding from AD was significantly associated with the total number of AD (OR 1.4 (95 % CI 1.1-1.7) p = 0.01) and closure time in PFA/collagen-epinephrine test (OR 1.0 (95 % CI 1.0-1.0) p < 0.01). The total number of AD correlated significantly with age (r = 0.36; p = 0.01). AD were mainly detected in the upper small intestine (> 30 %). Although patients with aortic stenosis suffered not significantly more frequently from bleeding from AD, they demonstrated a loss of high molecular multimers of VWF. CONCLUSIONS: The amount of AD is clearly correlated to the age of the patient. A higher number of ADs and inhibition of primary hemostasis increase the risk of bleeding.

Aortic stenosis and anemia with an update on approaches to managing angiodysplasia in 2018.

Angiodyplasia and aortic stenosis are both conditions that are highly prevalent in elderly people and can often co-exist. Recent studies suggest that this association is related to subtle alterations in plasma coagulation factors. The von Willebrand factor is the strongest link between aortic stenosis and bleeding associated with gastrointestinal angiodysplasia. With an ageing population, the disease burden of aortic stenosis and its association with angiodysplasia of the bowel makes this an incredibly underdiagnosed yet important condition. Clinicians should be aware of this association when dealing with elderly patients presenting either with unexplained anemia, gastrointestinal bleeding or with aortic stenosis. A high index of suspicion and appropriate diagnostic techniques followed by appropriate and prompt treatment could be life-saving. No clear guidelines exist on management but surgical aortic valve replacement is thought to offer the best hope for long-term resolution of bleeding. With a growing number of technological armamentarium in the management of such patients, especially with the advent of transcatheter aortic valve implantation, new options can be offered even to elderly patients with comorbidities for whom conventional surgery would have been impossible.

Alarming Increasing Trends in Hospitalizations and Mortality With Heyde's Syndrome: A Nationwide Inpatient Perspective (2007 to 2014).

We studied the trends and outcomes of patients with intestinal angiodysplasia-associated gastrointestinal bleeding (Heyde's syndrome [HS]) with aortic stenosis (AS) who underwent surgical aortic valve replacement (SAVR) versus transcatheter aortic valve implantation (TAVI). The National Inpatient Sample (2007 to 2014) and International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify HS hospitalizations, pertinent co-morbidities, and outcomes of SAVR versus TAVI from 2011 to 2014. The incidence of HS with AS was 3.1%. The trends in hospitalizations and all-cause inpatient mortality showed relative surges of 29.16% (from 48 to 62 per 100,000) and 22.7% (from 3.7 to 4.54 per 100,000) from 2007 to 2014. HS patients were older (mean age ∼80 vs 77 years) females (54.3% vs 52.2%) compared with AS without HS. The all-cause mortality (6.9% vs 4.1%), length of stay (LOS) (∼7.0 vs 5.8 days), and hospitalization charges ($58,519.31 vs $57,598.67) were higher in HS (p<0.001). No differences were reported in all-cause mortality and hospital charges in HS patients who underwent either SAVR or TAVI. However, the TAVI cohort showed lower rates of stroke (1.7% vs 10.0%) and blood transfusion (1.7% vs 11.7%), a shorter LOS (18.3 vs 23.9 days; p<0.001), and more routine discharges (21.7% vs 14.8%, p = 0.01). An older age, male gender, Asian race, congestive heart failure, coagulopathy, fluid and/or electrolytes disorders, chronic pulmonary disease, and renal failure raised the odds of mortality in HS patients. In conclusion, we observed increasing rates of hospitalizations with HS and higher inpatient mortality from 2007 to 2014. The HS patients who underwent TAVI had fewer complications without any difference in the all-cause mortality compared with SAVR.

Gastrointestinal lesions in chronic kidney disease patients with anaemia. / Lesiones gastrointestinales en pacientes con enfermedad renal crónica y anemia.

INTRODUCTION: Despite the frequency with which anaemia is present in patients with chronic kidney disease (CKD), its relationship with gastrointestinal lesions has not been studied. METHOD: A cross-sectional, analytical, observational study involving one year of recruitment was carried out to determine the prevalence of endoscopic gastrointestinal lesions and associated risk factors in asymptomatic patients with chronic kidney disease stages 1-5 and anaemia who had a positive qualitative immunochemical faecal occult blood test. RESULTS: A total of 9,658 patients with CKD were analysed, of which 286 (2.9%) had anaemia; 198 had a positive faecal occult blood test (47% male, 71.1±11.8 years). The endoscopic study revealed 255 lesions, with at least one lesion in 68.2% of patients, with the most prevalent being: adenomatous colorectal polyps (39.6%), acute lesions of the gastric mucosa (22.6%), neoplastic lesions 15.1%), angiodysplasia (14.4%), oesophagitis (8.4%), inflammatory bowel disease (4.8%) and ischaemic colitis (3.1%). Uraemia and acetylsalicylic acid were identified as risk factors for acute gastric mucosal lesions. Angiodysplasia was associated with alcoholism, a more advanced stage of chronic kidney disease, anaemia, and lack of response to erythropoiesis-stimulating agents. Age and refractory anaemia were risk factors for adenomatous polyps and colorectal cancer. CONCLUSION: Renal patients with anaemia could benefit from an endoscopic study due to their high prevalence of gastrointestinal lesions, particularly adenomatous polyps and colorectal cancer, which are more common in those over 50 years of age with CKD stages 3-5.

Clinical characteristics and risk factors of active bleeding in colonic angiodysplasia among the Taiwanese.

BACKGROUND: Colonic angiodysplasia (AGD) is a common cause of gastrointestinal bleeding. However, information on the characteristics and prevalence of colonic AGD is limited. We determined the clinical features of and risk factors for active bleeding in colonic AGD in a Taiwanese population. METHODS: From February 2007 to December 2016, 13,047 patients undergoing 16,760 colonoscopies at the Tri-Service General Hospital were included in this study. Eighty-four patients were diagnosed with AGD. We conducted a retrospective study by analyzing the medical records of these patients. The clinical features and endoscopic findings were evaluated. Furthermore, we distinguished colonic AGD into bleeding and non-bleeding types and identified the risk factors for bleeding in colonic AGD. RESULTS: In our study, the prevalence of colonic AGD was 0.6% among all patients who received colonoscopy. Among patients with colonic AGD, we found that many were aged; in all, 58.3% of patients with colonic AGD were older than 65 years. More than half of the patients had hypertensive cardiovascular disease (53.6%) and the AGD lesions were predominantly located in the left-sided colon (41.7%). We analyzed several factors to identify those associated with bleeding colonic AGD. Our results indicated that age (p < 0.001), hypertension (p = 0.020), atrial fibrillation (p = 0.027), and in-patient status (p = 0.006) were significant factors associated with active bleeding lesions. On multivariate analysis, old age was the only significant risk factor. CONCLUSION: Angiodysplastic lesions in Taiwanese patients were predominantly identified in the left-sided colon. Old age was an independent risk factor associated with active bleeding in colonic angiodysplasia.

Association of aortic valve disease with intestinal angioectasia: data from the Nationwide Inpatient Sample.

OBJECTIVE: Since the description of a correlation between aortic stenosis and angioectasia, controversy has persisted about whether these diseases are truly associated or coincidental findings of older age. Our objective was to determine the association of aortic valve disease and bleeding intestinal angioectasia from a large database. PATIENTS AND METHODS: We used the 2011 Nationwide Inpatient Sample database to identify hospitalizations in the USA in patients with bleeding intestinal angioectasia. International Classification of Diseases, 9th revision, Clinical Modification codes were used to identify patients with aortic valve disease, mitral valve disease, and known risk factors for angioectasia (including diagnosed von Willebrand disease, left ventricular assist device, and chronic kidney disease). Univariate and multivariate logistic regression were used to determine the odds of association between the valvular diseases and angioectasia. RESULTS: A total of 32 079 intestinal angioectasia-related hospitalizations were identified of which 7.02% (n=2253) cases had coexistent aortic valve disease. The unadjusted odds of aortic valve disease in association with bleeding intestinal angioectasia versus those without bleeding angioectasia was 4.95 [95% confidence interval: (CI): 4.43-5.54, P<0.001]. The association of intestinal angioectasia with mitral valve disease was not significant (odds ratio=1.56, 95% CI: 0.59-4.14, P=0.38). When adjusted for age and known risk factors, the odds of aortic valve disease in bleeding intestinal angioectasia was still significant (odds ratio=2.37, 95% CI: 2.10-2.66, P<0.001). CONCLUSION: Our findings support an important association between aortic valve disease and bleeding intestinal angioectasia, not identified in valvular heart valvular diseases with lower shear stress (mitral valve disease).

Prevalence, variability, and outcomes in portal hypertensive colopathy: a study in patients with cirrhosis and paired controls.

BACKGROUND: Management of portal hypertensive colopathy (PHC) has been challenged by controversial results in its prevalence and clinical relevance. OBJECTIVE: To describe the PHC prevalence and to evaluate the variability in diagnosis, the relation to severity of liver disease, and the incidence of severe outcomes. DESIGN: Cross-sectional study. SETTING: Endoscopic unit of a tertiary-care academic center in Rio de Janeiro, Brazil. PATIENTS: Patients with cirrhosis with portal hypertension and controls paired for age and sex. INTERVENTIONS: All patients were submitted to standard and image-enhanced colonoscopies, which were recorded in a coded video file and analyzed twice by a blinded endoscopist. MAIN OUTCOME MEASUREMENTS: The prevalence of PHC. RESULTS: A total of 51 patients with cirrhosis (55% male, mean age 59 years) and 51 healthy controls (43% male, mean age 61 years) were included. The top ranking colonoscopic findings were angiodysplasia-like lesions, nonspecific vascular pattern, red spots, and colorectal varices, all significantly more frequent in patients with cirrhosis compared with controls. PHC prevalence was 71% in patients with cirrhosis. For PHC, interobserver and intraobserver agreement (k values [standard error]) were 0.68 (0.09) and 0.63 (0.10), respectively. Intraobserver agreement for colonoscopic findings was satisfactory. PHC was not related to more severe liver disease or liver stiffness. Only 5 patients developed severe outcomes during follow-up. LIMITATIONS: The exclusion of patients with cirrhosis without esophageal varices and the absence of an interobserver agreement analysis by double-blinded endoscopists. CONCLUSION: PHC was highly prevalent in patients with cirrhosis, and its diagnostic agreement was satisfactory. PHC is not associated with relevant severe outcomes in a 12-month follow-up.

Review article: gastrointestinal angiodysplasia - pathogenesis, diagnosis and management.

BACKGROUND: Angiodysplasia (AD) of the gastrointestinal (GI) tract is an important condition that can cause significant morbidity and -rarely - mortality. AIM: To provide an up-to-date comprehensive summary of the literature evaluating this disease entity with a particular focus on pathogenesis as well as current and emerging diagnostic and therapeutic modalities. Recommendations for treatment will be made on the basis of the current available evidence and consensus opinion of the authors. METHODS: A systematic literature search was performed. The search strategy used the keywords 'angiodysplasia' or 'arteriovenous malformation' or 'angioectasia' or 'vascular ectasia' or 'vascular lesions' or 'vascular abnormalities' or 'vascular malformations' in the title or abstract. RESULTS: Most AD lesions (54-81.9%) are detected in the caecum and ascending colon. They may develop secondary to chronic low-grade intermittent obstruction of submucosal veins coupled with increased vascular endothelial growth factor-dependent proliferation. Endotherapy with argon plasma coagulation resolves bleeding in 85% of patients with colonic AD. In patients who fail (or are not suitable for) other interventions, treatment with thalidomide or octreotide can lead to a clinically meaningful response in 71.4% and 77% of patients respectively. CONCLUSIONS: Angiodysplasia is a rare, but important, cause of both overt and occult GI bleeding especially in the older patients. Advances in endoscopic imaging and therapeutic techniques have led to improved outcomes in these patients. The choice of treatment should be decided on a patient-by-patient basis. Further research is required to better understand the pathogenesis and identify potential therapeutic targets.

Increased incidence of angiodysplasia of the gastrointestinal tract and bleeding in patients with continuous flow left ventricular assist devices (LVADs).

BACKGROUND: Continuous flow left ventricular assist devices (cfLVADs) are used in clinical practice for the management of end-stage heart failure. Axial flow cfLVADS have been associated with increased rates of adverse gastrointestinal events such as bleeding angiodysplasia. The purpose of this study was to determine the incidence of bleeding gastrointestinal tract angiodysplasia and the profile of patients supported with the centrifugal cfLVAD, referred for endoscopy. METHODS: A retrospective analysis of 66 patients implanted with Ventrassist (n = 33) and Heartware (n = 33) centrifugal continuous flow LVADs was performed. All patients were on warfarin, aspirin and/or clopidogrel. Endoscopy was performed in all patients with either active gastrointestinal bleeding (n = 6) or anemia with positive fecal occult blood (n = 6). RESULTS: Bleeding gastrointestinal angiodysplasia was demonstrated in 5 out of the 12 (41.6%) patients who underwent endoscopy from the cohort of 66 cfLVAD supported patients (7.6%). The incidence of bleeding angiodysplasia was higher than the age-standardized rate of andiodysplasia from literature (0.8%). Active gastrointestinal bleeding in one other patient was due to diverticulosis. The five patients with bleeding angiodysplasia tended to be older than the remaining 61 patients (58.8 ± 10.3 vs 49.6 ± 15.7 years, p = 0.2). CONCLUSIONS: We found excess bleeding angiodysplasia in patients on centrifugal cfLVAD support. It may be appropriate to screen for angiodysplasia particularly in older patients prior to support by centrifugal cf LVADs. Reasons for the higher rate of bleeding angiodysplasia in cfLVAD patients warrant further study.

Small bowel angiodysplasia and novel disease associations: a cohort study.

OBJECTIVE: Gastrointestinal angiodysplasias recurrently bleed, accounting for 3-5% of obscure gastrointestinal bleeding. The advent of small bowel capsule endoscopy (SBCE) has led to an increased recognition of small bowel angiodysplasias (SBAs) but little is known about their etiology. Previous small cohorts and case reports suggest an equal gender incidence and associations with cardiovascular disease, renal impairment, and coagulopathies. METHODS: Patients with SBA were identified from our SBCE database. A control group, in whom gastrointestinal bleeding had been excluded, was also identified. Information on patient demographics, past medical/surgical/social history and medications was prospectively obtained. RESULTS: A total of 82 patients and 95 controls were identified. Data was available from 81% (n = 66) of SBA patients. The mean age of patients and controls was 66.9 years (35-90) and 69.2 years (54-77), and 60% (n = 40) and 58% (n = 55) were females, respectively. There was a higher rate of all comorbidities in the SBA group 92% (61/66) versus controls 76% (72/95) p < 0.002. Significant associations were found with: hypertension (odds ratio [OR] 2.8), ischemic heart disease (OR 4.25), arrhythmias (OR 4.36), valvular heart disease (OR 18), congestive heart failure (OR 4.22), chronic kidney disease (CKD) (OR 8.4), chronic respiratory conditions (OR 2.0), and previous venous thromboembolism (VTE) (OR 6.4). Anticoagulant use was higher in patients with SBA, 50% (n = 33) versus 27% (n = 26) of controls, p < 0.002, specifically warfarin and asasantin retard. CONCLUSIONS: SBA occurs in elderly patients with cardiovascular disease and CKD, as previously suggested. This study identifies a previously unrecognised risk in females, patients with chronic respiratory conditions and VTE, and the use of warfarin and asasantin retard. These associations should raise awareness of possible underlying SBA in risk patients with anemia.

Angiodysplastic lesions as a cause of colonic bleeding in patients with chronic renal disease: is there an association?

Gastrointestinal bleeding due to angiodysplastic lesions of the large bowel is a common problem among patients receiving hemodialysis and may sometimes be life-threatening. Several hypotheses have been advanced in order to explain the increased incidence of these lesions in this cohort of patients, including degenerative, metabolic, circulatory and other systemic factors. In terms of diagnosis, several advances have been made with sophisticated techniques, but endoscopy seems to be the most effective, having a dual role in diagnosis and treatment. Although most bleeds stop spontaneously, conservative treatment may not be enough. Endoscopic treatment, embolization with infusion of vasopressin, surgical resection of the bleeding intestinal segment and hormone administration may be useful therapeutic tools.

Heyde's syndrome: A critical review of the literature.

Heyde's syndrome is an uncommon association between aortic stenosis and gastrointestinal bleeding. Although initially described during the late 1950s, with subsequent reports of a possible link between these disorders, controversy persists regarding the incidence, pathogenesis, and treatment of this syndrome. The main disagreements center on the actual association of aortic stenosis and angiodysplasia, though other controversies include the pathogenesis of Heyde's syndrome, ranging from von Willebrand factor deficiency and age-related degeneration to mucosal ischemia and cholesterol embolization. A variety of treatment modalities of the syndrome has been applied, including medical management, endoscopic therapy, embolization, and aortic valve replacement. Here, the controversies surrounding Heyde's syndrome, which focus on pathogenesis and treatment, are reviewed with the aim of providing a clearer understanding of the syndrome and the implications for patient care.

Interobserver agreement in describing video capsule endoscopy findings: a multicentre prospective study.

BACKGROUND AND AIM: Few studies have specifically addressed interobserver agreement in describing lesions identified during capsule endoscopy. The aim of our study is to evaluate interobserver agreement in the description of capsule endoscopy findings. MATERIALS AND METHODS: Consecutive short segments of capsule endoscopy were prospectively observed by 8 investigators. Seventy-five videos were prepared by an external investigator (gold standard). The description of the findings was reported by the investigators using the same validated and standardized capsule endoscopy structured terminology. The agreement was assessed using Cohen's kappa statistic. RESULTS: As concerns the ability to detect a lesion, the agreement with the gold standard was moderate (kappa 0.48), as well as the agreement relating to the final diagnosis (κ 0.45). The best agreement was observed in identifying the presence of active bleeding (κ 0.72), whereas the poorest agreement concerned the lesion size (κ 0.32). The agreement with the GS was significantly better in endoscopists with higher case/volume of capsule endoscopy per year. Diagnostic concordance was better in the presence of angiectasia than in the presence of polyps or ulcers/erosions. CONCLUSIONS: Correct lesion identification and diagnosis seem more likely to occur in presence of angiectasia, and for readers with more experience in capsule endoscopy reading.

Clinical implication of gastrointestinal bleeding in degenerative aortic stenosis: an update.

Gastrointestinal (GI) bleeding due to colonic angiodysplasias can be associated with calcifying aortic stenosis (AS). GI angiodysplasias and AS are defined as chronic degenerative disorders, and the prevalence of both diseases increases with age. Moreover, degenerative AS is associated with increased destruction of high molecular weight multimers of von Willebrand factor which can promote bleeding from intestinal angiodysplasias. The coincidence of gastrointestinal bleeding angiodysplasias and AS has been known for many years as Heyde's syndrome. Aortic valve replacement is the first line therapy for advanced stage AS-patients, but can also be an effective treatment for co-existent bleeding angiodysplasias and acquired von Willebrand disease. In this study, we tried to collect as well as systemized data about the etiopathogenesis of AS coagulation abnormalities and diagnostic, clinical and therapeutic implications of AS-patient with GI angiodysplasias.

Gastrointestinal angiodysplasia in chronic renal failure.

Gastrointestinal (GI) hemorrhage is a frequent and sometimes life-threatening complication of end-stage renal failure. Angiodysplasia (AD), vascular malformation, is the most common cause of recurrent lower-intestinal hemorrhage in patients with renal failure. We report four chronic hemodialysis patients with AD. All patients presented with severe anemia requiring transfusion. GI hemorrhage ceased spontaneously in three cases and after treatment with argon plasma coagulation in another. Diagnosis of AD is usually challenging, since its cause is still unknown, and its clinical presentation is variable. Lesions are multiple in 40-75% of cases, often located in the stomach and duodenum but can affect the colon and the jejunum. Diagnosis is improved by endoscopy which has a much higher sensitivity compared to angiography. Capsular endoscopy may reveal the hemorrhage site in the small intestine when regular endoscopy fails, and therapeutic intervention usually include argon plasma coagulation.

[The role of laser doppler flowmetry in the assessment of microcirculatory disturbances at angiodysplasias].

The paper presents the data on the use of laser Doppler flowmetry (LDF) for microcirculation assessment in patients with lower limb angiodysplasias. Preliminary results suggest that LDF can be successfully used both for the quantification of microcirculatory disturbances and for the diagnosis of arterio-venous micro fistulas. LDF was used as a monitoring tool for compressive therapy effectiveness in patients with arterio-venous and venous forms of lower limb angiodysplasias. Compression stockings Relaxsan III class were shown to improve microcirculation in this patient population after 1 month wearing.