Homocysteine Level and Risk of Hemorrhage in Brain Arteriovenous Malformations.

OBJECTIVE: We aimed to investigate the risk factors associated with hemorrhage and clarify the relation of homocysteine (Hcy) with brain arteriovenous malformations (bAVMs). METHOD: We retrospectively reviewed bAVM patients from Beijing Tiantan Hospital between January 2019 and December 2019. Clinical and laboratory variables were analyzed in enrolled patients with bAVMs. Potential predictors associated with hemorrhage were evaluated by logistic regression analysis. RESULTS: A total of 143 bAVM patients were identified in the study, including 69 unruptured and 74 ruptured cases. Patients with hemorrhage were less likely to have hyperhomocysteinemia (P = 0.023). Logistic regression analysis showed that increased maximum diameter of bAVM lesions (odds ratio (OR) 0.634, 95% confidence intervals (CI) 0.479-0.839; P = 0.001) and serum Hcy level (OR 0.956, 95% CI 0.920-0.993; P = 0.021) were associated with lower risk of hemorrhage in bAVMs. CONCLUSION: The present study provided evidence regarding the association between serum Hcy and hemorrhage in patients with bAVMs. Higher Hcy level was correlated with a lower risk of rupture. Detection of factors for subsequent hemorrhage is necessary to develop therapeutic strategies for bAVMs preferably.

Arterial endoglin does not protect against arteriovenous malformations.

INTRODUCTION: Endoglin (ENG) forms a receptor complex with ALK1 in endothelial cells (ECs) to promote BMP9/10 signalling. Loss of function mutations in either ENG or ALK1 genes lead to the inherited vascular disorder hereditary haemorrhagic telangiectasia (HHT), characterised by arteriovenous malformations (AVMs). However, the vessel-specific role of ENG and ALK1 proteins in protecting against AVMs is unclear. For example, AVMs have been described to initiate in arterioles, whereas ENG is predominantly expressed in venous ECs. To investigate whether ENG has any arterial involvement in protecting against AVM formation, we specifically depleted the Eng gene in venous and capillary endothelium whilst maintaining arterial expression, and investigated how this affected the incidence and location of AVMs in comparison with pan-endothelial Eng knockdown. METHODS: Using the mouse neonatal retinal model of angiogenesis, we first established the earliest time point at which Apj-Cre-ERT2 activity was present in venous and capillary ECs but absent from arterial ECs. We then compared the incidence of AVMs following pan-endothelial or venous/capillary-specific ENG knockout. RESULTS: Activation of Apj-Cre-ERT2 with tamoxifen from postnatal day (P) 5 ensured preservation of arterial ENG protein expression. Specific loss of ENG expression in ECs of veins and capillaries led to retinal AVMs at a similar frequency to pan-endothelial loss of ENG. AVMs occurred in the proximal as well as the distal part of the retina consistent with a defect in vascular remodelling during maturation of the vasculature. CONCLUSION: Expression of ENG is not required in arterial ECs to protect against AVM formation.

Ammonia Predicts Hepatic Involvement and Pulmonary Hypertension in Patients With Hereditary Hemorrhagic Telangiectasia.

INTRODUCTION: Hepatic involvement in hereditary hemorrhagic telangiectasia (HHT) is common and can be associated with severe clinical consequences, including portal hypertension, cardiac failure, and encephalopathy. However, there are no reliable clinical predictors of hepatic involvement and its associated complications, limiting appropriate identification of these patients. In this work, we define the utility of serum ammonia and liver biochemical tests (LFTs) in predicting hepatic HHT involvement and its complications. METHODS: We performed a retrospective study examining a well-characterized cohort of patients with HHT. Clinical characteristics, laboratory tests, liver imaging, transthoracic echocardiography assessment of right ventricular systolic pressure (RVSP), and history of other HHT-related outcomes were assessed. Patients were followed for the development of encephalopathy. RESULTS: Of 45 patients with definite HHT, 18 (40%) had elevated ammonia levels. An elevated ammonia associated with the presence of hepatic arteriovenous malformations (AVMs) on imaging (P < 0.03) and when combined with elevated liver tests increased the sensitivity for hepatic AVMs by 18% (55% for LFTs vs 73% for LFTs plus ammonia). Furthermore, an elevated serum ammonia in patients with HHT associated with an elevated RVSP (>35 mm Hg), providing an 80% sensitivity and 71% specificity for predicting the presence of pulmonary hypertension. In contrast, there was no association with an elevated serum ammonia and encephalopathy over a total of 859 months of follow-up. DISCUSSION: Elevated ammonia in a cohort of patients with HHT was associated with the presence of hepatic AVMs and elevated RVSP, but no other complications of HHT, including encephalopathy.

Angiopoietin-2 predicts morbidity in adults with Fontan physiology.

Morbidity in patients with single-ventricle Fontan circulation is common and includes arrhythmias, edema, and pulmonary arteriovenous malformations (PAVM) among others. We sought to identify biomarkers that may predict such complications. Twenty-five patients with Fontan physiology and 12 control patients with atrial septal defects (ASD) that underwent cardiac catheterization were included. Plasma was collected from the hepatic vein and superior vena cava and underwent protein profiling for a panel of 20 analytes involved in angiogenesis and endothelial dysfunction. Ten (40%) of Fontan patients had evidence of PAVM, eighteen (72%) had a history of arrhythmia, and five (20%) were actively in arrhythmia or had a recent arrhythmia. Angiopoietin-2 (Ang-2) was higher in Fontan patients (8,875.4 ± 3,336.9 pg/mL) versus the ASD group (1,663.6 ± 587.3 pg/mL, p < 0.0001). Ang-2 was higher in Fontan patients with active or recent arrhythmia (11,396.0 ± 3,457.7 vs 8,118.2 ± 2,795.1 pg/mL, p < 0.05). A threshold of 8,500 pg/mL gives Ang-2 a negative predictive value of 100% and positive predictive value of 42% in diagnosing recent arrhythmia. Ang-2 is elevated among adults with Fontan physiology. Ang-2 level is associated with active or recent arrhythmia, but was not found to be associated with PAVM.

Embolization of Arteriovenous Malformations: Effect of Flow Control and Composition of n-Butyl-2 Cyanoacrylate and Iodized Oil Mixtures with and without Ethanol in an in Vitro Model.

Purpose To elucidate the effect of flow control (ie, balloon occlusion) and the composition of various mixtures of n-butyl-2 cyanoacrylate (NBCA) and iodized oil, with and without the addition of ethanol, for the treatment of arteriovenous malformations in an in vitro model. Materials and Methods A simulation circuit device that featured an artificial nidus was filled with heparinized swine blood obtained during exsanguination from another Institutional Animal Care and Use Committee-approved protocol and was constructed to generate pulsatile flow. Mixtures of NBCA and iodized oil (NL) at a 1:1 ratio (NL 1:1); NL and ethanol (NLE) at a 1:1:3 ratio (NLE 1:1:3) with or without flow control; and NL at 1:3, 1:5, and 1:10 ratios without flow control were injected six times each for a total of 42 trials. Embolization was classified as complete filling, proximal occlusion, pass through, or distal overpenetration after occlusion balloon deflation, and the trial results were compared. The results of the embolization test were evaluated by using the Fisher exact probability test to compare optimal and suboptimal embolization groups. Results NLE 1:1:3 with flow control completely filled the nidus in all six trials. NL 1:1 delivered with flow control achieved complete nidus filling in three of six injections, as did the NL 1:5 ratio trial without flow control. Complete embolization with NLE 1:1:3 with flow control was more feasible to achieve complete nidus filling than was NL 1:1 with flow control or NL 1:5 without flow control, although there was no statically significant difference (all, P = .09). None of the other mixtures produced complete embolization. Conclusion NLE 1:1:3 showed consistent and reproducible complete embolization with flow control and was stable after balloon deflation, making it an acceptable material for embolization in an in vitro arteriovenous malformation model. Further study should be performed before the NLE 1:1:3 mixture is used in routine clinical practice. (©) RSNA, 2015.

Vacunación en el paciente con telangiectasia hemorrágica hereditaria / Vaccination of patients with hereditary hemorrhagic telangiectasia

No disponible

Pulmonary shunt fraction measurement compared to contrast echocardiography in hereditary haemorrhagic telangiectasia patients: time to abandon the 100% oxygen method?

BACKGROUND: The presence of pulmonary right-to-left shunting (RLS) is associated with severe neurological complications from paradoxical embolisation in patients with hereditary haemorrhagic telangiectasia (HHT) and screening is warranted. Pulmonary shunt fraction measurement with the 100% oxygen method can be used for the detection and quantification of functional pulmonary RLS, although transthoracic contrast echocardiography (TTCE) has emerged as the gold standard over the last few years. OBJECTIVE: The aim of this study was to determine the true diagnostic accuracy of the established 100% oxygen method in detecting pulmonary RLS, as compared to TTCE. METHODS: We analysed 628 persons screened for HHT between 2004 and 2010, all of whom underwent TTCE. A quantitative 3-point grading scale was used to differentiate between minimal, moderate or extensive pulmonary RLS on TTCE (grade 1-3, respectively). Additional shunt fraction measurement with the 100% oxygen method was pursued in cases of pO2 <13 or <12 kPa in patients younger or older than 30 years, respectively. A shunt fraction >5% was considered pathological. RESULTS: Both TTCE and the 100% oxygen method were performed in 210 subjects. Although the presence of a pathological shunt fraction correlated with an increased pulmonary shunt grade on TTCE, the 100% oxygen method confirmed a >5% shunt fraction in only 51% of patients with pulmonary RLS on TTCE (14, 20 and 72% for grade 1, 2 and 3, respectively). CONCLUSION: Pulmonary shunt fraction measurement with the 100% oxygen method is not a useful screening technique for the detection of pulmonary RLS in HHT as its sensitivity is too low and large pulmonary shunts on TTCE may remain undetected using this method.

Uterine arteriovenous malformations following gestational trophoblastic neoplasia: a systematic review.

Uterine arteriovenous malformation (AVM) following gestational trophoblastic neoplasia (GTN) is a rare condition. It can be associated with chronic vaginal bleeding or life-threatening heavy bleeding, even after complete resolution of the tumor following chemotherapy. This analysis aimed to perform an extensive systematic review highlighting clinical symptoms, imaging, management and prognosis of this rare complication of GTN. We also describe an additional case of uterine AVM following GTN. We conducted a literature search using Medline, Embase and Cochrane library to analyze the clinical data of 49 published cases of uterine AVM following GTN. Median age of the women diagnosed with AVM was 29 years (range 15-49). Median gravidity was 2 (range 1-8) and 50% of women were nulligravida. Complete molar pregnancy was the most common initial gestational trophoblastic diagnosis (48%). Overall, 44 patients (88%) were symptomatic and presented with chronic or acute abnormal vaginal bleeding. Only 3 patients had an undetectable HCG level at the time of uterine AVM diagnosis. Hypo-echoic space in the myometrium is the most relevant finding on ultrasonography but the gold standard for the definitive diagnosis of AVMs is angiographic examination. Uterine artery embolization was the most common treatment option performed in 82% of the patients and was successful in controlling the bleeding in 85% of cases. We identified 20 pregnancies after successful embolization of uterine AVM following a GTN and 90% of them were successful. Because of the risk of life-threatening heavy bleeding, the diagnosis of uterine AVM should always be considered in patients with a history of recurrent unexplained vaginal bleeding after gestational trophoblastic neoplasia. Angiographic embolization is successful in the majority of cases and does not appear to compromise future pregnancy.

Large pulmonary arteriovenous malformations: long-term results of embolization with AMPLATZER vascular plugs.

PURPOSE: To analyze the long-term results of endovascular treatment of large pulmonary arteriovenous malformations (PAVMs) using the AMPLATZER vascular plug (AVP; AGA Medical Corp, Golden Valley, Minnesota). MATERIALS AND METHODS: Between May 2007 and April 2011, 18 patients with 24 large PAVMs, defined as PAVMs that had a feeding artery with a diameter of ≥ 8 mm, were treated with AVP I or AVP II. A single AVP device was used for each PAVM. Aneurysmal sac diameters, sac perfusion, sac shrinkage, and complete resolution before and after the intervention were analyzed. Complete histories, laboratory values, physical examinations, and multidetector computed tomography images were reviewed. The mean occlusion time for AVP I and AVP II and the mean arterial oxygen saturation (SaO2) before and after the intervention were compared. RESULTS: The mean diameter of the feeding artery was 11.46 mm ± 2.18 (range, 8-13.3 mm). The mean occlusion time was 7.34 minutes ± 1.23 for AVP I and 6.25 minutes ± 1.12 for AVP II (P = .11). The mean SaO2 before and after the intervention was 63.71% ± 8.10% (range, 51%-76%) and 96.28% ± 0.49% (range, 96%-97%), respectively (P = .045). No major periprocedural complications were observed. The mean follow-up duration was 36.33 months ± 10.63 (range, 28-56 mo). During the follow-up period, there were no persistent sac perfusions, migration of the AVPs, major complications, or recanalizations. CONCLUSIONS: Treatment of large PAVMs with AVPs is an effective method for obtaining excellent long-term results. Embolization of large feeding arteries can be accomplished with AVPs without major complications.

Ultrasonographic indications for conservative treatment in pregnancy-related uterine arteriovenous malformations.

BACKGROUND: Uterine arteriovenous malformations (AVMs) are known to spontaneously regress. PURPOSE: To assess the predictive value of ultrasonography for patients requiring conservative treatment for pregnancy related to AVMs. MATERIAL AND METHODS: Our prospective study included 75 patients (conservative management:therapeutic management = 45:30) with vaginal bleeding from pregnancy-related AVM. Clinical and ultrasonography examinations were reviewed, and the following information was gathered: complete blood count, AVM maximal diameter, AVM echogenicity, retained product of conception, number of blood vessels, and spectral Doppler (pulsatility index [PI], resistance index [RI], peak systolic velocity [PSV], time-averaged maximum velocity [TAMXV]). The Doppler criteria by Timmerman (mean PSV >70 cm/s: therapeutic management, mean PSV < 52 cm/s: conservative management) were used for the initial management selection. The association between experimental variables and outcomes was assessed to determine their usefulness for predicting conservative management. RESULTS: Features strongly associated with conservative management and their accuracy were PSV 89.6%, hemoglobin 84.7%, RI 83.1%, TAMXV 79.3%, and PI 78.6%. The overall accuracy for correct outcome classification was 64 (85.3%) of 75 patients. Most patients with conservative management had quicker improvement of symptoms and spontaneous regression at follow-up. CONCLUSION: Ultrasonography can accurately predict selection of conservative management.

[Large venous malformations increase the risk of thromboembolic complications]. / Store venøse malformationer øger risikoen for tromboemboliske komplikationer.

Venous malformations (VM) represent vascular developmental errors. They are low-flow lesions composed of ectatic vessels that histologically and morphologically are similar to veins. Episodic thromboses commonly occur in VM. Moreover, pulmonary emboli, sudden death and chronic thromboembolic pulmonary hypertension have been described in children and adults with extensive VM. This article discusses the management and treatment of patients with extensive VM.

Uterine arteriovenous malformation.

Uterine arteriovenous malformation (AVM) is a little known condition of which, to date, very few cases have been described. It has a very diverse symptomatology, even though in most cases, it is diagnosed during a severe and acute haemorrhagic event. Its treatment can vary from expectant management to hysterectomy; however, current evidence suggests that the embolisation of uterine arteries is the most effective approach, especially if fertility is to be preserved. We present a case report classified as AVM, with additional images that show the appearance of this pathology in a short span of time. This case has a number of peculiarities: unusual persistence of human chorionic gonadotropin hormone (ß-HCG), asymptomatic patient, quick establishment of the lesion and its duration with unchanging characteristics and finally its spontaneous resolution without further consequences. This entity shows an aetiopathogenesis, that is, not well established or described. We discuss its physiopathology and aetiopathogenesis.

Elevated D-dimer level in the differential diagnosis of venous malformations.

OBJECTIVE: To evaluate if elevated D-dimer level is specific for venous malformations (VMs) and thus useful for differential diagnosis, which can be problematic even in specialized interdisciplinary centers. Localized intravascular coagulopathy, characterized by elevated D-dimer levels, has been observed in approximately 40% of patients with VMs. DESIGN: Prospective convenience sample accrued from 2 interdisciplinary sites. SETTING: Two interdisciplinary centers for vascular anomalies in Brussels, Belgium, and Caen, France PARTICIPANTS: The study population comprised 280 patients with clinical data, Doppler ultrasonograms (for 251 patients), and coagulation parameter measurements. Main Outcome Measure Measurement of D-dimer levels. RESULTS: A VM was diagnosed in 195 of 280 patients (69.6%), and 83 of them had elevated D-dimer levels; the sensitivity of D-dimer dosage was 42.6% (95% confidence interval, 35.6%-49.5%). Among the 85 patients without VM, D-dimer levels were elevated only in 3 patients; the specificity of the dosage was 96.5% (95% confidence interval, 92.5%-100%). CONCLUSIONS: Elevated D-dimer level is highly specific for VMs (pure, combined, or syndromic), and therefore this easy and inexpensive biomarker test should become part of the clinical evaluation of vascular anomalies. It can detect hidden VMs and help differentiate glomuvenous malformation (normal D-dimer levels) from other multifocal venous lesions. Elevated D-dimer level also differentiates a VM from a lymphatic malformation. Moreover, slow-flow Klippel-Trenaunay syndrome (capillaro-lymphatico-venous malformation with limb hypertrophy) can be distinguished from fast-flow Parkes Weber syndrome (capillary malformation with underlying multiple microfistulas and limb hypertrophy). For these reasons, D-dimer level measurement is a useful complementary tool for diagnosing vascular anomalies in everyday practice.

Characterization of the integrin alpha v beta3 in arteriovenous malformations and cavernous malformations.

BACKGROUND: Alpha V beta 3 (alphavbeta3) is an integrin specifically expressed on the endothelial cells of central nervous system (CNS) neoplasms. However, no data exist on the expression of alphavbeta3 in vascular malformations of the CNS. In this study, we investigate the expression of alphavbeta3 in arteriovenous malformations (AVMs) and cavernous malformations (CMs). METHOD: Frozen samples of AVMs from 12 patients and CMs from 5 patients were obtained intraoperatively. Once the final pathology had been confirmed, immunohistochemistry was performed using an antibody to the integrin alphavbeta3. The alphavbeta3 expression pattern was graded according to the percentage of positively staining vessels. RESULTS: Ten of 12 AVMs demonstrated alphavbeta3 immunopositivity. Six of these 10 AVMs had moderate or strong staining. Most notably, 5 of the 6 moderate or strongly staining AVMs came from patients 22 years of age or younger. Four of these 6 AVMs had previously been embolized. None of the cavernous malformations demonstrated alphavbeta3 immunopositivity. DISCUSSION: alphavbeta3 may contribute to the formation of AVMs in younger patients. alphavbeta3 may also provide a potential therapeutic target. The lack of alphavbeta3 expression in cavernous malformations, despite their high vascular densities, suggests that the pathophysiology of their formation differs from that of AVMs.

Embolotherapy of pulmonary arteriovenous malformations: long-term results in 112 patients.

PURPOSE: To evaluate the long-term results of embolotherapy of pulmonary arteriovenous malformations (PAVMs) in a large group of patients. MATERIALS AND METHODS: Between July 1988 and August 2001, 134 consecutive patients underwent embolotherapy of PAVMs with feeding arteries larger than 3 mm or that had previously caused bleeding or systemic complications. The mean follow-up was 62.2 months. The primary endpoints of the study were the efficacy of embolotherapy, decrease in right-to-left shunt, and increase in partial arterial oxygen pressure (PaO(2)); the secondary endpoint was the prevalence of complications. Standard follow-up consisted of yearly history, chest radiography, and arterial blood gas measurement. RESULTS: Follow-up was available in 112 patients. Initially, 296 PAVMs were embolized in these patients. Nineteen patients (17%) underwent a second procedure and four patients underwent a third procedure because of recanalization of originally occluded feeding arteries (25 PAVMs, 8%) or interval enlargement of untreated PAVMs (53 PAVMs). In total, 349 PAVMs were embolized in 157 sessions. The mean diameter of occluded vessels was 4.7 mm. The long-term outcomes of embolotherapy were successful in 83% of patients overall and in 96% of patients in whom all angiographically visible PAVMs were embolized. Recanalization occurred in 12 of 16 patients who underwent repeat treatment because of enlargement of nonembolized PAVMs. Postprocedural pleurisy occurred after 14 of 157 sessions (9%). Periprocedural complications occurred in 12 sessions (8%) and included migration of an embolic device, transient ischemic attack (TIA), angina pectoris, and early cerebral infarction after embolization. Three patients experienced TIA and two patients experienced a cerebral abscess during follow-up after embolotherapy. CONCLUSIONS: Embolotherapy of PAVMs is efficacious and durable in the majority of patients. Patients should remain under regular review because recanalization of PAVMs or enlargement of untreated PAVMs can occur years after treatment.

Pulmonary arteriovenous malformation treated by lobectomy.

Pulmonary arteriovenous malformation (PAVM) may occur primarily or in association with hereditary hemorrhagic telangiectasia. We present a case of PAVM in the central lower lobe of the left lung of a 75-year-old woman, which was successfully treated by lobectomy. Contrast echocardiography is an excellent tool for evaluation of this uncommon lesion. Advances in interventional radiology have led to the introduction of obliterative techniques for the treatment of PAVM. However, in the presence of a large solitary malformation centrally located, as in our case, and in high-risk patients, surgery is still a safe and effective first option.