Personalised stroke evaluation and management: tailoring individualised patient care for hereditary haemorrhagic telangiectasia.

SummaryHereditary haemorrhagic telangiectasia (HHT) has an estimated prevalence of 1 in 5000-8000 individuals globally with pulmonary arteriovenous malformations (PAVMs) affecting approximately 15%-50% of HHT patients. Ischaemic stroke is a known complication of PAVMs that affects ≤30% of patients with PAVMs. Studies have shown that patients with PAVMs have ischaemic stroke a decade earlier than routine stroke. The predominant mechanism of ischaemic stroke in HHT patients is paradoxical embolism due to PAVMs, but most HHT-related PAVMs are asymptomatic. Additionally, HHT is often underdiagnosed in patients and poses a challenge to physicians due to its rarity. We present a case of a patient with ischaemic stroke who was subsequently diagnosed with HHT and found to have a PAVM on further evaluation. This case highlights the importance of using an individualised patient-centred stroke evaluation and screening for PAVMs in patients who had a stroke with possible or suspected HHT and definite HHT.

Use of Polyurethane-Covered Stents for Exclusion of Pulmonary Arteriovenous Malformations.

PURPOSE: To evaluate the safety, technical success and short-term effectiveness of polyurethane-covered stent (PK Papyrus, BioTronik, Berlin) in the treatment of pulmonary arteriovenous malformations (PAVMs) that are not amenable to embolotherapy. MATERIALS AND METHODS: In this IRB-approved, retrospective study, data from patients who received polyurethane-covered stents for exclusion of PAVMs were analyzed. The study included 5 patients (all women) with a median age of 40 years (range 25-60). Patients presented with hypoxemia, TIAs, and/or epistaxis; 4 were confirmed to have HHT. All had multiple PAVMs diagnosed on chest CT and underwent embolization with other devices in addition to the polyurethane-covered stent. The indication for stent placement in all cases was a short and/or tortuous feeding artery. Safety was assessed by immediate or short-term complications, e.g., migration, stent thrombosis, and fracture. Technical success was defined as the ability to accurately place the stent at the intended location. Effectiveness was defined as successful exclusion of PAVM with no perfusion across the AVM. RESULTS: Technical success of stent placement was 100%. AVM exclusion rate was 80% after single stent deployment; in the case of incomplete exclusion, success was achieved using an overlapping stent to completely cover a second feeding artery. During the median follow-up period of 5 months (range 2-10), all stents remained patent, and AVMs were excluded without other complications. CONCLUSION: Exclusion of PAVMs with polyurethane-covered stents is technically feasible, safe, and shows short-term effectiveness for PAVMs with a short/tortuous feeding artery when traditional embolization techniques are not possible.

Preliminary Experience with a Low-Profile High-Density Braid Occluder for Transcatheter Embolization of Pulmonary Arteriovenous Malformations.

This brief report describes safety, technical feasibility, and early treatment effectiveness of the low-profile braided occluder (LOBO; Okami Medical, San Diego, Caliornia) for embolization of 9 pulmonary arteriovenous malformations (PAVMs) in 4 patients (3 female and 1 male; age range: 33 to 63 years; 3 patients showed positive results for hereditary hemorrhagic telangiectasia genes). A total of 10 occluders were deployed in 10 vessels (median treated vessel diameters, 3 and 4 mm for LOBO-3 and LOBO-5 groups, respectively). All devices were successfully deployed into the feeder pulmonary arteries, achieving complete cessation of flow. There were no severe adverse events or device migrations. Available short-term follow-up computed tomography (6 PAVMs: median, 7 months; range, 1.5-7 months) demonstrated complete occlusion without persistence or recanalization. The early experience of embolization of PAVMs using a low-profile braided occluder showed it to be safe and effective. Further studies with larger cohorts and longer follow-up periods are warranted.

Executive summary of the 14th HHT international scientific conference.

Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant vascular disorder characterized by small, dilated clustered vessels (telangiectasias) and by larger visceral arteriovenous malformations (AVMs), which directly connect the feeding arteries with the draining veins. These lesions are fragile, prone to rupture, and lead to recurrent epistaxis and/or internal hemorrhage among other complications. Germline heterozygous loss-of-function (LOF) mutations in Bone Morphogenic Protein 9 (BMP9) and BMP10 signaling pathway genes (endoglin-ENG, activin like kinase 1 ACVRL1 aka ALK1, and SMAD4) cause different subtypes of HHT (HHT1, HHT2 and HHT-juvenile polyposis (JP)) and have a worldwide combined incidence of about 1:5000. Expert clinicians and international scientists gathered in Cascais, Portugal from September 29th to October 2nd, 2022 to present the latest scientific research in the HHT field and novel treatment strategies for people living with HHT. During the largest HHT scientific conference yet, participants included 293 in person and 46 virtually. An impressive 209 abstracts were accepted to the meeting and 59 were selected for oral presentations. The remaining 150 abstracts were presented during judged poster sessions. This review article summarizes the basic and clinical abstracts selected as oral presentations with their new observations and discoveries as well as surrounding discussion and debate. Two discussion-based workshops were also held during the conference, each focusing on mechanisms and clinical perspectives in either AVM formation and progression or current and future therapies for HHT. Our hope is that this paper will represent the current progress and the remaining unanswered questions surrounding HHT, in order to serve as an update for those within the field and an invitation to those scientists and clinicians as yet outside of the field of HHT.

Multidisciplinary coordinated care of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease).

Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu disease, is a rare disorder with a case prevalence as high as one in 5000, causing arteriovenous malformations in multiple organ systems. HHT is familial with autosomal dominant inheritance, with genetic testing allowing confirmation of the diagnosis in asymptomatic kindreds. Common clinical manifestations are epistaxis and intestinal lesions causing anemia and requiring transfusions. Pulmonary vascular malformations predispose to ischemic stroke and brain abscess and may cause dyspnea and cardiac failure. Brain vascular malformations can cause hemorrhagic stroke and seizures. Rarely, liver arteriovenous malformations can cause hepatic failure. A form of HHT can cause juvenile polyposis syndrome and colon cancer. Specialists in multiple fields may be called to care for one or more aspects of HHT, but few are familiar with evidence-based guidelines for HHT management or see a sufficient number of patients to gain experience with the unique characteristics of the disease. Primary care physicians and specialists are often unaware of the important manifestations of HHT in multiple systems and the thresholds for their screening and appropriate management. To improve familiarity, experience, and coordinated multisystem care for patients with HHT, the Cure HHT Foundation, which advocates for patients and families with this disease, has accredited 29 centers in North America with designated specialists for the evaluation and care of patients with HHT. Team assembly and current screening and management protocols are described as a model for evidence-based, multidisciplinary care in this disease.

The role of interventional radiology in treatment of patients with hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) also known as Osler-Weber-Rendu disease is a rare autosomal dominant, multi-organ disorder that leads to formation of abnormal vascular connections resulting in devastating and life-threatening complications. Due to its multisystem character, wide range of clinical manifestations and variable expressivity, HHT remains a diagnostic challenge and requires close cooperation of specialists from various medical fields. Interventional radiology plays a key role in the management of this disease, helping maintain the health of HHT patients and minimize the risk of fatal complications. The aim of this article is to review clinical manifestations, diagnostic guidelines and criteria of HHT as well as to present the means of endovascular therapy in the management of HHT patients.

Endovascular embolization for the treatment of epistaxis: Systematic review and meta-analysis.

BACKGROUND: Endovascular embolization (EE) is a treatment option for epistaxis refractory to first-line interventions. Data regarding embolization is limited to small case series and a meta-analysis has not been performed. METHODS: PubMed, Scopus, and EMBASE were used to identify studies that reported outcomes for at least 10 patients undergoing EE for epistaxis. Outcomes included procedural success, rebleeding, and complications. Pooled rates for each outcome were obtained with random effects models. RESULTS: A total of 44 studies comprising 1664 patients met the inclusion criteria. The mean age ranged from 28.1 to 67 years and there were 28.4% females. The pooled procedural success rate was 87% (95% CI 83.9-89.6, I2 = 53%). Age (OR 0.95, 95% CI 0.91-1) and hereditary hemorrhagic telangiectasia ([HHT], OR 0.97, 95% CI 0.96-0.99) were associated with decreased odds of success. The pooled rebleeding rate was 16.4% (95% CI 13.6-19.6, I2 = 48%), and HHT was associated with greater odds of rebleeding (OR 1.02, 95% CI 1-1.03). The pooled overall complication rate was 14.4% (95% CI 9.8-20.6, I2 = 85.8%). The pooled rates of stroke and vision loss were 2.1% (95% CI 1.5-3.1, I2 = 1.5%) and 1.8% (95% CI 1.2-2.6, I2 = 0%), respectively. CONCLUSION: EE for epistaxis has a high rate of procedural success. Interventionalists should be aware of the risk for rebleeding, especially among patients with HHT.

Sclerotherapy for Hereditary Hemorrhagic Telangiectasia-Related Epistaxis: A Systematic Review.

OBJECTIVES: Hereditary hemorrhagic telangiectasia (HHT) is a common inherited condition characterized by mucosal telangiectasias, recurrent epistaxis, and arteriovenous malformations. HHT results in detriment to quality of life. Morbidity and mortality result from severe anemia. Conventional interventions for HHT-related epistaxis include nasal packing, diathermy, lasers, coblation, microdebridement, bevacizumab (topical and systemic), as well as septodermoplasty and nasal closure. Sclerotherapy has been recently described in the literature as a novel approach to HHT-related epistaxis. We hypothesize that sclerotherapy is an effective treatment for HHT-related epistaxis and improves upon the current standard of care for this disease. METHODS: A systematic review was conducted to study sclerotherapy for treating HHT-related epistaxis. Ovid MEDLINE, Ovid EMBASE, Scopus, and Web of Science were searched. Articles were evaluated and excluded according to PRISMA guidelines and reviewed by 2 authors. Reported variables included number of injections, months of follow up, changes in Epistaxis Severity Score, previous treatments used to control epistaxis, and post-injection side effects. RESULTS: Seven studies with a total of 196 patients met inclusion criteria. Three studies reported significant improvement as measured by the Epistaxis Severity Score scale. One reported improvement through subjective patient surveys and others used the Bergler-Sadick scale to measure frequency and intensity of epistaxis. All studies reported improvement in HHT-related epistaxis. The lack of uniform reporting measures however precluded formal meta-analysis. CONCLUSIONS: Based on limited data, sclerotherapy appears to be effective for treating HHT-related epistaxis and offers promise for treating this recalcitrant condition. However, larger, prospective, multi-centered studies using universally validated instruments for epistaxis are needed to definitively evaluate outcomes from sclerotherapy.

[Hereditary hemorrhagic telangiectasia (Rendu-Osler syndrome)]. / Nasledstvennaya gemorragicheskaya teleangiektaziya (sindrom Randyu­Oslera).

The analysis of publications is carried out and current data concerning the etiology, pathogenesis, diagnosis, and principles of treatment of hereditary hemorrhagic telangiectasia are presented.

The Importance of a Multidisciplinary Approach in a Patient with Long-term Multisystemic Manifestations of Unrecognized Hereditary Hemorrhagic Telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT), also called Rendu-Osler-Weber syndrome, is a rare autosomal dominant multisystemic vascular disorder, characterized by widespread mucocutaneous teleangiectasias, frequent visceral arteriovenous malformations (AVM) and a tendency for bleeding. This diagnosis should be suspected in all dermatological patients with generalized mucocutaneous vascular lesions at sites of predilection, associated frequent epistaxis and a positive family history. The aim of this paper is to emphasize the importance of a multidisciplinary approach, the role and timely cooperation of dermatologists and otorhinolaryngologists in the early clinical recognition and diagnosis of the disease. We present a family case of a 63-year - old patient with typical clinical features of HHT and long-standing multisystemic complications of unrecognized disease.

Periodontal treatment of patients with hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is a rare condition in which fragile vascular walls lead to increased risks of bleeding, cerebral abscesses, arteriovenous malformations, anemia, and thrombosis. To date, no protocol has been established for optimizing the clinical outcomes of periodontal treatment in patients with this condition. The aim of this case report is to describe a safe clinical approach to periodontal treatment in a patient with HHT. A 39-year-old woman had a history of multiple macules on the oral mucosa, and a diagnosis of HHT was made based on the Curaçao diagnostic criteria (epistaxis, telangiectases, visceral lesions, and family history). Evaluation of the patient's periodontal clinical parameters and radiographs led to a diagnosis of generalized periodontitis, stage IV, grade C. The patient underwent nonsurgical periodontal therapy consisting of supragingival and subgingival scaling and root planing under a careful and specific protocol that included antibiotic prophylaxis before each session. Two months after therapy, the periodontal reevaluation showed improvement in the clinical parameters at most sites. Sites with remaining periodontal pockets were re-treated according to the same protocol, including the antibiotic prophylaxis. The patient was enrolled in a periodontal maintenance program, and her HHT was routinely monitored by her physician. Periodontal treatment may promote secondary complications in patients with HHT if appropriate systemic care is not provided, and the periodontal treatment plan should be designed individually for each patient. Establishing the correct HHT diagnosis and coordinating care with the patient's physician are essential to safe, effective treatment.

CT Appearance of Pulmonary Arteriovenous Malformations and Mimics.

A pulmonary arteriovenous malformation (PAVM) is a fistulous connection between a pulmonary artery and a pulmonary vein that bypasses the normal pulmonary capillary bed resulting in a right-to-left shunt. Because of the potential for paradoxical emboli, PAVMs are treated when their feeding arteries exceed 3 mm or patients are symptomatic. PAVMs are often encountered in patients with suspected hereditary hemorrhagic telangiectasia (HHT). Sporadic cases are uncommon. The radiologist may be called on to diagnose a PAVM after positive transthoracic contrast-enhanced echocardiography in a patient with suspected HHT to direct patient management and avoid potential complications. The radiologist may also be required to evaluate a potential PAVM detected at CT performed for other reasons. Through the authors' experiences at an HHT Center of Excellence in an area endemic with histoplasmosis, the authors have gained a unique perspective on the diagnosis of PAVMs and differentiation of PAVMs from their mimics. Understanding the CT appearance of PAVMs limits misdiagnosis, directs appropriate treatment, and allows subsequent family screening for HHT (and avoidance of unnecessary screening when a PAVM mimic is encountered). Both vascular and nonvascular pulmonary lesions can mimic PAVMs. Vascular mimics include fibrosing mediastinitis, venovenous collaterals, arterial collaterals, pulmonary artery pseudoaneurysms, hepatopulmonary vessels, Sheehan vessels, meandering pulmonary veins, and pulmonary vein varices. Nonvascular mimics include granulomas, nodules, mucoceles, bronchoceles, ground-glass opacities, and atelectasis. The authors review the CT technique for evaluating PAVMs and the appearance of PAVMs and their mimics. ©RSNA, 2022.

Safety of reduced or absent antithrombotic therapy after left atrial appendage closure in patients affected by hereditary hemorrhagic telangiectasia and atrial fibrillation.

BACKGROUND: Left atrial appendage (LAA) closure represents a novel therapeutic chance for patients with contraindications to long-term anticoagulation therapy, such as those affected by hereditary hemorrhagic telangiectasia (HHT) and atrial fibrillation (AF). Nevertheless, current experts' indications suggest the postprocedural administration of antithrombotic therapies to minimize the residual thromboembolic risk due to AF and to the need for device endothelialization. The aim of our study was to investigate the safety and effectiveness of LAA closure in preventing arterial thromboembolism in a very high-bleeding risk group, such as HHT patients, who are at risk not to tolerate even the mild postprocedural antithrombotic therapy usually recommended. METHODS: Eight HHT-affected patients with non-valvular AF, high-bleeding risk and/or known intolerance to antiplatelet and anticoagulant therapy were treated with interventional LAA occlusion with the Amplatzer™ Cardiac Plug™ and Amplatzer™ Amulet™ devices. Device implantation was successful in all patients. RESULTS: Postprocedural antiplatelet/anticoagulation therapy was attempted in seven patients: adherence to therapy exceeded 6 months only for one, while four patients suspended all antithrombotic medications within 30 days from the procedure due to an increase in bleeding frequency and/or severity and the other two discontinued treatment within 6 months; a single patient was not prescribed any antithrombotic therapy. At a medium follow-up of 22.4±14.3 months no thromboembolic episodes attributable to AF or device related thrombosis were reported. Two deaths were recorded 1231 and 783 days after the procedure which were classified as unrelated to any cerebral or cardiovascular accident. CONCLUSIONS: Our study suggests that the percutaneous LAA closure in HHT patients with AF could be safe and effective in preventing arterial systemic thromboembolism, also in the presence of reduced or absent postinterventional antithrombotic treatment. LAA occluder implantation can represent a valid and potentially life-saving alternative to lifelong anticoagulant therapy in HHT, as in other very high-bleeding risk patients.

Improvement in epistaxis management: the experience of a dedicated hereditary haemorrhagic telangiectasia clinic.

BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is a rare genetic vascular disorder which is characterised by the development of arteriovenous malformations and telangiectasias. A key clinical manifestation is recurrent epistaxis. This study examined the impact of a dedicated HHT clinic in a major Australian tertiary hospital on epistaxis symptoms and subjective quality of life. METHODS: A multidisciplinary HHT clinic was established in 2015. All patients satisfied either genetic diagnosis or fulfilled Curacao criteria. A protocol based clinical assessment was performed and a standardised treatment regimen was implemented. Patients completed quality of life and epistaxis severity score (ESS) questionnaires at each review. RESULTS: Participants of the dedicated clinic included 21 females (58.3%) and 15 males (41.7%), with a mean age of 49.0 ± 24.0 years. The ACVRL1 variant was the most common (n = 20, 55.6%). A statistically significant reduction in epistaxis severity was noted between the baseline and second review (P = 0.02) and was maintained to the third visit (P = 0.015). Patients older than 50 years demonstrate a consistently higher ESS than those less than 50 years old (P = 0.03). This trend is noted throughout the follow up period with the dedicated clinic. CONCLUSION: The introduction of a multidisciplinary, dedicated HHT clinic to provide enhanced assessment, monitored treatment regimen and greater access to care, resulted in improvement in the management of epistaxis and quality of life in these patients.

The European Rare Disease Network for HHT Frameworks for management of hereditary haemorrhagic telangiectasia in general and speciality care.

Hereditary haemorrhagic telangiectasia (HHT) is a complex, multisystemic vascular dysplasia affecting approximately 85,000 European Citizens. In 2016, eight founding centres operating within 6 countries, set up a working group dedicated to HHT within what became the European Reference Network on Rare Multisystemic Vascular Diseases. By launch, combined experience exceeded 10,000 HHT patients, and Chairs representing 7 separate specialties provided a median of 24 years' experience in HHT. Integrated were expert patients who focused discussions on the patient experience. Following a 2016-2017 survey to capture priorities, and underpinned by more than 40 monthly meetings, and new data acquisitions, VASCERN HHT generated position statements that distinguish expert HHT care from non-expert HHT practice. Leadership was by specialists in the relevant sub-discipline(s), and 100% consensus was required amongst all clinicians before statements were published or disseminated. One major set of outputs targeted all healthcare professionals and their HHT patients, and include the new Orphanet definition; Do's and Don'ts for common situations; Outcome Measures suitable for all consultations; COVID-19; and anticoagulation. The second output set span aspects of vascular pathophysiology where greater understanding will assist organ-specific specialist clinicians to provide more informed care to HHT patients. These cover cerebral vascular malformations and screening; mucocutaneous telangiectasia and differential diagnosis; anti-angiogenic therapies; circulatory interplays between anaemia and arteriovenous malformations; and microbiological strategies to counteract loss of normal pulmonary capillary function. Overall, the integrated outputs, and documented current practices, provide frameworks for approaches that augment the health and safety of HHT patients in diverse health-care settings.