Screening for pulmonary and brain vascular malformations is the North American standard of care for patients with hereditary hemorrhagic telangiectasia (HHT): A survey of HHT Centers of Excellence

Kilian, Alexandra; Clancy, Marianne; Olitsky, Scott E.; Gossage, James R.; Faughnan, Marie E.

doi:10.1177/1358863x20974452

Cited by 11 publications

(8 citation statements)

References 18 publications

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“…Presence of pulmonary AVMs is not associated with worse mRS scores in the HHT patient population reported here. Serious complications, such as stroke, brain abscess and pulmonary hemorrhage have been associated with untreated pulmonary AVMs [ 41 ], though current practice is for routine asymptomatic screening and preventative management of pulmonary AVMs [ 23 ], since at least 2009 with publication of the first HHT Guidelines [ 24 ], and therefore the absence of association with poor functional scores is expected.…”

Section: Discussionmentioning

confidence: 99%

“…The study protocol was approved by the institutional review board at each recruiting centre. Patients were screened for organ VMs and other clinical features as part of their routine clinical care according to standard clinical practice [ 23 ] and International HHT Guidelines [ 24 , 25 ], including: comprehensive history, physical, routine blood tests, screening for pulmonary AVM by contrast echocardiography (in adults and children), brain VM screening by magnetic resonance imaging (in adults and children), clinical screening for liver VM (assessment for chronic right upper quadrant pain, portal hypertension, high-output heart failure, liver bruit on examination, abnormal liver function tests) and clinical screening for recurrent spontaneous epistaxis (> 1 episode per month for > 1 year), and HHT-related GI-bleeding (anemia, iron deficiency, known GI telangiectases on endoscopy, melena, rectal bleeding). As part of their routine clinical care, if screening was positive for pulmonary AVM or brain VM, patients underwent further diagnostic imaging and treatment, where appropriate.…”

Section: Methodsmentioning

confidence: 99%

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Utility of modified Rankin Scale for brain vascular malformations in hereditary hemorrhagic telangiectasia

Thompson

Nelson

Kim

et al. 2021

Orphanet J Rare Dis

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Background Approximately 10% of hereditary hemorrhagic telangiectasia (HHT) patients harbour brain vascular malformations (VMs). Intracranial hemorrhage (ICH) from brain VMs can lead to death or morbidity, while treatment options for brain VMs also have associated morbidity. The modified Rankin Scale (mRS) may provide an approach to identifying HHT-brain VM patients with poor outcomes, and their predictors. We aimed to measure the relationship between mRS score and brain VM, brain VM number, as well as other aspects of HHT, at enrollment and during prospective follow-up. Methods 1637 HHT patients (342 with brain VMs) were recruited from 14 HHT centres of the Brain Vascular Malformation Consortium since 2010 and followed prospectively (mean = 3.4 years). We tested whether the presence of brain VM, other HHT organ involvement, and HHT mutation genotype were associated with worse mRS scores at baseline and during follow-up, using linear mixed models, adjusting for age, sex, and year of visit. Results Presence of brain VMs was not associated with worse mRS score at baseline and there was no significant worsening of mRS with prospective follow-up in these patients; 92% had baseline mRS of 0–2. HHT-related gastrointestinal (GI) bleeding was associated with worse mRS scores at baseline (0.37, 95% CI 0.26–0.47, p < 0.001), as were history of anemia (0.35, 95% CI 0.27–0.43, p < 0.001) and liver VMs (0.19, 95% CI 0.09–0.30, p < 0.001). Presence of pulmonary arteriovenous malformations (AVMs) was not associated with worse mRS scores at baseline. mRS score was not associated with either HHT genotype (Endoglin vs ACVRL1). Only GI bleeding was associated with a significantly worsening mRS during prospective follow-up (0.64, 95% CI 0.21–1.08, p = 0.004). Conclusion Most HHT-brain VM patients had good functional capacity (mRS scores 0–2) at baseline that did not change significantly over 3.4 mean years of follow-up, suggesting that mRS may not be useful for predicting or measuring outcomes in these patients. However, HHT patients with GI bleeding, anemia history or liver VMs had worse mRS scores, suggesting significant impact of these manifestations on functional capacity. Our study demonstrates the insensitivity of the mRS as an outcomes measure in HHT brain VM patients and reinforces the continued need to develop outcomes measures, and their predictors, in this group.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Utility of modified Rankin Scale for brain vascular malformations in hereditary hemorrhagic telangiectasia

Thompson

Nelson

Kim

et al. 2021

Orphanet J Rare Dis

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“…Thus, screening for PAVMs is recommended in suspected and confirmed HHT to prevent serious sequelae, 7 and is currently the standard of care at North American accredited centers. 36 Transthoracic saline contrast echocardiography (‘bubble echo’) is the preferred initial screening test for pulmonary AVM. 7 In cases of grade 2 to 3 shunting or a high suspicion of PAVM with low grade (grade 1) or indeterminate shunts, we perform contrast-enhanced chest computed tomography angiography (CTA) using a modified pulmonary embolism protocol with a low-dose technique.…”

Section: Pulmonary Avms and Other Cardiopulmonary Manifestationsmentioning

confidence: 99%

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

Alkhalid,

Darji,

Shenkar

et al. 2023

Vasc Med

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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.

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“…Most cases of HHT are caused by mutations in ENG (endoglin) [3] or ACVRL1 (activin receptor like kinase 1, ALK1) [4] leading to HHT type 1 (HHT1) or HHT type 2 (HHT2), respectively. The clinical phenotypes are similar but HHT2 has lower penetrance and later onset and the frequency of pulmonary and cerebral AVMs is higher in HHT1 families [5,6].…”

Section: Introductionmentioning

confidence: 97%

Thresholds of Endoglin Expression in Endothelial Cells Explains Vascular Etiology in Hereditary Hemorrhagic Telangiectasia Type 1

Galaris

Montagne

Thalgott

et al. 2021

IJMS

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Hereditary Hemorrhagic Telangiectasia type 1 (HHT1) is an autosomal dominant inherited disease characterized by arteriovenous malformations and hemorrhage. HHT1 is caused by mutations in ENDOGLIN, which encodes an ancillary receptor for Transforming Growth Factor-β/Bone Morphogenetic Protein-9 expressed in all vascular endothelial cells. Haploinsufficiency is widely accepted as the underlying mechanism for HHT1. However, it remains intriguing that only some, but not all, vascular beds are affected, as these causal gene mutations are present in vasculature throughout the body. Here, we have examined the endoglin expression levels in the blood vessels of multiple organs in mice and in humans. We found a positive correlation between low basal levels of endoglin and the general prevalence of clinical manifestations in selected organs. Endoglin was found to be particularly low in the skin, the earliest site of vascular lesions in HHT1, and even undetectable in the arteries and capillaries of heterozygous endoglin mice. Endoglin levels did not appear to be associated with organ-specific vascular functions. Instead, our data revealed a critical endoglin threshold compatible with the haploinsufficiency model, below which endothelial cells independent of their tissue of origin exhibited abnormal responses to Vascular Endothelial Growth Factor. Our results support the development of drugs promoting endoglin expression as potentially protective.

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Screening for pulmonary and brain vascular malformations is the North American standard of care for patients with hereditary hemorrhagic telangiectasia (HHT): A survey of HHT Centers of Excellence

Cited by 11 publications

References 18 publications

Utility of modified Rankin Scale for brain vascular malformations in hereditary hemorrhagic telangiectasia

Utility of modified Rankin Scale for brain vascular malformations in hereditary hemorrhagic telangiectasia

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

Thresholds of Endoglin Expression in Endothelial Cells Explains Vascular Etiology in Hereditary Hemorrhagic Telangiectasia Type 1

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