Predictors of mortality in patients with hereditary hemorrhagic telangiectasia

Thompson, K. P.; Nelson, Jeffrey; Kim, Helen; Pawlikowska, Ludmila; Marchuk, Douglas A.; Lawton, M; Faughnan, Marie E.

doi:10.1186/s13023-020-01579-2

Cited by 13 publications

(7 citation statements)

References 38 publications

(52 reference statements)

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“…It has been previously demonstrated that HHT patients with GI bleeding experience significant morbidity, requiring more transfusions and more emergency room and hospital admissions than other HHT patients [ 30 ]. Additionally, we recently reported that chronic GI bleeding is associated with increased mortality in HHT patients [ 31 ], in keeping with our observed higher mRS scores associated with this HHT manifestation. Further, a report on acute ischemic stroke patients (not HHT) demonstrated that patients who developed GI bleeding had a higher rate of mortality and disability (mRS grade greater than or equal to 4) than those who did not [ 32 ].…”

Section: Discussionsupporting

confidence: 92%

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: Discussionsupporting

confidence: 92%

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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“…Among HHT patients, 20 (48%) had BAVM, 30 (71%) had pulmonary arteriovenous malformation (PAVM), 9 (21%) had gastrointestinal (GI) bleeding, and 3 of 37 with information (8%) had symptomatic liver vascular malformations (LVM). HHT organ involvement was defined as previously described [ 18 ].…”

Section: Resultsmentioning

confidence: 99%

Pilot investigation of circulating angiogenic and inflammatory biomarkers associated with vascular malformations

Wetzel-Strong

Weinsheimer

Nelson

et al. 2021

Orphanet J Rare Dis

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Background Vascular malformations in the central nervous system are difficult to monitor and treat due to their inaccessible location. Angiogenic and inflammatory proteins are secreted into the bloodstream and may serve as useful biomarkers for identifying patients at risk for complications or with certain disease phenotypes. Methods A validated multiplex protein array consisting of 26 angiogenic and inflammatory biomarkers (Angiome) was assessed in plasma isolated from healthy controls and patients with either sporadic brain arteriovenous malformation (BAVM), familial cerebral cavernous malformation (CCM), or hereditary hemorrhagic telangiectasia (HHT). These samples were obtained from archives of ongoing research studies at the University of California San Francisco and through prospective collection at the Toronto HHT Centre at St. Michael’s Hospital. Results We compared circulating biomarker levels from each patient group to healthy controls and analyzed each pairwise combination of patient groups for differences in biomarker levels. Additionally, we analyzed the HHT samples to determine the association between biomarker levels and the following HHT-specific phenotypes, BAVM, pulmonary arteriovenous malformation (PAVM), liver vascular malformation (LVM), and gastrointestinal (GI) bleeding. Compared to controls, levels of SDF1 were significantly elevated in HHT patients (Proportional Increase [PI] = 1.87, p < 0.001, q = 0.011). Levels of sENG were significantly reduced in HHT patients compared to controls (PI = 0.56, p < 0.001, q < 0.001), reflecting the prevalence of HHT1 patients in this cohort. Levels of IL6 (PI = 3.22, p < 0.001, q < 0.001) and sTGFβR3 (PI = 0.70, p = 0.001, q < 0.029) differed significantly in CCM patients compared to controls. Compared to controls, ten of the biomarkers were significantly different in sporadic BAVM patients (q-values < 0.05). Among the pairwise combinations of patient groups, a significant elevation was observed in TGFβ1 in CCM patients compared to sporadic BAVM patients (PI = 2.30, p < 0.001, q = 0.034). When examining the association of circulating biomarker levels with HHT-specific phenotypes, four markers were significantly lower in HHT patients with BAVM (q-values < 0.05), and four markers were significantly higher in patients with LVM (q-values < 0.05). Conclusions This pilot study suggests that the profile of circulating angiogenic and inflammatory biomarkers may be unique to each type of vascular malformation. Furthermore, this study indicates that circulating biomarkers may be useful for assessing phenotypic traits of vascular malformations.

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“…The liver is the most commonly affected organ (hepatic AVMs) ( 8 ); however, the treatment options are limited and unsatisfactory. Although the vast majority of liver VMs are asymptomatic and do not require treatment, symptomatic liver VMs must be treated aggressively since they increase mortality ( 9 ). Intravenous bevacizumab helps relieve symptoms and has been used as a bridge to orthotopic liver transplant (OLT) ( 10 ).…”

Section: Discussionmentioning

confidence: 99%

Right hemihepatectomy combined with ligation of the common hepatic artery and gastroduodenal artery for the treatment of intrahepatic HHT: A case report

et al. 2022

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Hereditary haemorrhagic telangiectasia (HHT) is a rare disease that lacks effective treatment. Here, the authors report the case of a 30-year-old woman presenting with abdominal pain accompanied by severe malnutrition. After a definite diagnosis of HHT involvement in the liver, liver transplantation was the first-choice treatment according to the guidelines of HHT. However, the patient firmly refused liver transplantation. Finally, a new type of surgery, right hemihepatectomy combined with ligation of the common hepatic artery and gastroduodenal artery, was performed based on careful study of the case and with the maximum benefit of the patient in mind. Although the patient developed transient liver dysfunction after surgery, she eventually recovered well and continued to be followed up. As far as we know, this is the first report of this kind of surgery for the treatment of intrahepatic HHT.

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Predictors of mortality in patients with hereditary hemorrhagic telangiectasia

Cited by 13 publications

References 38 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

Pilot investigation of circulating angiogenic and inflammatory biomarkers associated with vascular malformations

Right hemihepatectomy combined with ligation of the common hepatic artery and gastroduodenal artery for the treatment of intrahepatic HHT: A case report

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