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Predictors of mortality in patients with hereditary hemorrhagic telangiectasia.

Publication ,  Journal Article
Thompson, KP; Nelson, J; Kim, H; Pawlikowska, L; Marchuk, DA; Lawton, MT; Faughnan, ME ...
Published in: Orphanet J Rare Dis
January 6, 2021

BACKGROUND: Retrospective questionnaire and healthcare administrative data suggest reduced life expectancy in untreated hereditary hemorrhagic telangiectasia (HHT). Prospective data suggests similar mortality, to the general population, in Denmark's centre-treated HHT patients. However, clinical phenotypes vary widely in HHT, likely affecting mortality. We aimed to measure predictors of mortality among centre-treated HHT patients. HHT patients were recruited at 14 HHT centres of the Brain Vascular Malformation Consortium (BVMC) since 2010 and followed annually. Vital status, organ vascular malformations (VMs) and clinical symptoms data were collected at baseline and during follow-up (N = 1286). We tested whether organ VMs, HHT symptoms and HHT genes were associated with increased mortality using Cox regression analysis, adjusting for patient age, sex, and smoking status. RESULTS: 59 deaths occurred over average follow-up time of 3.4 years (max 8.6 years). A history of anemia was associated with increased mortality (HR = 2.93, 95% CI 1.37-6.26, p = 0.006), as were gastro-intestinal (GI) bleeding (HR = 2.63, 95% CI 1.46-4.74, p = 0.001), and symptomatic liver VMs (HR = 2.10, 95% CI 1.15-3.84, p = 0.015). Brain VMs and pulmonary arteriovenous malformations (AVMs) were not associated with mortality (p > 0.05). Patients with SMAD4 mutation had significantly higher mortality (HR = 18.36, 95% CI 5.60-60.20, p < 0.001) compared to patients with ACVRL1 or ENG mutation, but this estimate is imprecise given the rarity of SMAD4 patients (n = 33, 4 deaths). CONCLUSIONS: Chronic GI bleeding, anemia and symptomatic liver VMs are associated with increased mortality in HHT patients, independent of age, and in keeping with the limited treatment options for these aspects of HHT. Conversely, mortality does not appear to be associated with pulmonary AVMs or brain VMs, for which patients are routinely screened and treated preventatively at HHT Centres. This demonstrates the need for development of new therapies to treat chronic anemia, GI bleeding, and symptomatic liver VMs in order to reduce mortality among HHT patients.

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Published In

Orphanet J Rare Dis

DOI

EISSN

1750-1172

Publication Date

January 6, 2021

Volume

16

Issue

1

Start / End Page

12

Location

England

Related Subject Headings

  • Telangiectasia, Hereditary Hemorrhagic
  • Retrospective Studies
  • Prospective Studies
  • Humans
  • Genetics & Heredity
  • Endoglin
  • Arteriovenous Fistula
  • Activin Receptors, Type II
  • 3202 Clinical sciences
  • 3105 Genetics
 

Citation

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Thompson, K. P., Nelson, J., Kim, H., Pawlikowska, L., Marchuk, D. A., Lawton, M. T., … Brain Vascular Malformation Consortium HHT Investigator Group, . (2021). Predictors of mortality in patients with hereditary hemorrhagic telangiectasia. Orphanet J Rare Dis, 16(1), 12. https://doi.org/10.1186/s13023-020-01579-2
Thompson, K. P., J. Nelson, H. Kim, L. Pawlikowska, D. A. Marchuk, M. T. Lawton, Marie E. Faughnan, and Marie E. Brain Vascular Malformation Consortium HHT Investigator Group. “Predictors of mortality in patients with hereditary hemorrhagic telangiectasia.Orphanet J Rare Dis 16, no. 1 (January 6, 2021): 12. https://doi.org/10.1186/s13023-020-01579-2.
Thompson KP, Nelson J, Kim H, Pawlikowska L, Marchuk DA, Lawton MT, et al. Predictors of mortality in patients with hereditary hemorrhagic telangiectasia. Orphanet J Rare Dis. 2021 Jan 6;16(1):12.
Thompson, K. P., et al. “Predictors of mortality in patients with hereditary hemorrhagic telangiectasia.Orphanet J Rare Dis, vol. 16, no. 1, Jan. 2021, p. 12. Pubmed, doi:10.1186/s13023-020-01579-2.
Thompson KP, Nelson J, Kim H, Pawlikowska L, Marchuk DA, Lawton MT, Faughnan ME, Brain Vascular Malformation Consortium HHT Investigator Group. Predictors of mortality in patients with hereditary hemorrhagic telangiectasia. Orphanet J Rare Dis. 2021 Jan 6;16(1):12.
Journal cover image

Published In

Orphanet J Rare Dis

DOI

EISSN

1750-1172

Publication Date

January 6, 2021

Volume

16

Issue

1

Start / End Page

12

Location

England

Related Subject Headings

  • Telangiectasia, Hereditary Hemorrhagic
  • Retrospective Studies
  • Prospective Studies
  • Humans
  • Genetics & Heredity
  • Endoglin
  • Arteriovenous Fistula
  • Activin Receptors, Type II
  • 3202 Clinical sciences
  • 3105 Genetics