Hereditary Hemorrhagic Telangiectasia (HHT) and Survival: The Importance of Systematic Screening and Treatment in HHT Centers of Excellence.

Els M De Gussem,Steven Kroon,Martijn C Post,Johannes J Mager,Anna E Hosman,Johannes C Kelder,Repke J Snijder

doi:10.3390/jcm9113581

Abstract

Hereditary hemorrhagic telangiectasia (HHT), an autosomal dominant disease, is characterized by telangiectases and arteriovenous malformations (AVMs). Untreated AVMs, especially in the lungs—pulmonary AVMs (PAVMs)—can result in morbidity with a decreased life expectancy. We have investigated whether HHT patients, systematically screened for HHT-related organ involvement and treated if needed, have a similar survival as persons without HHT. We included all individuals screened for HHT between 2004 and 2016 with a genetically or clinically confirmed diagnosis (HHT group) or excluded diagnosis (non-HHT control group). The social security number was used to confirm status as dead or alive in December 2019. We included 717 HHT patients and 471 controls. There was no difference in survival between the HHT and the non-HHT control group. The HHT group had a life expectancy of 75.9 years (95% confidence interval (CI) 73.3–78.6), comparable to the control group (79.3 years, 95% CI 74.8–84.0, Mantel–Cox test: p = 0.29). In conclusion, the life expectancy of HHT patients systematically screened for HHT-related organ involvement and treated if needed in an HHT center of excellence was similar compared to their controls, justifying systematic screening and treatment in HHT patients.

Highlights

Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disease, with prevalence rates between 1:5000 and 1:8000 and with approximately 85,000 affected citizens in Europe [1,2]
The prevalence of pulmonary arteriovenous malformation (PAVM) and cerebral vascular malformation (CVM) depends on the HHT type: PAVMs occur in up to 60% of patients with HHT type 1 and 5–10% of patients with HHT type 2, and CVMs occur in 8–16% in HHT type 1 and in 0.5–1.5% in HHT type 2 [5]
We found that the life expectancy of patients with HHT who have been systematically screened for HHT-related organ involvement, treated if needed and followed in a center with HHT expertise did not differ from the life expectancy of the non-HHT control group

Summary

Introduction

Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disease, with prevalence rates between 1:5000 and 1:8000 and with approximately 85,000 affected citizens in Europe [1,2]. HHT is characterized by multi-systemic vascular lesions, known as telangiectases, and visceral arteriovenous malformations (AVMs). The visceral AVMs are usually asymptomatic but can result in severe morbidity and mortality. Much rarer than PAVMs, cerebral vascular malformations (CVMs) can result in severe morbidity and mortality. A PAVM is a direct connection between the pulmonary artery and pulmonary vein with the absence of a normal capillary bed. Due to the absence of the normal capillaries, septic or non-septic emboli can enter the systemic circulation resulting in strokes and brain abscesses [6]. For patients with CVMs, treatment versus conservative management, should be considered on a case-by-case basis [7]

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Conclusion