Abstract W MP120: Hemorrhage Rates from Brain Arteriovenous Malformations in HHT Patients

Abstract

Introduction: Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disease caused by mutations in transforming growth factor-beta signaling genes (ENG, ALK1, or SMAD4), and is characterized by mucocutaneous telangiectasia and arteriovenous malformations (AVM) primarily in brain, lung and liver. In contrast to sporadic brain AVM, HHT brain AVMs are often multiple though small series to date have suggested that they may have a lower risk of intracranial hemorrhage (ICH). We sought to describe ICH rates and characteristics in HHT patients with brain arteriovenous malformations (HHT-BAVM). Methods: We collected data from the first 134 HHT-BAVM patients with follow-up enrolled in the BVMC HHT Project, including age, sex, race, HHT gene mutation, and ICH at diagnosis. We performed Kaplan-Meier survival analysis to estimate ICH rates after diagnosis censoring at date of first treatment, death or last follow-up, out to 15 years. Results: The majority of patients were female (57%) and Caucasian (93%). HHT gene mutation status was known in 57%, of which 74% had ENG mutations, 23% ALK1, and 3% SMAD4. The mean age at BAVM diagnosis was 30±19 years (range: 0-70), with over half of cases diagnosed based on asymptomatic screening (54%). Among symptomatic cases, 32% presented initially with ICH. During 482 person-years of follow-up, there were 5 ICH events corresponding to a rate of 1.04% per year (95% CI: 0.43 - 2.49%). ICH-free survival differed significantly by ICH presentation (P=0.003); ruptured cases had a higher rate (5.23%, 95% CI: 1.31 - 20.89%) than unruptured cases (0.51%, 95% CI: 0.13 - 2.04%). ICH-free survival did not differ by gender (P=0.285). Conclusions: HHT-BAVM patients who present with hemorrhage are at a higher risk for rehemorrhage compared to BAVMs detected presymptomatically in HHT patients. Correlation with unruptured sporadic BAVM cases will however need a larger sample and number of events in the HHT BAVM cohort. Ongoing recruitment of HHT-BAVM patients into the BVMC study will increase precision of ICH estimates and ability to examine additional risk factors such as angiographic features that may differ from sporadic BAVM.