Hanny Al-Samkari, Cassi Friday, R. Kasthuri, James R. Gossage, Charles Griffin Murphy, Peter Hountras, Karen Smith, Kristi Jackson Kirkland, Vivek Iyer, Vikas Prasad, Vaibhav Ahluwalia, Josanna Rodriguez-Lopez, Alison S. Witkin, Miles Conrad, S Hetts, Michael A. Ohliger, Murali M. Chakinala, Bryan A. Sisk, Melissa Beasley, P. Kirkpatrick, Jonathan Lindquist, John T. Battaile, An Lu, Joseph G. Parambil, KR McCrae, V. Sheynzon, Kevin Whitehead, Cassidy Sion, Justin P. McWilliams, Lucas R. Cusumano, Scott O. Trerotola, Theodore G. Drivas, Mark S. Chesnutt, Claire Kaufman, Melissa Ann Dickey, Danielle Boyce, Nolie Krock, Crystal Cottrill, Tania Competiello, Hara Levy, Marianne S. Clancy, Katharine Henderson, J. Pollak
ABSTRACT: Hereditary hemorrhagic telangiectasia (HHT), an autosomal dominant vasculopathy affecting 1 in 5000 individuals, is the second most common inherited bleeding disorder worldwide. Despite this prevalence, comprehensive data on disease manifestations and complications remain limited. To address this gap, the US Congress allocated funding leading to the Comprehensive HHT Outcomes Registry of the United States (CHORUS), a prospective, 15-center longitudinal registry enrolling unselected patients with confirmed HHT. In this initial report, we describe findings from the first 600 participants, with a median age of 53 (range, 0-88) years and 60% female. Despite most participants developing typical HHT manifestations by age 13 years, the majority (63%) were not diagnosed until mid-to-late adulthood. Recurrent spontaneous epistaxis occurred in 95% of participants, chronic gastrointestinal bleeding in 30%, and heavy menstrual bleeding in 35% of postmenarche females, together resulting in moderate-to-severe mucosal bleeding in 76%. Iron deficiency and/or anemia were diagnosed in 68%, with 41% requiring IV iron and 25% requiring red cell transfusions. Serious complications of solid-organ arteriovenous malformations were frequent, including intracranial hemorrhage (3%), pulmonary hemorrhage (2%), venous thromboembolism (7%), arterial thromboembolism (11%), heart failure (7%), and pulmonary hypertension (7%). These data from CHORUS, the first national US registry of its kind, provide reliable, real-world estimates of the incidence, prevalence, and severity of numerous HHT manifestations and complications. HHT has a high burden of moderate-to-severe bleeding, anemia, thrombosis, and major neurologic and cardiopulmonary complications. There is a mean interval between first symptoms and diagnosis of >2 decades, during which substantial, serious, and preventable HHT morbidity, including early intracranial hemorrhage, may occur. This trial was registered at clinicaltrials.gov as NCT06259292.