Cure HHT

This case report describes a 45-year-old female with HHT type 1 (ENG mutation) and congenital heart disease (sinus venosus atrial septal defect and partial anomalous pulmonary venous return), diagnosed with severe PAH at age 16. Despite long-term treatment with epoprostenol, treprostinil, macitentan, and tadalafil, her condition progressed, leading to evaluation for lung transplantation. In May 2024, sotatercept, a novel TGF-β superfamily ligand trap, was initiated, resulting in significant improvement in exertional capacity and quality of life. The patient experienced increased epistaxis frequency (2–4 episodes/week), though hemoglobin levels rose from 13.0 to 15.4 g/dL. No new telangiectasias or other adverse events were noted. This is the first reported case of sotatercept use in PAH with HHT, highlighting its potential efficacy but also the need for careful monitoring due to increased bleeding risk.

BackgroundPatients with hereditary hemorrhagic telangiectasia (HHT) are at risk for organ vascular malformations including arteriovenous malformations (AVMs) in the brain and lungs. North American HHT Centers of Excellence (CoEs) routinely screen for brain and lung AVMs, with the primary goal of detecting AVMs which can be treated before complications arise. Current international HHT guidelines provide recommendations for initial screening for brain and lung AVMs among children and adults with the disease, but rescreening recommendations are not comprehensively addressed and have not been reported. We determined current rescreening practices for brain and lung AVMs for children and adults with HHT among North American HHT CoEs.MethodsWe surveyed North American HHT CoEs regarding rescreening practices for new brain and lung AVMs in children and adults with initial negative screening.ResultsAll thirty CoEs responded; 28 regarding pediatric (93.3%) and 30 (100%) regarding adult HHT care. The median duration of practice experience in HHT was 11.5 (range 3–30) years for providers of pediatric HHT care and 11.5 (range 3–35) years for providers of adult HHT care. The median number of patients followed at each CoE was 60 for children (range 8–500) and 375 for adults (range 30–1500). 25/28 CoEs (89.3%) reported rescreening children for brain AVMs, most commonly with enhanced MRI (21/25, 84%). 25 CoEs rescreen children for lung AVMs, most commonly every 5 years (15/25). Only 4/30 CoEs (13.3%) rescreen adults for brain AVMs. 26/30 CoEs (86.7%) reported rescreening adults for lung AVMs, most commonly every 5 years (18/26, 69.2%).ConclusionsMost HHT CoEs routinely rescreen children for brain and lung AVMs and adults for lung AVMs when initial screening is negative, but adults are infrequently rescreened for brain AVMs. Long-term data regarding risk for new brain and lung AVMs are required to establish practice guidelines for rescreening.

Develop a multi-functional imaging system that combines 1.7 µm optical coherence tomography/angiography (OCT/OCTA) to accurately interrogate Hereditary Hemorrhagic Telangiectasia (HHT) skin lesions. The study involved imaging HHT skin lesions on five subjects including lips, hands, and chest. We assessed the attributes of both HHT lesions and the healthy vasculature around them in these individuals, employing quantifiable measures such as vascular density and diameter. Additionally, we performed scans on an HHT patient who had undergone anti-angiogenic therapy, allowing us to observe changes in vasculature before and after treatment. The results from this pilot study demonstrate the feasibility of evaluating the HHT lesion using this novel methodology and suggest the potential of OCTA to non-invasively track HHT lesions over time. The average percentage change in density between HHT patients' lesions and control was 37%. The percentage increase in vessel diameter between lesion and control vessels in HHT patients was 23.21%. In this study, we demonstrated that OCTA, as a functional extension of OCT, can non-invasively scan HHT lesions in vivo. We scanned five subjects with HHT lesions in various areas (lip, ear, finger, and palm) and quantified vascular density and diameter in both the lesions and adjacent healthy tissue. This non-invasive method will permit a more comprehensive examination of HHT lesions. This method of non-invasive imaging could offer new insights into the physiology, management, and therapeutics of HHT-associated lesion development and bleeding.

Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant vascular disorder characterized by small, dilated clustered vessels (telangiectasias) and by larger visceral arteriovenous malformations (AVMs), which directly connect the feeding arteries with the draining veins. These lesions are fragile, prone to rupture, and lead to recurrent epistaxis and/or internal hemorrhage among other complications. Germline heterozygous loss-of-function (LOF) mutations in Bone Morphogenic Protein 9 (BMP9) and BMP10 signaling pathway genes (endoglin-ENG, activin like kinase 1 ACVRL1 aka ALK1, and SMAD4) cause different subtypes of HHT (HHT1, HHT2 and HHT-juvenile polyposis (JP)) and have a worldwide combined incidence of about 1:5000. Expert clinicians and international scientists gathered in Cascais,Portugal from September 29th to October 2nd, 2022 to present the latest scientific research in the HHT field and novel treatment strategies for people living with HHT. During the largest HHT scientific conference yet, participants included 293 in person and 46 virtually. An impressive 209 abstracts were accepted to the meeting and 59 were selected for oral presentations. The remaining 150 abstracts were presented during judged poster sessions. This review article summarizes the basic and clinical abstracts selected as oral presentations with their new observations and discoveries as well as surrounding discussion and debate. Two discussion-based workshops were also held during the conference, each focusing on mechanisms and clinical perspectives in either AVM formation and progression or current and future therapies for HHT. Our hope is that this paper will represent the current progress and the remaining unanswered questions surrounding HHT, in order to serve as an update for those within the field and an invitation to those scientists and clinicians as yet outside of the field of HHT.

The authors assessed the accuracy of cause(s) of subfertility as reported by women in a self-administered questionnaire in comparison with medical record information, in a nationwide cohort study of women receiving in vitro fertilization treatment in the Netherlands (n = 9,164) between 1983 and 1995. Validity was expressed as sensitivity and specificity, and reliability was expressed by the kappa statistic and overall agreement between self-reports and medical records for various subfertility categories. The sensitivity for subfertility attributed to tubal, male, hormonal, cervical, uterine, and idiopathic factors and for endometriosis was 84%, 78%, 65%, 40%, 46%, 59%, and 83%, respectively. The corresponding kappas were 0.79, 0.71, 0.38, 0.34, 0.13, 0.50, and 0.52, respectively. For 54% of all women who reported two or more causes of subfertility, the medical record revealed only one major factor. Conversely, for 43% of all women whose subfertility was attributed to two or more major factors in the record, only one factor was reported by the women. Older age at the time of filling out the questionnaire, low educational level, long duration of subfertility, and pre-in vitro fertilization treatment were associated with less accurate reporting. The results indicate that the validity of self-reports for tubal and male subfertility is satisfactory. For unexplained subfertility, the validity is moderate; for other causes of subfertility and when two causes of subfertility play a role, the validity is low.