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

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.

Second International Guidelines for the Diagnosis and Management of Hereditary Hemorrhagic Telangiectasia.

DESCRIPTION: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease with an estimated prevalence of 1 in 5000 that is characterized by the presence of vascular malformations (VMs). These result in chronic bleeding, acute hemorrhage, and complications from shunting through VMs. The goal of the Second International HHT Guidelines process was to develop evidence-based consensus guidelines for the management and prevention of HHT-related symptoms and complications. METHODS: The guidelines were developed using the AGREE II (Appraisal of Guidelines for Research and Evaluation II) framework and GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. The guidelines expert panel included expert physicians (clinical and genetic) in HHT from 15 countries, guidelines methodologists, health care workers, health care administrators, patient advocacy representatives, and persons with HHT. During the preconference process, the expert panel generated clinically relevant questions in 6 priority topic areas. A systematic literature search was done in June 2019, and articles meeting a priori criteria were included to generate evidence tables, which were used as the basis for recommendation development. The expert panel subsequently convened during a guidelines conference to conduct a structured consensus process, during which recommendations reaching at least 80% consensus were discussed and approved. RECOMMENDATIONS: The expert panel generated and approved 6 new recommendations for each of the following 6 priority topic areas: epistaxis, gastrointestinal bleeding, anemia and iron deficiency, liver VMs, pediatric care, and pregnancy and delivery (36 total). The recommendations highlight new evidence in existing topics from the first International HHT Guidelines and provide guidance in 3 new areas: anemia, pediatrics, and pregnancy and delivery. These recommendations should facilitate implementation of key components of HHT care into clinical practice.

Screening children for pulmonary arteriovenous malformations: Evaluation of 18 years of experience.

BACKGROUND: Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disease with multi-systemic vascular dysplasia. Early diagnosis through screening is important to prevent serious complications. How best to screen children of affected parents for pulmonary arteriovenous malformations (PAVMs) is often subject to debate. Transthoracic contrast echocardiogram (TTCE) is considered optimal in screening for PAVMs in adults. Guidelines for the screening of children are not specific, reflecting the lack of scientific evidence on the best method to use. OBJECTIVE: Aims of this study are (i) to evaluate our current screening method, consisting of history, physical examination, pulse oximetry, and chest radiography and (ii) to assess whether postponing more invasive screening for PAVMs until adulthood is safe. METHODS: This is a prospective observational cohort study using a patient database. RESULTS: Over a period of 18 years (mean follow-up 9.21 years, SD 4.72 years), 436 children from HHT families were screened consecutively. A total of 175/436 (40%) children had a diagnosis of HHT. PAVMs were detected in 39/175 (22%) children, 33/39 requiring treatment by embolotherapy. None of the screened children suffered any PAVM-associated complications with this screening method. CONCLUSION: This study shows that a conservative screening method during childhood is sufficient to detect large PAVMs and protect children with HHT for PAVM-related complications. Postponing TTCE and subsequent chest CT scanning until adulthood to detect any smaller PAVMs does not appear to be associated with major risk.

Outcomes of pregnancy in women with hereditary hemorrhagic telangiectasia.

OBJECTIVE: To describe pregnancy outcomes in women with hereditary hemorrhagic telangiectasia (HHT). METHODS: This was a retrospective descriptive study of women with HHT (18-55 years of age) from the Toronto HHT Database using a telephone questionnaire regarding pregnancy, delivery, and neonatal outcomes. RESULTS: A total of 244 pregnancies were reported in 87 women with HHT. Miscarriages occurred in 20%. Hereditary hemorrhagic telangiectasia-related complications included minor hemoptysis during two pregnancies (1.1%) and hemothorax during four pregnancies (2.1%). One patient presenting with a hemothorax had presented during a previous pregnancy with a transient ischemic attack, most likely resulting from paradoxical emboli. One patient presented with an intracranial hemorrhage, and one patient presented with heart failure. These complications occurred in women previously unscreened and untreated for arteriovenous malformations. Other complications not clearly related to HHT were deep vein thrombosis (n=1), pulmonary embolism (n=1), myocardial infarction (n=1), and myocardial ischemia (n=1). Women noticed an increased frequency of epistaxis and development of new telangiectases during pregnancy. Epidural or spinal anesthesia was performed in 92 of 185 deliveries (50%) without complications. None of these women had undergone screening for spinal arteriovenous malformation before anesthesia. CONCLUSION: Women with HHT who have not been screened for arteriovenous malformations are at risk for serious pregnancy complications.