Ultra-low dose chest CT for the diagnosis of pulmonary arteriovenous malformation in patients with hereditary hemorrhagic telangiectasia.

PURPOSE: The purpose of this study was to compare ultra-low dose (ULD) and standard low-dose (SLD) chest computed tomography (CT) in terms of radiation exposure, image quality and diagnostic value for diagnosing pulmonary arteriovenous malformation (AVM) in patients with hereditary hemorrhagic telangiectasia (HHT). MATERIALS AND METHODS: In this prospective board-approved study consecutive patients with HHT referred to a reference center for screening and/or follow-up chest CT examination were prospectively included from December 2020 to January 2022. Patients underwent two consecutive non-contrast chest CTs without dose modulation (i.e., one ULD protocol [80 kVp or 100 kVp, CTDIvol of 0.3 mGy or 0.6 mGy] and one SLD protocol [140 kVp, CTDIvol of 1.3 mGy]). Objective image noises measured at the level of tracheal carina were compared between the two protocols. Overall image quality and diagnostic confidence were scored on a 4-point Likert scale (1 = insufficient to 4 = excellent). Sensitivity, specificity, positive predictive value and negative predictive value of ULD CT for diagnosing pulmonary AVM with a feeding artery of over 2 mm in diameter were calculated along with their 95% confidence intervals (CI) using SLD images as the standard of reference. RESULTS: A total of 44 consecutive patients with HHT (31 women; mean age, 42 ± 16 [standard deviation (SD)] years; body mass index, 23.2 ± 4.5 [SD] kg/m2) were included. Thirty-four pulmonary AVMs with a feeding artery of over 2 mm in diameter were found with SLD images versus 35 with ULD images. Sensitivity, specificity, predictive positive value, and predictive negative value of ULD CT for the diagnosis of PAVM were 100% (34/34; 95% CI: 90-100), 96% (18/19; 95% CI: 74-100), 97% (34/35; 95% CI: 85-100) and 100% (18/18; 95% CI: 81-100), respectively. A significant difference in diagnostic confidence scores was found between ULD (3.8 ± 0.4 [SD]) and SLD (3.9 ± 0.1 [SD]) CT images (P = 0.03). No differences in overall image quality scores were found between ULD CT examinations (3.9 ± 0.2 [SD]) and SLD (4 ± 0 [SD]) CT examinations (P = 0.77). Effective radiation dose decreased significantly by 78.8% with ULD protocol, with no significant differences in noise values between ULD CT images (16.7 ± 5.0 [SD] HU) and SLD images (17.7 ± 6.6 [SD] HU) (P = 0.07). CONCLUSION: ULD chest CT provides 100% sensitivity and 96% specificity for the diagnosis of treatable pulmonary AVM with a feeding artery of over 2 mm in diameter, leading to a 78.8% dose-saving compared with a standard low-dose protocol.

Antiplatelet and anticoagulant therapies in hereditary hemorrhagic telangiectasia: A large French cohort study (RETROPLACOTEL).

BACKGROUND: It is unclear whether hereditary hemorrhagic telangiectasia (HHT) patients can tolerate antithrombotic therapies (AT) including antiplatelet (AP) and/or anticoagulant (AC) agents. OBJECTIVES: Primary endpoint was tolerance to AT in HHT. Secondary endpoints were to identify factors associated with major bleeding events (MBE) and premature discontinuation of AT. METHODS: Retrospective multicenter study in French national HHT Registry patients exposed to AT. RESULTS: We included 126 patients with 180 courses of AT. Median follow-up was 24 [11-52] months. Mean age was 65.6 ± 13.1 years. The first 3 months of AT exposure had an increased risk of hospitalization for hemorrhage (p < 0.001) and transfusions (p < 0.001). MBE (n = 63) occurred more frequently in the first 3 months of AT exposure (p < 0.001). Premature discontinuation of AT occurred in 61 cases. Rate of premature discontinuation was 29 % under both AP and AT therapy but significantly higher under dual AP therapy (n = 4/7, 57 % p = 0.008). Risk factors for MBE were: age ≥ 60 years (HR 2.34 [1.12;4.87], p = 0.023), prior hospitalization in the 3 months before starting AT for hemorrhage (HR 3.59 [1.93;6.66], p < 0.001) or transfusion (HR 3.15 [1.61;6.18], p = 0.001), previous history of gastro-intestinal bleeding (HR 2.71 [1.57;4.65], p < 0.001) or MBE (HR 4.62 [2.68;7.98], p < 0.001). Frequency of MBE did not differ between groups except for a higher risk in the dual AP group (HR 3.92 [1.37;11.22], p = 0.011). CONCLUSION: Tolerance of AC or AP therapy was similar in HHT population but not dual AP therapy. We identified risk factors for MBE occurrence or premature discontinuation under AT.

Obstetrical and neonatal complications in hereditary haemorrhagic telangiectasia: A retrospective study.

OBJECTIVE: To retrospectively describe a large series of pregnancies in women with hereditary haemorrhagic telangiectasia followed in our reference centre, plus neonatal outcomes, to better understand the risks of complications and to improve their prevention. DESIGN: A retrospective descriptive study conducted through a phone questionnaire. SETTING: Reference centre for hereditary haemorrhagic telangiectasia in Lyon, France. POPULATION: Women meeting the following criteria: (1) alive and aged ≥18 years; (2) with a definite clinical and/or genetic diagnosis of hereditary haemorrhagic telangiectasia; and (3) with at least one full-term pregnancy. MAIN OUTCOME MEASURES: Maternal and perinatal outcomes of pregnancies in women with hereditary haemorrhagic telangiectasia. RESULTS: Five hundred and sixty-two pregnancies were reported in 207 women with hereditary haemorrhagic telangiectasia. A total of 271 complications (48.2%) were registered. Of these, 149 (55%) non-specific complications, 110 (40.6%) non-severe specific complications and 12 (4.4%) severe specific complications were registered. There were four cases of haemoptysis and two cases of transient ischaemic attack related to pulmonary arteriovenous malformations. Four patients had severe decompensated dyspnoea, related to pulmonary arteriovenous malformations in three cases and to pulmonary arteriovenous malformations associated with severe hepatic arteriovenous malformations in one case. Hepatobiliary necrosis occurred in one case. Epidural or spinal anaesthesia was performed in 139 of 452 deliveries (31%), without complications. There were 12 reports of congenital anomalies in 461 live births (3%). CONCLUSIONS: Most pregnancies in hereditary haemorrhagic telangiectasia women are uneventful; complications are rare but can be severe. Women thus need to be educated about screening and possible pregnancy-related risks before becoming pregnant.

Embolization of Recurrent Pulmonary Arteriovenous Malformations by Ethylene Vinyl Alcohol Copolymer (Onyx®) in Hereditary Hemorrhagic Telangiectasia: Safety and Efficacy.

OBJECTIVES: To evaluate short- and long-term safety and efficacy of embolization with Onyx® for recurrent pulmonary arteriovenous malformations (PAVMs) in hereditary hemorrhagic telangiectasia (HHT). METHODS: In total, 45 consecutive patients (51% women, mean (SD) age 53 (18) years) with HHT referred to a reference center for treatment of recurrent PAVM were retrospectively included from April 2014 to July 2021. Inclusion criteria included evidence of PAVM recurrence on CT or angiography, embolization using Onyx® and a minimal 1-year-follow-up CT or angiography. Success was defined based on the standard of reference criteria on unenhanced CT or pulmonary angiography if a recurrence was suspected. PAVMs were analyzed in consensus by two radiologists. The absence of safety distance, as defined by a too-short distance for coil/plug deployment, i.e., between 0.5 and 1 cm, between the proximal extremity of the primary embolic material used and a healthy upstream artery branch, was reported. RESULTS: In total, 70 PAVM were analyzed. Mean (SD) follow-up was 3 (1.3) years. Safety distance criteria were missing in 33 (47%) PAVMs. All procedures were technically successful, with a short-term occlusion rate of 100% using a mean (SD) of 0.6 (0.5) mL of Onyx®. The long-term occlusion rate was 60%. No immediate complication directly related to embolization was reported, nor was any severe long-term complication such as strokes or cerebral abscesses. CONCLUSIONS: In HHT, treatment of recurrent PAVM with Onyx® showed satisfactory safety and efficacy, with an immediate occlusion rate of 100% and a long-term rate of 60%.

Hereditary haemorrhagic telangiectasia and pregnancy: a review of the literature.

BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited genetic vascular disorder that has prevalence of 1:5000 to 1:8000, and which is characterised by recurrent epistaxis, cutaneous telangiectasia, and arteriovenous malformations (AVMs) that affect many organs including the lungs, gastrointestinal tract, liver, and central nervous system. The aim here was to carry out a review of the literature on HHT complications during pregnancy in order to guide management decisions. MAIN BODY: A literature review was carried out to analyse all publications on complications that occurred during pregnancy in women with HHT. The PubMed/Medline and Scopus databases were searched. The complications observed in HHT women during pregnancy were then described. The authors identified 5 case series and 31 case reports that describe the evolution of 1577 pregnancies in 630 women with HHT. The overall maternal death rate described in the case series was estimated at 1.0% of pregnancies in the case series and 2 maternal deaths occurred in 31 pregnancy case reports. Severe maternal complications occurred in 2.7 to 6.8% of pregnancies in the case series. Severe complications occurred mostly in the second and third trimester in non-diagnosed and non-screened HHT patients. Severe complications were related to visceral involvement. The most frequent complications were related to pulmonary arteriovenous malformations (PAVMs) (haemothorax (n = 10), haemoptysis (n = 4), and severe hypoxaemia (n = 3)). Neurological complications were related to PAVMs in one case (right to left shunt) and to cerebral arteriovenous malformations (CAVM) and intracranial haemorrhage in 2 cases. Complications were related to hepatic arteriovenous malformations (HAVMs) in 8 cases (acutely decompensated heart failure due to hepatic involvement (n = 1), dyspnoea related to heart failure (n = 5), and hepatobiliary necrosis (n = 2)). CONCLUSION: Based on the literature review, most pregnancies in HHT women occur normally. However, these pregnancies should be considered high-risk, given the potential life-threatening events related to AVM rupture. Furthermore, there is currently no international consensus regarding the medical follow-up of pregnancy in women with HHT and the aim here was to carry out a review of the literature in order to guide screening and management decisions for this rare disease.