Frequency of treatable and complex pulmonary arteriovenous malformations in hereditary hemorrhagic telangiectasia, according to HHT1 versus HHT2 genotype.

Purpose: Hereditary hemorrhagic telangiectasia (HHT) is attributable to mutations of either the ENG (HHT1) or ALK-1 (HHT2) gene in approximately 85% of patients. Phenotypic expression differs between the HHT1 and HHT2 populations; these differences may dictate distinct clinical considerations in screening and management. Current screening for pulmonary arteriovenous malformations (PAVMs) uses contrast echocardiography (CE) to identify right-to-left shunting; if positive, patients are referred for chest CT to identify any PAVMs. Treatment is more challenging in patients with complex PAVMs. The purpose of the present study is to analyze the number and type of PAVMs in these two populations. Materials and Methods: With IRB approval, retrospective review of consecutive visits to our HHT Center by patients with known HHT1 or HHT2 status identified 101 patients with positive CE who had undergone chest CT screening. 46 patients were HHT1, 55 were HHT2. Chest CTs were reviewed to evaluate the frequency and type of PAVMs. Results: Of HHT1 patients, 35/46 (76.1%) had PAVM on chest CT, compared to 21/55 (38.2%) of HHT2 patients with PAVM (p<0.001). Average age of HHT1 patients with PAVM was 37.9 years, versus 41.0 years for HHT2 patients with PAVM (p=0.86). HHT1 patients with PAVM had a mean of 4.7 (+/- 12.44) PAVMs each, whereas HHT2 patients with PAVM had a mean of 1.6 (+/- 1.36) PAVMs each (p=0.152). In HHT1 patients with PAVM, 23/35 (65.7%) had at least 1 treatable PAVM; in HHT2 patients, 12/21 (57.1%) had at least 1 treatable PAVM (P=0.536). Amongst those with treatable PAVMs, 8/23 HHT1 patients (34.8%) had 1 or more complex PAVM, whereas 5/12 HHT2 patients (41.7%) had at least 1 complex PAVM (p=0.706). Conclusion: On chest CT, the incidence of identifiable PAVMs is significantly higher in HHT1 than HHT2. However, in patients demonstrating any PAVM, the number of PAVMs per patient, rate of treatable PAVMs, and rate of complex treatable PAVMs were not statistically different between the 2 groups. These findings add to our understanding of phenotypic differences between HHT1 and HHT2, and cognizance of these findings will guide the Interventionalist toward greater success in managing these patients. [Copyright &y& Elsevier]