Pulmonary Arteriovenous Malformations Background Pulmonary arteriovenous malformations (PAVMs) are structurally abnormal vessels that bypass the pulmonary capillary bed through direct communication between the pulmonary artery and pulmonary vein and thus create an anatomic right-to-left shunt These malformations result in a low-resistance, high-flow state causing impairment in gas exchange and impaired filtration of the systemic venous blood (Fig 50.6).46,47 The degree of right-to-left shunting causes varying degrees of hypoxemia, from asymptomatic to profoundly symptomatic PAVMs predispose to complications such as paradoxical systemic embolization, stroke, and cerebral abscess Treatment of asymptomatic PAVMs is recommended to prevent long-term complications, TCE is currently the accepted standard of care,46,47 and this can be achieved using low doses of x-ray radiation.47–50 PAVMs were historically considered to be rare based on early autopsy studies,51 but modern sophisticated diagnostic tools have suggested a prevalence of 2 to 3 per 100,000,52,53 with a male to female ratio ranging from 1 : 1.5 to 1.8.54 A population-based cancer screening program suggests the incidence to be 1 in 2630 of PAVMs that are sufficiently large to be detected by CT.55 PAVMs may be single or multiple, simple or complex, or diffuse, which are mostly confined to the lower lobes.56–58 The simple PAVMs receive blood from a single artery involving a single sac (Figs 50.7 and 50.8), whereas complex PAVMs can involve two or three arteries creating a plexiform mass of dilated vascular channels or tortuous communications between artery and vein (see Fig 50.7).59 A small subset of patients have a more diffuse and severe type of PAVMs involving single or several segmental pulmonary arteries The diffuse PAVMs are more common in both lungs (72%) FIG 50.6 Primary functions of the pulmonary capillary vascular beds that are bypassed in patients with pulmonary arteriovenous malformations (Modified from Sholvin CL, Chamali B, Santhirapala V, et al Ischaemic strokes in patients with pulmonary arteriovenous malformations and hereditary hemorrhagic telangiectasia: associations with iron deficiency and platelets PLoS One 2014;9[2]:e88812.) FIG 50.7 Illustration demonstrating normal pulmonary capillary bed (A) and types of pulmonary arteriovenous malformation (PAVM): Simple PAVM (B) and complex PAVM (C) (Modified from Trerotola SO, Pyeritz RE PAVM embolization: an update AJR Am J Roentgenol 2010;19[4]:837–845.) FIG 50.8 Thoracic chest computed tomography (A) and angiogram (B) demonstrating solitary pulmonary arteriovenous malformation (PAVM) with afferent (black arrow) and efferent limbs (white arrow) Embolization at the neck of the aneurysm (C) using an Amplatzer vascular plug Most PAVMs are hereditary, occurring in 90% of patients with HHT, and the remaining are sporadic or idiopathic.46,60–62 HHT is the most common cause of PAVMs It is a genetic disorder with an autosomal dominant trait, affecting 1 in 50,000 to 80,000 people.63,64 It is characterized by dermal, mucosal, and visceral telangiectasias and visceral AVMs (pulmonary, hepatic, gastrointestinal, and cerebrovascular) Gene coding mutations are responsible for HHT, and 85% of the cases are caused by one of three gene mutations: ENG coding for endoglin (HHT 1) on chromosome 9, ACVLR1/ALK 1 (HHT2) (Activin A Receptor, Type II-Like Kinase 1) mutation on chromosome 12, or SMAD4 (HTJP) gene coding on chromosome 18 that is associated with juvenile polyposis.46,60–62,65,66 There are currently two further unidentified genes causing HHT, mapped to chromosome 5q (HHT 3) and chromosome 7p (HHT4).61 The prevalence of PAVMs is related to the genotype of HHT In one large study, PAVM was commonly associated with ENG mutation in 58% compared with only 18% with ACVL1/ALK 1.67 The recognition of PAVMs has increased due to awareness of HHT, such that 59% of patients with PAVMs who were previously unaware were diagnosed with HHT.68 The HHT Foundation international guidelines working group established the Curacao criteria as the basis of diagnosis and an indication for subsequent genetic testing to confirm the diagnosis The diagnosis of definite HHT is accepted if at least three of the following characteristics of the disease are met: (1) spontaneous and recurrent epistaxis, (2) family history of a first-