In the normal pulmonary circulation, blood leaves the right ventricle of the heart via the pulmonary artery, and the entire blood volume is routed to the pulmonary capillary bed adjacent to alveoli, allowing for gas exchange. The normal diameter of blood vessels making up the pulmonary capillary bed is approximately 6 µm.1 After drainage from the pulmonary capillaries, the blood then returns to the heart via the pulmonary veins. Pulmonary arteriovenous malformations (PAVMs) are abnormal vascular connections between pulmonary arteries and pulmonary veins, preventing exposure of blood to normal pulmonary capillaries and many times leading to hypoxemia due to shunting of deoxygenated blood into the pulmonary venous system and into the systemic circulation. Additionally, the size of these abnormal connections is typically larger than the size of pulmonary capillaries, allowing for transmission of particles in the blood stream (e.g., venous thromboemboli) from the venous circulation into the arterial circulation, leading to complications like stroke or septic emboli. Pulmonary AVMs are commonly aneurysmal and can frequently be seen macroscopically on advanced imaging (e.g., CT angiography).
Pulmonary AVMs were first described by Churton in 1897 in an autopsy case report of a 12-year-old boy with hemoptysis, epistaxis, and edema.2 In the early 20th century, PAVMs were found to be associated with hereditary hemorrhagic telangiectasia3 (HHT; also known as Osler–Weber–Rendu syndrome), a genetic vascular disorder manifesting with mucocutaneous telangiectasia and AVMs of various organ systems, including the lung. It is now known that at least 60% to 70% of PAVMs are associated with HHT,4,5 although some reports indicate rates of up to 95%.6
In this chapter, we discuss the epidemiology, pathobiology, and etiologies of pulmonary AVMs, clinical manifestations and diagnostic evaluation of these abnormalities, associated complications, and management options.
EPIDEMIOLOGY OF PULMONARY AVMs
PAVMs are generally uncommon, occurring in only 3 cases among 15,000 consecutive autopsies performed at Johns Hopkins Hospital7 (translating to a disease prevalence of 0.02%). However, disease frequency has been found to be higher in populations of patients with HHT—reported in case series as ranging from 17%8 to 48%.9 PAVMs occur about twice as often in women compared with men,4,10 although a majority of cases identified in newborns occur in males.11
Disease frequency of HHT varies between populations, estimated at 1 in 8000 in a northern Japanese population,12 1 in 6000 in European populations,13 and 1 in 16,500 the U.S. state of Vermont.5 A study of U.S. insurance claims data found a disease prevalence of 0.33 cases per 10,000 individuals.14 However, a few geographically isolated populations show higher prevalence, likely due to founder events; for example, 1 in 1331 individuals was found to be affected in the Afro-Caribbean population of the Netherlands Antilles.15 These statistics likely underestimate the true disease prevalence of this rare disease ...