Pulmonary Arteriovenous Malformations

Matthew F. Abts, MD, and Susanna A. McColley, MD, FAAP, FCCP

Introduction/Etiology/Epidemiology

Definition

Pulmonary arteriovenous malformations (PAVMs) are abnormal fistulous connections between pulmonary arteries and veins that bypass the alveolar-capillary network and prevent the exchange of oxygen.

Etiology/Epidemiology

•PAVMs have an incidence rate of 2 to 3 per 100,000 people, with a female-to-male ratio of 1.5 to 1.0.

•Congenital (>80%): May be idiopathic or associated with hereditary hemorrhagic telangiectasia (HHT), an autosomal dominant disorder characterized by vascular shunts in multiple organ systems

•Acquired (<20%): May be due to infection, chest trauma, cardiac surgery, hepatic cirrhosis, Fanconi anemia, malignancy, and/or pregnancy

Pathophysiology

Underlying Pathogenesis

•Possibly due to incomplete resorption of vascular septae during fetal capillary development and the formation of cavernous, thin-walled vascular beds

•HHT-associated PAVMs due to mutations in the endoglin (ENG) gene, activin A receptor type II kinase 1 (ALK1/ACVRL1) gene, or MADH4 gene

Anatomic Characteristics

•Defect commonly occurs at the arteriolar level but may be more proximal.

•HHT-associated PAVMs are usually multiple, involving the lower lobes.

•Idiopathic PAVMs are usually isolated or single lesions with no lobe preference.

•Most PAVMs are peripheral and frequently involve the pleura.

—Simple (80%): Aneurysmal fistulous sac with a single afferent artery and 1 or more draining veins

—Complex (20%): Multilobed fistulous sac with multiple feeding arteries and draining vessels

—Diffuse (rare): May involve whole lung segments or entire lobe(s)

—Telangiectatic: Subtle, multiple, and associated with HHT

Physiology

•Right to left intrapulmonary shunting and systemic hypoxemia

•Deoxygenated pulmonary arterial blood from the right side of the heart flowing through 1 or more fistulous vascular conduits (PAVMs) and directly into the pulmonary venous circulation, thereby completely bypassing the alveolar-capillary network

Natural History

•Time, hemodynamic stress, and hormonal changes as seen during puberty and pregnancy may cause progressive enlargement and wall necrosis or erosion of PAVMs.

Clinical Features

•Half of cases are asymptomatic and may not appear until early adulthood.

•Symptoms are more common when lesions are large in size and/or number.

•Symptoms and signs usually do not appear until right-to-left shunt accounts for >20% of systemic cardiac output.

Signs and symptoms include

•Dyspnea

•Chest pain

•Cough

•Cyanosis

•Clubbing

•Hemoptysis

•Thoracic bruit or thrill

•Hypoxemia that does not improve with administration of supplemental oxygen

•Platypnea: Dyspnea in the upright position that is relieved with recumbence

•Orthodeoxia: Decrease in oxyhemoglobin saturation ≥2% in the upright position

•Hepatopulmonary syndrome

—Seen in the context of chronic liver disease and portal hypertension

—Intrapulmonary capillary and/or venous dilations with right-to-left shunting and clinical manifestations that overlap with PAVMs

•Radiographically, PAVMs may be confused with

—Pulmonary artery aneurysmal disease

—Pulmonary sequestration

—Congenital pulmonary airway malformation

—Bronchogenic cyst

—Bronchocele

—Infection or pneumonia

—Vascular tumors

Diagnostic Considerations

Chest Radiography

•PAVMs are well-circumscribed, round areas of soft-tissue density (usually 1–2 cm in diameter) with accompanying linear extensions that represent afferent or efferent vessels.

•Small or complex PAVMs may be less well defined.

•The preferred initial screening test for those with suspected PAVM, this modality is useful in diagnosing hepatopulmonary syndrome.

•It is a noninvasive and highly sensitive test that confirms the presence of right-to-left shunting (sensitivity of 100% and negative predictive value of 100% for PAVMs).

•Imaging is performed by injecting agitated saline (“microbubbles”) into the peripheral venous system and observing its passage through the cardiopulmonary cycle via 2-dimensional echocardiography.

•Right-to-left shunting is confirmed by the presence of unfiltered microbubbles within the left atrium. If present, the quantity of microbubbles (grading) present in the left atrium over time (timing) is helpful in predicting the location and size of the suspected lesion.

Management

Not all PAVMs require intervention, particularly in the asymptomatic child. The decision to pursue therapy should be based on individual patient characteristics, the size and number of vascular lesions, and the relative risks and/or benefits of each type of procedure.

Embolotherapy

•If HHT is suspected, international HHT guidelines suggest referral to a center experienced in caring for patients with this relatively rare condition.

•Iron supplementation may be indicated if iron-deficiency anemia is present.

•Avoid air emboli during intravenous infusions.

•Antibiotic prophylaxis may be indicated for nonsterile surgeries (eg,  dental work).

•The patient should avoid scuba diving because of the risk of air emboli.

Expected Outcomes/Prognosis

Complications

•Reactive polycythemia due to chronic hypoxemia

•Iron deficiency anemia

•Pulmonary hemorrhage due to ruptured PAVM

•Hemothorax due to ruptured PAVM

•Paradoxical emboli

•Migraine headaches

•Cerebrovascular or transient ischemic attacks

•Brain abscesses and/or endocarditis

•Pulmonary hypertension

•High-output cardiac failure (usually only seen in HHT)

Short-term Complications after Embolization

•Pleuritic chest pain (the most common complication; may respond to short-term corticosteroids)

•Transient ischemic attacks, stroke

•Dislodgement and migration of embolic material

•Arterial perforation

Long-term Complications after Embolization

•Growth of pulmonary or systemic collateral vessels

•Worsening pulmonary hypertension

•Chronic pleurisy

Prognosis

•PAVMs do not resolve spontaneously.

•Prognosis is dependent on the severity of lesion(s) and presence of comorbidities.

•Prognosis is worse in high-risk individuals (adolescents, pregnant women).

•Embolotherapy carries a success rate as high as 98%.

•Children with unexplained hypoxemia should be referred to an experienced pulmonologist for thorough evaluation.

•Any suspicion for underlying HHT necessitates referral to a medical center with staff experienced in caring for patients with this relatively rare condition.

When to Admit

•Persistent hypoxemia, dyspnea, and/or hemoptysis

•Acute neurological or mental status changes in the setting of known PAVM

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