Pulmonary Arteriovenous Fistulae 

Updated: Jan 29, 2015
Author: Barry A Love, MD; Chief Editor: Howard S Weber, MD, FSCAI 

Overview

Background

Pulmonary arteriovenous malformations (PAVMs) were first described in 1897. They consist of abnormal communications between the pulmonary arteries and the pulmonary veins. These are also referred to as pulmonary arteriovenous fistulae.

Most patients with pulmonary arteriovenous malformations have the autosomal dominant disease hereditary hemorrhagic telangiectasia (HHT). However, at least 15% of patients with pulmonary arteriovenous malformations do not meet criteria for the diagnosis of HHT and have no other systemic disease. Pulmonary arteriovenous malformations may also be an acquired condition found in patients with liver disease, mainly liver cirrhosis. In these patients, absence of a hepatic "factor" may lead to the development of pulmonary arteriovenous malformations. Patients with congenital heart disease in whom the systemic venous return to the lungs does not include blood return from the hepatic veins also develop pulmonary arteriovenous malformations.

Pulmonary arteriovenous malformations may also be acquired rarely secondary to chronic infections such as schistosomiasis, actinomycosis, tuberculosis, and metastatic thyroid cancer. These arteriovenous malformations may form a communication between pulmonary artery and pulmonary vein or between a bronchial artery and the pulmonary vein.

Hereditary hemorrhagic telangiectasia

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder. The clinical manifestations are secondary to growth of vascular malformations in various organs, most commonly the skin, nasopharynx, GI tract, lungs, and brain. HHT is generally recognized as a triad of cutaneous telangiectasia, recurrent epistaxis, and a family history of this disorder (see the image below).[1]

Mucosal telangiectasias are shown in a patient wit Mucosal telangiectasias are shown in a patient with hereditary hemorrhagic telangiectasia (HHT).

Approximately 70% of pulmonary arteriovenous malformation cases are associated with HHT. Conversely, approximately 15-35% of persons with HHT have pulmonary arteriovenous malformations.

Anatomy

Approximately 53-70% of pulmonary arteriovenous malformations are found in the lower lobes. See the images below.

Left lower lobe arteriovenous malformation (AVM). Left lower lobe arteriovenous malformation (AVM).
Lateral radiograph showing a left lower lobe arter Lateral radiograph showing a left lower lobe arteriovenous malformation (AVM).

Approximately 70% of patients have unilateral disease, 36% have multiple lesions, and 50% of those with multiple lesions have bilateral disease. Pulmonary arteriovenous malformations may be microscopic (ie, telangiectasis), but they are typically 1-5 cm. Occasionally, pulmonary arteriovenous malformations as large as 10 cm are encountered. Approximately 10% of patients may have diffuse microvascular pulmonary arteriovenous malformations in combination with larger, radiographically visible pulmonary arteriovenous malformations.

The vascular channels are thin walled and lined with a layer of endothelium. The connective tissue stroma is scant and has no communication with the surrounding lung. Most pulmonary arteriovenous malformations drain into the left atrium, but anomalous drainage to the inferior vena cava or innominate veins has been reported. The malformations may appear as one of the following: a large single sac, a plexiform mass of dilated vascular channels, or a dilated tortuous direct communication between artery and vein.

Anatomy of subtypes

Pulmonary arteriovenous malformations can be classified as simple or complex types on the basis of their architecture. Simple pulmonary arteriovenous malformations have a single feeding segmental artery leading to single draining pulmonary vein. Approximately 79% of pulmonary arteriovenous malformations are of the simple type;[2] most of the associated aneurysms are nonseptate and occur in the lower lobes. Approximately 21% of pulmonary arteriovenous malformations are complex, having 2 or more feeding arteries or draining veins. They often occur in the lingula and right middle lobe distributions. See the image below.

Large left lower lobe arteriovenous malformation ( Large left lower lobe arteriovenous malformation (AVM) showing a feeding vessel to the left atrium.

Pathophysiology

Physiology

In a pulmonary arteriovenous malformation, blood bypasses the normal oxygen-exchanging pulmonary capillary bed, returning desaturated to the pulmonary veins. When the return of desaturated blood to the pulmonary veins becomes significant, measurable arterial oxygen desaturation and cyanosis results. Because most pulmonary arteriovenous malformations are found in the lower lobes and, in the upright position, more blood is directed to the lower lobes because of gravity, the patient with significant pulmonary arteriovenous malformations demonstrates orthodeoxia, which is a fall in arterial oxygen saturation when in the upright position. If the patient becomes significantly desaturated in the upright position, the patient also demonstrates platypnea, which is dyspnea in the upright position, although this symptom is seen only in advanced cases.

The resultant cyanosis leads to a compensatory rise in hematocrit and hemoglobin concentration roughly proportional to the degree of chronic desaturation. However, bleeding from epistaxis and from GI telangiectasias may reduce the hemoglobin concentrations in patients with HHT and lead to iron deficiency anemia.

Larger arteriovenous malformations allow particles of significant size to pass unfiltered from the systemic venous system to the left atrium and systemic arterial circulation. Stroke from paradoxical embolization is a risk in patients with macroscopic arteriovenous malformations.

Unlike systemic arteriovenous malformations, pulmonary arteriovenous malformations do not lead to high-output cardiac failure even when large. This is because the rate-limiting portion of the circulation is the systemic arterial resistance. Systemic arteriovenous malformations lower the overall total systemic venous resistance and increase venous return, which is a synonym for cardiac output. The pulmonary vascular resistance is normally low and is not rate-limiting. Lowering the total pulmonary vascular resistance further does not increase the cardiac output. See the Cardiac Output and the Pulmonary Vascular Resistance calculators.

A few caveats with this explanation are necessary. First, by causing cyanosis, pulmonary arteriovenous malformations cause the cardiac index to somewhat increase in order to maintain adequate oxygen delivery. Second, liver cirrhosis by itself causes systemic vasodilation and a hyperdynamic circulation, even in the absence of pulmonary arteriovenous malformations. Third, patients with HHT may have other systemic arteriovenous malformations, especially cerebral and hepatic, which may lead to reduced systemic vascular resistance and a high cardiac output state.

In HHT, mutations of 2 genes make up most cases. Endoglin gene mutations lead to the clinical subtype of HHT-1, and mutations in the activin A receptor type II-like 1 gene (ACVRL1) lead to the clinical subtype HHT-2. Most mutations described are family-specific without a "common mutation" pattern that is often seen in other inherited conditions.

Endoglin and ACVRL-1 bind tumor growth factor-beta (TGFβ), which is implicated in angiogenesis. Pulmonary arteriovenous malformations likely develop as a result of interplay of various factors among diverse cells and matrix during vascular insults. Changes in endoglin and ALK might cause endothelial cells to respond abnormally to TGFβ during the process of vascular remodeling, resulting in the formation of arteriovenous malformations.

The pathogenesis of pulmonary arteriovenous malformations in liver and congenital cardiac disease is not understood. A postulated absence of "hepatic factor" is made based on the following observations:

In congenital heart disease where the pulmonary circulation lacks any component from the hepatic veins (ie, following a Glenn-type palliation in which the superior vena cava is directly connected to the pulmonary arteries as the sole source of pulmonary blood flow), pulmonary arteriovenous malformations begin to develop after several years and enlarge further if no change is made to the circulation.

Some patients with liver disease, mainly cirrhosis, develop pulmonary arteriovenous malformations. Initially, these are microscopic and progress in the absence of intervention to larger macroscopic arteriovenous malformations.

Patients with congenital cardiac disease with a Glenn-type circulation have regression of small pulmonary arteriovenous malformations if venous return from the hepatic veins is provided to the pulmonary circulation. Larger pulmonary arteriovenous malformations may not regress, implying a threshold over which humoral control is no longer possible.

Patients with liver disease who develop pulmonary arteriovenous malformations have regression of the pulmonary arteriovenous malformations if they undergo liver transplantation. Patients with extensive pulmonary arteriovenous malformations due to liver disease and significant arterial desaturation at rest may not be candidates for liver transplantation because of the very high mortality in this setting.

In the early phases of progression of arteriovenous malformations seen in both congenital heart disease and liver disease, administration of 100% oxygen usually overcomes the A-a gradient, and the patient becomes fully saturated with a high PaO2. This implies that the pathophysiology of the arteriovenous malformations in these conditions is dilation of the normal capillary bed.

In the early phases, a normal PAO2 is insufficient to overcome the diffusion gradient to the center of these dilated beds, resulting in some desaturation and an A-a gradient. However, with administration of 100% FiO2, the A-a gradient may be overcome, and the PaO2 increases to near-expected levels, abolishing the A-a gradient. In later stages, when the arteriovenous malformations become macroscopic, even 100% FiO2 does not overcome the A-a gradient, and the patient remains desaturated. See the A-a Gradient calculator.

Pathogenesis

The exact pathogeneses of pulmonary arteriovenous malformations is unknown. In the terminal arterial loops, a defect that allows dilatation of the thin-walled capillary sacs may occur. Alternatively, pulmonary arteriovenous malformations are the result of incomplete resorption of the vascular septa that separate the arterial and venous plexus, which normally anastomose during fetal development. Some have also suggested that multiple small pulmonary arteriovenous malformations develop as a result of capillary development failure during fetal growth. The large saccular pulmonary arteriovenous malformations develop by means of progressive dilation of the smaller plexus, leading to the formation of tortuous loops and multiloculated sacs. With time, the intervening vascular walls may rupture, resulting in the formation of a single large saccular pulmonary arteriovenous malformation.

Natural history

The natural history of pulmonary arteriovenous malformations has not been studied carefully. The initial manifestation of HHT is the appearance of cutaneous telangiectases or epistaxis. Fewer than 10% of patients who have visceral involvement by arteriovenous malformations have visceral signs and symptoms (eg, dyspnea or GI bleeding) as the initial manifestation of HHT. The visceral manifestations occur in adults, reflecting the additional time needed for the enlargement of arteriovenous malformations.

In one study of 16 patients, serial chest radiographs obtained over a median observation period of 18.9 years demonstrated enlargement in 4 patients and near total regression in 1 patient. The growth rate tended to be slow, with an increase of approximately 5-10 mm every 5-15 years.

Epidemiology

Frequency

United States

In a 1953 study from The Johns Hopkins Hospital, 3 cases of pulmonary arteriovenous malformations were detected in 15,000 consecutive autopsies. The Mayo Clinic encountered 63 cases during the 20 years ending in 1972, and 38 cases were encountered during the subsequent 9 years ending in 1981. Approximately 70% of the cases of pulmonary arteriovenous malformations are associated with HHT, which is an autosomal dominant disorder. Conversely, approximately 15-35% of persons with HHT have pulmonary arteriovenous malformations.

To screen for occult brain, lung, and liver arteriovenous malformations in pediatric patients with confirmed HHT, a study undertook molecular analysis and clinical assessment.[3] The molecular analysis demonstrated the mutation-carrier status in 22 of 35 children. Nasal telangiectases were found in 68%, mucocutaneous telangiectases (fingers, lips, oral cavity) in 79%, pulmonary arteriovenous malformations in 53%, hepatic arteriovenous malformations (HAVMs) in 47%, and cerebral arteriovenous malformations and/or cerebral ischemic changes secondary to pulmonary arteriovenous malformations in 12%.

Mortality/Morbidity

Mortality of pulmonary arteriovenous malformations is somewhat difficult to determine because of the association in many with HHT. Patients with HHT may also have arteriovenous malformations in the liver and head, as well as intestinal telangiectasias that also put them at risk for premature mortality.

Mortality caused by pulmonary arteriovenous malformations is due to rupture, brain abscess, and stroke due to paradoxical embolization. In addition, therapeutic interventions for pulmonary arteriovenous malformations carry a low risk of mortality.

The risk of mortality appears to be significantly higher in patients with bilateral, diffuse pulmonary arteriovenous malformations. In study of 26 patients followed for 27 years with diffuse bilateral pulmonary arteriovenous malformations, 2 died of complications related to the pulmonary arteriovenous malformations directly: one due to hemoptysis from rupture, and the other from cerebral abscess.[4] Seven others died from other organ involvement with HHT.

Sex

Pulmonary arteriovenous malformations occur twice as often in women than in men, but a male predominance is observed among newborns.

Age

Approximately 10% of the cases of pulmonary arteriovenous malformations are identified in infancy or childhood; however, the incidence gradually increases through the fifth and sixth decades of life.

 

Presentation

History

Symptoms caused by pulmonary arteriovenous malformations (AVMs) are often insidious, as the arteriovenous malformations slowly enlarge.

Dyspnea, especially with exercise, may develop over many years. In severe cases, dyspnea in the upright position (platypnea) may be present. Visible cyanosis may be present if a significant degree of desaturation is present.

Hemoptysis and rarely massive hemoptysis may occur.

Less common complaints include chest pain, cough, migraine headaches, tinnitus, dizziness, dysarthria, syncope, vertigo, and diplopia. The cause of these symptoms is not entirely clear, but it may be related to hypoxemia, polycythemia, or paradoxical embolization through the pulmonary arteriovenous malformations.

Physical

Murmurs or bruits over the location of the pulmonary arteriovenous malformations are heard in patients with large pulmonary arteriovenous malformations. These murmurs are most audible during inspiration and are called machinery murmurs.

Digital clubbing and cyanosis may be observed.

The phenomenon of orthodeoxia (desaturation with upright position) is characteristic. Because pulmonary arteriovenous malformations are more frequently found in the lower lobes, with upright position, more blood is directed to the lower lobes because of the effects of gravity, exacerbating the degree of shunting. In addition, platypnea (dyspnea with upright position) may also be noted because of the increased degree of cyanosis.

Because most patients with pulmonary arteriovenous malformations also have HHT, the characteristic mucocutaneous telangiectasias are frequently observed in patients with pulmonary arteriovenous malformations. These lesions are papular, slightly rounded, and sharply demarcated from surrounding skin. They have a few dendritic projections that are ruby colored and partially blanche with pressure. The lesions are present on the face, mouth, chest, and upper extremities (see the image below).

Mucosal telangiectasias are shown in a patient wit Mucosal telangiectasias are shown in a patient with hereditary hemorrhagic telangiectasia (HHT).

Certainly, the finding of mucocutaneous telangiectasias should prompt a workup for HHT and include evaluation for pulmonary arteriovenous malformations.

Causes

Epidemiology

Great heterogeneity of symptoms is noted among different families and within single large families with HHT. Some families with HHT predominantly have the pulmonary arteriovenous malformations and cerebral arteriovenous malformations; whereas other affected families predominantly have GI mucosal telangiectasis, which lead to GI bleeding and iron-deficiency anemia.

Inheritance

HHT is an autosomal dominant disorder; however, 20% of cases involve no family history of telangiectasia or recurrent bleeding. Penetrance is age related and nearly complete by age 40 years. Although the arteriovenous malformations in HHT are inherited and should be present at birth, they commonly manifest clinically during adult life, after the vessels have been subjected to pressure for several decades.

Associated syndromes

Communication between pulmonary arteries and pulmonary veins has been reported in cases of trauma and in hepatic cirrhosis, schistosomiasis, mitral stenosis, actinomycosis, Fanconi syndrome, and metastatic thyroid carcinoma. Communications between bronchial arteries and pulmonary arteries that cause a left-to-right shunt develop in chronic inflammatory conditions such as bronchiectasis. Most individuals with pulmonary arteriovenous malformations have HHT. The diagnostic criteria for a definite diagnosis of HHT include at least 3 of the following:

  • Recurrent and spontaneous epistaxis

  • Multiple mucocutaneous telangiectases

  • Visceral lesions (eg, GI arteriovenous malformations, pulmonary arteriovenous malformations)

  • First-degree relative with HHT by these criteria

Associated noncardiac conditions

The most frequently reported associated noncardiac conditions are CNS complications, which occur in 30% of patients. Strokes occur in 18% of patients with CNS complications, transient ischemic attacks occur in 37%, brain abscesses occur in 9%, migraine headaches occur in 43%, and seizures occur in 8%. Paradoxic embolism across pulmonary arteriovenous malformations is the most likely mechanism for major noninfectious strokes. Embolism of infected material accounts for solitary or recurrent brain abscesses. These complications most commonly occur when the feeding arteries are larger than 3 mm in diameter. Hemoptysis and hemothorax are other potentially life-threatening complications. Hemoptysis occurs from ruptured pulmonary arteriovenous malformations or endobronchial telangiectasia.

Idiopathic congenital pulmonary arteriovenous malformations

Idiopathic congenital pulmonary arteriovenous malformations are likely to be single. They are less likely to become enlarged, and the are associated with fewer physical findings than other pulmonary arteriovenous malformations. Idiopathic pulmonary arteriovenous malformations are diagnosed by using the same criteria as for other pulmonary arteriovenous malformations. Idiopathic congenital pulmonary arteriovenous malformations are successfully treated with embolotherapy.

Acquired arteriovenous malformations in hepatopulmonary syndrome

Hepatopulmonary syndrome (HPS), increased alveolar-arterial oxygen gradient (see the A-a Gradient calculator), and intrapulmonary right-to-left shunting (defined as the triad of liver disease) may occur in as many as 47% of patients with end-stage liver disease. All types of chronic liver disease may give rise to this syndrome. Approximately 80% of affected patients have signs and symptoms of end-stage liver disease before symptoms from pulmonary arteriovenous malformations develop. These patients have dyspnea, platypnea, clubbing, cyanosis, hypoxia, and orthodeoxia. Pulmonary function results indicate normal lung volumes and expiratory flow rates with low diffusing capacity.

In contrasts to patients with HHT, patients with HPS rarely have discrete arteriovenous malformations on chest radiographs. The calculation of the shunt fraction with the use of 100% oxygen, contrast echocardiography, and radionuclide scanning are diagnostic tests for HPS.

Results of HPS management have been disappointing. Liver transplantation may result in the resolution of HPS, and HPS is not a contraindication to liver transplantation. An improvement in HPS-related pulmonary shunting after therapeutic transjugular intrahepatic portosystemic shunting has been described.

Acquired arteriovenous malformations after surgery for congenital cyanotic heart disease: Pulmonary arteriovenous malformations may develop after Glenn or modified Fontan procedures for congenital cyanotic heart disease. Pulmonary arteriovenous malformations are a known late complication of Glenn anastomosis (ie, superior vena cava [SVC] to right pulmonary artery [RPA]), which occur in as many as 25% of cases. The Fontan operation (ie, SVC to right atrium and proximal RPA; hepatic veins to left pulmonary artery) was designed as a surgical repair for congenital tricuspid atresia. Contrast echocardiography and radionuclide shunt studies have been used to diagnose pulmonary arteriovenous malformations, and embolotherapy has been used successfully to occlude the pulmonary arteriovenous malformations in these cases.

 

DDx

Diagnostic Considerations

Consider the diagnosis of pulmonary arteriovenous malformations (PAVM) in individuals with any of the following presentations: (1) 1 or more pulmonary nodules associated with typical chest radiographic findings of pulmonary arteriovenous malformations; (2) mucocutaneous telangiectases; (3) unexpected findings such as dyspnea, hemoptysis, hypoxemia, polycythemia, clubbing, cyanosis, cerebral embolism, or brain abscess.

Differential Diagnoses

 

Workup

Laboratory Studies

With chronic hypoxemia, the hemoglobin and hematocrit rise. The rise is roughly proportional to the degree of cyanosis.

However, because may patients with pulmonary arteriovenous malformations (AVMs) also have hereditary hemorrhagic telangiectasia (HHT), bleeding from epistaxis and GI telangiectasias may lead to anemia.

Imaging Studies

Pulse oximetry

Pulse oximetry is a useful tool in initial screening for pulmonary arteriovenous malformations. Pulse oximetry should be performed in the supine and upright position. Oxygen saturations less than 95% are suggestive of either right-to-left shunting, or pulmonary disease. With significant pulmonary arteriovenous malformations, the oxygen saturation typically decreases in the upright position.

Echocardiogram

Echocardiogram is a useful tool for excluding other sources of intracardiac right-to-left shunt.

Echocardiogram with bubble contrast

A peripheral intravenous catheter is inserted and a solution of 8 mL of saline mixed with 1 mL of the patient's blood and 1 mL of air is agitated to produce microbubbles in the solution. The solution is then injected rapidly while the heart is imaged, preferably in a 4-chamber view. The microbubbles produce a bright echo reflection as they enter the echo field of view.

Normally, the right atrium and right ventricle are brightly opacified and then the microbubbles, which are less than 50 microns in diameter, are filtered out at the pulmonary capillary bed. and no bubbles are seen in the left atrium or left ventricle. In the presence of pulmonary arteriovenous malformations, the bubbles pass through the arteriovenous malformations and are seen in the left atrium and left ventricle.

Care needs to be taken not to inject any visible air, as this could lead to systemic air embolization. The classic teaching was that pulmonary arteriovenous malformations could be differentiated from intracardiac shunt by the timing of when bubbles first appear in the left atrium. The dogma is that bubbles appearing within one cardiac cycle are due to intracardiac shunt, whereas bubbles that appear within one cardiac cycles after first seen in the right atrium represent pulmonary arteriovenous malformations. Unfortunately, because of various factors, this does not appear to be the case.

Chest radiography

Examples are shown in the images below.

Left lower lobe arteriovenous malformation (AVM). Left lower lobe arteriovenous malformation (AVM).
Lateral radiograph showing a left lower lobe arter Lateral radiograph showing a left lower lobe arteriovenous malformation (AVM).
Small arteriovenous malformations (AVMs) in the ri Small arteriovenous malformations (AVMs) in the right and left lower lobes.
Lateral radiograph shows a left lower lobe arterio Lateral radiograph shows a left lower lobe arteriovenous malformation (AVM).

Chest radiographs reveal some abnormality in many patients with large arteriovenous malformations. The classic abnormal radiographic finding is a round or oval mass of uniform opacity. The mass is frequently lobulated and most commonly appears in the lower lobes. A chest radiograph can reveal features that may be undetectable on plain chest radiographs; examples include a feeding vessel, an artery radiating from the hilus, and the vein deviating toward the left atrium.

In a patient who has clinical features suggestive of pulmonary arteriovenous malformation but normal chest radiographic findings, further evaluation with other modalities should be performed. Patients with microscopic pulmonary arteriovenous malformations may have normal chest radiographic findings. Pulmonary arteriovenous malformations should also be considered in the differential diagnosis of a pulmonary nodule. A cautious approach to these patients is suggested before diagnostic needle biopsy is undertaken.

Contrast-enhanced CT scanning

Examples are shown in the images below.

Large left lower lobe arteriovenous malformation ( Large left lower lobe arteriovenous malformation (AVM) showing a feeding vessel to the left atrium.
Another view of the infused CT scan of the left lo Another view of the infused CT scan of the left lower lobe arteriovenous malformation (AVM).
Contrast-enhanced CT scan showing a left lower lob Contrast-enhanced CT scan showing a left lower lobe arteriovenous malformation (AVM).
Right lower lobe arteriovenous malformation (AVM). Right lower lobe arteriovenous malformation (AVM).
CT scan obtained after coil embolotherapy. CT scan obtained after coil embolotherapy.
Left lower lobe embolotherapy performed at the sam Left lower lobe embolotherapy performed at the same sitting as the coil embolotherapy depicted in the previous image.

The presence of a pulmonary arteriovenous malformation and its vascular anatomy can also be evaluated by means of contrast-enhanced ultra-fast CT. CT allows for the detection of 90% of pulmonary arteriovenous malformations, whereas, in one study, angiography allowed for the detection of only 60% of pulmonary arteriovenous malformations. The superior sensitivity of CT is attributed to the absence of superimposition of lesions on CT views.

Three-dimensional (3D) helical CT scanning produces images of vascular structures that are continuously reconstructed by a helical CT scanner. The accuracy of 3D helical CT scanning is reported to be 95%.

Contrast echocardiography

Contrast echocardiography is an excellent tool for evaluating cardiac or intrapulmonary shunts. This technique involves the injection of 5-10 mL of agitated saline into a peripheral vein while simultaneously imaging the right and left atria with 2-dimensional echocardiography. In patients without right-to-left shunting, contrast is rapidly visualized in the right atrium and then gradually dissipates. In patients with intracardiac shunts, contrast is visualized in the left heart chambers within 1 cardiac cycle, after its appearance in the right atrium. In patients with pulmonary arteriovenous malformations, contrast is visualized in the left atrium after a delay of 3-8 cardiac cycles. Contrast echocardiography is almost 100% sensitive in detecting clinically important pulmonary arteriovenous malformations.

The finding of an intrapulmonary shunt by means of contrast echocardiography warrants further evaluation with standard pulmonary angiography or contrast-enhanced CT scanning.

In one case series, pulmonary arteriovenous malformations were visible in 11 of 14 patients with positive contrast echocardiographic findings who underwent pulmonary angiography. Six had abnormal chest radiographic results, and 8 had an increased A-a gradient. Contrast echocardiography had 100% sensitivity in this study.

Similarly, a study by Karam et al indicated that transthoracic contrast echocardiography can be used to effectively screen pediatric patients with hereditary hemorrhagic telangiectasia (HHT) for pulmonary arteriovenous malformations. The report, which involved 92 children, found the sensitivity and specificity of this modality for the detection of these malformations to be 100% and 95.1%, respectively, with positive and negative predictive values of 96% and 100%, respectively.[5]

Radionuclide perfusion lung scanning

Radionuclide perfusion lung scanning is also useful in the diagnosis of pulmonary arteriovenous malformations, particularly if contrast echocardiography is not available.

In patients without an intrapulmonary shunt, the peripheral intravenous injection of technetium 99m–labeled macroaggregated albumin results in the filtering of these particles by the lung capillaries. However, anatomic shunts with dilated pulmonary vascular channels allow these particles to pass through the lung, with subsequent filtering by the capillaries in the brain and kidneys.

Pulmonary angiography

An example is shown in the image below.[6]

Pulmonary angiographic findings are required not o Pulmonary angiographic findings are required not only to confirm the diagnosis but also to plan therapeutic embolization.

Despite advances in noninvasive diagnostic techniques, contrast-enhanced pulmonary angiography remains the criterion standard in the diagnosis of pulmonary arteriovenous malformations. This test is usually necessary if embolotherapy is being considered. Perform pulmonary angiography in all lobes of the lungs to look for unsuspected pulmonary arteriovenous malformations.

Currently, digital subtraction angiography appears to be replacing conventional angiography. Whether CT or MRI can replace standard pulmonary angiography in the diagnosis of pulmonary arteriovenous malformations requires further comparative studies. Presently, CT and MRI are appropriate noninvasive modalities for the follow-up evaluation of patients with proven pulmonary arteriovenous malformations.

MRI

MRI has been reported to be useful in the diagnosis of pulmonary arteriovenous malformations. Rapidly flowing blood results in an absent or minimal MR signal, a so-called flow void. However, pulmonary arteriovenous malformations may be indistinguishable from adjacent air-filled lungs on MRI, a significant limitation in screening for small lesions. Therefore, spin-echo MRI has reduced sensitivity and specificity for detection of pulmonary arteriovenous malformations, compared with those of other techniques. Better results are obtained with phase-contrast cine sequences, and MR angiography can be used to define the vascular anatomy of a pulmonary arteriovenous malformations. A combination of MR techniques may be useful in differentiating pulmonary arteriovenous malformations from various other lesions, but more comparative data are required before the routine use of MRI is recommended.

Other Tests

Pulmonary function tests

Oxygenation is commonly affected in individuals with PAVM. Most patients have saturation levels of less than 90% at rest. Orthodeoxia is a decrease in PaO2 or SaO2 that occurs when one assumes an upright position from the supine position. Patients with this finding have normal spirometric findings and a mildly reduced diffusing capacity. Recent case series have indicated that 80-100% of patients with pulmonary arteriovenous malformations have either a PaO2 of less than 80 mm Hg or an SaO2 of less than 98% on room air.

Shunt fraction measurement

The shunt fraction is most accurately assessed by using the 100% oxygen method, which involves the measurement of PaO2 and SaO2 after the patient breathes 100% oxygen for 15-20 minutes. The fraction of cardiac output that shunts right-to-left circulation is elevated in patients with pulmonary arteriovenous malformations; normal values are less than 5%. A shunt fraction of more than 5%, as determined by using the 100% oxygen method, has a sensitivity of 87.5% and a specificity of 71.4%.

Exercise testing

Patients with pulmonary arteriovenous malformations have reduced exercise tolerance. In most patients, incremental exercise testing results in decreased saturation. One case series of patients showed that the average maximum oxygen consumption was 61% of the predicted value; saturation decreased from 86% at rest to 73% with peak exercise. See the Oxygen Consumption calculator.

Procedures

Right heart catheterization

Most patients with pulmonary arteriovenous malformations have normal or low pulmonary arterial pressure. Despite severe oxygen desaturation, the mean pulmonary arterial pressure is low in most patients.

Their cardiac output is generally normal to moderately elevated. See the Cardiac Output calculator.

Patients may develop new pulmonary hypertension or increased baseline pulmonary hypertension after embolization or resection of a large pulmonary arteriovenous malformation.[7]

Radionuclide method

The radionuclide method of shunt calculation is expensive and not routinely available at most hospitals; however, it has several advantages compared with the 100% oxygen method.

ABG sampling is not needed.

The 100% oxygen method may overestimate intrapulmonary shunt.

The radionuclide method is more suitable for shunt measurement during exercise.

 

Treatment

Medical Care

The role of hormonal therapy in patients with recurrent bleeding secondary to GI or nasopharyngeal mucosa has been reported in the literature. Findings from these small studies have suggested a modest benefit. Anecdotal reports have also suggested successful treatment of epistaxis and GI hemorrhage by using danazol, octreotide, desmopressin, and aminocaproic acid. One preliminary study reported a decrease in the duration and number of episodes of epistaxis with bevacizumab.[8]

Definite therapy for pulmonary arteriovenous malformations (PAVM) involves therapeutic embolization or surgical resection.

Catheter intervention - Therapeutic embolization

Embolization therapy (ie, embolotherapy) is a form of treatment based on occluding the feeding arteries to a pulmonary arteriovenous malformation.

The first successful case of embolotherapy of a pulmonary arteriovenous malformation was reported in 1977 and involved the use of handmade steel coils. Since then, embolization with coils and/or detachable balloons has been reported in numerous series of more than 250 patients. Other embolic materials include polyvinyl alcohol, cotton wool coils, and stainless steel coils.

Indications for embolotherapy include the following:

  • Progressive enlargement of the lesions

  • Paradoxic embolization

  • Symptomatic hypoxemic

  • Feeding vessels of 3 mm or larger

The technique of coil embolotherapy involves the localization of the pulmonary arteriovenous malformation by means of angiography, followed by selective catheterization of the feeding artery. A steel coil is advanced through the catheter and placed distal to any branch of the vessel. Sometimes, more than 1 coil is required to completely occlude the vessel. Multiple pulmonary arteriovenous malformations can be embolized in a single session.

The second embolotherapeutic technique uses detachable balloons. After localization of a pulmonary arteriovenous malformation, a balloon catheter is exchanged over a guidewire and positioned at the neck of the pulmonary arteriovenous malformation.

Follow-up CT scans obtained 1 or more years after embolotherapy indicate that 96% of pulmonary arteriovenous malformations are either undetectable or reduced in size. These findings occur secondary to thrombosis and retraction of the aneurysmal sac after successful vascular obstruction.

In one series of 45 patients who underwent embolotherapy of large (>8 mm) pulmonary arteriovenous malformations, 98% of the pulmonary arteriovenous malformations were occluded during the initial attempt, 84% of patients remained successfully treated, and 16% of patients had persistent pulmonary arteriovenous malformations. The persistence of the pulmonary arteriovenous malformations was caused by recanalization of initial successful occlusion in 5 patients, and it was caused by interval growth of new feeding vessels in 3 patients. All 8 of the persistent pulmonary arteriovenous malformations were successfully occluded during a second procedure, although one pulmonary arteriovenous malformation required a third procedure for permanent occlusion.

A summary of 10 published series of therapeutic embolization for pulmonary arteriovenous malformation documented an average success rate of 98.7%. Balloon embolotherapy is generally used in pulmonary arteriovenous malformations with feeding vessels larger than 7-10 mm.

Embolotherapy appears to be the treatment of choice because major surgery, general anesthesia, and loss of pulmonary parenchyma may be avoided.[9] Embolotherapy is a clear choice in patients with multiple or bilateral pulmonary arteriovenous malformations or in patients who are poor surgical candidates.

Postcatheterization precautions include hemorrhage, vascular disruption after balloon dilation, pain, nausea and vomiting, and arterial or venous obstruction from thrombosis or spasm.

Possible complications include rupture of blood vessels, tachyarrhythmias, bradyarrhythmias, and vascular occlusion.

Pleuritic chest pain is the most common complication and is observed in 12% of patients. This pain usually responds well to analgesics. Radiographic evidence of pulmonary infarction is observed in 3% of patients.

Air embolism during embolotherapy is suspected in 4.8% of patients; they developed transient symptoms such as angina, perioral paraesthesias, and bradycardia.

Device migration has been reported in 1.2% of embolization attempts.

Long-term follow-up evaluation has shown potentially serious complications in 2% of patients treated with embolotherapy.

Symptomatic recanalization was observed with 0.5% of procedures.

A new or increased pulmonary hypertension after embolization has been reported in several patients. Incidence of complication appears to be higher when the feeding vessels of more than 8 mm were occluded.

Surgical Care

Until 1977, surgery was the only method of treatment. Ligation, local excision, segmentectomy, lobectomy, or pneumonectomy was performed in most cases. The reported perioperative mortality rate from surgery varied from 0-9%. Postoperative follow-up evaluation shows recurrence or enlargement of the pulmonary arteriovenous malformation in as many as 12% of patients. Surgery is the best choice for patients with an untreatable allergy to the contrast material.

Indications

Indications for surgery are progressive pulmonary arteriovenous malformation enlargement, paradoxic embolization, and symptomatic hypoxemia. The treatment of all pulmonary arteriovenous malformations with feeding vessels 3 mm or larger is also recommended.

Techniques

Standard thoracic surgical techniques, such as ligation of pulmonary arteriovenous malformation, local excision, segmentectomy, lobectomy, or pneumonectomy, have been performed. In some cases, staged bilateral thoracotomies are performed. Recently, video-assisted thoracoscopic resection of a small pulmonary arteriovenous malformation has been performed.[10]

Results

Postoperative follow-up evaluation shows recurrence or enlargement of another pulmonary arteriovenous malformation in as many as12% of patients. During a follow-up evaluation performed 8 years after surgery, one case of stroke and one case of mortality related to pulmonary arteriovenous malformation occurred. Reports also suggest the development of pulmonary arterial hypertension. Moderate surgical techniques for the resection of pulmonary arteriovenous malformations are associated with a negligible mortality rate, but they are associated with the morbidities that accompany a thoracotomy.

Complications

According to various reported series, the perioperative mortality has varied from 0-9.1%. Most of the studies that reveal high mortality rates were reported before 1960. Postoperative morbidities have been well reported.

Activity

Patients with pulmonary arteriovenous malformations have reduced exercise tolerance.

Other

Long-term clinical and imaging results of technically successful pulmonary arteriovenous malformations embolization in 150 patients were reviewed. Four hundred and fifteen pulmonary arteriovenous malformations were occluded during 205 procedures. Complications included respiratory symptoms (n = 13), cerebral ischemia (n = 4), brain abscess (n = 5), hemoptysis (n = 3), and seizure (n = 1). Imaging showed pulmonary arteriovenous malformation involution in 97% of embolized lesions and 11 residual lesions (2.8%) in 10 patients (6.9%). The other 97 previously small pulmonary arteriovenous malformations had enlarged to a significant size in 28 patients (18%). These data emphasize ongoing clinical and anatomic evaluation after pulmonary arteriovenous malformation embolization.[11]

Large pulmonary arteriovenous fistulas (PAVFs) present significant difficulty for transcatheter treatment. However, initial experience with Amplatzer duct occluder (ADO) looks promising. One case series reported 5 patients, aged 3-73 years, with large PAVFs who underwent successful transcatheter closure with ADO. No complications occurred and the patients' arterial oxygen saturation and exercise tolerance improved. Thus, transcatheter closure of large PAVFs with the ADO is effective and can eliminate the need for surgical intervention. The newly designed Amplatzer vascular plug is undergoing clinical trials.[12]

 

Medication

Medication Summary

Drug therapy is not currently a component of the standard of care for pulmonary arteriovenous malformations (PAVMs).

Patients with pulmonary arteriovenous malformations should be given antibiotic prophylaxis before dental and surgical procedures to prevent seeding of the pulmonary arteriovenous malformation and the subsequent development of a cerebral abscess.

Antibiotics, prophylactic

Class Summary

Antibiotic prophylaxis is given to patients before performing procedures that may cause bacteremia.

Amoxicillin (Amoxil, Trimox)

Interferes with synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria. Used as prophylaxis in minor procedures.

Ampicillin (Marcillin, Omnipen)

For prophylaxis in patients undergoing dental, PO, or respiratory tract procedures. Coadministered with gentamicin for prophylaxis in GI or GU procedures.

Clindamycin (Cleocin)

Used in penicillin-allergic patients undergoing dental, PO, or respiratory tract procedures. Useful for treatment against streptococcal and most staphylococcal infections.

Gentamicin (Garamycin)

Aminoglycoside antibiotic for gram-negative coverage. Used in combination with both an agent against gram-positive organisms and one that covers anaerobes. Used in conjunction with ampicillin or vancomycin for prophylaxis in GI or GU procedures.

Vancomycin (Vancocin)

Potent antibiotic directed against gram-positive organisms and active against Enterococcus species. Useful in the treatment of septicemia and skin structure infections. Indicated for patients who cannot receive or have failed to respond to penicillins and cephalosporins or have infections with resistant staphylococci. Use creatinine clearance to adjust dose in renal impairment. Used in conjunction with gentamicin for prophylaxis in penicillin-allergic patients undergoing GI or GU procedures.

Erythromycin base (EES, E-Mycin, Eryc)

Used for prophylaxis in penicillin-allergic patients undergoing dental, PO, or respiratory tract procedures.

Cefazolin (Ancef)

First-generation semisynthetic cephalosporin that arrests bacterial cell wall synthesis, inhibiting bacterial growth. Primarily active against skin flora, including Staphylococcus aureus.

Cephalexin (Keflex)

First-generation cephalosporin that arrests bacterial growth by inhibiting bacterial cell wall synthesis. Bactericidal activity against rapidly growing organisms. Primary activity against skin flora and used for skin infections or prophylaxis in minor procedures.

Cefadroxil (Duricef)

First-generation cephalosporin arrests bacterial growth by inhibiting bacterial cell wall synthesis. Bactericidal activity against rapidly growing organisms. Primary activity against skin flora and used for skin infections or prophylaxis in minor procedures.

Azithromycin (Zithromax)

Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Clarithromycin (Biaxin)

Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

 

Follow-up

Deterrence/Prevention

See Medication for the recommended prophylactic regimen for dental, oral, sinus, and genitourinary, and GI procedures in patients with pulmonary arteriovenous malformations (PAVMs).

  • Amoxicillin 3 g orally (PO) 1 hour or 2 g intravenously (IV) 30 minutes before the procedure, followed by 1.5 g PO/IV hours after the initial dose

  • For patients who are allergic to penicillin, erythromycin 1000 mg PO 2 hours before the procedure, followed by 500 mg PO 6 hours after the initial dose

  • For patients who are allergic to penicillin, clindamycin 300 mg PO 1 hour or 300 mg IV 30 minutes before procedure, followed by 150 mg PO/IV 6 hours after initial dose

The recommended prophylactic regimen for genitourinary and GI procedures includes one of the following:

  • Amoxicillin 3 g PO 1 hour before the procedure, followed by 1.5 g PO 6 hours after the initial dose, plus gentamicin 1.5 mg/kg IV 1 hour before the procedure; this may be repeated 8 hours after the initial dose.

  • For patients who are allergic to penicillin, vancomycin 1 g IV over 1 hour plus gentamicin 1.5 mg/kg IV 1 hour before the procedure; this may be repeated 8 hours after the initial dose.

Complications

See the list below:

  • Seizure

  • Migraine headaches

  • Transient ischemic attack

  • Cerebral vascular accident

  • Brain abscess

  • Hypoxemia, orthodeoxia

  • Hemothorax

  • Life-threatening hemoptysis

  • Pulmonary hypertension

  • Congestive heart failure

  • Polycythemia

  • Anemia

  • Infectious endocarditis

Patient Education

Thoroughly educate patients with pulmonary arteriovenous malformations and patients with hereditary hemorrhagic telangiectasia (HHT) about their diagnosis and its clinical implications, complications, and hereditary nature.