Introduction
Background
First described in 1897, pulmonary arteriovenous malformation (PAVM) is an abnormal communication between the pulmonary artery and the pulmonary vein. PAVMs are usually congenital in origin; however, they may be acquired in a variety of conditions, such as hepatic cirrhosis, schistosomiasis, mitral stenosis, trauma, actinomycosis, and metastatic thyroid carcinoma.
After the initial description of telangiectasia and epistaxis by Henry Jules Rendu, in 1896, Sir William Osler reported a family known to have hereditary hemorrhagic telangiectasia (HHT). In 1907, Frederick Weber described other manifestations of this disorder; since then, HHT has come to be known as Rendu-Osler-Weber syndrome (or, alternately, as Osler-Weber-Rendu syndrome). Approximately 70% of PAVMs are associated with HHT, and about 15-30% of individuals with HHT have a PAVM.1 (Also, see the eMedicine article Osler-Weber-Rendu Syndrome.)
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Pathophysiology
In HHT, telangiectases and arteriovenous malformations (AVMs) are the 2 primary vascular abnormalities. Telangiectasia is a localized, convoluted enlargement of the postcapillary venule, and it involves smooth muscle proliferation and perivascular lymphocytic infiltration. An AVM is a direct connection between the pulmonary artery and the pulmonary vein, and it may be associated with dilatation and localized aneurysmal enlargement of the feeding vessel.
Approximately 50-70% of PAVMs are located in the lower lobes. About 70% of patients have unilateral disease, 36% have multiple lesions, and 50% may have bilateral disease. The size of the PAVMs may vary from microscopic to the typical size of 1-5 cm.
Pathogenesis
Although their pathogenesis is not well delineated, PAVMs are considered to result from incomplete resorption of the vascular septa. These vascular septa separate the arterial plexus and the venous plexus, which normally anastomose during fetal development. Progressive dilatation of the smaller plexus leads to the formation of tortuous loops and multiloculated sacs. With rupture of intervening vascular walls, a single large, saccular PAVM develops.
Genetics of HHT
Some of the genetics of HHT have been elucidated. These genetic abnormalities may also be present in patients with PAVM who do not have HHT. Two linkage groups for HHT have been discovered: HHT1 has been linked to band 9q33, and HHT2 has been linked to band 12q13. Endoglin is identified as the gene product for HHT1 on band 9q33. Approximately 13 mutations of the endoglin gene have been reported. Endoglin and activin receptorlike kinase-1 (ALK-1) protein bind transforming growth factor beta (TGF beta), which is implicated in angiogenesis. PAVM likely develops as a result of the interplay of various factors among diverse cells and the matrix as a result of vascular insults from a variety of causes.
Frequency
United States
Three cases of PAVM were detected in 15,000 autopsies performed at Johns Hopkins Hospital in 1953. At the Mayo Clinic, 63 cases were detected during the 20 years ending in 1972.2 Over the subsequent 9 years, ending in 1981, 38 additional cases were encountered.2 Overall, the frequency of PAVM may be variable, but it generally appears to be 1 case per 39,216 persons.
International
Regional variations in frequency are known to occur. A frequency as high as 1 case per 2351 persons has been reported in some regions of France.
Mortality/Morbidity
- Short-term follow-up studies have revealed mortality rates of 0-15%.
- Morbidity may be significant and includes stroke, brain abscess, massive hemoptysis, infective endocarditis, and congestive heart failure.
Sex
PAVM occurs twice as often in women as in men, but a male predominance exists in newborns.
Age
Approximately 10% of PAVM cases are identified in infancy or childhood; however, the incidence gradually increases through the fifth and sixth decades of life.
Anatomy
The PAVMs consist of vascular channels that are thin walled and lined with endothelium. They have minimal connective-tissue stroma and drain into the left atrium. The malformation may appear as a large single sac, a plexiform mass of dilated vascular channels, or a dilated, tortuous, direct communication between the pulmonary artery and the pulmonary vein.
PAVMs can be classified as simple or complex types, based on their architecture. Simple PAVMs have a single feeding segmental artery leading to single draining pulmonary vein. Approximately 79% of PAVMs are of the simple type and occur in lower lobes; these are associated with nonseptate aneurysms. Approximately 21% of PAVMs are complex; these have 2 or more feeding arteries or draining veins. They often occur in the distributions of the lingula and the right middle lobe.
Presentation
General clinical presentation
The clinical presentation of PAVMs may vary from no symptoms to severe illness. Symptoms generally develop between the fourth and fifth decades of life. Symptoms occur more commonly in patients who have PAVM and HHT than in those who have PAVM without HHT.
The most common initial complaint is epistaxis. Dyspnea is the second most common complaint. Patients may also describe platypnea. Hemoptysis is the third most common symptom, and occasionally, massive hemoptysis may occur.
Patients may also develop gastrointestinal hemorrhage (15-30%). The other less-common clinical features are chest pain, coughing, dizziness, syncope, polycythemia, and cerebral vascular complications.
The most common physical finding in patients with PAVM is superficial telangiectases. These lesions generally appear on the face, mouth, chest, and upper extremities. Patients may also have digital clubbing and cyanosis. On auscultation of the lungs, a murmur may be heard over the PAVM; this is most audible during inspiration.
The patients may eventually develop signs and symptoms of congestive heart failure and/or respiratory failure.
Other clinical presentations
Idiopathic congenital PAVMs are congenital PAVMs that are not associated with HHT. These PAVMs are likely single and are associated with fewer physical findings than other types. These PAVMs have a natural history similar to that of other PAVMs.
PAVMs may present with primarily neurologic manifestations when pulmonary symptoms are absent or unrecognized. Brain abscess, embolic stroke, and hemorrhage from concomitant brain AVM are well-recognized complications.3 The pathogenesis of neurologic complications is not entirely known, but embolization of thrombus or the infected material appears to be the most plausible explanation.
Acquired AVMs may occur in patients with hepatopulmonary syndrome. Approximately 47% of patients with end-stage liver disease acquire abnormal arterial venous communications. These patients have dyspnea, platypnea, clubbing, cyanosis, hypoxemia, and orthodeoxia.
Acquired AVMs may also appear after surgery for congenital cyanotic heart disease. PAVMs may develop following Glenn or modified Fontan procedures for the treatment of congenital cyanotic heart disease. PAVMs are late complications of both of these procedures. The clinical features of these PAVMs are similar to those of other PAVMS, and therefore, the surgery-related PAVMs are similarly diagnosed.
Preferred Examination
Diagnostic approach in a patient with a suspected PAVM
A PAVM may be suspected in the following clinical situations:
- An incidental finding of a solitary pulmonary nodule on chest radiographs
- The presence of mucocutaneous telangiectases
- A situation in which the patient presents with clinical findings of dyspnea, hemoptysis, hypoxemia, polycythemia, clubbing, cyanosis, cerebral embolism, or brain abscess.
Whenever a PAVM is suspected, the presence of a right-to-left shunt should be confirmed by the performance of a 100% oxygen study, contrast-enhanced echocardiography, or radionuclide perfusion lung scanning. A definitive diagnosis is established by means of direct imaging of the PAVM with a contrast-enhanced study, such as a computed tomography (CT) scan or a pulmonary angiogram.
Imaging examination
Chest radiography reveals some abnormality in most patients. However, further evaluation is needed, with a test to confirm the presence of a right-to-left intrapulmonary shunt and with an imaging study to confirm the presence of PAVM.
Contrast-enhanced echocardiography is extremely sensitive in detecting clinically important PAVMs. If contrast-enhanced echocardiography is not available, radionuclide perfusion lung scanning may be used.
Contrast-enhanced CT scanning remains the criterion standard in the diagnosis of PAVM. Although pulmonary angiography is less sensitive than contrast-enhanced CT scanning, it is performed to accurately define the anatomy, specifically before therapeutic embolization is performed. Although pulmonary angiography may also be a criterion standard for confirmation of a PAVM, angiography is required only when further intervention is planned. Otherwise, in most situations, contrast-enhanced CT scanning is sufficient to confirm the diagnosis.
Although magnetic resonance imaging (MRI) is reportedly useful in the diagnosis of PAVM, it may be less useful than contrast-enhanced CT scanning. Therefore, if the plain chest radiographs suggest a PAVM, contrast-enhanced CT scan remains the preferred examination for confirming its presence.
Limitations of Techniques
Chest radiographs may suggest a PAVM, but these images are not helpful in distinguishing between the various causes of a lung nodule. Contrast-enhanced echocardiography may be useful for distinguishing between intracardiac and intrapulmonary shunts, although this identification may be difficult at times.
Contrast-enhanced CT scans may not depict microscopic PAVMs, but the diagnostic yield with spiral CT scanning has been improving. Pulmonary angiography is less sensitive in identifying small or microscopic PAVMs, and MRI has significant limitations in screening for small lesions and in differentiating PAVM from lesions of other causes.
Differential Diagnoses
| Bronchogenic Cyst | Lung, Carcinoid |
| Hamartoma, Lung | Lung, Metastases |
| Lung Cancer, Non-Small Cell | Solitary Pulmonary Nodule |
| Lung Cancer, Small Cell | Vascular Anomalies |
More on Lung, Arteriovenous Malformation |
 Overview: Lung, Arteriovenous Malformation |
| Imaging: Lung, Arteriovenous Malformation |
| Follow-up: Lung, Arteriovenous Malformation |
| Multimedia: Lung, Arteriovenous Malformation |
| References |
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References
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Further Reading
Keywords
pulmonary AVM, PAVM, pulmonary arteriovenous fistula, arteriovenous malformation, AVM, Osler-Weber-Rendu syndrome, HHT, hereditary hemorrhagic telangiectasia, Rendu-Osler-Weber syndrome, simple PAVM, complex PAVM, idiopathic congenital PAVM, acquired AVM
