Pulmonary arteriovenous fistula, also known as pulmonary arteriovenous malformation, is a rare pulmonary disorder that is an abnormal communication between the pulmonary arteries and pulmonary veins.PAVMs were identified at autopsy by Churton in 1897 and were first clinically reported by Smith et al. in 1939.Most congenital PAVMs are associated with hereditary hemorrhagic capillary dilation (HHT). The disease is approximately twice as common in females as in males. PAVMs are diagnosed in infancy or childhood, with increasing rates of disease outgrowth with advancing age.
I. Etiology
1. The majority of PAVMs are congenital malformations, and the embryogenesis of the disease is still unclear, and a combination of opinions from the literature suggests the following possibilities.
(1) capillary hypoplasia due to impaired development of the septum of the original connection between the arteriovenous plexus during the lung bud period, resulting in the formation of PAVMs.
(2) Lack of terminal capillary collaterals between single pulmonary arterioles at the embryonic stage, which predisposes to the formation of vascular sacs with large lumen and thin walls.
(3) Cystic dilatation of the pulmonary terminal capillary beds between multiple pulmonary arterioles at embryonic stage to form PAVMs.
2. It has been found that most congenital PAVMs are associated with HHT, which is an autosomal dominant disorder. HHT is known to be associated with at least three chromosomal loci, with HHT1 caused by a mutation at chromosome 9q3 and HHT2 caused by a mutation at chromosome 12q.
3. PAVMs can also be caused by acquired lesions, such as cirrhosis, trauma, surgery, mitral stenosis, actinomycosis, tuberculosis, schistosomiasis, metastatic thyroid cancer, Fanconi’s syndrome, etc.
II. Pathology
PAVMs occur in the lower lobes of both lungs and are mostly unilateral lesions, with about 1/3 being multiple. The fistulae are mostly close to the pleura, and those in the lung parenchyma are rare. Pathologically, there are two types, namely cystic and diffuse. In the former case, the fistula forms a sinuous, flexural, mass-like angiomatous capsule with uneven wall thickness, which is divided into simple and complex types. In the simple type, one blood supplying pulmonary artery communicates directly with one draining pulmonary vein, and there is no separation of the capsule; in the complex type, two or more blood supplying pulmonary arteries communicate directly with the draining pulmonary vein, and the capsule cavity is often separated. The diffuse type may be confined to one lobe or spread to both lungs, with only a few small fistulas connecting the arteries and veins, and no bursa formation.
Clinical manifestations
Symptoms associated with PAVMs often appear at the age of 40-60 years and are more common in patients with concomitant HHT. The severity of symptoms is closely related to the size of the lesion. The most common and early appearing clinical symptom is rhinorrhea, followed by dyspnea, hemoptysis, and then bleeding from the skin, dilated capillaries of the gastrointestinal tract, chest pain, cough, migraine, tinnitus, and dizziness. Common signs include capillary dilatation of skin and mucous membranes, cyanosis, pestle-like fingers (toes) and murmurs at the lesion site, with cyanosis and pestle-like fingers appearing when the right-to-left shunt flow is high. Murmurs can be heard in the chest in about 1/2 of PAVMs and are evident on inspiration. Since PAVMs are mainly lower lobe lung lesions, patients may present with upright hypo-O2emia.
IV. Complications
PAVM can produce serious complications, the most common being neurological complications, especially seen in diffuse small pulmonary arteriovenous fistulas, including stroke, migraine, transient ischemic attack, brain abscess, and seizures. There are also pulmonary hypertension, paradoxical embolism, infective endocarditis, anemia, hemoptysis, hemothorax, and erythrocytosis, with hemothorax and hemoptysis being the complications that can be life-threatening.
V. Diagnosis
There are many methods to diagnose PAVMs, and several of the more sensitive methods commonly used in clinical practice are summarized below.
1.Pure oxygen test
The pure oxygen test is highly sensitive and has a close diagnostic rate for those PAVMs with clinical significance, and is simple, easy and inexpensive, and is currently the preferred screening method in clinical practice.
2.Chest X-ray photography
Chest radiography is simple, sensitive, non-invasive and economical, and is currently used as the first-line screening test for PAVMs. Localized PAVMs usually have typical radiographic signs, and most of them can be diagnosed clearly when combined with clinical data; diffuse PAVMs mostly lack typical radiographic signs, which makes the diagnosis difficult and requires further tests to confirm the diagnosis.
3.Echocardiogram
The sensitivity of echocardiographic sonography in diagnosing clinically significant PAVMs can detect even those small PAVMs without clinical significance, and because it is non-invasive, it is now widely used. This is done as follows: an injection of shaken saline from a peripheral vein (when small bubbles can be produced) is followed by an echocardiogram. Under normal conditions the small bubbles will be completely blocked in the pulmonary capillaries and will not enter the left atrium. However, when PAVMs are present, bubbles appear in the left atrium very quickly (usually after 3-5 cardiac cycles). It has the disadvantage that the site and extent of the lesion cannot be determined and the shunt fraction cannot be measured.
4.Pulmonary perfusion nuclide scan
Pulmonary perfusion nuclide scan is a highly sensitive method for diagnosing PAVMs. It can determine the site and extent of the lesion and can measure the fraction of shunt flow.
5.CT
Spiral CT and electron velocity CT are an effective means of diagnosing PAVMs. Remy et al. found that contrast-enhanced EBCT is significantly better than pulmonary arteriography in the correct diagnosis of PAVMs and in the display of anatomical structures. 3-D spiral CT uses surface shadowing to display vascular structures from all angles with high accuracy.
6.Magnetic resonance
Magnetic resonance is a non-invasive examination method. Some studies have shown that phase contrast cine sequence is the most accurate method for diagnosing PAVMs in MRI technology, which can clarify the lesion site, morphology, and the extent of involvement, while spin-echo pulse sequence and gradient-echo pulse sequence have low sensitivity and specificity for the diagnosis of PAVMs. In recent years, the application of contrast-enhanced magnetic resonance angiography (CEMRA) has increased the accuracy of diagnosis.
7.Pulmonary arteriography
Pulmonary arteriography has high temporal and spatial resolution and can clarify the location, morphology, extent and degree of involvement of PAVMs, and is still the gold standard for the diagnosis of PAVMs. Digital subtraction angiography has gradually replaced conventional cardiovascular angiography in the last decade or so, but there are no systematic comparative studies of these two techniques. Because angiography is an invasive test, it is mainly used to confirm the diagnosis of PAVMs before treatment and as a component of interventional therapy, while it is generally not used in post-treatment follow-up.
VI. Screening All HHT patients and their family members belong to the screening of PAVMs
Routine screening should be done. The currently preferred first-line methods are pure oxygen test and chest radiography. Among them, special attention should be paid to the fact that HHT patients must have routine examinations before they become pregnant, because the chance of complications of hemothorax and hemoptysis in the second half of pregnancy is high.
VII. Treatment
It is traditionally believed that not all PAVMs require treatment, but only those with progressive enlargement of the lesion, paradoxical embolism, and symptomatic hypoxemia. However, recent studies have found that many patients with asymptomatic or minimal lesions can develop severe neurological complications (e.g., stroke, brain abscess, etc.), so White et al. advocated that all patients with PAVMs with a supply artery diameter ≥3 mm should be treated regardless of symptoms. The aim of treatment is to improve hypoxic symptoms and prevent serious complications such as stroke, brain abscess, and hemoptysis. Current treatments for PAVMs include surgical procedures, catheter embolization, and drug therapy.