Pulmonary AVM Embolization

Pulmonary arteriovenous malformations (PAVMs) are rare fistulous connections between pulmonary arteries and veins that, as in our case, are commonly associated with hereditary hemorrhagic telangiectasia (HHT). Embolotherapy, the mainstay of treatment for PAVMs, is a procedure in which the feeding arteries of a malformation are endovascularly occluded under fluoroscopic guidance. Effective and well-tolerated, embolotherapy has been shown to decrease right-to-left shunting following treatment and decrease risks of paradoxical embolization and lung hemorrhage and to improve pulmonary gas exchange and lung function. Patients are selected for treatment according to clinical suspicion for the presence of a PAVM and feeding artery diameter. The occlusion of PAVMs with arteries that exceed 2–3 mm in diameter is recommended.

Diagnostic contrast-enhanced pulmonary angiography is performed via injection of contrast through a percutaneous catheter to characterize and confirm PAVMs suitable for embolization. Lesions are then treated by catheter-directed placement of embolic material— vascular plugs in our case—into the feeding artery, terminating blood flow to the area of the lesion. Although multiple PAVMs may be embolized during a single session, in patients with HHT, who may present with large numbers of PAVMs, treatment is limited by maximum contrast dosage, and additional sessions may be performed if PAVMs remain perfused.

Pulmonary arteriovenous malformations (PAVMs) are rare fistulous connections between pulmonary arteries and veins that, as in our case, are commonly congenital and associated with hereditary hemorrhagic telangiectasia (HHT).¹ Acquired PAVMs may occur secondary to liver disease or systemic disease, or following palliation of complex cyanotic congenital heart disease. Lesions may progress, with significant growth believed to occur during childhood and early adulthood as well as during pregnancy, leading to hemodynamic changes and intrapulmonary shunting.² Clinically, this may manifest as hypoxemia, leading to cyanosis, clubbing, polycythemia, and impaired exercise tolerance. Pulmonary hemorrhage and paradoxical systemic embolization with stroke and cerebral abscesses may also occur with untreated lesions.^3, 4

The patient in this case was a 14-year-old female with occasional nosebleeds and past medical history of HHT (diagnosed clinically and confirmed with genetic testing). The patient also had family history pertinent for HHT in the patient’s biological mother. A screening chest CT found multiple PAVMs, two of which met the criteria for therapeutic embolization. A lesion with a 2.5-mm feeding artery was detected in the right upper lobe, and the other PAVM with a 2-mm feeding artery was visualized in the left lower lobe.

Absence of symptoms does not preclude the diagnosis of PAVM, as case series have reported that 13–55% of adult and child patients with PAVMs are asymptomatic clinically. Dyspnea on exertion, attributable to hypoxemia from right-to-left shunting, is the most common presenting symptom.³ Epistaxis, headaches, hemoptysis, palpitations, chest pain, and cough are also frequently reported, and PAVMs should always be suspected in a patient with a history of stroke or brain abscess. Presentation of symptoms often correlates with saccular size. Lesions less than 2 cm in diameter on chest radiography are typically asymptomatic.^3, 5

Abnormal physical findings arising from vascular malformations are reported to be present in up to 75% of patients with PAVMs and most commonly include: cyanosis, clubbing, and pulmonary vascular murmurs or bruits over the area in which the PAVM is located. Intensity of the murmurs may be increased through inspiration and when the PAVM is in a dependent position, due to increased pulmonary blood flow. Expiration and the Valsalva maneuver decrease intensity of the murmur.⁵ Mucosal surfaces, trunk, and fingertips should be inspected for telangiectasias as roughly 66% of HHT patients with PAVMs will also present with mucocutaneous lesions.^3, 6 Pulse oximetry readings may show decreased oxygen saturation at room air postexercise and at rest due to shunting.⁶ Blood gasses may also provide evidence of hypoxemia.

CT has a sensitivity of more than 95% when screening for PAVMs. Many patients present with abnormal findings on CT since contrast-enhanced pulmonary angiography is not routinely used for diagnostic evaluation of suspected lesions unless they are suitable for embolotherapy. Classic diagnostic CT findings include a round or oval nodule (<3 cm) or mass (>3 cm) of uniform density representing the sac, typically 0.5–5 cm in diameter and occasionally exceeding 10 cm in diameter, with visible feeding and draining vessels. Contrast-enhanced pulmonary arterial angiography is the gold standard for defining the anatomy of a previously identified PAVM for embolotherapy or definitive diagnosis. For sacs greater than 0.5 cm, findings typically include regions of contrast-enhancement with a feeding artery leading to abnormal arteriovenous communication and drainage subsequently by a pulmonary vein. Rendered three-dimensional images of complex malformations facilitate planning for transarterial embolizations and are especially helpful in lesions involving more than one feeding vessel.^7, 8After the procedure is planned by CT scan, either non-contrast or CTA, diagnostic angiography is still needed to supply the roadmap for angiographic catheterization of the PAVM.

The natural history of PAVMs and true estimates of morbidity and mortality associated with untreated lesions are poorly understood, as the data consists primarily of retrospective case series. In the setting of HHT, morbidity and mortality are attributed to devastating neurological sequelae, stroke and brain abscess, from paradoxical emboli of thrombotic or septic origin. Hypoxemic respiratory failure and life-threatening hemoptysis and hemothorax may also occur.^9-12

When left untreated, complication rates have been reported to reach 50% and exceed this value during pregnancy.¹³ Diffuse forms are associated with greater complications, with neurological morbidity reaching 70% in untreated lesions.¹⁴ Resultantly, current recommendations include screening at regular intervals in HHT families. This has given rise to questions regarding protocols as they pertain to children, as the need to minimize lifetime exposure to ionizing radiation must be balanced with the need to identify and mitigate risks associated with PAVM.^15, 16

To minimize the risk of neurologic and other complications from PAVM, embolotherapy is currently the preferred treatment in the majority of patients. Alternative therapies include surgical excision and lung transplantation. The possibility of excision exists for patients who have had repeated failed embolization attempts as well as patients with life-threatening acute hemorrhage in a facility without access to embolotherapy. Depending on the location and extent of PAVMs, surgical treatment of PAVMs includes vascular ligation, local excision, lobectomy, and pneumonectomy via either video-assisted thoracoscopic surgery or open thoracotomy, with morbidity and mortality for surgical intervention being comparable to other forms of thoracic surgeries. The size threshold for treatment is variable, but this author typically recommends definite embolization for 3 mm or larger and strongly consider it for 2 mm or larger unless there are innumerable PAVMs that make that technically impossible without sacrificing an extensive amount of adjacent normal lung. Lung transplantation is reserved for patients with refractory, often bilateral and diffuse disease, and those who are at increased risk of dying from complications.^9, 17

Although the optimal guidelines for screening and management of PAVMs in children and adolescents remain controversial, endovascular embolization is a feasible and safe method for treating pediatric PAVMs. The first large case series of pediatric patients undergoing embolization for PAVMs in 2004 by Faughnan et al. demonstrated that embolotherapy was safe in children and young adults and that complication rates were similar to those in adult patients.¹⁴ Reperfusion rates were noted to be 15% at 7 years.¹⁴ Although reperfusion rates remain relatively high in pediatric patients undergoing embolization therapy, in comparison to surgical intervention, the parenchyma-sparing benefit of embolization therapy as well as lower morbidity and shorter hospital stay make this the treatment of choice.^2, 14, 18

Currently, embolization therapy is the preferred treatment of PAVMs and is performed in the absence of contraindications such as severe pulmonary hypertension, renal failure, and early pregnancy.¹⁹

There is no strong data on measuring RH/PA pressures prior to performing embolization. Embolizing a PAVM actually reduces overall PA flow in addition to possibly increasing resistance, so the effect on PA pressure is not predictable. If there are multiple feeders, PA pressure can be measured after embolizing each to check if there is a worrisome change.

Reperfusion or persistence of PAVM can occur by recanalization, accessory feeders that were there to begin with and not initially occluded, pulmonary artery collaterals, and systemic collaterals. The major issues remain as for a non-treated PAVM, but if all large PA channels have dense embolic material within them, even if recanalized, then the risk of larger size paradoxical embolization should be negligible.

In 1988, White et al. documented techniques and long-term outcomes of embolotherapy in patients with PAVMs, the majority of whom had underlying HHT, and emphasized the necessity for screening in these families due to the high risk of catastrophic neurological sequelae.²⁰ Over the course of the following 3 decades, although developments in equipment and imaging have improved interventional outcomes and permitted the embolization of multiple and bilateral PAVMs during a single session, the guiding principles of treatment have largely remained constant.^1, 15 Occlusion of the feeding artery is designed to eliminate flow to the lesion, allowing for thrombosis and sac retraction.¹⁵

The first component of the procedure is diagnostic. Contrast-enhanced pulmonary angiography is used to confirm and characterize the presence of PAVMs, including lesions that were missed on previous CT imaging, that are suitable for embolization. Visualization of the lesions is achieved through insertion of a percutaneous catheter through the transfemoral or transjugular veins and injection of contrast into the right and left main pulmonary arteries.¹⁵

The second component of the procedure, limited by the maximum contrast dose per patient, is therapeutic embolization. Heparin is typically provided during the procedure to minimize the risk of thrombus formation on the catheter that could result in paradoxical emboli, estimated at less than 1%.¹⁵ To further reduce the risk of paradoxical emboli formation through entry of air into the circulation, it is recommended that air filters be applied to all IV lines and that wire and catheter exchanges be performed under saline immersion.²¹

The process of embolization begins with the localization of lesions within the lung parenchyma through selective contrast injections. Contrast is used to guide the placement of embolic material, most commonly non-ferrous coils or vascular plugs, into the feeding artery of the malformation until flow across the connection ceases. When using coils, the initial one should be 20–30% wider than the feeding artery.²² Vascular plugs, although more expensive and time-consuming, as they take longer to occlude flow, allow for precise deployment near the sac and have a lower risk of device migration.¹⁵ Furthermore, only 1 plug is generally needed compared with multiple coils, often offsetting their greater expense. Lastly, Amplatzer and Microvascular Plugs have also been shown to have lower recanalization rates than coils and so are preferred if technically possible to place.

Postprocedure, patients are typically held for 2–3 hours in recovery and discharged the same day. The presence of additional PAVMs not treated in the first session may warrant additional intervention over the weeks or months following completion of the initial procedure.

The most common postprocedural complication, occurring in approximately 10% of patients, is self-limited pleuritic chest pain from thrombosis of the feeding artery and sac and/or pulmonary infarction.²¹ Rates of pleurisy are often higher in patients with feeding vessels measuring greater than 8 mm. Postprocedural complications related to systemic arterial embolization of clot, air, or the embolic device occur in less than 2.3% of cases and may manifest as TIAs, angina, or bradycardia.²²

With regards to treatment follow-up, patients are followed longitudinally, usually through their HHT center. In the immediate postoperative period, expected physiologic and symptomatic changes are evaluated through the use of pulse oximetry and clinical observation.²³ In most patients, reported immediate clinical and radiographic outcomes following embolotherapy include reduced flow across the lesion on radiographic imaging and improvement of oxygenation and symptoms such as dyspnea. Long-term benefits include decreased risk of ischemic stroke and cerebral abscess formation.^15, 24

The optimal regimen for follow-up is currently unknown, as more frequent follow-ups raise concerns for radiation exposure. Patients are initially seen 3–12 months at the clinic to monitor clinical improvement, including symptoms and oxygenation, and evaluate the status of the coils and feeding vessels through multi-detector contrast-enhanced chest CT with 1–2-mm thin slice formatting. Imaging findings consistent with treatment success are reductions in diameter of the draining vein, a minimum of 70% reduction in sac size, and lack of contrast enhancement. Non-contrast CT-imaging is then obtained every 3–5 years following the initial visit, unless the patient’s symptoms change and warrant additional surveillance.²³

Recanalization has been estimated to occur in 10–25% of cases, with rates purported to be higher in pediatric patients, and is evidenced by findings of draining veins consistent in size when compared to preprocedure measurements and unchanging soft tissue masses associated with coils on imaging.^{2, 6, 1415, 2528} The risk of reperfusion through recanalization of the embolized lesion is dependent upon angioarchitecture, coil-to-sac distance, coil number, and feeding artery diameter.^{1, 21, 2728} A study by Kawai et al. reported that time-resolved MRI is more sensitive and specific than unenhanced CT when assessing for residual flow and may provide a more accurate diagnosis of reperfusion during follow-up than current methods of imaging.²⁹

Further evaluation through pulmonary angiography is recommended for patients who present with worsening clinical features and radiographic findings, as these may be signs of recanalization or the development of new lesions.^15, 28

Although rates of permanent occlusion have been reported in the majority of patients undergoing embolization therapy, increased rates of patency, recanalization, and development of new lesions have served as obstacles in the successful treatment of PAVMs within the pediatric population. This has made the development of guidelines for the diagnosis and management of HHT in pediatric patients difficult and evidence for screening children has been deemed to be lacking by expert panels.²³ Overall, pediatric patients have been reported to have much lower rates of neurological complications from PAVMs when compared with adults, especially those without clinical manifestations of disease.^{2, 12, 25, 30} As lesions are thought to grow throughout puberty and the rate of reperfusion due to the development of secondary feeding arteries may be higher during this time, recommendations exist to delay screening and treatment of PAVMs until after the primary period of growth in childhood.² However, although this approach may allow for the use of fewer recurrent angiograms and interventions, overall, more research is needed to evaluate the hemorrhagic and neurological outcomes of delayed intervention in asymptomatic and symptomatic HHT pediatric patients.²

Amplatzer Vascular Plug (St. Jude Medical, St. Paul, MN).

The authors have no potential conflicts of interest with respect to the research, authorship, and/or publication.

The patient and family referred to in this video article have given their informed consent to be filmed and are aware that information and images will be published online.

We would like to thank our patient for her contribution to medical education. We would like to thank the faculty and staff of Yale New Haven Health for their courtesy and expertise during the filming process.