Pulmonary Arteriovenous Malformations

Background Pulmonary AVMs

Pulmonary AVMs are associated with HHT in more than 80% of patients [1]. If not associated with HHT, pulmonary AVMs are considered idiopathic [2]. Rarely, pulmonary AVMs have been reported in association with hepatopulmonary syndrome, mitral stenosis, trauma, schistosomiasis or actinomycosis, Fanconi’s syndrome, and metastatic thyroid carcinoma [3]. The detection of pulmonary AVMs, or their complications, may predate the HHT diagnosis, particularly as HHT is an under-recognized disorder.

HHT is an autosomal dominant disorder, characterized by the presence of vascular malformations (telangiectases and AVMs) and caused by a mutation in either the Endoglin gene or the Activin-A type II like kinase 1 (ACVRL1) gene in 85% of families [4]. Approximately 2% of persons with HHT are affected by a mutation in the SMAD4 gene and these patients typically have an overlap syndrome with Juvenile Polyposis [5]. Pulmonary AVMs have a higher prevalence in patients with an Endoglin mutation (49–75%) than in patients with an ACVRL1 mutation (5–44%) [6–8].

Anatomy Pulmonary AVMs

Most (80%) pulmonary AVMs are simple stulas consisting of a single feeding artery directly connected to a draining vein, with only an intervening aneurysmal sac but no capil-

a

laries (Fig. 26.3). About 20% of pulmonary AVMs are complex with multiple feeding arteries, or multiple draining veins, or a septated aneurysmal sac [9]. A diffuse form of pulmonary AVMs is present in approximately 5% of pulmonary AVM cases (Fig. 26.4). Diffuse pulmonary AVMs have been de ned as AVMs involving every subsegmental artery of at least one pulmonary lobe [10, 11].

Clinical Presentation of Pulmonary AVMs

Patients with pulmonary AVMs do report exertional dyspnea, though only in approximately 50% of patients. Less than 10% of patients present with classical features such as cyanosis, clubbing, and pulmonary bruit. More typically, patients present with complications from pulmonary AVMs, such as a massive hemorrhage or stroke. Hemorrhagic complications develop due to spontaneous rupture of a pulmonary AVM, leading to massive hemoptysis or hemothorax. This complication has typically occurred in 3–13% of patients by the time of diagnosis of pulmonary AVMs. Even more frequently patients develop neurologic complications due to paradoxical emboli, such as stroke, transient ischemic attack, or cerebral abscess, with frequencies of 10–60%, by the time of diagnosis of pulmonary AVMs [1, 12–14]. The presumed mechanism for stroke is via paradoxical embolization of thrombus from the leg deep venous system or alternatively from in situ thrombus in the AVM. Cerebral abscess in these patients can be caused by a variety of pathogens but is most commonly due to pathogens typical of periodontal

b

Fig. 26.3  (a, b) Pulmonary AVM in the right lower lobe. Screening for the presence of pulmonary AVMs is done by an unenhanced low-dose CT chest. (a) shows the feeding artery (narrow arrow) and the draining

vein (bold arrow) of the pulmonary AVM, (b) shows the nidus of the pulmonary AVM

source [15–17]. Interestingly, migraine is also frequently reported in HHT patients with a pulmonary AVM, particularly migraine with aura [18, 19]. There are multiple mechanistic theories for the connection between migraine and pulmonary AVM, from impaired pulmonary capillary clearance­ (due to shunting) of vasoactive molecules to recurrent paradoxical emboli through pulmonary AVMs.

Screening Pulmonary AVMs

Pulmonary AVM complications can be largely prevented, with appropriate screening and preventative therapy. The International HHT Guidelines [20, 21] recommend screening all patients with HHT (or suspected HHT) for pulmonary AVMs and treating them preventatively. The recommendedrst-line screening test is transthoracic contrast echocardiography (TTCE) with agitated saline, for the detection of a right-to-left shunt. This is a low-risk and minimally invasive screening test with high sensitivity (93%) and an excellent negative predictive value (99%) for the presence of a pulmonary AVM [22–24]. When there is evidence of right-to-left shunt on TTCE, CT chest is the recommended diagnostic test to con rm or rule out the presence of pulmonary AVMs [20] and this can be done without enhancement in most cases.

The degree of shunt on TTCE can be graded (1–3) according to the number of microbubbles appearing in the left ventricle after four or more cardiac cycles [24]. The number of

cardiac cycles after which contrast appears in the left ventricle is not predictive of an intracardiac or intrapulmonary shunt [25]. Increasing shunt grade is associated with increased positive predictive value of the presence of pulmonary AVMs requiring embolization [23, 25, 26].

For patients with HHT with negative TTCE at baseline, rescreening is recommended every 5 years. Patients who are found to have small pulmonary AVMs on CT chest, with feeding artery <2 mm diameter and not causing complications, can be observed and followed with repeat CT chest every 1–3 years to detect growth and subsequent indication for embolization.

Pulmonary AVM precautions are recommended in all HHT patients with pulmonary AVMs, regardless of treatment, and all HHT patients with a right-to-left shunt on TTCE, even if there are no CT-detectable pulmonary AVMs [20]. First, patients should receive prophylactic antibiotics for all bacteremic procedures, to prevent cerebral abscess and other septic emboli. In addition, dental hygiene should be optimized. The speci c choice of antibiotics for prophylaxis depends on the procedure, following the antibiotic choices detailed in the Subacute Bacterial Endocarditis (SBE) guidelines of the American Heart Association [20, 27]. Second, to reduce the risk of air embolus, caution should be used to avoid air bubble introduction with intravenous access, preferably by the use of an air-elimination lter, if available. Finally, it is recommended that patients avoid SCUBA diving to prevent complications from decompression.

Treatment Pulmonary AVMs

Preventative transcatheter embolotherapy is recommended, by an experienced interventional radiologist with the goal to occlude pulmonary AVMs with a feeding artery of 2–3 mm or greater [20]. Currently, there are several devices being used for embolization, including various types of coils and Amplatzer plugs. The reperfusion rates (mostly secondary to recanalization) after embolization with coils and Amplatzer plugs are similar, 7–10% [28]. Embolization is generally performed as a day procedure, or with overnight admission, under local anesthesia and conscious sedation.

The most common complication of embolization is pleuritic chest pain post-procedure, occurring in up to 30% of patients. The pain is usually self-limiting, lasting on average 7–10 days, and treated with non-steroidal anti-infammatory drugs, as needed. Other complications, although rare, include lung infarction, transient hemoptysis (vessel perforation), migration of the device into the systemic circulation, and very rare complications are angina pectoris, transient ischemic attack, cerebral infarction [28, 29]. A migrating device typically occurs at the time of device placement and in most cases, the device can be retrieved by the interventional radiologist via the catheter, during the same procedure.

Follow-up after embolization is routinely performed 1 month after the procedure with an arterial blood gas (including oxygen shunt testing where available) to document improvement in PaO2 and a chest X-ray to assess for early involution of the aneurysmal sac and draining vein. Subsequent follow-up is recommended 6–12 months after embolization, with a repeat unenhanced CT chest to con rm involution of the aneurysm and of the draining vein of the embolized AVMs [20, 30]. If there is not suf cient involution, reperfusion is suspected, and retreatment should be considered. The second goal of CT is to detect the growth of residual small AVMs and the rare development of new AVMs. In the case of a negative CT chest after embolization, repeat followup by CT chest is recommended after 3 years [20].

Pregnancy and Pulmonary Arteriovenous

Malformations

Pregnancy is associated with an increased risk of hemorrhage from pulmonary AVM [17, 31], presumably secondary to the increased cardiac output and increased stroke volume [32]. To reduce this risk, screening for the presence of pulmonary AVMs in women with HHT is recommended prior to pregnancy, with preventative embolotherapy if indicated. If not screened prior to pregnancy, women with HHT should be screened with TTCE in the early second trimester [19]. When pulmonary AVMs are newly diagnosed during pregnancy, embolization is recommended during the early second tri-

mester to prevent complications [19]. If pulmonary AVMs are present and not treated during pregnancy, the pregnancy should be considered high-risk [19]. If embolization is performed during pregnancy, it should be performed by an experienced radiologist, with every effort to minimize radiation exposure for the fetus. Exposure reduction can be achieved by covering the abdomen and pelvic area with a lead apron, collimation of the radiation eld, and limiting the fuoroscopy time. Taking these precautions will expose the fetus to a radiation dose of 0.01–0.66 mGy, which is below the estimated threshold dose of 250 mGy that could potentially have an effect on the fetus in the second trimester [33].

Children with Hereditary Hemorrhagic Telangiectasia

Children with HHT should be screened for pulmonary AVMs as well [21, 34]. Twenty-three percent of asymptomatic children with HHT diagnosis have pulmonary AVMs, of these 70% with a signi cant feeding artery diameter of ≥3 mm [35, 36]. Initial screening for pulmonary AVMs in the pediatric population can be done by the combination of history, physical examination, saturation on pulse oximetry ≥96% and chest radiography and/or TTCE [21, 35, 36]. When screening is positive, CT chest is recommended, as it is in adults, to con rm the presence of pulmonary AVMs and measure the feeding artery diameter. Embolization is recommended in children who are symptomatic of the pulmonary AVMs, who are hypoxemic, or who are found to have a large pulmonary AVM on imaging. Treatment of asymptomatic children should be considered on a case-by- case basis [21]. Treatment by transcatheter embolotherapy in children is low risk in experienced hands, with complication rates comparable to those in adults [37]. Screening for the presence of pulmonary AVMs in asymptomatic children with HHT or at risk of HHT should be repeated every 5 years [21].

Reports of pulmonary AVMs in neonates are rarer. There are 18 case reports of neonates with pulmonary AVMs, 39% died within the rst week. We suspect there is a reporting bias here, with primarily severe cases being identi ed and reported at birth. Embolization can be performed in neonates, as in children.

Difuse Pulmonary Arteriovenous

Malformations

Diffuse pulmonary AVMs are pulmonary AVMs occurring in every subsegmental artery of one or more pulmonary lobes. They occur in 4.4% of patients with pulmonary AVMs and these patients more frequently present with cyanosis,