Introduction

Pulmonary arteriovenous malformations (PAVM) are often comprised of an abnormal vascular connection between a pulmonary artery and a pulmonary vein. Commonly, PAVMs are seen in patients with hereditary hemorrhagic telangiectasia (HHT) [1]. An autosomal dominant disease, HHT can present with epistaxis, mucocutaneous telangiectasias, and AVMs in various organs, such as the lung, spine, and brain [6]. The abnormal connections made by PAVMs can lead to intrapulmonary right to left shunting, therefore, causing hypoxemia and complications such as stroke [1]. Reports of HHT in pregnancy are rare, and the general population carries an incidence of 1 in 5000 to 80,000 [4]. We present a pregnant patient diagnosed with multiple PAVMs and HHT who underwent multiple, successful treatments of PAVMs during pregnancy.

Case presentation

A 23-year-old gravida-4-para-2-0-1-2 Hispanic female, dated by an 8-week ultrasound, with a spontaneously conceived singleton pregnancy, was referred to Maternal-Fetal Medicine (MFM) after initial presentation to an outside hospital with expressive aphasia and ultimate diagnosis of a left middle cerebral artery (MCA) cerebrovascular accident. In that workup, she was found to have multiple bilateral PAVMs (nine on the right, five on the left; largest 2 cm in size) and a patent foramen ovale (PFO). She was discharged on 80 mg Lovenox, subcutaneously, twice daily. When seen in our clinic, she had worsening epistaxis (history of epistaxis since childhood); her Lovenox was discontinued and she began 81 mg of aspirin daily. Sequencing and deletion/duplication testing of ENG and ACVRL1 revealed one pathogenic mutation in the ENG gene, verifying the diagnosis of hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu (OWR). Magnetic resonance imaging (MRI) of the spine was attempted to rule out AVMs but was unable to be completed due to the patient’s claustrophobia; a later attempt allowed only a sagittal thoracic view, void of AVMs.

The patient complained of shortness of breath walking from room to room and 2-pillow orthopnea at follow-up appointments. At 16+1 weeks of gestation, she was seen by a pulmonologist and managed to walk a total of 1070 feet with no rest. She was diagnosed with exercise induced desaturation (94%–90%), not warranting supplemental oxygen. An electrocardiogram revealed normal sinus rhythm. The patient was discussed at a multidisciplinary meeting consisting of the departments of Perinatology, Neonatology, Interventional Radiology, Pulmonology, Cardiology, and Anesthesiology; a decision was made to proceed with transcatheter embolotherapy (TCE). Pre-operative venous ABG was: pH 7.37, CO₂ 37, O₂ 32, HCO₃ 21, and oxygen saturation 90%–92%.

The patient underwent bilateral selective pulmonary arteriography and pulmonary artery embolization at 22+2 weeks of gestation. Her abdomen was shielded and she received conscious sedation. Through the right groin a 7 French Cook sheath was advanced through the tricuspid and pulmonic valve into the right pulmonary artery. Selective pulmonary angiography verified multiple, large PAVMs in the right lung (Figure 1). Five PAVMs were embolized: three in the posterior inferior lung segments using 6–8 mm coils (Penumbra Ruby Embolizing Coils, Penumbra Inc, Alameda, CA, USA) each and two in the lower and middle lobe requiring coiling up to 24 mm in diameter and a 12 mm Amplatzer 2 device (St. Jude Medical, St. Paul, MN, USA), respectively. The exam was concluded to reduce further radiation and contrast dosing (radiation 10Gy, 130 min fluoroscopy time, contrast 150 mL Omnipaque 300). Pulmonary angiogram showed two small PAVMs in the left lung.

Figure 1

Pulmonary angiography of maternal right lung.

The patient experienced hemoptysis as the procedure concluded, which resolved overnight. Chest X-ray on postoperative day 1 showed four bundles of coils and one Amplatz device overlying the right lower thorax with alveolar opacities noted in the right lung base (Figure 2), and pulmonary venous congestion with a mildly enlarged heart. The patient was discharged on postoperative day 1 with stable vital signs and pain control with oral Tylenol. On postoperative day 2 she experienced discomfort with deep breathing, relieved with oral Tylenol, and by postoperative day 4 she had increasing shortness of breath, pain with coughing, and hemoptysis. She came to the hospital for evaluation, vital signs: oxygen saturation 90% on room air and 97% on 5 L nasal cannula, heart rate (HR) 113, respiratory rate (RR) 40, blood pressure (BP) 117/66 and temperature (T) 36.6°C. Computed tomography (CT) without contrast showed streak artifact from embolization coils in the right lower lobe, two stable PAVMs in the left lower lobe, a prominent, stable PAVM in the right upper lobe, and a focal consolidation adjacent to the region of embolization with evidence of air-bronchograms. It was felt the patient was experiencing pleurisy from the recent TCE and was treated with supportive therapy (incentive spirometry, analgesics, anti-pertussis medication). Vital signs at discharge: HR 89, 92%–98% on room air, RR 18, T 35.9°C, BP 92/59.

Figure 2

Chest X-ray after first transcatheter embolotherapy; each emoblized lesion is labeled with an arrow (vascular plug is faintly seen in the most left upper quadrant of image).

At follow-up prenatal visits, the patient remained without shortness of breath, orthopnea, or hemoptysis. The following TCE of the remaining PAVMs [one large in right upper lobe (Figure 3), and two small in the left lung] was performed at 26+6 weeks of gestation, thus, the patient received antenatal corticosteroids (betamethasone 24 h with two doses) prior to the procedure. Vitals prior to procedure: oxygen saturation 95% on room air, HR 91, RR 19, BP 119/71, T 35.9°C. Continuous electronic fetal monitoring and tocometry was performed during the procedure and 5 h postoperatively until discharge; no decelerations or contractions were noted.

Figure 3

Pulmonary angiography of the right lung following placement of a new coil placement (solid arrow). The two prior superior, embolized lesions, one coil, and one vascular plug (dashed arrows) can clearly be seen.

A routine growth ultrasound at 33+5 weeks of gestation showed a 2.2×2.0×1.8 cm hypoechoic fetal cerebral AVM (CAVM) with increased color flow between the right cerebellar lobe and the right cerebral hemisphere (Figure 4), with an abnormal circle of Willis. In addition, a dilated right atrium and increased cardiac circumference (156 mm to chest of 226 mm) was noted, without pericardial effusion or evidence of hydrops. The amniotic fluid index (AFI) was 24.55 cm (94%) and estimated fetal weight was 2372 g (69%). Weekly ultrasounds and twice weekly non-stress testing (NST) was performed. In 1 week, AFI and CAVM were stable. In 2 weeks, at 35+6 weeks of gestation, the AFI was 24 cm (91%) and the CAVM had increased, now 2.44×2.21×1.87 cm, with extension posteriorly into the right lobe of cerebellum; the circle of Willis was dilated and tortuous. Increased globular wall thickening was noted in the enlarged fetal heart without evidence of pericardial/pleural effusions or ascites. The patient was sent to the hospital for prolonged monitoring and continued follow-up with twice-weekly NSTs, which were reassuring. The decision was made to proceed with elective primary cesarean delivery at term in hopes of decreasing any trauma to the fetal CAVM. At 37+6 weeks of gestation, a 3200 g male with Apgar scores of 9 and 9 at 1 and 5 min, respectively, was delivered and taken to the Infant Special Care Unit (ISCU). MRI/magnetic resonance angiography showed a 2.8×2.3×2.2 cm right parieto-occiptal AVM with two main feeders from the right posterior cerebral artery draining to the right transverse sinus, which itself was enlarged at 11 mm. Chest X-ray showed moderate to severe cardiomegaly. The neonate experienced tachypnea at 9 h of life and was immediately stabilized and transferred for a higher level of care.

Figure 4

Fetal cerebral arteriovenous malformation noted at the antenatal ultrasound at 33 weeks of gestation that measured approximately 2.2×2.0×1.8 cm.

Genetics consultation and testing of the infant for HHT verified a familial frameshift mutation in ENG, consistent with the diagnosis of the neonate’s mother. An echocardiogram showed a PDA, small secundum ASD or PFO with bidirectional (mainly left to right) shunting, dilated right atrium and ventricle, pulmonary hypertension, and dilated aorta at level of the PDA. Chest CT revealed no PAVMs, cardiomegaly with pulmonary edema, and tortuous aortic arch branching vessels.

The infant underwent partial embolization of the right parietal AVM, Spetzler Martin Grade II, with injection of N-butyl cyanoacrylate (nBCA) on day of life 38 and immediately following injection experienced hypertension and tachycardia. Dyna CT showed a large intracranial hemorrhage and extravasation of contrast into the brain and ventricular system requiring external ventricular drain (EVD) placement. Two days later he experienced seizures; EVD was removed on postoperative day 5. MRI of the brain 11 days postoperatively showed a vascular lesion of the right cerebral hemisphere with large varix or aneurysm in the inferior right parieto-occipital region with surrounding enlarged arteries and veins with enlarged feeding arteries from the right MCA in the right Sylvian fissure. A decision was made to not proceed with further CAVM procedures until the infant was larger and older. He was discharged at 63 days of life and noted to have a 1-month delay of his developmental milestones; he is scheduled for a 6-month follow-up to assess his neurological status.

Discussion

The diagnosis of HHT was made in our patient after her initial presentation with expressive aphasia and stroke. She had a history of epistaxis and was found to have vascular visceral involvement in the form of multiple PAVMs. The confirmatory diagnosis can be made by testing for mutations in the ENG or ACVRL1 gene. Our patient, and her son, were found to have a frameshift mutation in ENG, which codes for endoglin, and when this is the genetic concern, PAVMs are more commonly found [2]. Strokes are a known possible complication of HHT, and maternal deaths have been reported [4]. As our patient had experienced a stroke in this pregnancy, and had a PFO, the current recommended therapy of daily aspirin was begun [7].

A reported overall rate of PAVMs causing life-threatening hemorrhage is 1.4%, with the majority occurring in the early third trimester [4]. PAVMs are abnormal connections between the venous and arterial pulmonary system causing right to left shunting and are often associated with HHT [1]. Gold-standard treatment for PAVMs is TCE [1]. A recent review helping to guide management of patients with HHT states that overall risk of complications from PAVMs in pregnancy is considered low in a patient without symptoms [4], yet in a retrospective review of 161 pregnancies, of 23 with known PAMVs, 10 (43%) had deterioration of their PAVMs [5]. This study also showed two maternal deaths from PAVM hemorrhage and three strokes [5]. A prospective study performed TCE on 13 PAVMs in seven pregnant women, from the gestational age of 16–36 weeks, and no intraoperative or postoperative complications were identified [3]. This study held promise for our patient to undergo TCE in pregnancy, although her lesions were much larger in size and quantity than the seven patients in this study, who each only had 1-4 PAVMs embolized [3]. The estimated fetal radiation (50–220 mRad) and fluoroscopy time (17–49 min) [3] was less than our patient, but this was expected given our patient’s large and numerous PAVMs. Our goal was to perform TCE of the largest lesions, which required starting with the lung containing the most PAVMs, followed by a second procedure to assure embolization of all lesions of significant size to reduce the patient’s risk of possible hemorrhage. Furthermore, PFO closure was deferred until the postpartum period.

Our patient was managed in an intensive care setting overnight after her first TCE for close monitoring due to the length of her procedure and her known PFO. Pleurisy, which would be expected after the extensive manipulation during TCE, was managed with oral pain medication and use of an incentive spirometer. In the seven patients who underwent TCE in pregnancy, two experienced pleurisy later in their pregnancy [3]. Vaginal delivery appears safe in a pregnant patient with PAVMs, even after TCE is performed during the pregnancy [3]. However, in light of the fetal CAVM seen on antenatal ultrasound, and with no clear consensus from limited case reports regarding fetal CAVM identified in utero, we chose to proceed with a cesarean delivery with the goal of decreasing any potential trauma to the fetal brain.

No current recommendations exist regarding the increased need for antenatal ultrasounds in the pregnant patient with HHT [4]. However, given the CAVM found in our patient, as well as the reported findings of intracranial hemorrhage, infarct, or cerebral AVM in neonates, all male, from women with known HHT [6], we recommend frequent growth ultrasounds in women with known HHT to evaluate for fetal AVMs. Women with HHT should have an MRI to evaluate the spine and assist with the decision for regional anesthesia, as well as consideration for a brain MRI if there are any cerebral symptoms [4]. Finally, women with HHT should be counseled that the risk of birth defects in their fetus is not necessarily higher [6], but they are considered a high-risk pregnancy [4], and thus, should be followed as such.