Intracardiac versus extracardiac shunt in a young man with ischaemic stroke

Abstract

A 24-year-old man with a history of recent ischaemic stroke was diagnosed with patent foramen ovale (PFO) and referred for closure at our hospital. At admission, besides low peripheral oxygen saturation (88%), physical examination was otherwise normal. We performed intraprocedural transoesophageal echocardiogram that revealed no PFO, although agitated saline injection demonstrated bubbles lately on the left atrium. The atrial septum could not be crossed. We suspected an extracardiac shunt, so pulmonary angiograms were performed that revealed the presence of a left pulmonary arteriovenous malformation (PAVM). A Konar-MF Occluder was used to occlude the PAVM, with a satisfactory result. At 6 months follow-up, the patient had normal peripheral oxygen saturation and a new pulmonary angiogram showed no residual shunt. Intrapulmonary shunts are a rare and under-recognised cause of paradoxical emboli in young patients; physicians should be aware of this diagnosis as percutaneous occlusion is indicated and critical to avoid recurrent ischaemic episodes.

Background

Paradoxical embolism due to an intracardiac or extracardiac shunt is probably responsible for most of the ‘embolic stroke of undetermined source’ (ESUS) among young patients.^{1 2} The term ESUS was introduced in 2014 and defines a subset of patients with ischaemic and cryptogenic stroke (unknown aetiology) in whom embolism was the likely mechanism and sufficient diagnostic assessment was made to exclude major-risk cardioembolic sources, occlusive atherosclerosis and lacunar stroke.¹ Reported frequencies of ESUS ranged, in average, from 9% to 25%^{3 4} with the highest reported frequency being 42% in a study restricted to young patients with stroke.⁵ The most common cause of a paradoxical embolism is an intracardiac right-to-left shunt through a patent foramen ovale (PFO), which has a prevalence that varies from 25% to 58% among ESUS patients who underwent transoesophageal echocardiogram (TEE).^{3 6} On the other hand, intrapulmonary shunts, a form of extracardiac shunting, are rare but recognised cause of paradoxical emboli.⁷ Hereby, we present a case of a paradoxical cerebral embolism in a young patient with a pulmonary arteriovenous malformation (PAVM) misdiagnosed as a PFO.

Case presentation

A 24-year-old man presented at our adult congenital heart disease unit for percutaneous closure of PFO. He had a clinical history of an ESUS 1 year earlier, initially presented with left hemiparesis from which he had totally recovered after 1 month. Subsequent investigations at his local hospital, namely thrombophilia screen, allowed the identification of a prothrombotic, homozygous mutation C667T in the methyl-tetrahydrofolate reductase gene (MTHFR). In addition, a PFO was diagnosed in TEE and he was referred for consideration of percutaneous closure at our hospital. The images taken during the TEE were not available. He was discharged under warfarin, with a target therapeutic international normalised ratio ranging between 2 and 3. His clinical history also included a thoracic and abdominal trauma with secondary hypo/asplenia due to splenic lesion when he was 4 years old. The patient denied former or current smoking, previous thoracic surgery and history of recurrent bleeding. He also denied family history of hereditary haemorrhagic telangiectasia (HHT) or thrombophilia.

On physical examination, he had a good general appearance, blood pressure of 125/65 mm Hg, heart rate of 88 bpm and a maximal peripheral oxygen saturation by pulse oximeter of 88% in all extremities despite no signs of hypoperfusion, cyanosis, clubbing, tachypnoea or use of accessory respiratory muscles. He had no mucocutaneous telangiectasias, and cardiopulmonary auscultation and the remaining physical examination were normal.

Investigations

Routine haematological and biochemical parameters showed non-significant changes. Routine chest radiography was apparently normal with the exception of a triangular and hypotransparent image near the left cardiophrenic angle (figure 1). Transthoracic echocardiogram showed an interatrial septum with a small tunnel suggestive of PFO, but no shunt through it was seen on colour Doppler at rest or during Valsalva manoeuvre (video 1). No additional intracardiac shunts were documented on colour Doppler, biventricular dimensions and function were preserved, and no valvular abnormalities were detected. Ascending aorta, pulmonary artery and its branches had normal dimensions. A twelve-lead ECG showed no arrhythmia.

Figure 1.

Chest radiography was apparently normal with the exception of a triangular and hypotransparent image (blue arrow) near the left cardiophrenic angle that retrospectively was perceived as a pulmonary arteriovenous malformation. Chest radiography shows abnormalities in about 98% of the patients.

Video 1.

bcr-2021-247877supp001.mp4 ^{(668.9KB, mp4)}

DOI: 10.1136/bcr-2021-247877.video01

With the purpose of treatment, catheterisation was performed through the right femoral vein. Several unsuccessful attempts to cross the interatrial septum with different guidewires were made and a right atrium contrast injection confirmed the absence of PFO (video 2). Thus, intraprocedural contrast TEE was performed using agitated saline injected on a peripheral vein that revealed the presence of bubbles in the left atrium only three cardiac cycles after right atrial opacification (video 3). This raised the suspicion of a pulmonary shunt that was confirmed by pulmonary artery angiograms on the left side showing a macrovascular PAVM of the inferior pulmonary lobe. The inferior lobar artery measured 11 mm in diameter and displayed a large fistula, fed by two main arterial branches measuring 8 mm and 4 mm, draining to the left superior pulmonary vein (figure 2A, B; video 4). Right pulmonary artery injection revealed no evidence of PAVMs (video 5).

Video 2.

bcr-2021-247877supp002.mp4 ^{(668.9KB, mp4)}

DOI: 10.1136/bcr-2021-247877.video02

Video 3.

bcr-2021-247877supp003.mp4 ^{(668.9KB, mp4)}

DOI: 10.1136/bcr-2021-247877.video03

Figure 2.

Percutaneous occlusion of the pulmonary arteriovenous malformation. Selective pulmonary angiogram of the inferior lobar branch of the left pulmonary artery showing a macrovascular pulmonary arteriovenous malformation or cavernous angioma: (A) Arterial phase, PAVM fed by two main arterial branches and (B) venous phase with drainage to the pulmonary vein. (C) Vascular occlusion using a Konar-MF ventricular septal defects occluder 9/7 mm (Lifetech scientific, Shenzhen, China). (D) Satisfactory final result after occlusion. PAVM, pulmonary arteriovenous malformation.

Video 4.

bcr-2021-247877supp004.mp4 ^{(668.9KB, mp4)}

DOI: 10.1136/bcr-2021-247877.video04

Video 5.

bcr-2021-247877supp005.mp4 ^{(668.9KB, mp4)}

DOI: 10.1136/bcr-2021-247877.video05

Differential diagnosis

Initial TEE allowed the exclusion of intracardiac masses or thrombus as the source of cerebral embolisation and raised the suspicion of the presence of a PFO. At our hospital, contrast TEE using agitated saline demonstrated bubbles in the left atrium lately, thus lowering the likelihood of both PFO and other intracardiac shunt and raising the suspicion of an extracardiac shunt, namely a pulmonary shunt, that could also justify the low peripheral oxygen saturation and the chest radiographic finding. Accordingly, a macrovascular PAVM was diagnosed. Regarding the aetiology of the PAVM, this patient had no personal or family history of recurrent epistaxis or mucocutaneous telangiectasia potentially related to HHT and described a significant trauma with secondary hypo/asplenia in the past. Therefore, the macrovascular PAVM was likely congenital, although a traumatic cause could not be excluded, and was probably the site for paradoxical embolism whereas the inherent thrombophilia may have facilitated or triggered thrombosis.

Treatment

At the same procedure, the inferior lobar branch of the left pulmonary artery was catheterised using a 0.035-inch hydrophilic guidewire and a 6Fr multipurpose catheter. A 0.035-inch Amplatz Super Stiff guidewire (Boston Scientific, Boston, Massachusetts, USA) was used to support the progression of a 6Fr Ceraflex delivery sheath (Lifetech Scientific, Shenzhen, China). A Konar-MF Ventricular Septal Defects (VSD) Occluder 9/7 mm (Lifetech Scientific, Shenzhen, China), with disc diameters of 14 mm, was felt to be the best available device and was used to occlude the PAVM. As the vessels involved are often very distensible, a device size of between 120% and 150% should be used and that was the reason why we chose a 14 mm disc diameter device to occlude a 11 mm vessel.⁸ A satisfactory result was achieved (figure 2C, D; video 6), with normal pulmonary artery pressure at the end of the procedure (16/11/13 mm Hg), and very mild residual flow through the device.

Video 6.

bcr-2021-247877supp006.mp4 ^{(668.9KB, mp4)}

DOI: 10.1136/bcr-2021-247877.video06

Outcome and follow-up

After the procedure, the patient remained asymptomatic, and his peripheral oxygen saturation raised to normal values. No complications were documented. At discharge, he was maintained on warfarin due to the homozygous mutation in the MTHFR gene and previous ischaemic stroke. At 6 months follow-up, the patient had no unscheduled visits to the hospital. Repeated pulmonary angiogram was performed with four inferior left pulmonary artery injections (video 7) that showed no residual shunt and successful device occlusion of PAVM. The decision on whether to maintain anticoagulant therapy will be made by a multidisciplinary team.

Video 7.

bcr-2021-247877supp007.mp4 ^{(668.9KB, mp4)}

DOI: 10.1136/bcr-2021-247877.video07

Discussion

PAVMs are defined as abnormal vessels that connect the pulmonary arterial and venous systems, providing a right-to-left shunt.^8–10 Its prevalence is 1–2600 individuals¹¹ and the male to female ratio varies from 1:1.5 to 1:8.^{12 13} Two varieties are described: macrovascular variety, or cavernous angioma, usually fed by one or more tortuous and dilated branches of the pulmonary artery; and microvascular variety or capillary telangiectasia, which forms a net of capillaries and is usually associated with HHT.^{8 14} PAVMs can be either congenital/primary (80% of cases) or acquired/secondary.^{9 12 15} Previous authors have estimated that 25%–75% of congenital PAVMs are associated with HHT, also known as Osler-Weber-Rendu syndrome¹⁴ and the possibility of HHT should be investigated in all patients with PAVMs.¹⁰ This syndrome is characterised by a vascular dysplasia that causes multiple telangiectasias and recurring haemorrhages.¹⁶ It is inherited as an autosomal dominant trait and most commonly results from a pathogenic sequence variant in endoglin and ALK-1 genes.¹⁷ Acquired PAVM, although very rare, can be caused by chest trauma, thoracic surgery, hepatic cirrhosis, metastatic carcinoma, mitral stenosis, infections (actinomycosis, schistosomiasis) and systemic amyloidosis.⁹

The majority of cases of PAVMs are diagnosed in the first three decades of life.^{12 18} Asymptomatic patients account for 13%–55% in different series.^{12 13} Paradoxical emboli may occur in patients with PAVMs of any size but only a very small proportion result in a clinical ischaemic stroke.^19–22 Less common complications include endocarditis, haemoptysis and haemothorax. Respiratory symptoms are frequently absent unless the arterial oxygen pressure is less than 60 mm Hg.^{9 23} A meticulous physical examination will detect abnormal physical findings in up to 75% of patients,⁹ the most common being hypoxaemia and pulmonary vascular bruit.^{12 13}

Contrast echocardiogram, either with transthoracic or transoesophageal approach using agitated saline or specific dye, is recommended as the first-line investigation to look for the presence of a right-to-left shunt and also to suggest its location.^{1 2} In patients without right-to-left shunt, bubbles appear in the right atrium but do not reach the left atrium due to trapping in the pulmonary circulation. In intracardiac shunt, bubbles will be visualised in the left atrium within one cardiac cycle after their appearance in the right atrium. In intrapulmonary shunt, bubbles have a delay of three to eight cardiac cycles before they reach the left atrium.^{18 24} A bubble study with a pattern suspicious for PAVM can be followed by a contrast enhanced CT, which is often adequate to diagnose and is also a key imaging modality for planning interventional occlusion.⁸ Nevertheless, pulmonary angiogram remains the gold standard for both diagnosis and treatment planning.9 12 13 18 A chest radiography may suggest the diagnosis as it shows abnormalities in about 98% of the patients.⁹

The morbidity associated with PAVM can be present in up to 50% of untreated patients compared with 3% in patients who received treatment.^{9 12 13} Microvascular PAVMs tend not to be amenable to direct interventional therapies and management relies on aetiology related medical therapeutic options.⁸ In contrast, macrovascular varieties show minimal response to medical therapy and interventional treatment is recommended even for asymptomatic patients.^{8 10} Coil embolisation has been used to occlude PAVMs, but when the vessels involved are large, they are more effectively dealt with vascular occlusion plugs.⁸ Accordingly, these devices are currently the first line for percutaneous treatment of PAVMs.⁸ No specific occlusion device is recommended and this should be chosen using a sizing strategy that takes into account the local anatomy and also the characteristics of the device.⁸ In this case, a Konar-MF VSD occluder was preferred and, as far as we know, it is the first report using this device. This device is similar to some plugs, with a central body and two terminal disks, one of which is fixed to the central body of the device and the other connected with it by a central piece, allowing some angulation. The use of these devices for fistula embolisation expands the options of available material. In our patient, this was particularly helpful as we did not have a 14–16 mm diameter plug available. Surgical treatment should be reserved for patients with PAVMs that are unsuitable or have failed repeated percutaneous treatment.^{8 10}

Long-term follow-up is recommended with thoracic CT every 1 to 5 years for untreated PAVMs, and within 6–12 months after embolisation and then every 3 years for treated patients.^{8 16} Pulmonary angiogram can be an alternative for imaging follow-up as performed in our patient, if the inherent risks to the invasive procedure are acceptable.

An additional learning point of this clinical case is the differential diagnosis of embolic stroke in young adults and the importance of multimodality imaging, including contrast echocardiogram, in these patients’ assessment. PAVMs are rare but should be considered specially if red flags for the diagnosis are present.¹ Most recently, complex morphologies of the left atrial appendage and altered left atrium dynamics have also been identified as independent predictors of ESUS in young patients but further studies are needed before any clinical recommendation are made in this field.^{25 26}

To conclude, in the presented clinical case, a paradoxical embolism was the first clinical manifestation of a macrovascular PAVM. Hypoxaemia, chest radiography and contrast echocardiogram findings were the red flags that raised the suspicion of an extra-cardiac shunt. Pulmonary angiogram confirmed the diagnosis and percutaneous occlusion was performed. This clinical case aims to illustrate, review and draw attention to a rare cause of paradoxical embolism whose diagnosis and treatment are critical to avoid recurrent ischaemic episodes and other related complications.

Learning points.

• In young patients with ischaemic stroke, besides thrombophilia, always investigate the presence of cardiopulmonary shunt.

• When agitated saline injection test demonstrates bubbles on the left atrium after at least three cardiac cycles following right atrial opacification, an extracardiac shunt should be suspected.

• Pulmonary arteriovenous malformations (PAVM) may be a cause of extracardiac shunt and consequent paradoxical embolism.

• Contrast-enhanced CT or pulmonary angiogram can be used to diagnose and plan percutaneous occlusion of PAVM.

• Percutaneous treatment is indicated and critical to avoid recurrent ischaemic episodes and other related complications.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).