AMPLATZER Septal Occluder Failure Resulting in Paradoxical Cerebral Embolism

Abstract

Patent foramen ovale and atrial septal defect are risk factors for paradoxical embolism and subsequent cerebral ischemic events. The transseptal passage of emboli from the right to the left cardiac chambers appears to play an important role. The therapeutic options are medical therapy (anti-aggregation or anticoagulation), surgical closure, or transcatheter closure. Transcatheter closure of atrial septal defects affords the advantage of closing an atrial defect without the associated morbidity of open-heart surgery and the bleeding sequelae of oral anticoagulation. After closure, however, the presence of a residual shunt is independently associated with an increased risk of recurrent ischemic events. Newer devices, such as the AMPLATZER Septal Occluder, have decreased the risk of residual shunting and thromboembolic events. In addition, they have a very low risk of device dislodgement, migration, and embolization.

We describe the case of a 60-year-old woman with Ebstein anomaly and recurrent ischemic strokes who presented with acute ischemic infarcts and paradoxical embolism 3 years after undergoing transcatheter closure of an atrial septal defect. A right-to-left shunt through a displaced AMPLATZER Septal Occluder was detected. Pulmonary hypertension and resultant right ventricular failure and right atrial dilation could have contributed to the persistent shunting and paradoxical embolism.

To our knowledge, the delayed dysfunction of an AMPLATZER Septal Occluder has not been reported. In addition to describing the patient's case, we review the relevant medical literature.

WEBSITE FEATURE

A right-to-left intracardiac shunt due to patent foramen ovale (PFO) or atrial septal defect (ASD) increases the risk of cerebrovascular events (stroke, transient ischemic attack [TIA], or peripheral emboli) due to paradoxical embolism. The transseptal passage of emboli from the right to the left cardiac chambers due to transient increases in right-side pressures (from the Valsalva maneuver or coughing) or persistent elevation (as in pulmonary hypertension or Eisenmenger syndrome) appears to play an important role. The therapeutic options are medical therapy (anti-aggregation or anticoagulation), which yields an annual recurrence rate of 3% to 4% for stroke or TIA; surgical closure; or percutaneous transcatheter closure. Whereas long-term medical therapy increases the risk of bleeding sequelae, percutaneous closure of ASDs has been equally efficacious and offers the advantage of closing a defect without the associated morbidity of open-heart surgery or the bleeding sequelae of oral anticoagulation. Several single-center, nonrandomized studies have shown the safety of transcatheter PFO closure and its protective effects against recurrent neurologic events.^1–4 The totality of evidence suggests that device closure is a safe and effective alternative to surgical closure for preventing recurrent episodes of paradoxical embolism.^5,6 Along with fewer complications, percutaneous treatment offers other advantages over open surgery, such as shorter hospital stays, earlier return to normal activities, and better cosmesis.⁷ Although rare, device displacement leading to failure and cardiac erosion is a known and severe sequela of device closure.

Ebstein anomaly is a congenital cardiac malformation characterized by apical displacement of the septal and posterior tricuspid valve leaflets, leading to various degrees of hypertrophy and thinning of the atrialized portion of the right ventricle. An associated atrial septal communication, whether an ASD or a PFO, can enable right-to-left shunting with right atrial pressure elevation, particularly upon exertion (when cardiac output is increased and the right ventricle is required to accept more volume).⁸ We report the case of a woman with Ebstein anomaly in whom device displacement occurred, and we review other cases of device-related sequelae.

Case Report

In April 2009, a 60-year-old woman with type 2 diabetes mellitus, hypertension, Ebstein anomaly, heart failure, and multiple ischemic strokes presented with generalized tonic-clonic seizures. She was intubated for treatment of hypoxia and for airway protection and was admitted to the medical intensive care unit. Her blood pressure was 100/60 mmHg, her heart rate was 98 beats/min, her respiratory rate was 27 breaths/min, and her oxygen saturation was 93% on 100% forced inspiratory oxygen. Physical examination revealed central cyanosis, jugular venous distention, displaced point of maximal impulse, a parasternal heave, a loud and palpable pulmonic S₂, a grade 4 pansystolic murmur, bilateral coarse breath sounds, a pulsatile and enlarged liver, clubbing, and anasarca. An electrocardiogram revealed atrial fibrillation with rapid ventricular response and right bundle branch block. A computed tomographic scan of the brain showed multiple remote infarcts involving the cerebellar hemispheres bilaterally in the left posterior cerebral artery territory. Ischemic changes involving the right cerebral hemisphere were seen in the middle cerebral artery territory and in the region of the watershed with the right posterior cerebral artery. Magnetic resonance imaging of the brain revealed small, acute cortical ischemic infarcts of the right occipital lobe, the right caudate head, the left occipital lobe, and the left parietal lobe, suggesting embolic strokes (Fig. 1). An echocardiogram showed the Ebstein anomaly with interval increase (compared with one from 2006) in the right-side cardiac chambers, worsening of left ventricular ejection fraction (from 0.40–0.44 in 2006 to 0.25–0.30 currently), and a large right-to-left interatrial shunt through a cranially displaced AMPLATZER® Septal Occluder (St. Jude Medical, Inc.; St. Paul, Minn), without any obvious thrombus (Fig. 2). An echocardiographic study with saline contrast medium confirmed the presence of a right-to-left shunt (Fig. 3). Computed tomographic angiography of the chest showed cardiomegaly, bilateral pleural effusions, and a small pericardial effusion. Bilateral lower-extremity Doppler ultrasonography did not show any evidence of thrombosis. Carotid Doppler ultrasonography revealed no significant stenosis.

Fig. 1 Magnetic resonance image of the brain shows infarcts in the A) right occipital lobe, B) right caudate head, C) left occipital lobe, and D) left parietal lobe.

Fig. 2 Transthoracic echocardiogram shows A) an interatrial shunt (color-flow Doppler) and B) the displaced AMPLATZER Septal Occluder.

Fig. 3 Transthoracic echocardiogram shows A) opacification of the right chambers upon the injection of saline contrast medium, and B) immediate opacification of the left chambers, suggesting a large right-to-left shunt.

The patient eventually recovered from the acute episode and was extubated after 10 days with no complications. Her medical history included embolic strokes before the septal occluder had been implanted. An earlier transesophageal echocardiogram had shown normal left atrial size and no intracardiac thrombi. The patient reported that the AMPLATZER device had been placed percutaneously in February 2006 to prevent recurrent paradoxical embolism, and that she had experienced no subsequent TIAs or cerebrovascular accidents. Furthermore, whereas right atrial enlargement had been seen on her most recent previous echocardiogram, her left atrial size was normal, indicating that the atrial fibrillation was acute in onset.⁹ The atrial fibrillation was rate-controlled with metoprolol, amiodarone, and digoxin therapy. The right-to-left shunt through the displaced occluder was considered to be responsible for the paradoxical emboli that had led to the acute ischemic infarcts. She was started on warfarin for the prevention of further strokes and was discharged to a long-term acute care facility.

Discussion

The first transcatheter device closure of an ASD was reported by King and Mills in 1976.¹⁰ A residual shunt after the implantation of an ASD closure device is associated with an increased risk of recurrent ischemic events.¹¹ Paradoxical embolism is now recognized as an independent indication (Class IIa) for closure of an ASD.¹² In 2001, the AMPLATZER Septal Occluder was approved by the United States Food and Drug Administration for use in children and adults with secundum ASDs. The AMPLATZER occluder uses the shape memory of nitinol, which is an alloy of nickel and titanium. Each occluder is made of a nitinol wire mesh that is shaped into 2 flat discs and a middle, or “waist,” to fit the defect size, with polyester fabric inserts designed to help to close the defect and provide a foundation for the growth of tissue over the occluder after its placement. The percutaneous closure of ASDs with the AMPLATZER device in adults has been shown to be safe and effective.⁶ No randomized controlled trial has been conducted to compare surgical closure of ASDs with percutaneous device closure; however, a comparative study between 2 cohorts who underwent surgical or percutaneous closure was performed in Singapore. Device closure was a safe and effective alternative to surgical correction, with shorter hospital and intensive care unit stays. The risk of complications was slightly higher in surgical closure (relative risk=1.33; 95% confidence interval, 0.30–5.95) than in transcatheter closure.⁷ Earlier-generation devices achieved complete closure in only 78% of patients. Newer devices such as the AMPLATZER occluder had a complete closure rate of 100% at 6 months, as determined by means of transesophageal echocardiography. The occurrence of major sequelae during a mean follow-up period of 3.4 ± 2.8 years was higher in patients who underwent ASD closure with the CardioSEAL or STARFlex device than in patients who received the AMPLATZER device (17.2% vs 2.9%; P = 0.005).¹³ There was also a significant difference in regard to the complete closure of ASDs and the annual risk of thromboembolism, with more residual shunts and recurrent thromboembolic events in the CardioSEAL and STARFlex groups than in the AMPLATZER group.¹⁴

Cardiac erosion, perforation, and arrhythmias, and thrombosis, sepsis, and device migration are some of the major sequelae documented in percutaneous device closure. Most of these have been reported early after implantation, and late device migration or perforation is very rare. We reviewed reported cases of sequelae associated with AMPLATZER ASD closure (Table I).^15–27 Percutaneous device closure of secundum ASDs and PFOs has yielded excellent overall clinical results in short- to medium-term studies; however, only scant data are available on long-term outcomes and possible complications. One large study²⁸ confirmed the complete closure of ASDs in 99% of cases after long-term follow-up (mean, 6 ± 2 yr), and no patient required repeat surgical or percutaneous closure. Pulmonary hypertension and resultant right ventricular failure and dilation in our patient with Ebstein anomaly could have contributed to the persistent shunting and paradoxical embolism. A study has shown that shunting 24 hours postprocedurally is an independent risk factor for a residual shunt at 6 months, and that percutaneous reintervention with a second device implantation for moderate-to-large residual shunts is both safe and effective.¹¹

TABLE I. Reports of Major Sequelae Associated with ASD Closure with Use of an AMPLATZER Septal Occluder

The investigators in 2 ongoing multicenter randomized trials (RESPECT PFO Clinical Trial and CLOSURE I) are using different PFO-closure devices to determine their safety and efficacy versus standard medical therapy in patients with stroke or TIA due to presumed paradoxical embolism through a PFO. Preliminary results from CLOSURE I indicate that PFO closure with use of the STARFlex device is not superior to optimal medical therapy in the prevention of recurrent stroke or TIA. However, an earlier trial¹³ proved the increased risk of residual shunting with use of the STARFlex occluder, as compared with use of the AMPLATZER device. Until the final results of the ongoing trials are reported, it is imperative that patients undergo close, long-term, 2-dimensional echocardiographic follow-up to detect device migration and residual shunting as early as possible so that appropriate and timely intervention can prevent sequelae such as paradoxical embolism.⁴