1.1

Devices

The Amplatzer (AGA Medical, Golden Valley, MN, USA) and Premere (St. Jude Medical, Maple Grove, MN, USA) are currently being used for PFO closure internationally . The single-sized 25-mm Premere device is only recommended for smaller PFO (<15 mm) with an interatrial septal aneurysm (ASA) excursion of less than 1 cm on each side of the midline. The Premere device is designed to close small PFO of variable size and length with right and left anchor arms connected by an adjustable flexible tether to suit the PFO anatomy. The device has a low profile and a small surface area on the left atrial side which may reduce the likelihood of thrombus formation. There is greater experience with the heavier Amplatzer device. The Amplatzer device is suitable for most PFO but is preferred in the presence of ASA, significant septal redundancy, hypermobility of the septum (excursion greater than 1 cm from the midline), and in cases of multiple small fenestrations . Deployment via a femoral vein sheath and user-friendly delivery system is accomplished using both fluoroscopic and echocardiographic guidance.

There is limited data reported on outcomes using newer improved devices and technology which is vital to the future of this procedure. The main objective in this prospective study was to monitor the outcomes of patients undergoing transcatheter PFO closure to establish procedural safety and efficacy including medium- to long-term results. We also describe our preprocedural assessment and methodology used in deploying transcatheter percutaneous PFO closure devices.

2.1

Recruitment and data collection

In a prospective study, data was collected from patients undergoing transcatheter closure of PFO in Brisbane, Queensland, Australia. The Prince Charles Hospital and the Gold Coast Hospital were the two study sites. Proctorship and training in preprocedural PFO assessment, vascular access, multimodality imaging including intracardiac echocardiography (ICE) were provided by the Prince Charles Hospital Cardiac Catherisation Laboratory.

The Amplatzer or Premiere device was used in a nonrandomized choice based on the preprocedural assessment of the defect at operator discretion. This choice was made taking the location, size, interatrial septal excursion distance, rim characteristics, number of defects, and shunt size into account. Indications for percutaneous transcatheter closure were presence of PFO with presumed paradoxical embolism as the cause of the presenting condition. The most common indication was cryptogenic stroke. Exclusion criteria were atrial septal defect (ASD), PFO with another source of embolus (e.g., left ventricular thrombus), hemorrhagic stroke, or concomitant life-threatening comorbidities.

Patients with stroke were assessed and referred by a neurologist for percutaneous PFO closure. Prior to endothelialization of the device, the left atrial disk may carry a risk of thrombosis. The inherent risk of the deployed device was explained to both stroke and nonstroke patients and to the neurologist. Clinical and radiological evidence of paradoxical embolism was mandatory to be considered in the study. Radiological evidence had to be a computed tomography or magnetic resonance imaging demonstrating a cerebral infarct. A diagnosis of cryptogenic stroke was accepted by exclusion if further investigation failed to demonstrate another source of embolus .

2.2

Preprocedural workup

All patients underwent a detailed history and clinical examination to document their current clinical status. A thrombophilia screen was taken in all patients to assess the thrombotic risk. Patients were assessed for polycythemia rubravera, protein C and protein S deficiencies, antithrombin III deficiency, lupus screen, and factor 5 Leiden. All patients were negative. Patients were reviewed by a neurologist for exclusion of other causes of stroke, or TIA echocardiography, carotid duplex scanning, and 24-h Holter monitor were recorded before recruitment into the study. Transthoracic (TTE) and transesophageal (TEE) echocardiograms revealed the position, size, number, and structure of the defect. The presence of an interatrial septal aneurysm was documented and the aneurysm was characterized by the excursion distance which affected the choice of the closure device . A right-to-left shunt was demonstrated on TEE or TTE using color Doppler and saline bubble study. Abdominal compression, a cough reflex, and the Valsalva maneuver were used to induce or accentuate the shunt from right to left. A PFO was diagnosed when the defect was seen as a tunnel at the insertion edge of the interatrial septum. An ASD is an open communication (a tissue defect) persisting between the atria after septation. ASDs are usually seen as larger central defects in the interatrial septum. The position of the defect was confirmed using color Doppler across the septum .

A “bubble study” using 10 ml of agitated saline injected through a femoral vein was used to detect a right-to-left shunt across the PFO. The shunt magnitude was determined by counting the number of bubbles crossing the interatrial septum. Left atrial bubbles were counted within three to five cardiac cycles after right heart opacification with agitated saline. Mild shunts were regarded as one to five bubbles; moderate, was six to 20; and severe, more than 20. The maneuvers were repeated three to four times . ASA was defined by a septal excursion >1 cm and a diameter >1.5 cm . Patients were prescribed a device based ultimately on operator discretion using the following criteria:

• 1.
  

  Premere device (standard size 25 mm) for small defects (PFO) <15 mm with ASA <1 cm excursion.

  
  
• 2.
  

  Amplatzer devices (three sizes 18/25/35 mm) were available for use in all defect sizes, ASA ≥2 cm, or when a more stable device was required .

The Amplatzer is a self-expanding nitinol wire mesh with a right atrial disc and a much smaller left atrial disc with a connector. The available sizes are 18/25/35 mm with a waist of 4 mm. The nitinol device has a unique ability to adopt the shape of the septum and has a longer proven track record. Interventionalists were trained in the deployment of these devices by an experienced and skilled in-lab proctor for precision and accuracy in device positioning.

Procedures were conducted in the cardiac catheterization laboratory with the patient conscious but under mild sedation (midazolam 2–5 mg). Sedation was given to relieve anxiety and enable the imaging cardiologist to perform a TEE during the procedure. A 7-Fr femoral sheath was inserted into the left femoral vein. The right femoral vein was used to insert the ICE catheter for further visualization of the septal defect. If ICE catheters were not available, a TEE was performed to provide imaging. A 5-Fr sheath in the femoral artery provided intra-arterial blood pressure monitoring. All patients received antibiotics, aspirin, and clopidogrel the day of the implantation and were heparinized during the procedure to an activated clotting time of at least 250 s. Balloon sizing of the PFO was not performed routinely in all patients. The septum was usually crossed with a Cournand or multipurpose catheter on a J-tipped wire. This wire was exchanged for an Amplatz stiff wire and positioned in the left upper pulmonary vein to allow passage of the delivery sheath.

The devices reached the defect in delivery catheters using multimodality imaging. Optimal positioning and final release were accomplished after the echocardiologist and the interventionalist (deploying the device) were in agreement. Immediate procedural success was determined by assessing the residual shunt on color Doppler and visualizing the device and the closed defect on ICE/TEE. The patient underwent standard cardiac catheterization monitoring and nursing during the procedure.

Postprocedure, the patient was started on aspirin and clopidogrel for a period of 3 months. Lifelong aspirin was only recommended for cryptogenic stroke by the neurologist. Patients were allowed to mobilize postsedation when hemostasis was achieved with removal of the venous sheaths. The patient was then admitted to the cardiac ward for a monitored overnight stay.

On Day 1 postprocedure, a transthoracic echo was done to exclude device embolization and assessment for “coin slotting” and positioning. This was repeated at 3 months, 6 months, and 1 year. At 6 months, a TEE was done to assess the residual shunt when the shunt was deemed to be greater than mild on color Doppler after 1 month . Trivial and mild shunts postprocedure are expected to disappear with endothelialization of the device which can take up to 30 days.

2.1

Recruitment and data collection

In a prospective study, data was collected from patients undergoing transcatheter closure of PFO in Brisbane, Queensland, Australia. The Prince Charles Hospital and the Gold Coast Hospital were the two study sites. Proctorship and training in preprocedural PFO assessment, vascular access, multimodality imaging including intracardiac echocardiography (ICE) were provided by the Prince Charles Hospital Cardiac Catherisation Laboratory.

The Amplatzer or Premiere device was used in a nonrandomized choice based on the preprocedural assessment of the defect at operator discretion. This choice was made taking the location, size, interatrial septal excursion distance, rim characteristics, number of defects, and shunt size into account. Indications for percutaneous transcatheter closure were presence of PFO with presumed paradoxical embolism as the cause of the presenting condition. The most common indication was cryptogenic stroke. Exclusion criteria were atrial septal defect (ASD), PFO with another source of embolus (e.g., left ventricular thrombus), hemorrhagic stroke, or concomitant life-threatening comorbidities.

Patients with stroke were assessed and referred by a neurologist for percutaneous PFO closure. Prior to endothelialization of the device, the left atrial disk may carry a risk of thrombosis. The inherent risk of the deployed device was explained to both stroke and nonstroke patients and to the neurologist. Clinical and radiological evidence of paradoxical embolism was mandatory to be considered in the study. Radiological evidence had to be a computed tomography or magnetic resonance imaging demonstrating a cerebral infarct. A diagnosis of cryptogenic stroke was accepted by exclusion if further investigation failed to demonstrate another source of embolus .

2.2

Preprocedural workup

All patients underwent a detailed history and clinical examination to document their current clinical status. A thrombophilia screen was taken in all patients to assess the thrombotic risk. Patients were assessed for polycythemia rubravera, protein C and protein S deficiencies, antithrombin III deficiency, lupus screen, and factor 5 Leiden. All patients were negative. Patients were reviewed by a neurologist for exclusion of other causes of stroke, or TIA echocardiography, carotid duplex scanning, and 24-h Holter monitor were recorded before recruitment into the study. Transthoracic (TTE) and transesophageal (TEE) echocardiograms revealed the position, size, number, and structure of the defect. The presence of an interatrial septal aneurysm was documented and the aneurysm was characterized by the excursion distance which affected the choice of the closure device . A right-to-left shunt was demonstrated on TEE or TTE using color Doppler and saline bubble study. Abdominal compression, a cough reflex, and the Valsalva maneuver were used to induce or accentuate the shunt from right to left. A PFO was diagnosed when the defect was seen as a tunnel at the insertion edge of the interatrial septum. An ASD is an open communication (a tissue defect) persisting between the atria after septation. ASDs are usually seen as larger central defects in the interatrial septum. The position of the defect was confirmed using color Doppler across the septum .

A “bubble study” using 10 ml of agitated saline injected through a femoral vein was used to detect a right-to-left shunt across the PFO. The shunt magnitude was determined by counting the number of bubbles crossing the interatrial septum. Left atrial bubbles were counted within three to five cardiac cycles after right heart opacification with agitated saline. Mild shunts were regarded as one to five bubbles; moderate, was six to 20; and severe, more than 20. The maneuvers were repeated three to four times . ASA was defined by a septal excursion >1 cm and a diameter >1.5 cm . Patients were prescribed a device based ultimately on operator discretion using the following criteria:

• 1.
  

  Premere device (standard size 25 mm) for small defects (PFO) <15 mm with ASA <1 cm excursion.

  
  
• 2.
  

  Amplatzer devices (three sizes 18/25/35 mm) were available for use in all defect sizes, ASA ≥2 cm, or when a more stable device was required .

The Amplatzer is a self-expanding nitinol wire mesh with a right atrial disc and a much smaller left atrial disc with a connector. The available sizes are 18/25/35 mm with a waist of 4 mm. The nitinol device has a unique ability to adopt the shape of the septum and has a longer proven track record. Interventionalists were trained in the deployment of these devices by an experienced and skilled in-lab proctor for precision and accuracy in device positioning.

Procedures were conducted in the cardiac catheterization laboratory with the patient conscious but under mild sedation (midazolam 2–5 mg). Sedation was given to relieve anxiety and enable the imaging cardiologist to perform a TEE during the procedure. A 7-Fr femoral sheath was inserted into the left femoral vein. The right femoral vein was used to insert the ICE catheter for further visualization of the septal defect. If ICE catheters were not available, a TEE was performed to provide imaging. A 5-Fr sheath in the femoral artery provided intra-arterial blood pressure monitoring. All patients received antibiotics, aspirin, and clopidogrel the day of the implantation and were heparinized during the procedure to an activated clotting time of at least 250 s. Balloon sizing of the PFO was not performed routinely in all patients. The septum was usually crossed with a Cournand or multipurpose catheter on a J-tipped wire. This wire was exchanged for an Amplatz stiff wire and positioned in the left upper pulmonary vein to allow passage of the delivery sheath.

The devices reached the defect in delivery catheters using multimodality imaging. Optimal positioning and final release were accomplished after the echocardiologist and the interventionalist (deploying the device) were in agreement. Immediate procedural success was determined by assessing the residual shunt on color Doppler and visualizing the device and the closed defect on ICE/TEE. The patient underwent standard cardiac catheterization monitoring and nursing during the procedure.

Postprocedure, the patient was started on aspirin and clopidogrel for a period of 3 months. Lifelong aspirin was only recommended for cryptogenic stroke by the neurologist. Patients were allowed to mobilize postsedation when hemostasis was achieved with removal of the venous sheaths. The patient was then admitted to the cardiac ward for a monitored overnight stay.

On Day 1 postprocedure, a transthoracic echo was done to exclude device embolization and assessment for “coin slotting” and positioning. This was repeated at 3 months, 6 months, and 1 year. At 6 months, a TEE was done to assess the residual shunt when the shunt was deemed to be greater than mild on color Doppler after 1 month . Trivial and mild shunts postprocedure are expected to disappear with endothelialization of the device which can take up to 30 days.