This document addresses the transcatheter approach for closure of patent foramen ovale and left atrial appendage when performed to prevent stroke using cardiac occlusion devices, which are deployed under transesophageal echocardiographic or fluoroscopic guidance as a nonsurgical alternative to open heart surgery.

Note: Please see the following related document for additional information

• SURG.00096 Surgical and Ablative Treatments for Chronic Headaches

Medically Necessary:
Transcatheter closure of a patent foramen ovale (PFO) is considered medically necessary for the prevention of subsequent stroke in individuals with a history of cryptogenic stroke who have failed conventional drug therapy, (e.g., warfarin), or who are not candidates for conventional drug therapy.

Investigational and Not Medically Necessary:

Transcatheter closure of a patent foramen ovale for the prevention of stroke is considered investigational and not medically necessary when the criteria above are not met.

Transcatheter closure of a left atrial appendage is considered investigational and not medically necessary for all indications.

There is limited evidence supporting the net benefit of transcatheter closure of a patent foramen ovale (PFO), in individuals with a history of cryptogenic stroke who have failed, or are not candidates for, medical anticoagulation therapy mostly in the form of case series. These studies reported that the risk of an embolic event after transcatheter closure was comparable to open surgical closure, with minimal complications. A recent advisory article by O'Gara and colleagues (2009) reviewed studies of participants that underwent transcatheter closure for the treatment of patent foramen ovale (PFO) for stroke prevention. There is no clear objective evidence to demonstrate that either medical therapy (antiplatelet agents or vitamin K antagonists), transcatheter closure, or open surgical closure are superior treatment options for the prevention of TIA or recurrent stroke in individuals with cryptogenic stroke. Randomized controlled trials are needed to establish the safety and efficacy, as well as to determine the benefits of one treatment option over another. Therefore, the Advisory has identified a need for clinicians to refer individuals with cryptogenic stroke and PFO to one of the ongoing clinical trials (O'Gara, 2009). Ongoing studies include the randomized evaluation of recurrent stroke comparing PFO to established current standard of care treatment (RESPECT) and phase III/IV clinical trials that are comparing device closure to medical therapy in individuals who have cryptogenic stroke with high risk PFO.

FDA approval has been granted to a few devices for specific indications, through the Humanitarian Device Exemption (HDE) process. The HDE approval process is applicable to devices intended to benefit individuals in the treatment or diagnosis of conditions or diseases that affect fewer than 4,000 individuals in the U.S. per year. An HDE application is not required to submit the results of scientifically valid clinical investigations demonstrating the effectiveness of the device for its intended use. However, the application must contain sufficient information for the FDA to determine that the device does not pose an unreasonable or significant risk of illness or injury and that the probable health benefit outweighs the risks from its use. In August 2006, the FDA notified two manufacturers of its intent to formally propose withdrawal of its HDE marketing approvals for two PFO occluders that had been previously approved for the treatment of individuals with recurrent cryptogenic stroke due to presumed paradoxical embolism through a PFO and who have failed conventional drug therapy, (i.e., individuals who have had at least one additional stroke despite treatment with appropriate medications). The affected devices were the CardioSEAL^® STARFlex^™ Septal Occlusion System (NMT Medical, Inc., Boston, MA) and the AMPLATZER^® PFO Occluder (AGA Medical Corporation, Golden Valley, MN). This decision on the part of the FDA was proposed because these devices no longer meet the criteria for an HDE, since the number of individuals treated annually with these devices exceeds 4,000 individuals. However, on August 14, 2006 both manufacturers agreed to voluntarily withdraw their HDEs, effective October 31, 2006. The FDA informed further that, although these devices will no longer be available for marketing in the U.S., individuals who meet the formerly approved HDE indication will continue to have access to these devices in the U.S., through an FDA-approved Investigational Device Exemption (IDE). An IDE allows an investigational device to be used in clinical studies, in order to collect safety and effectiveness data required to support a full premarket approval (PMA) from the FDA.

Transcatheter closure of a left atrial appendage (LAA) is a new treatment strategy for the prevention of blood clot formation in individuals with atrial fibrillation. The LAA closure systems is introduced in the right atrium and then passed into the left atrium through a PFO or through a puncture hole. The Holmes and colleagues (2009) randomized, non-inferority trial compared LAA closure using WATCHMAN^® LAA closure technology (Atritech Inc., Plymouth, MN) versus warfarin therapy for prevention of stroke in individuals with atrial fibrillation. The study evaluated efficacy between the interventional group and the warfarin group based upon the primary endpoint of reported cardiovascular death (n=5 vs. n=10), all types of stroke (n=16 vs. n=12), and systemic embolism (n=2 vs. n=0). Researchers reported a higher occurrence of primary safety events in the interventional group compared to the warfarin therapy group; serious adverse events included major bleeding, pericardial effusion and device embolization. The author concluded:

"Thus, our strategy for closing the LAA was non-inferior to warfarin therapy in terms of primary efficacy endpoint of all stroke, cardiovascular death, and systemic embolism. Although there is a higher initial safety event rate for device implantation, adverse events were without long term sequelae for most patients. Closure of the LAA might provide an alternative strategy to chronic warfarin therapy for stroke prophylaxis in patients with non-valvular atrial fibrillation."

A study by Reddy and colleagues (2011) reported on outcomes from the Watchman LAA System for Embolic Protection in Patients with AF (PROTECT AF) trial and Continued Access Registry (CAR). Although with improved procedural experience there was a decline in safety events reported there remains a higher risk of complications. The WATCHMAN LAA closure device is currently pending final PMA approval by the U.S. FDA, for device closure in individuals with non-valvular atrial fibrillation (AF) in facilities equipped for heart surgery. The safety and efficacy of transcatheter closure of LAA has not been conclusively demonstrated to be a superior treatment over the use of medical treatment with anticoagulation therapy. There is an ongoing clinical trial comparing the WATCHMAN LAA closure device to the LARIAT Suture Delivery Device (SentreHEART^®, Redwood City, CA) used as LAA device occlusion for the treatment of AF. Presently, no LAA closure system has been granted final approval by the FDA for this indication.

Patent Foramen Ovale (PFO)
PFO describes the persistence of a component of the fetal circulation between the right and left atrium. Although PFOs are found in 10-15% of adults, they are typically clinically insignificant. However, they may be associated with paradoxical embolus, in which an embolus arising in the venous circulation gains access to the arterial circulation through the PFO. It is estimated that individuals with a history of PFO and paradoxical embolism have a 3.4% and 3.8% yearly risk of recurrent stroke or transient ischemic attack. Therefore, there has been interest in either open surgery or transcatheter approaches to close the PFO, in individuals with a history of embolic stroke of unknown cause. Treatment alternatives include chronic warfarin therapy, based, in part, on the theory that clotting disorders may be present in individuals with embolic stroke. To date, an investigational device exemption (IDE) through the FDA addresses access to the CardioSEAL^® STARFlex^™ Septal Occlusion System and the AMPLATZER^® PFO Occluder for closure of a PFO in individuals with recurrent cryptogenic stroke due to presumed paradoxical embolism, through the PFO and who have failed conventional drug therapy with anticoagulants.

• Left Atrial Appendage
  In the U.S., AF is the most prevalent sustained cardiac arrhythmia resulting in significantly greater risk of stroke due to migration of clots that may form in the LAA. As confirmed by echocardiography and autopsy, LAA is identified as a leading source of thrombi in individuals with non-valvular AF. By closing off the LAA, the occlusion device is designed to reduce risk of stroke and other cardiovascular complications. The WATCHMAN LAA closure device, which is pending final FDA approval, is proposed as an alternative to warfarin therapy in individuals with non-valvular AF. The LARIAT Suture Delivery Device and Accessories provides another potential alternative to closure, currently being studied as an alternative to standard anticoagulation therapy.

Atrial fibrillation: A condition where there is disorganized electrical conduction in the atria, resulting in ineffective pumping of blood into the ventricle.

Cryptogenic stroke: A stroke or transient ischemic attack of obscure or unknown origin.

Left atrial appendage (LAA): A muscular pouch attached to the upper portion of the left atrium.

Patent foramen ovale (PFO): A component of the fetal circulation that consists of a communication between the left and right atria that generally closes after birth; if an opening remains after birth, the possibility of an embolus (blood clot that breaks free in the blood) getting to the brain exists, resulting in a stroke or transient ischemic attack.

The following codes for treatments and procedures applicable to this document are included below for informational purposes.  A draft of future ICD-10 Coding (effective 10/01/2014) related to this document, as it might look today, is included below for your reference.  Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy.  Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services may be Medically Necessary when criteria are met:

When services are Investigational and Not Medically Necessary:
For the procedure and diagnosis codes listed above when criteria are not met, or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary. 

When services are also Investigational and Not Medically Necessary:
When the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

Peer Reviewed Publications:

1. Holmes DR, Reddy VY, Turi ZG, Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomized non-inferiority trial. Lancet. 2009; 374(9689):534-542.
2. Kapadia SR. Patent foramen ovale closure: historical perspective. Cardiol Clin. 2005; 23:73-83.
3. Kay JD, O'Laughlin MP, Ito K, et al. Five-year clinical and echocardiographic evaluation of the Das AngelWings atrial septal occluder. Am Heart J. 2004; 147(2):361-368.
4. O'Gara PT, Messa SR, Tuzcu EM, et al. Percutaneous device closure of patent foramen ovale for secondary stroke prevention: a call for completion of randomized clinical trials. A science advisory from the American Heart Association/American Stroke Association and the American College of Cardiology Foundation. J Am Coll Cardiol. 2009; 53(21):2014-2018.
5. Onorato E, Melzi G, Casilli F, et al. Patent foramen ovale with paradoxical embolism: mid-term results of transcatheter closure in 256 patients. J Interv Cardiol. 2003; 16(1):43-50.
6. Patel HT, Hijazi ZM. Pediatric catheter interventions: a year in review 2004-2005. Curr Opin Pediatr. 2005; 17(5):568-573.
7. Reddy VY, Holmes D, Doshi SK, et al. Safety of percutaneous left atrial appendage closure: results from the watchman left atrial appendage system for embolic protection in patients with AF (PROTECT AF) clinical trial and the Continued Access Registry. Circulation. 2011; 123(4):417-424.
8. Ries M, Kampmann C, Rupprecht H-J, et al. Nickel release after implantation of the Amplatzer occluder. Am Heart J. 2003; 145:737-741.
9. Rome JJ, Kreutzer J. Pediatric interventional catheterization: reasonable expectations and outcomes. Pediatr Clin N Am. 2004; 51:1589-1610.
10. Windecker S, Wahl A, Chatterjee T, et al. Percutaneous closure of patent foramen ovale in patients with paradoxical embolism: long term risk of recurrent thromboembolic events. Circulation. 2000; 101(8):893-898.

Government Agency, Medical Society, and Other Authoritative Publications:

1. AGA Medical Corporation. Respect PFO Clinical Trial. NCT00465270. Last updated May 15, 2012. Available at: http://www.clinicaltrials.gov/ct2/show/study/NCT00465270?term=respect+and+pfo&rank=1. Accessed on February 18, 2013.
2. Dhanunjaya Lakkireddy, MD, FACC, University of Kansas Medical Center Research Institute. Safety and Efficacy of Left Atrial Appendage Occlusion Devices. NCT01695564. Last updated January 22, 2013. Available at: http://clinicaltrials.gov/ct2/show/NCT01695564?term=LARIAT&rank=1.  Accessed on: January 14, 2013.
3. U.S. Food and Drug Administration (FDA). Center for Devices and Radiological Health (CDRH). Summary of Safety and Effectiveness: Amplatzer^® PFO Occlusion System. Humanitarian Device Exemption No. H000007. Rockville, MD: April 5, 2002. Accessible at: http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/
   HDEApprovals/ucm161827.htm. Accessed on January 11, 2013.
4. U.S. Food and Drug Administration (FDA). Center for Devices and Radiological Health (CDRH). Summary of Safety and Effectiveness: CardioSeal^® Septal Occlusion System Humanitarian Device Exemption No. H990011. Rockville, MD: February 1, 2000. Accessible at: http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/
   HDEApprovals/ucm161827.htm. Accessed on January 11, 2013.

1. U.S. Food and Drug Administration (FDA). Center for Devices and Radiological Health (CDRH). Humanitarian Use Devices. Available at: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfHDE/HDEInformation.cfm#2. Accessed on January 11, 2013.
2. U.S. Food and Drug Administration (FDA). Center for Devices and Radiological Health (CDRH). Information for physicians and patients on the withdrawal of two humanitarian device exemptions (HDEs) for patent foramen ovale (PFO) occluders. Effective October 31, 2006. Available at: http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/
   PremarketSubmissions/HumanitarianDeviceExemption/ucm135747.htm. Accessed on January 11, 2013.

AMPLATZER^® Device
CardioSeal^® Device
LAA
LARIAT^® Suture Delivery Device
Left Atrial Appendage
Patent Foramen Ovale
PFO
Starflex
WATCHMAN 

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.