1. Atrial Septal Defects

   Aetna considers transcatheter closure of atrial septal defects (ASDs) using Food and Drug Adminsitration (FDA)-approved closure devices (e.g., the Gore Helex Septal Occulder) medically necessary in pediatric or adult members for either of the following indications:

   1. For the closure of the fenestration in individuals who have undergone a fenestrated Fontan procedure; or
   2. For the occlusion of ASDs in secundum position.

   Aetna considers transcatheter closure of ASDs experimental and investigational for migraine prophylaxis and for all other indications because its effectiveness for these indications has not been established.

2. Ventricular Septal Defects

   Aetna considers transcatheter closure of ventricular septal defects (VSDs) using FDA-approved closure devices medically necessary for complex VSDs in pediatric or adult members who are considered to be at high-risk for standard transatrial or transarterial surgical closure.

   Aetna considers transcatheter closure of VSDs experimental and investigational for all other indications because its effectiveness for indications other than the one listed above has not been established.

3. Patent Foramen Ovale

   Aetna considers transcatheter occlusion of patent foramen ovale (PFO) using FDA-approved closure devices medically necessary for persons with cryptogenic stroke, transient ischemic attacks, or arterial emboli due to presumed paradoxical embolism through a PFO.

   Aetna considers transcatheter closure of PFO experimental and investigational for migraine prophylaxis and for all other indications (e.g., orthodeoxia-platypnea and unexplained oxygen desaturation) because its effectiveness for these indications has not been established.

4. Patent Ductus Arteriosus

   Aetna considers transcatheter occlusion of patent ductus arteriosus (PDA) medically necessary using closure devices approved by the FDA for this indication.

   Aetna considers closure devices not approved by the FDA for transcatheter occlusion of PDA experimental and investigational for this indication.

5. Transmyocardial Transcatheter/Perventricular Closure of Septal Defects

   Aetna considers transmyocardial transcatheter/perventricular closure of ventricular septal defects with implants experimental and investigational because of an absence of published literature on the effectiveness of this approach.

Despite the success of standard operative repair with its mortality rate of less than 1 %, the risks and morbidity of open-heart surgery remain.  Over the last 2 decades, interventional cardiac catheterization techniques have evolved to a point where percutaneous transcatheter devices can be offered as an alternative to their open counterparts to repair certain cardiac defects, particularly in younger patients.  All of the devices require transesophageal echocardiographic guidance for optimal placement, and most procedures are performed under general anesthesia with transesophageal echocardiographic and/or fluoroscopic guidance to verify optimal placement, and to access the immediate results of the procedure.

In recent years many different systems for transcatheter closure of an atrial septal defect (ASD) have been developed and tested.  Initially, acute failures and complications were primarily due to poor selection of cases with too large a defect or selection of a defective device.  Over the years, stricter implantation and patient selection criteria have lead to more successful deployment of the devices in stable positions without inducing functional abnormality or anatomical obstruction.  Of utmost importance in choosing appropriate patients is the echocardiographic morphology of the ASD with reference to size, position in the interatrial septum, proximity to surrounding structures, and adequacy of septal rim.  Equally essential is accurate assessment of the stretched diameter of the inter-atrial communication by balloon sizing during catheterization to determine proper size of the ASD closure device.  Many of the ASD closure devices initially approved by the Food and Drug Administration (FDA) for investigational use have been withdrawn from the market due to complications (e.g., Clamshell double-umbrella device, and Angel Wing).  The most frequent complications include device embolization and thrombus formation.  Some ASD closure devices have been modified a number of times to improve technical feasibility, safety, and effectiveness.  Devices currently under investigation for ASD closure include the Buttoned Device, CardioSEAL Septal Occluder, StarFlex, Atrial Septal Defect Occluding System (ASDOS), Guardian Angel, and the Helex. 

The Amplatzer septal occluder (AGA Medical Corp., Golden Valley, MN) received FDA approval in 2001.  It is a self-centering device that consists of 2 round disks made of Nitinol wire mesh and linked together by a short connecting waist.  Studies have reported short-term results confirming an early high occlusion rate with no major complications when strict implantation and patient selection criteria are used.  According to the FDA approval, the Amplatzer septal occluder is indicated for ASD closure in individuals who have echocardiographic evidence of ostium secundum ASD and clinical evidence of right ventricular (RV) volume overload (i.e., 1.5:1 degree to left to right shunt or RV enlargement).  The device is also indicated in patients who have undergone a fenestrated Fontan procedure and who now require closure of the fenestration. 

Du et al (2002) compared the safety, effectiveness and clinical utility of the Amplatzer septal occluder for closure of secundum ASD with surgical closure.  A multi-center, non-randomized concurrent study was performed in 29 pediatric cardiology centers from March 1998 to March 2000.  Patients were assigned to either the device or surgical closure group according to the patient’s option.  Baseline physical examinations and echocardiography were performed pre-procedure and at follow-up (6 and 12 months for device group, 12 months for surgical group).  A total of 442 patients were in the group undergoing device closure, whereas 154 patients were in the surgical group.  The median age was 9.8 years for the device group and 4.1 years for the surgical group (p < 0.001).  In the device group, 395 (89.4 %) patients had a single ASD; in the surgical group, 124 (80.5 %) (p = 0.008) had a single ASD.  The size of the primary ASD was 13.3 +/- 5.4 mm for the device group and 14.2 +/- 6.3 mm for the surgery group (p = 0.099).  The procedural attempt success rate was 95.7 % for the device group and 100 % for the surgical group (p = 0.006).

The CardioSEAL Septal Occlusion System (Nitinol Medical Technologies, Inc., Boston, MA) is the second generation of the Clamshell occluder.  It received FDA approval for use in patients with complex ventricular septal defect (VSD) of significant size to warrant closure and who are considered to be at high risk for standard transatrial or transarterial surgical closure based on anatomical conditions and/or overall medical condition.  High- risk anatomical factors for transatrial or transarterial surgical closure include the following:

• Left ventriculotomy or an extensive right ventriculotomy is required
• Multiple apical and/or anterior muscular VSDs (“Swiss Cheese Septum”)
• Posterior apical VSDs covered by trabeculae

• Previous VSD closure that failed

The CardioSEAL high-risk study is a prospective, multi-center trial studying the use of the CardioSEAL Septal Occlusion System to close a variety of hemodynamically significant defects.  At the time the VSD data was analyzed and submitted to the FDA for approval, 74 patients with no additional anatomical lesions were enrolled in the study for closure of a VSD.  The types of VSDs closed with a CardioSEAL device were: congenital muscular (n = 26) and post-operative (n = 31).  The age of the patients ranged from 0.3 years to 70.1 years, with a median age of 3.7 years.  The investigators reported that despite a high degree of co-morbid illness within the treated group, 72 % of the patients improved clinically at 6 months after implantation, and 84 % of the patients had a reduction in flow through the defect or reduction in the anatomical defect size.  Peri-procedure events, including some serious events, occurred frequently, but all moderately serious or serious events had resolved by 6 months after the procedure.  The investigators concluded that the CardioSEAL Septal Occlusion System is safe and effective in the intended patient population.

The FDA has approved through humanitarian device exemptions 2 transcatheter occlusion devices for repair of patent foramen ovale (PFO): the CardioSEAL Septal Occlusion System and the Amplatzer Patent Foramen Ovale Occluder.  The FDA has approved the use of these devices for closure of PFO in persons with recurrent cryptogenic stroke due to presumed paradoxical embolism through a PFO and who have failed conventional drug therapy.

At present, it should be noted that none of these afore-mentioned technologies is widely used and few devices have undergone extensive clinical trials.  Many of these devices remain investigational and large-scale studies are underway to collect sufficient long-term data to validate these various applications as viable alternatives to surgery in the initial treatment of selected patients.  The FDA is requiring that both Nitinol Medical Technologies, Inc and AGA Medical Corp. continue to study their products over the next 5 years to better assess their long-term safety and effectiveness (Meadows, 2002).

Percutaneous transcatheter closure of patent ductus arteriosus (PDA) is an established procedure in the pediatric field.  In a multi-center clinical trial (n = 484, median age of the patients at catheterization was 1.8 years, with a range 0.2 to 70.7 years), Pass et al (2004) found that moderate to large PDAs can be effectively and safely closed using the Amplatzer ductal occluder, with excellent initial and 1-year results.  These authors concluded that this device should obviate the need for multiple coils or surgical intervention for these defects.  Butera et al (2004) reported that in experienced hands, percutaneous closure of moderate to large PDA in very young symptomatic children is safe, effectively closes the PDA, and solves clinical problems.  An assessment of endovascular closure of PDA conducted by the National Institute for Clinical Excellence (NICE, 2004) concluded that there is adequate evidence to support the use of this procedure.

Migraine headache (MHA) is present in 12 % of adults and has been associated with inter-atrial communications.  Azarbal et al (2005) examined the relationship between PFO or ASD with the incidence of MHA and evaluated if closure of the inter-atrial shunt in patients with MHA would result in improvement of MHA.  A sample of 89 (66 PFO/23 ASD) adult patients underwent transcatheter closure of an inter-atrial communication using the CardioSEAL (n = 22), Amplatzer PFO (n = 43), or the Amplatzer ASD (n = 24) device.  Before the procedure, MHA was present in 42 % of patients (45 % of patients with PFO and 30 % of patients with ASD).  At 3 months after the procedure, MHA disappeared completely in 75 % of patients with MHA and aura and in 31 % of patients with MHA without aura.  Of the remaining patients, 40 % had significant improvement (greater than or equal to 2 grades by the Migraine Disability Assessment Questionnaire) of MHA.  These investigators concluded that transcatheter closure of PFO or ASD results in complete resolution of MHA in 60 % of patients (75 % of patients with migraine and aura) and improvement in symptoms in 40 % of the remaining patients.  They noted that inter-atrial communications may play a role in the etiology of MHA either through paradoxic embolism or humoral factors that escape degradation in bypassing the pulmonary circulation.  The authors stated that a randomized trial is needed to ascertain if transcatheter closure of inter-atrial shunts is an effective treatment for MHA compared with medical therapy.

Reisman et al (2005) examined the effects of transcatheter PFO closure on the frequency of MHA in patients with paradoxical cerebral embolism.  A total of 162 consecutive patients underwent transcatheter PFO closure for prevention of recurrent cryptogenic stroke or transient ischemic attack.  A 1-year retrospective analysis of migraine symptoms before and after PFO closure was performed.  Active MHA was present in 35 % (57 of 162) of patients, and 68 % (39 of 57) experienced migrainous aura; 50 patients were available for analysis at 1 year.  Complete resolution of migraine symptoms occurred in 56 % (28 of 50) of patients, and 14 % (7 of 50) of patients reported a significant greater than or equal to 50 %) reduction in MHA frequency.  Patients reported an 80 % reduction in the mean number of MHA episodes per month after PFO closure (6.8 +/- 9.6 before closure versus 1.4 +/- 3.4 after closure, p < 0.001).  Results were independent of completeness of PFO closure at 1 year.  These researchers concluded that in patients with paradoxical cerebral embolism, MHA are more frequent than in the general population, and transcatheter closure of the PFO results in complete resolution or marked reduction in frequency of MHA.

In an editorial that accompanied the studies by Azarbal et al (2005) as well as Reisman et al (2005), Tsimikas (2005) stated that "before PFO closure can be proposed for migraine, a healthy skepticism should be in place, considering the high frequency of both migraine and PFO in the general population.  It will be necessary to obtain definitive evidence with randomized controlled trials and to define the appropriate clinical indications".

Spies and Schrader (2006) stated that reviewed the epidemiology and pathophysiology of MHA, its association with PFO, and the impact of PFO closure on MHA.  These researchers noted that primarily retrospective case-control studies demonstrated a link between PFO closure and improvement of MHA.  Few prospective data confirm the initial results.  However, the only randomized, controlled trial finished to date analyzing the effect of PFO closure on MHA failed to reach its primary outcome of resolution of migraine following the intervention.  The authors concluded that evidence of a benefit on MHA following PFO closure is not convincing, but certainly intriguing.  With currently ongoing trials, more information related to this topic can be expected.

Diener et al (2007) stated that although the results of uncontrolled observational studies suggest the PFO closure may have a beneficial effect on migraine frequency, a large randomized trial failed to support such a conclusion.  Until there is more evidence from ongoing large controlled trials, PFO closure should not be performed in clinical practice for the prophylaxis of migraine.

In a prospective, multi-center, double-blind, sham-controlled study, Dowson et al (2008) examined the effectiveness of PFO closure with the STARFlex septal repair implant to resolve refractory migraine headache.  Patients who suffered from migraine with aura, experienced frequent migraine attacks, had previously failed greater than or equal to 2 classes of prophylactic treatments, and had moderate or large right-to-left shunts (RLS) consistent with the presence of a PFO were randomized to transcatheter PFO closure with the STARFlex implant or to a sham procedure.  Patients were followed-up for 6 months.  The primary efficacy endpoint was cessation of migraine headache 91 to 180 days after the procedure.  In total, 163 of 432 patients (38 %) had RLS consistent with a moderate or large PFO.  A total of 147 patients were randomized.  No significant difference was observed in the primary endpoint of migraine headache cessation between implant and sham groups (3 of 74 versus 3 of 73, respectively; p = 0.51).  Secondary endpoints also were not achieved.  On exploratory analysis, excluding 2 outliers, the implant group demonstrated a greater reduction in total migraine headache days (p = 0.027).  As expected, the implant-arm experienced more procedural serious adverse events.  All events were transient.  The authors concluded that this trial confirmed the high prevalence of RLS in patients with migraine with aura.  Although no significant effect was found for primary or secondary endpoints, the exploratory analysis supports further investigation.

Rundek et al (2008) examined the association between PFO and migraine among stroke-free individuals in an elderly, multi-ethnic cohort.  As a part of the ongoing Northern Manhattan Study (NOMAS), 1,101 stroke-free subjects were assessed for self-reported history of migraine.  The presence of PFO was assessed by transthoracic echocardiography.  The mean age of the group was 69 +/- 10 years; 58 % were women; 48 % were Caribbean Hispanic, 24 % were white, 26 % were black, and 2 % were another race/ethnicity.  The prevalence of self-reported migraine was 16 % (13 % migraine with aura).  The prevalence of PFO was 15 %.  Migraine was significantly more frequent among younger subjects, women, and Hispanics.  The prevalence of PFO was not significantly different between subjects who had migraine (26/178, or 14.6 %) and those who did not (138/923, or 15.0 %; p = 0.9).  In an adjusted multi-variate logistic regression model, the presence of PFO was not associated with increased prevalence of migraine (odds ratio 1.01, 95 % confidence interval [CI]: 0.63 to 1.61).  Increasing age was associated with lower prevalence of migraine in both subjects with a PFO (odds ratio 0.94, 95 % CI: 0.90 to 0.99 per year) and those without PFO (odds ratio 0.97, 95 % CI: 0.95 to 0.99 per year).  The observed lack of association between PFO and migraine (with or without aura) was not modified by diabetes mellitus, hypertension, cigarette smoking, or dyslipidemia.  The authors concluded that in this multi-ethnic, elderly, population-based cohort, PFO detected with transthoracic echocardiography and agitated saline was not associated with self-reported migraine.  The causal relationship between PFO and migraine remains uncertain, and the role of PFO closure among unselected patients with migraine remains questionable.  In an editorial that accompanied the afore-mentioned article, Kurth et al (2008) stated that detection of PFO or PFO closure should not be recommended to patients who only have migraine.

In a review on dynamic optimization of chronic migraine treatment, Mathew (2009) stated that it is premature to recommend device-based treatments (e.g., occipital nerve stimulation, vagal nerve stimulation, and PFO closure) for chronic migraine because clinical trials are in the preliminary stages.  Furthermore, additional studies are needed to evaluate if RLS-associated migraine can be clinically identified.

Garg and colleagues (2010) evaluated the assumption of an association between MHA and the presence of PFO.  These investigators conducted a case-control study to assess the prevalence of PFO in subjects with and without migraine.  Case subjects were those with a history of migraine (diagnosed by neurologists at a specialty academic headache clinic).  Control subjects were healthy volunteers without migraine 1:1 matched on the basis of age and sex with case subjects.  Presence of PFO was determined by transthoracic echocardiogram with second harmonic imaging and transcranial Doppler ultrasonography during a standardized procedure of infused agitated saline contrast with or without Valsalva maneuver and a review of the results by experts blinded to case-control status.  Patent foramen ovale was considered present if both studies were positive.  Odds ratios were calculated with conditional logistic regression in the matched cohort (n = 288).  In the matched analysis, the prevalence of PFO was similar in case and control subjects (26.4 % versus 25.7 %; OR 1.04, 95 % CI: 0.62 to 1.74, p = 0.90).  There was no difference in PFO prevalence in those with migraine with aura and those without (26.8 % versus 26.1 %; OR 1.03, 95 % CI: 0.48 to 2.21, p = 0.93).  The authors concluded that they found no association between MHA and the presence of PFO in this large case-control study nor any association between migraine severity and PFO size.

In an editorial that accompanied the afore-mentioned study, Gersony and Gersony  (2010) stated that "[a]lthough in rare instances, exceptions may be proposed, closure of PFO for migraine should not be considered standard medical practice".

Rigatelli and Ronco (2010) provided a comprehensive review of the main concepts about PFO management.  Therapy is a controversial issue, since data on these patients are variable and accepted guidelines are missing.  Recurrent strokes are the most diffuse and accepted indication for transcatheter closure of PFO, but severe refractory migraine with aura, unexplained oxygen desaturation, orthodeoxia-platypnea (related to aortic elongation, allowing significant right-to-left shunt), and other conditions have been suggested to benefit from PFO closure.  Different devices and techniques have been proposed for this procedure, mainly depending on operator experience and preferences.  The authors concluded that PFO management is still a debated field: indications, pathophysiology and ideal closure techniques remain to be fully clarified and investigated before considering PFO closure a routine procedure.

Butera et al (2010) examined the role of transcatheter closure of PFO on the occurrence of migraine.  BioMedCentral, Google Scholar, and PubMed from January 2000 to December 2008 were systematically searched for pertinent clinical studies.  Secondary sources were also used.  Secondary prevention studies of transcatheter closure for PFO were required to include at least more than 10 patients followed for more than 6 months.  The primary end-point was the rate of cured or significantly improved migraine after percutaneous PFO closure.  After excluding 637 citations, these investigators included a total of 11 studies for a total of 1,306 patients.  Forty percent of the subjects included suffered from migraine, while most had a previous history of transient ischemic attack/stroke and were investigated retrospectively.  Quantitative synthesis showed that complete cure of migraine in 46 % (95 % CI: 25 to 67 %), while resolution or significant improvement of migraine occurred in 83 % (95 % CI: 78 to 88 %) of cases.  The authors concluded that notwithstanding the limitations inherent in the primary studies, this systematic review suggested that a significant group of subjects with migraine, in particular if treated after a neurological event, may benefit from percutaneous closure of their PFO.  However, the authors notedthat many questions remain unsolved.

Bendaly et al (2011) reported the mid-term results of perventricular device closure of muscular VSD (MVSD) at a single institution.  Between January 2004 and December 2009, 6 patients underwent attempted perventricular MVSD closure.  Mean age was 9.8 +/- 9.1 months; mean weight was 7.2 +/- 3.7 kg.  In 5 patients, closure was successful without use of bypass.  In 1 patient, the device embolized to the left ventricle after release and patch closure of the MVSD was performed on cardiopulmonary bypass.  The mean interval from the procedure to the most recent echocardiogram for the patients with successful perventricular closure was 39.8 +/- 25.2 months.  Three patients demonstrated no residual shunt at the last echocardiogram.  Two patients had mild, hemodynamically insignificant shunting; 1 had a left ventricular pseudoaneurysm that was embolized during repeat catheterization.  The authors concluded that perventricular closure of MVSDs is attractive because it overcomes the limitations of surgery and catheterization.  Additionally, it spares the need for cardiopulmonary bypass and its comorbidities.  In some instances, however, successful deployment of the device is not possible.  These mid-term results demonstrated overall success but identify possible complications that are not immediately identified in the short-term.

Zhang et al (2012) examined the feasibility of transthoracic echocardiographic (TTE) guidance for minimally invasive periventricular device closure of peri-membranous VSDs.  From June 2011 to September 2011, these researchers enrolled 18 young children with peri-membranous VSDs to receive minimally invasive device closure in their hospital.  All of the patients were examined by TTE to determine the VSD morphology, diameter, and rims.  During intra-operative device closure, real-time bedside TTE alone was used to guide device implantation.  Device implantation using TTE guidance was successful in 16 patients.  Symmetric devices were used in 14 patients, and asymmetric devices were used in 2 patients.  Only 1 patient experienced mild aortic regurgitation, and there were no instances of residual shunt, significant arrhythmias, thromboembolism, or device displacement.  Two patients were transferred to surgical closure, 1 due to residual shunting and the other as a result of unsuccessful wire penetration of the VSD gap.  The authors concluded that these findings indicated that TTE-guided VSD closure is feasible in young children, although a longer follow-up may be needed to document the long-term success.