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Percutaneous Closure of Intracardiac Defects in Adults: State of the Art
Abstract: The number of adults with congenital heart disease is expected to increase over the next decade. Although acquired defects are being increasingly recognized in adults, congenital heart disease remains the most common etiology. With advances in cardiac imaging, device technology, and transcatheter techniques, percutaneous closure is now feasible and safe for most intracardiac defects. Device closure is considered the first-line therapy for a variety of congenital intracardiac defects, including ostium secundum atrial septal defects and muscular ventricular septal defects. Percutaneous closure may prevent recurrent cerebrovascular events after a cryptogenic stroke in high-risk patients with patent foramen ovale. It is also an alternative therapeutic option for patients with acquired defects such as posttraumatic or postinfarction ventricular septal defects and paravalvular regurgitation associated with prosthetic valves. Complications after device closure are uncommon, and may be avoided with appropriate patient and device selection. This is a comprehensive review of the current transcatheter management of the most common intracardiac defects encountered in the adult population.
J INVASIVE CARDIOL 2015;27(12):561-572
Key words: patent foramen ovale, atrial septal defect, ventricular septal defect, paravalvular regurgitation, device closure
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Over the next decade, the number of adults with congenital heart disease is expected to increase to approximately 1 in 150 young adults.1 Although acquired defects are increasingly recognized in adults, congenital heart disease remains the most common etiology.2 Atrial septal defect (ASD) is the most commonly diagnosed congenital heart defect in adults.1,2 Other defects, such as ventricular septal defect (VSD), patent ductus arteriosus (PDA), and coronary and pulmonary fistulae, are more frequently diagnosed in the pediatric population. Occasionally, these defects present in adults and may be associated with significant hemodynamic consequences requiring closure. In the past, these defects have been managed surgically. However, with advances in cardiac imaging, device technology, and transcatheter techniques, percutaneous closure is now feasible and safe for most congenital and acquired intracardiac defects. This comprehensive review focuses on the current percutaneous transcatheter management of the most common intracardiac defects encountered in adults, including ASD, VSD, patent foramen ovale (PFO), and prosthetic valve paravalvular regurgitation (PVPR). Successful device closure has also been performed for other uncommon congenital or acquired defects in the adult population, including PDAs, Gerbode defect, left ventricular pseudoaneurysm, and coronary or pulmonary fistulae.3-6
Atrial Septal Defects
ASDs account for nearly one-third of congenital heart defects in adults.2 Ostium secundum ASD is the most common subtype, and is generally the result of an under-developed septum primum and/or excessive reabsorption of septum primum tissue. While many defects close spontaneously in infancy, the left-to-right shunt associated with larger secundum ASDs tends to increase in size over time, leading most commonly to dyspnea on exertion and atrial arrhythmias. Advances in percutaneous techniques and devices have allowed transcatheter closure of secundum ASDs to become a viable alternative to surgery, with excellent short-term and long-term outcomes. Surgical closure continues to be the preferred approach for sinus venosus, coronary sinus, or ostium primum ASDs.1 However, transcatheter closure of sinus venosus ASDs with partial anomalous pulmonary venous return, using a covered stent or the Immediate Release Patch (Custom Medical Devices), has been recently reported with excellent short-term results.7,8
Echocardiography is an essential tool for the diagnosis of ASDs and assesses the defect’s location, shape, size, rim characteristics, degree of shunt, and hemodynamic consequences. With the improvement in ultrasound technology and the introduction of real-time three-dimensional (3D) transesophageal echocardiogram (TEE), other diagnostic tools such as magnetic resonance imaging and diagnostic cardiac catheterization are now rarely required. Furthermore, the use of intracardiac echocardiography or 3D-TEE has now become standard during ASD and PFO device closure, and has resulted in better success rates and lower procedural and fluoroscopy times.9
The first device approved for the percutaneous closure of secundum ASDs was the Amplatzer septal occluder (ASO) (St. Jude Medical), which is composed of a nitinol wire mesh linking two disks together via a short connecting waist (Figure 1). The use of ASO implantation in a mixed pediatric and adult population has been reported to have a successful implantation rate of more than 90%, acute closure of ASD in 97%-100% of cases, and a procedure-related complication rate of <5%.10,11 In one of the larger registries, Masura and colleagues reported a 100% closure rate in 151 patients implanted with an ASO for moderately sized secundum ASDs (mean age at implant, 11.9 ± 11.6 years), with all patients alive and free of significant morbidity at a median follow-up of 6.5 years.11 Luernmans et al reported on 104 adult patients with secundum ASD followed for a mean of 3.4 years after ASO implantation. Major complications were seen in 3%, residual shunting was present in 14% (at 6-month echocardiographic follow-up), and the majority of patients were asymptomatic at follow-up.12
In 2006, the Gore Helex septal occluder (Gore Medical) was approved for use in secundum ASD closure. Composed of a low-profile double disk, the device is approved for closure of defects <17-18 mm in the stretched diameter (Figure 1). Because of its soft, conformable nature, the Helex is not associated with device erosion. In the initial multicenter trial, 247 patients (age range, 1.4-72.4 years) with secundum ASDs were randomized to either Helex device placement or surgical repair.13 Device implantation was successful in 88% of patients; 73% had complete shunt closure and 25% had a clinically insignificant leak at 12-month follow-up. Median time under anesthesia (160 minutes vs 202 minutes) and median time to hospital discharge (1 day vs 3 days) were significantly less in patients who underwent device closure (P<.001 for both). Several non-approved devices, including the CardioSeal, StarFlex, and BioStar (NMT Medical), have also been studied, and others remain under investigational use.
The current recommendations for percutaneous closure of ostium secundum ASDs of the American College of Cardiology/American Heart Association (ACC/AHA) guidelines for adults with congenital heart disease are listed in Table 1. Eligibility for percutaneous closure of a secundum ASD requires a maximal defect size of up to 30 mm diameter depending on the device, a sufficient rim of tissue of at least 5 mm surrounding the defect to avoid impingement on nearby cardiac structures, and the absence of advanced pulmonary vascular obstructive disease. Several case series including both pediatric and adult patients, however, have reported on the use of closure devices in large defects or defects with deficient rims, with efficacious results in most cases.14,15 The current ACC/AHA guidelines do not state a preference for percutaneous vs surgical closure of ASDs, although it is generally accepted that a percutaneous approach offers a shorter hospital length of stay and a faster recovery, with similar long-term outcomes.16,17 A meta-analysis that included 13 observational and retrospective studies, consisting of 3082 pediatric and adult patients who underwent either surgical or percutaneous secundum ASD closure, reported on procedural complications and overall mortality. The odds ratio (OR) for total complications (OR, 5.4; P<.001) and major complications (OR, 3.8; P=.01) was higher in the surgical group vs the percutaneous cohort, with similar mortality between the groups.16
Closure of ASDs in older adults and elderly patients has some additional technical and hemodynamic challenges. Age at the time of presentation was found to be an independent predictor of adverse events in patients with ASDs.18 Older patients typically present with advanced symptoms and several hemodynamic abnormalities, such as pulmonary hypertension, right ventricular overload, atrial arrhythmias, valvular regurgitation, and heart failure.19 Despite this fact, percutaneous closure of secundum ASD has been successfully performed in older adults and in the elderly. With device closure, these patients are able to achieve significant improvement in their symptoms, pulmonary artery pressure, right ventricular geometry, atrial arrhythmias, and valvular regurgitation.18-20 Furthermore, surgical closure in older adults carries an increased risk of complications and death when compared with transcatheter closure, and therefore this less-invasive approach is desirable in this population.21 Transcatheter ASD closure has also been done in adult patients with severe reversible pulmonary hypertension, achieving significant improvements in functional class, 6-minute walk tests, pulmonary artery pressure, and vascular resistance.22
Perhaps one of the most challenging situations during percutaneous closure of ASDs in older adults is the risk of congestive heart failure shortly after closure. Elderly patients are at an increased risk given their higher prevalence of comorbidities and impaired relaxation of the left ventricle, as well as the long-lasting hemodynamic consequences of the ASD itself.23 Diastolic dysfunction in elderly patients with ASDs may be the result of persistent right ventricular overload alone or in combination with increased left ventricular stiffness.23 It is key to identify patients in whom the predominant pathophysiologic abnormality is intrinsic to the left ventricle, placing them at risk of left atrial volume overload after ASD closure. For this purpose, ASD temporary balloon occlusion has been performed and accurately restratifies such patients.24 The management of high-risk individuals is controversial, and some groups have advocated for closure deferral. Left ventricular conditioning using the combination of dopamine, milrinone, and furosemide for 48-60 hours before closure and fenestrated closure devices has been used with acceptable results.25,26 On the other hand, some patients can tolerate conventional ASD device closure despite a significant increase in their left ventricular filling pressures.27
The technique for percutaneous closure of ASDs has been well described previously.28,29 The right atrium is approached through the right femoral vein and the ASD is then crossed with a floppy-tipped guidewire and/or a multipurpose guiding catheter by sliding along the intratrial septum under fluoroscopic and echocardiographic guidance. When intracardiac echocardiography (ICE) is used, a second venous access must be obtained and the imaging catheter advanced into the right atrium. Once access to the left atrium is obtained through the defect, the multipurpose catheter is manipulated into the left upper pulmonary vein and an exchange-length stiff guidewire advanced into the pulmonary vein. The catheter is removed and balloon sizing of the defect is then performed. Balloon sizing will push the softer tissue of the ASD rims away and yield a diameter that corresponds to the edge of the defect that will hold the device safely. After the balloon is withdrawn, the delivery system is advanced into the left atrium over the guidewire. The closure device is folded, placed in the delivery system, and advanced to the tip of the sheath in the left atrium. Both the device and the delivery system must be carefully flushed prior to insertion to avoid air embolization. Under echocardiographic guidance, the left-sided occluder is opened and firmly retracted against the septum, and then the right-sided occluder is finally opened. After device position and stability are confirmed with ICE, the closure device is released from the delivery system. Transcatheter retrieval is possible for all the commercially available systems in case of suboptimal device position before release. A final injection of agitated saline is performed to confirm success of the procedure.29
The most common complication in the early postimplant period are atrial arrhythmias, presumably caused by mechanical device-related irritation or inflammation of the septal tissue. Most frequently, premature atrial contractions are seen, and generally resolve within a few weeks post procedure. Supraventricular tachycardia or atrial fibrillation may occur in 2%-3% of patients.30 Device embolization or malposition is rare, and is often manageable via percutaneous retrieval approaches. Thrombus formation may occur prior to endothelialization; in a registry of 1000 patients with ASD and PFO closure devices, it was more common with the StarFlex (7%) and CardioSeal devices (6%) compared with the Helex occluder (1%) or ASO (0%).31 Device erosion (Figure 2) is a rare but potentially fatal complication that has been reported in 0.1%-0.3% of cases.32 Although late device erosion has been reported, it occurs within the first 6 months post implantation in most cases. Its consequences include pericardial effusion, cardiac tamponade, and fistula formation, which frequently require surgery.32 Device erosion is observed most often in patients with deficient anterior (retroaortic) and/or superior rims, and also with use of oversized devices resulting in encroachment of the occluder device on the roof of the left atrium.33 In fact, the United States Food and Drug Administration (FDA) has acknowledged the possible increased risk of erosion in patients with deficient retroaortic rims. Additional risk factors for erosion include splaying of the device around the aortic root, thicker device profile at the time of deployment, and excessive device motion.32 This emphasizes the importance of meticulous anatomic evaluation with periprocedural echocardiography to identify the patients at risk.
Ventricular Septal Defects
VSDs account for approximately 20% of all congenital heart defects, but are relatively rare in the adult population.28 In addition to congenital origin, VSDs in adults may be acquired, and include those that occur after a myocardial infarction (MI), residual shunts following previous surgical attempts, trauma, and iatrogenic related to surgical or transcatheter aortic valve replacement.28,34-36 Percutaneous closure techniques and devices have improved since the first successful percutaneous VSD closure in 1988.37 This approach avoids much of the morbidity and mortality associated with open-heart surgery, significantly lessens hospital stay and costs, and is cosmetically more acceptable.
VSDs are typically classified into perimembranous, muscular, outlet, and inlet defects.28 Perimembranous defects are the most common, accounting for 75% of VSDs. Muscular VSDs account for 10% of cases, and the remaining are either outlet or inlet VSDs. Only the muscular defects are universally approachable with the transcatheter approach, whereas device closure for other VSD types carries an increased risk of impingement on the cardiac valves and/or the conduction system.
VSDs in infancy typically manifest with left-to-right shunt, increased pulmonary flow, and left-sided chamber enlargement. This large volume overload can present with congestive heart failure and increased pulmonary artery pressures. Untreated VSDs can result in irreversible pulmonary hypertension, and eventually present with irreversible Eisenmenger’s physiology. In adults, closure is typically indicated for hemodynamically significant VSDs or small hemodynamically insignificant VSDs with an increased risk of infective endocarditis (Table 1).
While surgery is generally accepted as the standard of care for VSDs, the current guidelines recommend transcatheter closure of VSDs when left ventricular chamber enlargement or pulmonary arterial hypertension are present.1 These guidelines also recommend catheter-based closure for infundibular, postinfarction, iatrogenic, and traumatic VSDs, and also for some residual VSDs after surgical intervention. The European Society of Cardiology guidelines38 recommend surgery as the first option in most VSDs in adults, and percutaneous closure for patients with high surgical risk, history of multiple previous cardiac surgical interventions, or VSDs that are poorly accessible for surgical closure. For muscular VSDs that are located centrally in the interventricular septum, device closure is also recommended as an alternative to surgical closure. Although, there are no randomized trials to assess whether percutaneous closure is better than surgical repair, Zheng et al presented a retrospective analysis of the short-term outcomes of these two approaches.39 Pediatric and adult patients with mostly perimembranous VSDs underwent device closure (852 patients; age range, 2.5-15.5 years) or surgical repair (1326 patients; age range, 2.8-52.5 years). There were no differences in the success rates or major complication rates, including residual shunt, arrhythmias, or valvular insufficiency. However, the device closure group had significantly fewer minor complications, and a shorter hospital length of stay.39
The use of the Amplatzer device (Figure 1) for muscular VSD was first reported in 1999. Its efficacy has been demonstrated in human trials,40 and it is currently the only FDA-approved device for closure of this VSD type. The initial report of 75 patients, including children and adults, who underwent closure of muscular VSDs with the Amplatzer muscular occluder demonstrated a technical success rate of 86%.40 Procedure-related complications, most of which were minor, occurred in 37% of the patients. The procedure-related mortality was 2.7%, and device embolization or cardiac perforation occurred in 2.7 and 1.9%, respectively. The shunt closure rate at 1-year follow-up was 92.3%, and the rest of the patients had only trivial or small residual shunts.
Device closure of perimembranous VSDs has also been performed using the Amplatzer membranous VSD occluder (mVSD1). A study of 104 patients with a median age of 14 years (range, 0.6-63 years) who underwent perimembranous VSD device closure demonstrated a success rate of 96.2% with no procedure-related deaths.41 Significant complications occurred in 11.5%, most of which were complete atrioventricular block (6.7%), requiring permanent pacemaker implantation in 1.9% of the cases. After a median follow-up of 39 months, there were no deaths or cases of endocarditis, and the left ventricular dimensions returned to normal. Four additional patients developed complete atrioventricular block requiring permanent pacemaker during follow-up, and a multivariable analysis revealed that age at the time of closure was the only independent predictor of complete heart block. Given the increased risk of complete heart block with the initial device, the Amplatzer membranous VSD occluder 2 (mVSD2) has recently been developed.42 The initial experience in 19 patients (age range, 1.4-62 years) who underwent perimembranous VSD closure with the mVSD2 showed a technical success rate of 95%, no procedure-related complications (including complete heart block or significant valvular regurgitation), and only 17% residual shunt at 1-year follow-up.43 Various other devices have been used for perimembranous VSD closure with different success rates, including the ADO I and II, Clamshell, VSD-O, CardioSeal, buttoned devices, muscular VSD devices, and coils.28
The technique for VSD closure starts with a detailed angiographic and echocardiographic examination, typically using TEE, to carefully evaluate the size of the defect and its relationship with adjacent cardiac structures.28,29 The VSD is crossed from the left ventricle side via retrograde or transseptal approach using a right Judkins or right Amplatzer catheter. A soft, extension-length guidewire is passed through the defect, placed in the right ventricle, and then exteriorized at the femoral or internal jugular vein using a gooseneck snare device. Mid-muscular and apical VSDs are best approached from the internal jugular vein, while anterior defects are approached from the femoral vein. Balloon sizing of the defect may be done at this point to measure the largest defect dimension. When using a double-umbrella device or the Amplatzer muscular VSD occluder, the device size must exceed the defect size by 1.6-2.0 times or by 3 mm, respectively. The delivery system is then advanced into the left ventricle over the guidewire and its position is confirmed with TEE and angiography. After removing the guidewire, the device is delivered by opening the left ventricular occluder and retracting it against the septum, and then opening the right ventricular occluder. Adequate position and shunt resolution are confirmed with TEE and angiography, and the device is finally released.29
The complications associated with percutaneous VSD closure appear to be related to the site of the VSD. Atrioventricular block is more common with perimembranous defects, and is mostly seen in children. Its incidence ranges from 0%-4%, but can be as high as 5.7%.40,41,44 A significant number of patients develop late-onset complete atrioventricular block,41 most of which require permanent pacemaker implantation.45 In addition, transient conduction abnormalities and atrial arrhythmias can develop.28 Tricuspid regurgitation secondary to entrapment of tricuspid leaflets can occur, and it may rarely require device repositioning if severe regurgitation is present. Acute mitral regurgitation due to inadvertent trapping of anterior mitral leaflet has also been reported, and resolves if the left ventricular disc is repositioned.46 One of the more feared mechanical complications is device embolization, which has an estimated incidence of 2.7% in muscular VSD closure.40 Cardiac perforation is a rare but potentially lethal complication.40 Other complications include access-site hematomas, vessel wall injury, and hemolysis.44-46 Clinically significant residual shunts after percutaneous closure are rare, but occasionally may require surgery.41
Post-MI VSDs deserve a separate mention because these adult patients have a significantly different clinical course and poor outcomes.47,48 The incidence of VSD after an acute MI is about 0.2%. These VSDs are always muscular, and are typically located in the mid-apical region of the ventricular septum with a left anterior descending coronary artery infarct, or in the posterior and/or inferior septum when associated with a right coronary artery infarct.28,48,49 Conservative management is associated with a high mortality; thus, the current guidelines for the therapy of acute MI recommend emergency repair even in hemodynamically unstable patients.48,49 Since these patients represent a critically ill cohort with a very high surgical morbidity and mortality, percutaneous catheter-based closure has been explored as a less-invasive strategy. Holzer et al reported on postinfarction VSD repair with the Amplatzer device.34 The device was successfully deployed in 16 of 18 patients, and the 30-day mortality rate was 28%, even though 56% of the patients were in cardiogenic shock. The reported mortality appears at least comparable with the 20%-87% mortality rate in surgical series.49 Most of the deaths post procedure occurred within the first 6 days and in patients who were in cardiogenic shock at baseline. Although there are no randomized studies, Maltais et al reported a comparison between surgical repair vs device closure for postinfarction VSDs.50 The mortality rate in the percutaneous group was 42%, which was not significantly different from the surgical group (P=.56). They also noted that the time from MI to the VSD diagnosis and the presence of a residual VSD were significantly associated with an increased 30-day mortality rate. Based on these results, the authors proposed percutaneous closure as the first approach for VSDs <15 mm in diameter and surgery for larger VSDs.
Patent Foramen Ovale
It is difficult to consider a PFO a true congenital defect of the heart, given its prevalence of 25% in the general adult population.51 The persistence of a PFO into adult life has been associated with a number of clinical syndromes, including ischemic systemic and cerebrovascular events, migraine headache, platypnea-orthodeoxia syndrome, and decompression sickness. Like a secundum ASD, a PFO can be closed with any of the devices designed for ASD closure. The major challenge of PFO closure is determining which patients are optimally suited for the intervention, and which can be managed with medical therapy alone.
The incidence of migraine with aura is increased in patients with PFO.52 It is believed to be secondary to the shunting of chemical or physical triggers of migraine, and therefore PFO closure has been used in this setting.53 The Migraine Intervention with StarFlex Technology (MIST) trial randomized 147 patients to PFO closure vs sham procedure. The primary endpoint of migraine cessation at follow-up was similar between groups. However, PFO closure reduced the mean number of migraine days compared with the sham group.52 More recently, the results of the Percutaneous Closure of Patent Foramen Ovale in Migraine with Aura (PRISMA) trial were presented. A total of 107 patients were randomized to closure or medical therapy. Overall, there was no difference between the groups in the primary endpoint of migraine days at 12 months. However, PFO closure significantly reduced the number of migraine with aura days and attacks, and more patients in the closure group were free from migraine at 12 months.53
Although the incidence of major decompression illness (DCI) in scuba divers is low, the relationship between DCI and the presence of a PFO is well documented. Subjects with a PFO have a 5-fold increase in the risk of major DCI events compared with subjects without PFO – a relationship that is directly proportional to the PFO size.54 Paradoxical embolization of gas bubbles is thought to be the key pathophysiological mechanism in DCI in patients with PFO. Percutaneous PFO closure has been demonstrated to effectively eliminate the presence of arterial gas bubbles after simulated dives.55 More importantly, in a prospective non-randomized study of 104 scuba divers, transcatheter PFO closure significantly reduced the incidence of major symptomatic DCI and asymptomatic ischemic brain lesions after more than 5 years of follow-up.56 To date, there are no randomized controlled trials or guideline-based recommendations on PFO screening or closure in divers. Based on the currently available literature, patients with PFO and DCI events or large PFOs should be advised to stop diving, and catheter-based closure may be offered to those who are unwilling to stop.
Platypnea-orthodeoxia is a rare clinical syndrome that has also been associated with intraatrial right-to-left shunts, including PFO, in conjunction with distortion of the atrial anatomy. Surgical or transcatheter closure eliminates the intraatrial shunt and is indicated for its treatment.57 Case series of transcatheter PFO closure using multiple devices, including CardioSeal, StarFlex, Amplatzer PFO, septal occluders, and other devices have reported excellent clinical results for such patients.57-59 Device closure in this setting can provide immediate symptomatic relieve and improvement in oxygen saturation.
The association of PFO with stroke has been the focus of the majority of research in the field. In up to 40% of patients presenting with an acute ischemic stroke, the embolic source is not definitively identified, and thus classified as cryptogenic stroke.60 With the use of TEE, the incidence of PFO has been demonstrated in up to 45% of cryptogenic stroke survivors.61 The presence of a PFO carries a potential for paradoxical embolization of thrombi from the venous system, and it has been associated with cryptogenic ischemic stroke.61 Handke et al compared the incidence of PFO in 227 cryptogenic stroke patients with 276 control patients with a known cause of stroke.61 The presence of a PFO, with or without an atrial septal aneurysm, was significantly higher in patients with cryptogenic stroke, and was independently associated with an increased incidence of cryptogenic stroke.
Over 20 years ago, Bridges et al62 reported on transcatheter PFO closure for secondary prevention of paradoxical embolism. However, it remains controversial whether percutaneous PFO closure is superior to medical therapy for the prevention of recurrent embolic events after a cryptogenic stroke. Multiple observational and non-randomized studies examining the relationship between PFO closure and stroke have been published, and at least two meta-analyses of these studies suggest that percutaneous closure of PFO in this group of patients may be better than medical therapy alone.63
Despite the large number of publications, randomized data were unavailable until recently. The patient characteristics, primary study endpoints and results of CLOSURE I (StarFlex device), the PC trial (Amplatzer PFO occluder), and the RESPECT (Amplatzer PFO occluder) randomized studies are summarized in Table 2, and all study devices are pictured in Figure 1.64-66 These studies demonstrated a numerically (but not statistically significant) lower incidence of the primary endpoint with device closure vs medical therapy alone. These results may be explained by the modest statistical power of these trials, given the relatively limited number of patients due to frequent off-label uses for PFO closure, as well as the unexpectedly low event rates. Other factors may have also played a role in the results. For example, in the CLOSURE 1 trial, the StarFlex septal occluder was associated with an increased incidence of device-related complications, including arrhythmias and thrombosis.64 This unfavorable safety profile of the StarFlex device had been previously reported.67 Finally, 3 of the 9 recurrent stroke patients in the device-closure arm of the RESPECT trial never had the defects closed, significantly biasing the intention-to-treat results.68 Of note, the RESPECT study included two additional prespecified analyses (per-protocol and as-treated). In both populations, the incidence of the primary endpoint was significantly reduced in the closure cohort (hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.14-0.96; P=.03 and HR, 0.27; 95% CI, 0.10-0.75; P=.01, respectively). Important information was also derived from the RESPECT multivariable analysis, in which patients with substantial right-to-left shunts, an associated atrial septal aneurysm, or a superficial infarct on imaging benefited the most from the PFO closure. This may help define the appropriate candidates for device closure. Specific neuroradiologic findings in patients with cryptogenic stroke have been associated with a PFO-related stroke, including radiologically apparent, superficially located, or large strokes, and further delineate individuals who may benefit from PFO closure.69 Although the randomized clinical trials did not provide a definitive answer for the population as a whole, the results suggest that some patients may benefit.
In light of the prior evidence demonstrating possible benefits of PFO closure over medical therapy, the unexpected results of these three randomized controlled trials, and the uncertainty regarding the recommended treatment for this population, several meta-analyses trying to answer this question have been published within the past year.70,71 These meta-analyses demonstrated that percutaneous PFO closure reduces the incidence of recurrent neurological events in at least 30% in the intention-to-treat analysis, which increased to 46%-58% when only the outcomes of the Amplatzer PFO occluder were analyzed.70,71
At present, device closure of PFO is not approved by the FDA, and the 2014 AHA guidelines on stroke secondary prevention, which did not include data derived from the recent meta-analyses, stated a lack of benefit (class III recommendation) from PFO closure in patients without evidence of deep venous thrombosis.72 The only guideline-based indication (class IIb recommendation) is for patients with cryptogenic stroke and PFO with evidence of deep venous thrombosis (Table 1).72 Device closure may, however, be considered for higher-risk patients, including those with an associated atrial septal aneurysm, substantial shunts, hypercoagulable states, large and superficially located strokes, or additional strokes while on medical therapy. The final results of the ongoing PFO studies (REDUCE, CLOSE, DEFENSE-PFO, and RoPE) may further delineate the optimal management.
The technique for PFO closure is essentially identical to ASD closure. However, crossing the defect with the multipurpose guiding catheter may be challenging in some PFO cases, and a floppy-tipped guidewire may be used. During PFO closure, the device is typically sized at twice the balloon-stretched diameter of the defect. Additionally, balloon sizing also provides information in regard to the length and compliance of the PFO. Complications after PFO closure are rare, and also similar to those encountered during ASD closure. These include device embolization, air embolism, cardiac chamber perforation, thrombus formation, and atrial arrhythmias, among others.28,29
Prosthetic Valve Paravalvular Regurgitation
Paravalvular regurgitation (PVR) complicates up to 17% of surgically implanted prosthetic valves and may be caused by infection, calcification, suture rupture, or tissue friability.73 Moderate-to-severe PVR is also seen in up to 10% of patients undergoing transcatheter aortic valve replacement (TAVR).74 Patients with PVR can present with congestive heart failure and/or hemolysis, and reoperation has been the standard treatment for the severely symptomatic. However, reoperation carries significant risks, including frequent recurrence, higher morbidity, and a mortality rate of up to 15%.73 Given the unfavorable outcomes of reoperative valve surgery in this setting, catheter-based closure of PVR was first introduced and has been developed over the last two decades.75
Advanced cardiac imaging is almost always necessary, since the diagnosis of PVR is challenging using transthoracic echocardiography. Computed tomography and 3D-TEE provide higher sensitivity and specificity for the diagnosis, and may be used to guide the procedure along with ICE.73 Although a detailed technical description is outside the scope of this review, several aspects of the procedure should be mentioned. The access site for PVR percutaneous closure depends primarily on the location of the prosthetic valve, but also on the operator’s experience and the patient’s anatomy. Typically, mitral PVR is approached via femoral venous access with fluoroscopic and echocardiographic-guided transseptal puncture.73 After transseptal puncture is done with the standard technique using the Brockenbrough needle, we advance an Agilis steerable sheath (St. Jude Medical) into the left atrium.76 A 5 Fr coronary multipurpose catheter is then telescoped into a 6 Fr coronary guiding catheter and used to cross the paravalvular defect with the aid of a 0.035˝, stiff, J-tipped, exchange-length Glidewire (Terumo Medical Corporation). The closure device is then delivered in the usual fashion under echocardiographic and fluoroscopic guidance. When difficulty crossing the defect is encountered with this technique, smaller catheters are used or wire exteriorization to the contralateral femoral artery or the left ventricular apex may be needed for better support. Alternatively, if mitral PVR cannot be crossed transseptally, the transapical (either via a surgical incision or fully percutaneous) or retrograde aortic approaches can be used.73,76 The PVR defect’s size, shape, and distance to the prosthetic valve ring are key factors when sizing the closure device, and are assessed with comprehensive preprocedural 3D-TEE. Charts and algorithms have been developed to help size PVR closure devices.76 Most aortic PVRs are closed via a retrograde aortic approach under echocardiographic guidance (transthoracic, TEE, or ICE). Aortic PVRs are smaller compared with mitral defects and are typically closed with a single closure device; for most cases, wire anchoring is not needed.76 The defect is crossed with the same technique described for mitral PVRs, using the telescoped multipurpose coronary catheters and a 0.035˝ stiff Glidewire, and the closure device deployed in the usual fashion. Occasionally, an Amplatzer left 1 catheter may be needed to cross the defect. For larger aortic PVRs, multiple closure devices may be required. In such cases, closure can be done using two extra-stiff wires across the defect after the 6 Fr multipurpose guiding catheter is removed, and advancing two delivery catheters into the left ventricle. The wires are then removed and both closure devices deployed simultaneously. If the defect requires two closure devices, but is not large enough to accommodate two simultaneous delivery catheters, sequential deployment can be achieved by leaving a single stiff wire within the delivery catheter, allowing placement of the closure device without losing access to the left ventricle. Then, the first delivery system is removed and exchanged for a second delivery catheter that is advanced over the wire already in the left ventricle.76 Occasionally, an arteriovenous rail might be necessary for additional support during PVR closure.76
There are no dedicated devices for PVR closure currently being used in clinical practice. However, the first-in-man use of a new dedicated device for PVR closure was recently reported.77 Multiple other devices have been used “off-label” for PVR closure, including the Raskind umbrella, different coils, the CardioSeal Clamshell device, and several Amplatzer devices, including the septal occluder, muscular VSD occluder, duct occluder, and Vascular plugs II, III, and IV.73 The stiffer braid devices, including the Amplatzer muscular VSD and the duct occluders, have been associated with an increased incidence of device-induced hemolysis, and in current practice, the Amplatzer vascular plugs (Figure 1) are the most commonly used devices for PVR closure. Success of PVR closure depends in part on the device selection and its size.
Most of the clinical experience comes from studies that used the Amplatzer duct occluder or muscular VSD occluder devices. A report of 43 patients who underwent percutaneous closure of PVR demonstrated clinical success, defined as improvement in New York Heart Association functional class and/or resolution of hemolysis, in 89% of the patients.78 Complications occurred in 14% of the patients, and included 2 device embolizations and 2 cardiac perforations. The 30-day mortality rate was 5.4%, and the freedom from cardiac-related death at 18-month follow-up was 91.9%.
Acute and long-term follow-up of PVR percutaneous closures was described by Sorajja et al in a retrospective study that evaluated the outcomes of 126 patients who underwent device closure of mitral PVRs (78.5%) and aortic PVRs (21.4%).79 Closure was attempted in 154 PVRs using Amplatzer devices, achieving a success rate of 91.3%. Inability to cross the defect and leaflet impingement were the most common causes of failure, which highlights the need for intracardiac or 3D-TEE guidance. Moderate or severe residual regurgitation was noted in 24% of the patients, and although it was not found to alter the overall survival, it was significantly associated with persistence of heart failure symptoms and the need for subsequent cardiac surgery. Similarly, patients with persistent hemolytic anemia had lower survival free from cardiac surgery. The 30-day mortality was 2.4%, which was lower than the predicted STS mortality of 6.7%. After a mean follow-up period of 17 months, the overall mortality was 23% for a calculated 3-year survival rate of 64.3%.79 An updated series of 200 patients from the same institution who underwent transcatheter closure of 243 PVRs demonstrated a 30-day major adverse cardiac event rate (defined as death, stroke, MI, major bleeding, or emergency surgery) of 7% and a 30-day mortality rate of 2%.80 It was also demonstrated that the procedure time, contrast volume, fluoroscopy time, and the 30-day major adverse cardiac events, significantly decreased with increasing operator experience.80
Although a direct comparison of percutaneous PVR closure with medical therapy or surgical management is not available in the literature, the mortality rate of device closure appears to be better than medical therapy and is at least similar to that of cardiac surgery.80-82 However, the ACC/AHA guidelines for the management of valvular heart disease still recommend surgical management for operable patients with severely symptomatic PVR as a class I indication, and percutaneous closure for those symptomatic patients at high risk for surgery as a class IIa indication (Table 1).82 Ideal patients for device closure are those with significant symptoms, defects <10 mm comprising <20% of the sewing ring of the prosthetic valve, and without evidence of endocarditis.79,82 With the development of dedicated PVR occluders, as well as advances in cardiac imaging and catheter-based techniques, transcatheter PVR closure will most likely become the treatment of choice for symptomatic patients, avoiding the high morbidity and mortality associated with reoperative valve surgery.
PVR is more common after TAVR than surgical aortic valve replacement.83 In clinical trials involving both the balloon-expandable and self-expandable percutaneous aortic valves, the incidence of any degree of PVR and moderate-to-severe PVR ranged from 70%-80% and 7%-10%, respectively.83,84 However, the presence of any degree of PVR after TAVR is associated with an increased 3-year mortality, and therefore efforts to avoid or treat it are warranted.74 In this setting, PVR has been prevented and/or managed with adequate valve sizing, balloon postdilatation, valve repositioning, and valve-in-valve implantation.85 More recently, percutaneous PVR closure after TAVR was reported as a feasible treatment option. PVR closure with Amplatzer vascular plugs has been performed in a small number of patients after both Sapien and CoreValve percutaneous valve implantation, achieving good short-term clinical and echocardiographic results.86-88
Conclusion
Intracardiac defects are relatively common in the adult population. With the advances in imaging technology, device technology, and transcatheter techniques, percutaneous closure is now feasible and safe for most of these intracardiac defects, and has become the preferred treatment option for selected patients with ostium secundum ASD, PFO, VSD, and PVPR.
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__________________________________________
From 1The Columbia University Division of Cardiology at Mount Sinai Heart Institute, Miami Beach, Florida; 2the Division of Cardiology, Miami Childrens’ Hospital, Miami, Florida; 3Columbia University College of Physicians and Surgeons, New York, New York; and 4the Division of Cardiology, Mayo Clinic, Rochester, Minnesota.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Rihal reports personal fees from Abbott Vascular and grant funds from Edwards Lifesciences. The remaining authors report no conflicts of interest regarding the content herein.
Manuscript submitted January 20, 2015, provisional acceptance given January 26, 2015, final version accepted March 30, 2015.
Address for correspondence: Nirat Beohar, MD, Columbia University, Division of Cardiology Mount Sinai Heart Institute, 4300 Alton Road, Miami Beach, FL 33140. Email: Nirat.Beohar@msmc.com
