The aim of this review is to discuss the management of atrial septal defects (ASD) in the adult patient paying special attention to the elderly population and the most recent transcatheter advancements. ASDs are characterized by the following categories: ostium secundum, ostium primum, sinus venosus, and coronary sinus defects; though multiple defects may exist concurrently. Intervention for closure of ASDs are indicated with the development of right ventricular volume overload, or in the clinical context of paradoxical embolic stroke. Previously, there was significant disagreement regarding the timing of ASD closure in adult patients, but there is now general consensus that adult patients with clinical evidence of right ventricular overload should undergo closure of ASDs at the time of presentation. The present review describes the typical presentation of patients with symptomatic ASD’s, medical management, and whether surgical or percutaneous approach should be pursued. We will also discuss other important considerations for patient selection and potential early and late complications of transcatheter ASD closure such as congestive heart failure, device embolization, and tissue erosion. At the time of this writing, there are currently three FDA-approved devices for percutaneous VSD closure including the AmplatzerTM Septal Occluder (ASO, St. Jude Medical, St. Paul, MN), Gore HELEXTM Septal Occluder (W.L. Gore and Associates, Newark, NJ), and Gore CARDIOFORMTM Septal occluder (GCSO, W.L. Gore and Associates, Newark, NJ) devices. Many premarket approvals were granted for devices that never went to market due to poor investigational study performance. Likewise, the HELEX device has since been discontinued upon bringing the GCSO device to market. We will focus primarily on the ASO device with a brief review of current investigations into the GCSO device, both of which carry an indication for closure small to medium sized ASDs in the ostium secundum position. Additionally, this review covers the safety of transcatheter closure of ASDs with currently available devices, review studies associated with devices available outside the United States, and perioperative considerations for transcatheter intervention. Obstacles to device employment and countermeasures to overcome operational challenges will also be discussed. To this end, variations or similarities of currently approved devices will be emphasized throughout this discussion where possible. Lastly, we will offer insights into device evolution trends with the expectation of new device developments on the horizon. We will briefly discuss up and coming areas of active research, including the emerging fields of novel biomaterials and gene therapy.
Atrial septal defects (ASD) are one of the most common congenital cardiac abnormalities reported both in adolescent and adult populations. The incidence of newly diagnosed atrial septal defects are second only to bicuspid aortic valves as the most common congenital heart disease in children, with ASDs accounting for the majority of congenital malformations diagnosed in adults[
It is important to note that morphological variations of different types of ASDs, which determines whether a particular defect is amenable for transcatheter closure. Briefly, ASDs fit into four major classes: ostium secundum, ostium primum, sinus venosus, and unroofed coronary sinus
ASD locations. ASD: atrial septal defects
Clinical characteristics of ASDs differ significantly in pediatric populations as compared to adults. ASDs are detected in asymptomatic children with increasing frequency due to non-invasive screening modalities such as echocardiography, routine ECG, and even prior to birth during routine obstetric wellness sonograms[
Adult populations with ASDs are typically asymptomatic with great variability in the onset of symptoms. More common symptoms appear to be early onset atrial flutter or atrial fibrillation due to atrial stretch, and less commonly decompensated right heart failure in patients under 40 years of age[
Elderly patients with hemodynamically significant defects more frequently encounter complications with long-term adverse consequences such atrial arrhythmia, pulmonary hypertension, and atrioventricular valvular insufficiencies related to chronic ventricular volume overload[
Conventional transthoracic echocardiography (TTE) is capable of identifying the presence of ASDs, characterizing chamber dilatation, estimated pulmonary artery pressure, shunt ratio, and other coexisting cardiac conditions.
2D Doppler Echo demonstrating atrial septal defects left-to-right shunt
3D echocardiography provides better spatial visualization than conventional echocardiography. An example of a diagnostic 3D TEE visualizing an unrepaired defect can be seen in
3D transesophageal echocardiography visualization of atrial septal defects (A); same lesion after deployment of Amplatzer device (B)
The International Society of Ultrasound in Obstetrics and Gynecology recently published guidelines on the detection of fetal cardiac anomalies in 2017 with the goal of improving early detection by obstetricians and family practitioners[
Transcranial doppler ultrasonography (TCD) is a viable alternative to TTE or TEE for screening and follow-up evaluation of ASD. It offers a relative degree of comfort over TEE, and offers sensitivities equivalent to TTE in terms of identifying right to left shunts, but cannot detect other associated defects that echocardiography can[
Intracardiac echocardiography (ICE) offers superior visualization of the septal morphology during transcatheter device deployment[
ASDs are considered for closure in symptomatic patients where a left to right shunt is present with evidence of right heart pressure overload (right atrial or ventricular enlargement), and pulmonary to systemic blood flow ratio (Qp:Qs) is greater than 1.5:1[
Of great interest to clinicians in the age of readily available transcatheter repair of secundum type ASDs is the decision to pursue transcatheter or open surgical repair. One such study at Mayo Clinic sought to evaluate outcomes of surgically managed ASD cases as compared to medical management alone with a follow-up interval of 27 to 32 years after the index surgery. Study findings demonstrated that the survival rate was 74% as compared to 85% for age sex matched medically managed controls. In cases where surgical intervention occurred below the age of 24 years, survival rate reported was the same as age matched controls. Independent predictors of long-term survival were age at the time of operation and main pulmonary artery systolic Pressure (PASP)[
More recently the 2018 ACC/AHA task force undertook a meta-analysis seeking to understand differences in outcomes of medical vs interventional management of secundum type ASDs. Their analysis found 11 studies that met criteria for inclusion, and in most instances found a protective effect with bearing on reduction of symptoms, functional capacity, and improvement of hemodynamic characteristics following either surgical or transcatheter intervention[
At the time of this writing, only secundum type defects have transcatheter devices approved for intervention. Primum, Sinus Venosus, and Coronary sinus defects still carry the recommendation of open surgical intervention with only rare reports of transcatheter interventions published[
Of growing interest is the prospect of treating ASDs associated with sinus venosus defects, which are traditionally treated with open surgical repair. Presently, there are only case reports describing transcatheter approaches. Two such case reports technical success with correcting partial anomalous pulmonary venous return of the right upper pulmonary vein by deploying a covered stent graft into the affected pulmonary vein[
The origins of transcatheter ASD repair can be traced back to King’s report of non-operative ASD closure during cardiac catheterization in 1976[
St Jude Amplatzer Device, reproduced under creative commons license, Thomson and Quereshi 2015
Recent publications describing ASD device outcomes
Device name | Manufacturer | Approval | Recent/ongoing studies | Significant findings | |
---|---|---|---|---|---|
Cocoon | Vascular Concepts | CE Mark | Lairakdomrong |
63 | 100% closure at 12 mo, 3 early embolization requiring surgical |
Pakkret, Thailand | Thanopoulos |
92 | 100% closure at 6 mo, no adverse events | ||
Ultrasept II | Cardia | CE Mark | Mijangos-Vázquez |
30 | 100% closure at 6 mo, no adverse events |
Eagan, MN, USA | Bartel |
2 | 2 reports of fabric erosion requiring surgical removal | ||
Aubry |
9 | 2 out of 9 experienced fabric erosion requiring surgical removal | |||
Bozyel and Özcan[ |
9 | 3 out of 9 patients with device required surgical removal | |||
Chamié |
4 | 4 out of 70 developed early fabric erosion, treated with device in device | |||
Nit Occlude ASD-R | PFM Medical Mepro | CE Mark | Peirone |
73 | 98.6% closure at 11 mo, no adverse events |
Köln, Germany | Bulut |
30 | 98% closure at 10 mo, 1 erosion requiring surgical removal | ||
Ceraflex ASD | CE Mark | Astarcioglu |
58 | 100% closure at 6 mo, no adverse events | |
Apostolopoulou |
183 | 100% closure at 22 mo, no adverse events | |||
Figulla Flex II | Occlutech | CE Mark | Kenny |
107 | 94.4% closure at 6 mo, 1 device embolization |
Jena, Germany | Haas |
1315 | 97.3% closure at 12 mo, 5 device embolization, 3 AV block | ||
Godart |
31 | 90.3% closure at 36 mo, 1 device embolization, 1 AV block | |||
Roymanee |
77 | 97.4% closure at 43 year, 2 device embolization, non-inferiority to ASO | |||
Aytemir |
58 | 99.3% closure at 12 mo, 2 device embolization, 4 embolic events, 2 device thrombosis | |||
Kim |
152 | 100% closure at 25 mo | |||
Cardioform | WL Gore | CE Mark | GORE Assured Study, ongoing[ |
522 | Clinical Trial NCT02985684, enrollment complete, final results by 2022 |
Flagstaff, AZ, USA | FDA PMA | Hemptinne |
26 | 100% closure at 6 mo, 5 wire frame fractures | |
Kim |
17 | 100% closure at 23 mo | |||
Grohmann[ |
173 | 95.4% closure at 20 mo, 4 device embolization, 3 AV Block | |||
Amplatzer | St. Jude Medical | CE Mark | Turner |
1000 | 97.9% closure at 24 mo, 1 embolization, 3 cardiac erosion |
St. Paul, MN, USA | FDA | Spies |
170 | 100% closure at 12 mo, 4 embolization, 1 TIA, | |
Tomar |
529 | 100% closure at 56 mo, 96.7% symptom free, 1 stroke | |||
Kim |
98 | 100% closure at 29 mo, 1 embolization | |||
Post Market Surveilence (ASO 522)[ |
602 | Clinical Trial NCT02353351, study terminated, results not published yet |
Two crucial parameters should be evaluated in patients with secundum septal defect prior to intervention: maximal ASD and surrounding rim dimensions. Presently, the Amplatzer device is capable of closing defects with a maximum defect diameter less than 38 mm[
Echo Atrial septal defects sizing (left)
Transcatheter closure of ASDs with a maximal native diameter > 30 mm can be quiet challenging, and alternative techniques for deployment may be required, which will be discussed later. In regard to classification of surrounding rims, although there are some differences noted among studies, distances from ASD to aorta, superior vena cava, right upper pulmonary vein, inferior vena cava, coronary sinus, and atrioventricular valve are evaluated. Adequate tissue rim is defined by at least 5mm from the defect edge to the surrounding structures so as not to impinge on the vena cava, pulmonary vein, coronary sinus, tricuspid or mitral valve[
Tissue rim measurement areas
Posterior Rim in Short Axis View (A); AV Valve Rim in 4 Chamber View (B); SVC Rim in Bicaval View (C); IVC Rim in Bicaval View (D); and (E) Aortic Rim in 4 Short Axis
Comparative benefits from ASD closure in the elderly population have historically been underreported as compared younger populations. The paradigm of non-operative management of previous generations had, in some ways, stymied broad acceptance and given cause to thwart intervention where there was no perceived benefit. However, percutaneous management of ASD in elderly patients has gained reluctant enthusiasm, as evidenced by analyzing trends in hospitalizations captured by the National Inpatient Sample Database[
In two separate studies Swan and Khan both found that following ASD intervention, a small cohort of geriatric patients with a median age of 70 years old, saw improvement in their New York Heart Association (NYHA) class, 6 minute walk time and improvement in overall physical/mental health score in addition to an extremely high procedural success rate (98%)[
Similarly, in 2014 Komar
The most salient issue in elderly cases is not their primary pathology, but their co-morbid systemic and cardiac diseases. This necessitates careful preoperative evaluation of the associated risk factors as an essential aspect of successful treatment. Approximately one third of the patients showed systemic hypertension and systemic diseases like diabetes mellitus, and a considerable extent of pulmonary and neurological disease conditions were also present[
Similarly, diastolic dysfunction and stiffening of the LV causes increased left to right shunting, which may explain in part why the late diagnosis is established in elderly patients who were previously asymptomatic. Careful assessment of left ventricular and left atrial pressures via left heart catheterization during defect balloon occlusion and weighing potential hemodynamic consequences
Due to chronic right ventricular volume overload, elderly patients with hemodynamically significant ASDs have a tendency to present with pulmonary hypertension. Pulmonary hypertension develops as a result of increased pulmonary blood flow due to left-to-right shunting. However, the anomalous rise in pulmonary blood flow creates secondary physiologic changes such as pulmonary vascular intimal proliferation and medial hypertrophy that affect pulmonary vascular resistance[
In patients with superoanterior rim deficiency, the increased risk of serious complication, i.e., “cardiac erosion” may increase after implantation of the device. The exact mechanism of “cardiac erosion” is not been well understood; previous clinical experience proposed that an aortic rim deficiency and oversized occlusion device may be highly correlated with cardiac erosion[
The transcatheter ASD repair has evolved from employment in select patients unable to undergo open surgical repair, to applications in pediatric populations, and is now gaining traction in the elderly. Where currently secundum type ASDs and limited case-reports of closure in other varients of ASD are now being reported, we may expect future devices to address these limitations. On the other hand, complications arising from this procedure, especially cardiac erosion, are still being reported. Progress over the last several decades in terms of safety and efficacy are impressive and point to a bright future in the treatment of congenital heart defects. We conclude this review by looking to the near and long-term future in the state of the field.
Several technical modifications have been introduced over the years to address difficult transcatheter ASD closure, including delivery sheath modification, position deployment, or additional material to hold the left atrial disk inside the LA. Some advocate deployment with balloon assisted placement[
A well described early and mid-term complication of transcatheter ASD closure is device dislodgement and embolization. The rote response, if the device has been fully deployed, is to convert to open surgery for retrieval and repair. Improving techniques for endovascular retrieval are supported by case reports, case series, and retrospective reviews of experience[
Intracardiac devices that are malfunctioning, whether dislodged, malpositioned, or sub-optimally effective, are typically treated with open heart surgery for removal and remedy. At the present, there are only case reports describing “device-in-device” salvage to return function to such malfunctioning devices[
The goals of treatment in congenital cardiac malformations are ever shifting. Seventy-five years ago, researchers and clinicians sought to find appropriate screening criteria where risk factors for ASDs were poorly understood. With the advent of better screening methods and guidelines, the difficult decision of who should undergo surgery or medical management then became the diagnostic dilemma. With newer, safer, conventional and endovascular procedures well established, the next logical progression in the field is primary prevention of the disease process. Several reports proposing genes associated with ASD that may inform progress toward potential targets for gene therapy in genetically linked variants of ASD[
Until primary prevention with gene therapy is technically feasible, other interventions may be on the horizon. Tissue compatibility of ASD closure devices remains an area of interest for researchers and clinicians alike. Biocompatible and bioabsorbable based devices are currently under investigation[
Marguerite Zimmermann, MSN was responsible for creating the artwork contained in this article.
Made substantial contributions with initial draft, subsequent revisions, and approved final draft: Zimmermann E, Hussain H, Avgerinos D
Made substantial contributions with subsequent revisions and approval of final draft:
Worku B, Dougenis D
Not applicable.
None.
All authors declared that there are no conflicts of interest.
Not applicable.
Not applicable.
© The Author(s) 2019.