Contemporary Clinical Management of Atrial Septal Defects in the Adult

Gianluca Rigatelli; Paolo Cardaioli; Ziyad M Hijazi


Expert Rev Cardiovasc Ther. 2007;5(6):1135-1146. 

In This Article

Evidence Synthesis

Primum defects or atrioventricular septal defects (AVSD) are associated with Down syndrome in 40% of cases, and less frequently with Di George syndrome and Ellis-Van Creveld syndrome. ASD of different types are the most common cardiac abnormality associated with the Holt-Oram syndrome. Secundm ASD can occur in a familial form which has been related to GATA4 and NKX2.5 mutations and has a 3% recurrence risk rate in first-degree relatives.[3,4]

The ostium secundum ASD is a true defect of the atrial septum which involves the fossa ovalis region, whereas the other two types are defects of the endocardial cushions (ostium primum) (Figure 1) or of the junction of the right atrium and the superio/inferior vena cava (sinus venosus) (Figure 2). Secundum ASDs and more frequently sinus venosus defects can be associated with partial anomalous pulmonary venous return.[5] The magnitude of and direction of flow through an ASD depend on the size of the defect and the relative diastolic filling properties of the left and right ventricles. Conditions that reduce left ventricle compliance and mitral stenosis increase the left-to-right shunt, whereas conditions that reduce right ventricle compliance reduce the left-to-right shunt or cause a right-to-left shunt. A left-to-right shunt is significant when the Qp/Qs ratio is greater than 1.5:1 or when the right chambers are dilated. A significant Qp/Qs ratio is associated with adverse long-term outcomes. Many patients with secundum ASD are free of overt symptoms, although most will become symptomatic at some point in their lives. Often secundum ASD patients have a mitral valve prolapse. Exercise intolerance is the most common presentation along with atrial fibrillation or flutter due to the atrial dilation and stretching. This usually occurs around 40 years of age.[4] In older patients, decompensate right heart failure may develop and is often associated with pulmonary hypertension caused by excessive pulmonary flow over a long period of time.[6] Significant ASDs cause increased morbidity and mortality if untreated.

Schematic anatomical representation of ostium primum defect: note the absence of tissue outside the region of the fossa ovalis and near the atrioventricular right valve.

Schematic anatomical representation of the sinus defect. Note the absence of tissue in the wall of the SVC (superior sinus defect) and the IVC (inferior sinus defect) which communicate directly with the left atrium. IVC: inferior vena cava; SVC: Superior vena cava.

Diagnosing a secundum ASD is more often than not incidental because the defect normally causes symptoms late in adult life. Echocardiography and MRI have completely replaced catheterization in adults with ASD ( Table 1 ).

Typical findings in patients with ASD may include a prominent right ventricular impulse along the left sternal border, a systolic ejection murmur audible along the left upper sternal border caused by the increased flow across the right ventricle outflow tract and a split second heart sound. A diastolic murmur may be heard due to relative tricuspid stenosis. If pulmonary hypertension has developed, the split second heart sound is replaced by a narrowly split S2 with accentuated P2: the patient usually is cyanotic.[2]

A typical EKG shows an axis between 0 and +120°, an RSR is often present in V1, especially in significant defects. A radiogram may show enlargement of the right chambers in the lateral view and pulmonary artery dilation: even significant ASD often has a normal cardiac silhouette and normal pulmonary vascularity.

Echocardiogaphy records the size of the defect, can differentiate (with transthoracic when a good acoustic window is present, otherwise with transesophageal technique) between secundum, primum and sinus venosus defects and identifies the direction and magnitude of the shunt. The right chambers can be properly estimated by transthoracic echocardiography together with any abnormal paradoxical septal motion which suggests a right chamber volume overload, whereas the pulmonary artery pressure can be calculated or from the Doppler velocity of pulmonary or tricuspid regurgitation.[5,7,8] Pulmonary venous return can be evaluated by transthoracic echo and in difficult case should be evaluated by the transesophageal technique. Transthoracic 3D echocardiography enables the ASD location, ASD size and surrounding tissue of the atrial septum to be determined accurately, and might replace transesophageal echocardiography in patient selection for surgical or transcatheter closure.[9]

MRI can give us almost the same information as echocardiography as regards right chambers size, defect size, shunt ratio and any associated pulmonary venous return.[10,11]

Survival rates especially favor patients closed before 25 years of age compared with medically managed patients (85 vs 74% at 10 years) but improved quality of life can also be expected for patients closed over 40 years of age.[12,13]

Thus, surgical suture or catheter-based closure is indicated in patients with significant ASD (enlarged right heart chambers) irrespective of age. Catheter-based closure is preferable in patients with secundum ASD and suitable anatomy. Favorable anatomy includes: at least 5-mm rims of tissue on transesophageal echocardiography, no associated cardiac anomalies, such as partial anomalous pulmonary venous drainage and defect size less than 36-38 mm.[13]

Unfavorable clinical settings for device-based closure include patients with premum ASD or sinus venosus defect; patients with advanced pulmonary hypertension in whom the ASD may be needed to maintain an acceptable quality of life; patients with severe left ventricle dysfunction in whom the ASD works as a pop-off valve; secundum ASD associated with embryonic remnants of atrial septation, whether fenestrated or not, in which device closure may be problematic or impossible or in which more than two devices are required to seal the defect; secundum ASD with diameter over 36 mm, in which a very large device would have to be implanted due to the risk of late erosions or thrombosis. Patients with such features should be referred for surgical closure which, for secundum ASD, usually includes nearly always direct suture, and less frequently, pericardial patch or synthetic patch closure, whereas for primum ASD treatment includes patch closure and repair of the cleft valve. Lastly, a sinus defect requires baffles of the venous return.[14,15]

For the most frequent defect, the secundum ASD, percutaneous closure minimizes hospital stay and recovery time, avoids surgical wounds, and offers the same benefits as surgery. Successful closure can be obtained in over 95% of patients, although small residual shunts, which are not hemodynamically significant, may be observed in the immediate postclosure echocardiographic study but will usually close within 1 year of the procedure.[16]

Different latest generation devices, mainly made with Nitinol and synthetic tissue may be used nowadays in order to close secundum ASD including the most widely used Amplatzer Septal Occluder® (AGA Medical Corp., MN, USA), the Starflex Occluder™ (NMT Medical, MA, USA), the HELEX Septal Occluder™ (W.L. Gore and Associates, AZ, USA), the Cardia Intrasept® (Cardia Inc., Burnsville, MN, USA) and others. There are no trials comparing the performance of each device but, in general, the choice depends on operator experience and preference, and on the size of the defect.

Transcatheter closure of ostium secundum atrial septal defect has been performed for years using deep sedation or orotracheal intubation, transesophageal echocardiography and the sizing balloon technique for size measuring the 'stop-flow' diameter of the defect: the procedure includes passing a large compliant balloon inflated with contrast medium across the defect and the computation, via an electronic calliper of the echo or radiological equipment, of the balloon diameter when cessation of left-to-right shunt by color Doppler echocardiography occurs. In most laboratories, intracardiac echocardiography (ICE) is replacing transesophageal echocardiography (TEE), therefore, avoiding general anaesthesia and related morbidity and increasing patient comfort (Figure 3). The electronic device with color Doppler capability (AcuNav™, Acuson, A Siemens Company, CA, USA) and the mechanical device (Boston Scientific) with 360° scan can measure the fossa ovalis or the ASD surrounding rims in order to select the proper device size. In particular, the measurement of the aortic rim and of the entire atrial septum length is of paramount importance due to the risk of device impingement on the aortic wall when the aortic rim is too short or the device is oversized. Two orthogonal views are selected to measure the diameters of the fossa ovalis or of the ASD due to the elliptical shape of some defects. ICE has been shown to be equivalent to TEE in resolution and precision.[17] However, ICE has been suggested as the optimal imaging technique to size the defect and for monitoring the device implantation procedure, especially in cases with difficult anatomy.[18,19]

Patient with secundum atrial septal defect during transcatheter closure. After catheterization of both femoral veins, the delivery catheter and mechanical intracardiac echocardiography probe were advanced up to the right atrium. (A) transesophageal echocardiography revealed a defect located within the region of the fossa ovalis. (B) Intracardiac echocardiography appearance of the ASD as absence of tissue in the fossa ovale region surrounded by its rims. (C) The delivery catheter is moved forward across the ASD, whereas the intracardiac echocardiography probe is placed in front of the defect. (D) Opening of the left atrial disk. (E) Complete opening of the device. LA: Left atrium; MV: Mitral valve; RA: Right atrium; TV: Tricuspid valve.

Although there are no controlled, randomized trials of secundum ASD closure which compare surgical with catheter-based closure, most recent series have demonstrated that percutaneous device-based closure is as safe and effective as surgical closure and decrease the morbidity and mortality of the surgical approach ( Table 2 and Table 3 ). Unfortunately the series are very different for patient's age, operative techniques, and mean follow-up: this heterogenity makes any comparison insensitive. Nevertheless, the data retrieved from recent literature suggest that surgery and percutaneous repair are at least similar in success and closure rates: percutaneous closure is preferable for the less invasiveness, hospital stay duration and immediate complication rate.

Moreover, the recent advancements in mini-invasive surgical techniques for repair of secundum ASD such as mini-thoracotomy or endoscopic techniques make a matched comparison virtually impossible. However, it is likely that such techniques compare more favourably with percutaneous closure, due to less invasiveness and reduced hospital staying.

Costs analysis has been performed only by few authors[21,35] demonstrating a difference in costs of percutaneous devices between developed and developing countries that does not allow clear economic recommendations.

Butera et al. reported that the overall rate of complications was higher in the surgical group than in the percutaneous group: 44% (95% confidence interval [CI]: 39.8-48.2%) versus 6.9% (95% CI 5-8.7%; p <0.0001); major complications were also more frequent in the surgical group: 16% (95% CI: 13-19%) versus 3.6% (95% CI: 2.2-5.0%; p = 0.002). In that study, multiple logistic regression analysis showed that surgery was independently strongly related to the occurrence of total complications (odds ratio [OR]: 8.13; 95% CI: 5.75-12.20) and of major complications (OR: 4.03; 95% CI: 2.38-7.35).[26]

Post et al. observed in their study using different types of device that overall complications included transient arrhythmias in 15.4%, pericardial effusion in 1.5%, and transient ischemic attack in 1.5%. Complete closure 6 months after the procedure occurred in 79.6%, without difference between the devices.[33] Arrhythmias such as atrial fibrillation, atrial flutter and sick sinus syndrome are very uncommon among patients who undergo ASD closure (either surgical or percutaneous) during early adulthood, but older patients remain at risk for such arrhythmias, although they tend to decrease in the long-term follow-up.[36,37] Functional capacity in patients with ASD improved more widely and faster than reported in the surgical series: a 15% improvement in peak oxygen uptake at 6 months has been reported after percutaneous closure regardless of defect size and patient's age.[38] Improved left ventricular filling and systemic output have been reported after percutaneous closure.[39] Effects on cardiac remodeling also seem faster; reduced right cardiac chambers are apparent within 24 h of closure and the process appears to continue after 1 year, especially for the right ventricle.[40,41,42,43,44]

The degree of acceptable pulmonary hypertension, the need for concomitant atrial antiarrhythmia surgery and likelihood of symptomatic response, which depends on age at closure, are yet to be resolved. The optimal strategy for patients with secundum ASD larger than 38 mm still needs to be assessed, although an international registry of transcatheter closure has reported acceptable results.[45] Moreover, although catheter-based closure is the first-line treatment for isolated secundum ASD, some practical issues remain unresolved.

Metal allergy is one such problem. Currently, available devices are made of different materials. The Amplatzer is mainly made of nitinol, whereas Cardia Intrasept and Starflex for example are made of tissue-patch and a small amount of nitinol. Nitinol, a nickel-titanium alloy, is a valuable material in the construction of interventional endoluminal devices because of its biocompatibility, super elasticity, high resiliency and shape memory. The possibility of nickel toxicity has been raised with devices constructed of Nitinol. There is no increase of concentrations of nickel in the blood of patients who have received Amplatzer nitinol devices suggesting that nickel-titanium is an inert, corrosion resistant alloy.[46] Nevertheless, nickel seems to be released from the device, causing a systemic rise in serum levels of nickel, possibly until a calcium-phosphate layer has formed on the passive oxide film of the device or until endothelialization is complete.[34] Possible biological effects should be considered, particularly in young patients or patients with nickel hypersensitivity. Nickel intolerance or allergy is an issue to be considered in patients to be implanted. However, it is unlikely that skin allergy to nickel will be associated with allergy to an implantable device.

In the past, repair of primum defect was associated with a 5% risk of complete heart block, but nowadays this percentage has been reduced considerably by a better knowledge of the AV node.[47] AV valve insufficiency and subvalvular aortic stenosis are still possible late consequences of primum ASD repair. Superior vena cava obstruction has been reported after repair of anomalous right pulmonary vein and sinus venosus defect. Some complications have been reported with surgical closure of secundum ASD and include pericardial effusion, scar-induced supraventricular arrhythmias and stroke, although the risk is very low but still present. Complications, although rare, may also occur during and after device closure of secundum ASD in less than 1% of patients.[48] Perioperative complications, such as vascular complications, include groin hematomas, bleeding and arterio-venous fistula but these are very rare. Pericardial effusion or tamponade may occur when attempting to cross the ASD or maneuvering the large size sheath during device deployment, in particular, in young subjects with small atrial chambers. Rupture of the atrial septum during balloon sizing maneuver has been reported in the past but seems to have been overcome by new sizing techniques under ICE guidance. Embolization of the device is a rare but potentially life-threatening complication that occurs in less than 1% of cases. To avoid this complication, appropriate sizing is essential and, of course, use of echo guidance to deploy the device.[49]

Following interventional closure of ASDs with Amplatzer Septal occluders, an increased level of cTn-I has been described, which indicates some transient, reversible myocardial membrane instability due to the device or silent coronary embolism during the implantation procedure itself.[50] Careful detection and elimination of air bubbles during the preparation of the device, especially the Amplatzer Occluder, and the loading within the long sheath, are mandatory to avoid paradoxical coronary embolisms. Anomalous coronary artery, such as anomalous origin of the circumflex coronary artery from the right coronary sinus, have been known to cause myocardial ischemia especially when the anomalous artery is located between the aortic root and the ASD closing device.

On long-term follow-up, erosions have been described for many devices.[51,52] Amplatzer ASD occluder-associated erosions uniquely involve the anterosuperior atrial walls and adjacent aorta. Pathophysiology remains poorly understood. Some of the erosions have presented late after closure with 25% present weeks later and at longest, 3 years later. Other complications, such as mitral valve dysfunction and obstruction to systemic and pulmonary venous pathways, appear to be rare.

Several series have reported different percentages of thrombus formation after ASD device closure. The largest series revealed thrombus formation in 15 of the 593 (2.5%) ASD and patent foramen ovale patients.[48] The thrombus was diagnosed in 14 out of 20 patients after 4 weeks and in six out of 20 patients later on. The incidence was different for different devices: 7.1% for the CardioSEAL® device (NMT Medical, MA, USA); 5.7% for the StarFLEX® device (NMT Medical); 6.6% for the PFO-Star™ device (Applied Biometrics Inc., MI, USA); 3.6% for the ASDOS device (Dr. Ing, Osypka Corp., Grenzach-Wyhlen, Germany); 0.8% for the Helex device; and 0% for the Amplatzer device (AGA Medical Corp., Minnesota, USA). The difference in thrombus formation between the Amplatzer device on the one hand and the CardioSEAL device, the StarFLEX device, and the PFO-Star device on the other, was significant. Postprocedure atrial fibrillation and persistent atrial septal aneurysm had been found as significant predictors for thrombus formation.

Follow up of operated patients should include ASD clinical examination, Holter ECG and echocardiography every 12-18 months together with bacterial endocarditis prophylaxis for primum, whereas for secundum and sinus defect, physical examination, Holter EKG and echocardiography should be scheduled every 2 years.[53]

The correct follow-up of patients who received devices is more problematic since there is no consensus as to what defines appropriate follow-up after ASD closure. Most centers around the world follow the patients for at least one year after device implantation, and yearly thereafter. TEE was initially scheduled at 1 month and 1 year post implantation; however, thanks to the wide experience gained with the device, we believe transthoracic echocardiography should be sufficient. 24-h ECG monitoring at 1-6 month seems advisable to monitor presence of asymptomatic atrial fibrillation or flutter. Long-term therapy after closure with antiplatelets is a debated issue. Aspirin alone or in combination with ticlopidin or aspirin and clopidogrel have been used by different operators based on no particular scientific evidence. However, we believe after 6 months, one can discontinue such medication if the closure is complete. Endocarditis prophylaxis is also administered for a period of 6 months, after which if the defect is completely closed, one should not prescribe the antibiotics.[54,55]

Operated ASDs theoretically have no restrictions in any field of social and active life, including pregnancy and sport.[56,57,58] Specifically, following the guidelines of grown-up congenital heart disease,[59] patients with secundum or sinus ASD with no pulmonary vascular disease have no contraindications for pregnancy or restrictions regarding oral contraceptives. Moreover, they have no physical restrictions and are in class I for insurance companies if closed early. Patients with ostium primum or atrioventricular defects with no pulmonary vascular disease, have no restrictions to physical activity and pregnancy if closure was uncomplicated and they do not suffer from arrhythmias: they are in class II for insurance, if properly closed.

Owing to the small risk of paradoxical embolus, arrhythmias or heart failure, a cardiological consultation is always necessary during pregnancy but the only contraindication is once again the presence of severe pulmonary arterial hypertension.