From the Rush Center For Congenital & Structural Heart Disease, Rush University Medical Center, Chicago, Illinois. Disclosure: Dr. Hijazi is a non-paid consultant to Occlutech, a German device company. Manuscript submitted November 10, 2008 and accepted December 4, 2008. Address for correspondence: Ziyad M. Hijazi, MD, MPH, Rush Center for Congenital & Structural Heart Disease, 770 Jones, 1653 W. Congress Parkway, Chicago, IL 60612-3833. E-mail: Zhijazi@rush.edu
J INVASIVE CARDIOL 2009;21:70–75
Atrial septal defect (ASD) is a common form of congenital heart disease accounting for approximately 10% of all congenital heart defects.1 There are three types of ASDs with different anatomical and clinical features, and subsequently unique therapeutic approaches: ostium secundum, ostium primum and sinus venosus ASDs. While surgical correction remains the standard of care for the latter two, percutaneous device closure of secundum ASD is a safe and accepted alternative to surgical closure.2–4 However, elderly patients with this congenital deformity pose a clinical and therapeutic challenge. In this review we will illustrate the updated knowledge and advances in transcatheter closure of secundum ASD, focusing on the elderly population.
Clinical ChallengePatients with secundum ASD are mostly asymptomatic until the second-to-third decade of life when they present either on routine check-up with classic cardiac examination consisting of widely-fixed splitting of S2 and an ejection systolic heart murmur, or they present with exertional dyspnea, fatigue or palpitations. Elderly patients, if not diagnosed earlier in life, can present with clinical states that are an age-related reflection of atrial and ventricular remodeling and hemodynamic deterioration. Atrial dilatation increases the incidence of supraventricular arrhythmias such as atrial fibrillation and flutter that need to be addressed before and after closure of these defects. Chronic right atrial (RA) and ventricular volume overload may lead to adverse remodeling, tricuspid valve regurgitation and progressive pulmonary hypertension that will lead to advanced right-heart failure and, in some cases, to a contraindication for correction of the defect. Elderly patients tend to have reduced diastolic elasticity of the left ventricle, which is age-related, and can be complicated by certain comorbidities such as hypertension, ischemic heart disease and renal disease. This will result in high left ventricular (LV) and restrictive filling pressures. ASD provides a decompressive interatrial communication in this hemodynamic setting, and closing this pop-off valve without preprocedural management and meticulous follow up can lead to severe clinical consequences including acute pulmonary edema and prolonged mechanical and inotropic support. Ewert et al5 examined the hemodynamic changes that occurred after temporary balloon occlusion of a secundum ASD in 18 patients older than 60 years of age. In 7 patients, they observed a marked increase in left atrial pressure and an E/A ratio of the mitral valve. One patient with only a moderate increase in left atrial pressure in whom the decision was made to close the defect using an Amplatzer septal occluder (ASO) developed pulmonary edema and required mechanical as well as inotropic support after the procedure.
ProcedureSince the first attempt in 1976 by King and Mills,6 transcatheter closure of secundum ASD has evolved in the past three decades, with significant advances in device technology and imaging techniques.
Closure DevicesSeveral different devices are being used today to close ASDs. The only two United States FDA-approved devices are the Amplatzer septal occluder (ASO) (AGA Medical Corp., Plymouth, Minnesota) and the Gore Helex device (WL Gore & Associates, Flag Staff, Arizona). Other devices in addition to the above that are being used outside the U.S. include the CardioSEAL™ and STARflex® devices (Nitinol Medical Technologies, Inc., Boston, Massachusetts), the Figulla-Occlutech septal occluder (Occlutech GmbH, Jena, Germany), and the Cardia Atriasept device (Cardia Inc., Eagan, Minnesota), and there are many copy-cat Amplatzer ASD devices manufactured in China. The ASO is a self-expanding and self-centering device that consists of two expandable round discs with a 4 mm long connecting waist. Polyester mesh is added to the left and RA discs and the connecting waist to enhance thrombogenecity. The device size is dictated by the diameter of its waist and is available in various sizes ranging from 4–40 mm. The 40 mm model is not approved in the United States. The delivery system consists of a cable, loader, Mullins-type delivery sheath (6–12 Fr) and a pin vise. The published data indicate high closure success rates.2,7–9
TechniquePatients should receive aspirin 81 mg daily 48 hours prior to the procedure and should be continued on aspirin for 6 months after the procedure. In addition, some operators add clopidogrel 75 mg per day for 2–3 months post closure. Antibiotic prophylaxis (cephalexin), one dose during, and two after closure, are usually given. Patients should be adequately anticoagulated with unfractionated heparin (activated clotting time [ACT] > 200 seconds) before device placement. One or two venous sheaths (6–8 Fr) are placed if the procedure is performed under intra-cardiac echocardiographic (ICE) guidance. Complete hemodynamic evaluation should be performed in all patients, with emphasis on measurement of the pulmonary capillary wedge pressure, pulmonary artery pressure and measurement of left atrial pressure at baseline. Calculation of the shunt ratio as well as pulmonary vascular resistance is very important in such patients. We believe that adult patients with poor transthoracic echocardiographic (TTE) windows should have undergone full transesophageal echocardiographic (TEE) evaluation to assess the suitability of the ASD for device closure and to exclude the presence of an anomalous pulmonary vein connection. The presence of adequate rims (> 5 mm) surrounding the defect cannot be overemphasized. The least important rim is the anterior (retro-aortic) rim which in many patients measures (AGA Medical or NuMED sizing balloon [NuMED Inc., Hokinton, New York]) is introduced over an extra-stiff guidewire positioned in the left upper pulmonary vein. This should be performed under both fluoroscopic and echocardiographic guidance. While the balloon is across the defect, it is inflated with a mixture of saline and contrast until cessation of flow from left-to-right occurs, as seen by echocardiography. Once there is cessation, a freeze-frame is chosen by echocardiography and cine fluoroscopy and the diameter of the balloon is measured. We usually choose a device 0–2 mm larger than this diameter. However, in the elderly patient with a baseline left atrial pressure > 15 mmHg, temporary balloon occlusion of the defect as described above should be performed for 10–15 minutes. The left atrial pressure is measured using the endhole of the balloon catheter after removal of the guidewire at the end of the 10–15 minutes or measure the pulmonary capillary wedge pressure using a separate catheter. If the baseline mean left atrial or mean wedge pressure increases by more than 5 mmHg, the decision to close the defect permanently with a device is revised. In such patients with increased pressure, the procedure should be halted and the patient should be returned to the ward for further management. Patients should be treated with afterload-reducing agents as well as diuretic therapy for 1–2 weeks. At the end of this period, the patient should be brought back to the catheterization laboratory and the above step is repeated. If the baseline pressure does not increase by more than 5 mmHg, permanent closure of the defect can be carried out. However, if the baseline pressure still increases by more than 5 mmHg, a fenestrated device (small hole in the center of the device) should be used. Unfortunately, such fenestrated devices are not available commercially, so we self-fabricate them in our laboratory, as was illustrated in a case that we reported previously.10 After balloon sizing, and if the decision has been made to proceed with permanent closure of the defect, the appropriate-sized device is chosen as above. For the ASO, we choose a device 0–2 mm larger than this diameter, and for the Helex device, we choose a device that is 1.6 to 2 times this size. Leaving the guidewire in place, the appropriate-sized delivery sheath is advanced over the wire to the left upper pulmonary vein. To minimize the risk of air embolism, we fix the dilator and wire and advance the sheath over the wire once the tip of the sheath is at the RA-inferior vena cava junction. The tip of the sheath is advanced all the way into the entrance of the pulmonary vein. The delivery sheath proximally is positioned lower than the patient’s left atrium (between the legs) while removing the dilator and guidewire. Usually there is free flow-back of blood to ensure that there are no air bubbles in the system. After that, the appropriate-sized device is chosen and loaded and advanced under both fluoroscopic and echocardiographic guidance to the tip of the sheath. The left atrial disc is deployed deep into the left atrium; the remaining steps have been reported previously.7 Figures 1 and 2 illustrate the intracardiac and angiographic images of the closure of a secundum ASD in a 68-year old patient with a large secundum ASD. Patients are usually observed overnight and discharged home the following day. All patients should receive infective endocarditis prophylaxis when needed for a total of 6 months after device placement.
Indications for ClosureTable 1 summarizes the indications and contraindications for secundum ASD transcatheter closure. Sizable, significant secundum ASDs, as defined in Table 1, are associated with significant morbidity and mortality. Correction of the defect should be done electively soon after the diagnosis is established to minimize the incidence of age-related complications such as right ventricular (RV) failure, pulmonary hypertension, thromboembolic complications and atrial tachyarrhythmias.4,7,11 Studies in patients > 40 years of age have shown that even asymptomatic patients should have their defects closed to avoid the increased risks of severe disability and death.12 One of the controversial areas of debate is whether it is safe to close the defect when there is evidence of significant LV diastolic dysfunction. We reported on the case of an 85-year-old patient with hypertension and a 6-month history of symptoms suggestive of congestive heart failure.10 He was found to have a moderately large secundum ASD. Hemodynamic evaluation documented an increase in his left atrial pressure from a mean of 12 mmHg to a mean of 32 mmHg after balloon test occlusion of the ASD. Two months later, after adequate pretreatment with diuretics and afterload-reducing agents, he underwent successful closure of the ASD using a self-fabricated fenestrated ASO device, which resulted in mean post-implantation left atrial pressure of 18 mmHg. His recovery was unremarkable and the fenestration has remained patent for 3 months since implantation of the device. This unique case highlights the importance of meticulous preprocedure assessment of elderly patients for suitability of ASD device closure, and the feasibility of using a self-fabricated fenestrated ASO device to close interatrial communications in elderly patients with diastolic dysfunction of the left ventricle.
Surgical versus Transcatheter ClosureSurgical closure of ASDs has been practiced for many decades. The increased rate of morbidity with surgical closure, the prolonged hospital stay and the advances in closure device technology have allowed the emergence of transcatheter closure of secundum ASDs as the standard of care in most patients with appropriate defects. Harjula et al reported an operative mortality rate of 6% and a postoperative morbidity rate of 24% in the form of major complications in elderly patients > 60 years of age.13 In another study, the hospital stay after surgical repair of ASDs in patients > 60 years of age ranged from 8–20 days (average 11 days).14 There have been many clinical studies that compared transcatheter closure with historical surgical series.7,8,15,16 In a multicenter controlled study, Du et al demonstrated the efficacy, clinical utility and safety of ASOs for closure of secundum ASDs compared with concurrent surgical closure results.2 A total of 442 patients underwent device closure, whereas 154 patients were in the surgical group. The early, primary and secondary efficacy success rates for surgical versus device closure of ASDs were not statistically different, however, the complication rate was 7.2% for the device group and 24.0% for the surgical group (p 60 years of age using the ASO device.17 A total of 41 patients with indications for ASD closure underwent an attempt of transcatheter device closure using the ASO. The median Qp/Qs ratio was 2.3 (range 1–7.5). The median mean pulmonary artery pressure was 26 mmHg (range 11–52 mmHg). The median size of the ASD as measured by ICE (n = 38) or TEE (n = 3) was 18.9 mm (range 8–40 mm), and the median balloon-stretched (stop-flow technique) diameter (n = 32) was 23.5 mm (range 12–40 mm). The procedure was successful in all patients. Forty-four devices were deployed in the 41 patients (3 patients received 2 devices each). A 6 mm fenestration was created in a 30 mm device that was placed in 2 patients with left ventricle diastolic dysfunction. The median fluoroscopy time was 10 minutes (range 4–24.8 minutes), and the median procedure time was 60 minutes (range 26–110 minutes). Complications encountered during or within 24 hours after the procedure included: hematoma at the site of catheter insertion in 4 patients, small pericardial effusion in 5, and in 1 patient, the pacemaker lead was dislodged requiring reimplantation. Two patients did not return for follow up and 4 patients were known to have expired for reasons unrelated to their ASD closure. At a median interval of 6 months after closure, the RV end-diastolic dimension decreased from 38.9 ± 9 mm preprocedure to 26.6 ± 7 mm (p Anticipated Benefits of Transcatheter Closure of Atrial Septal Defect The following benefits of transcatheter closure of ASDs have been reported:
1. Improved New York Heart Association (NYHA) Functional Class, dyspnea index and maximal oxygen consumption.17–19 Improvement after transcatheter closure is evident 6 months after closure due to faster recovery time after device implantation, whereas improvement takes longer after surgical correction. Also, increased morbidity is associated with thoracotomy and cardiopulmonary bypass. 2. Improvements in RV and LV function, assessed by the Myocardial Performance Index (MPI), and reduction of left atrial (LA) size.20 Eidem et al demonstrated that in 16 patients who underwent surgical closure of ASDs, the preoperative RV MPI was 0.38 ± 0.04. Postoperative assessment revealed an RV MPI of 0.35 ± 0.03, which was not a statistically significant change from the preoperative state.21 The lack of reduction in RV MPI could be related to cardiopulmonary bypass that may negate any gain in the RV function from ASD closure, and perhaps impaired RV function as demonstrated in previous studies.22,23 3. Prevention and reversal of RV adverse remodeling, with reduction in RV mass, which will lead to the prevention of RV heart failure, a reduction in pulmonary hypertension and subsequent improvement in quality of life.4,7,11,20,24 Schoen et al reported on 20 patients with secundum ASDs who underwent transcatheter closure, with pre- and post-procedure MRI (6 and 12 months) performed to evaluate the effect of device closure on RV remodeling and function.24 There were statistically significant improvements in RV end-systolic volume (from 81 to 53 ml; p Complications The complications of the procedure depend on the level of experience of the operator, the type of device used and the anatomical characteristics of the ASD.
1. Thrombus formation on the device. Most commonly related to the CardioSEAL device (NMT Medical, Boston, Massachusetts) in the first few months. 2. Device migration or embolization is quite infrequent, is not associated with any reported deaths, and the device can be retrieved in the catheterization laboratory or operating room. 3. Residual shunts. Mostly are small, hemodynamically insignificant, and usually close spontaneously on follow-up. 4. Increase in left atrial pressure and pulmonary venous congestion in elderly patients with advanced LV diastolic and restrictive function. This can be avoided by meticulous pre and post-procedure assessment and management as described above. 5. Rarely, patients might have late complication of mitral valve dysfunction, and obstruction to systemic pulmonary venous pathways. This can be prevented by proper sizing and deployment of the device. 6. Cardiac perforation/erosions are more commonly reported with Amplatzer devices. The incidence of device erosion in the United States was 0.1% based on a review of the registry of complications of ASO devices that was conducted by a panel of interventional cardiologists.26 In all patients who developed hemodynamic compromise after ASO placement, echocardiograms (pre-, intra- and post-procedure), ASD size (nonstretched, stretched), size of the device used, cineangiograms and operative records were reviewed. The findings were compared to the pre-market approval data obtained from FDA-approved clinical trials that were conducted in the U.S. before the device was approved. A total of 28 cases (14 in the U.S.) of adverse events were reported to AGA Medical. All erosions occurred at the dome of the atria near the aortic root. A deficient aortic rim was seen in 89% and the defect was described as a high ASD, suggesting a deficient superior rim. The device-to-unstretched ASD ratio was significantly larger in the adverse event group when compared to the FDA trial group. The authors’ recommendations were:
• Avoid overstretching the balloon when balloon sizing the defect; • Use stop-flow technique (as described above) for maximum inflation of sizing balloon; • Be gentle when performing the Minnesota Wiggle, while the device is still attached to the delivery cable; • Patients with small pericardial effusions at 24 hours should have closer follow up; • Identify high-risk patients who will require closer follow up: - Patients with a deficient aortic rim and/or superior rim; - Patients who require a larger ASO (> 1.5 times) than the native diameter of the ASD; - Patients who develop small pericardial effusions at 24- hour follow up. - Patients with deformation of the ASO at the aortic root: * Mandatory 24-hour follow up for all patients; * Patient education about the risks of sudden-onset of symptoms and the need for echocardiography when this occurs.
FutureIn addition to the implantable devices, other technologies being investigated include bioabsorbable devices to minimize the amount of metals left in the heart and a transcatheter patch technique that will enable the closure of defects with absent rims.
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