Transcatheter Device Closure of Atrial Septal Defects in Patients
Older than 60 Years of Age: Immediate and Follow-Up Results

Percutaneous closure of atrial septal defects (ASDs) is a safe procedure and has been routinely performed in many centers around the world as an alternative to surgical closure.^1–5 However, in elderly patients with ASD, prolonged left-to-right shunt results in right ventricular volume overload and subsequent pulmonary artery hypertension. Several reports demonstrated the benefits of ASD closure in adults such as the prevention of ongoing congestive heart failure from volume overload, a reduction in pulmonary artery pressure and improvement in symptoms and quality of life.^3–6 However, it is unclear if device closure is a safe and effective treatment in elderly patients (age > 60 years). In this study, we report our results with ASD closure in patients > 60 years of age using the Amplatzer Septal Occluder (ASO) device (AGA Medical Corp., Golden Valley, Minnesota). We previously reported on a cohort of patients > 40 years of age who underwent device closure of their ASD³ until January 2005; since then, an additional 15 patients > 60 years of age have undergone ASD closure. This paper reports specifically on older patients (> 60 years of age) who underwent ASD closure with a longer follow-up period.

Methods
Study population. This was a retrospective study of all patients over 60 years of age who underwent an attempt at device closure of their secundum ASD using the ASO at a single tertiary referral center between September 1999 and March 2007. Forty-one patients (24 females; 17 males) at a median age of 71 years (range 62–87 years) and a median weight of 70 kg (range 50–115.8 kg) underwent attempted device closure of their defects. Indications for ASD closure were: hemodynamically significant secundum ASD < 40 mm in diameter with adequate rims (> 5 mm in length, except the anterior [retro-aortic] which was the least important for the Amplatzer device), and right ventricular enlargement and/or clinically symptomatic patients. The medical records of all patients were retrospectively reviewed. The Institutional Review Board reviewed and approved the study. Patients who had evidence of patent foramen ovale or partial anomalous pulmonary venous drainage and/or an ASD size > 40 mm were excluded.
Device closure procedure. The ASO was used in all patients. The description of the ASO and its delivery system have been reported previously.^7,8
From September 1999 to August 2000, all procedures were performed under endotracheal intubation and general anesthesia with transesophageal echocardiography (TEE) and fluoroscopic guidance. From August 2000 to the present, all procedures were performed under conscious sedation and intracardiac echocardiography (ICE) and fluoroscopic guidance. Baseline hemodynamic assessment was performed in every patient prior to closure. If the mean left atrial pressure at baseline was > 18 mmHg, a temporary balloon occlusion (15 minutes) of the ASD was performed, then the left atrial pressure was recorded using the distal tip of the balloon catheter after removing the guidewire. If the mean left atrial pressure increased by > 5 mmHg from baseline, the procedure was abandoned and the patient was sent back to the ward for afterload-reducing agent and diuretic therapy for several days. The patient was then brought back and the same technique was employed. If the mean left atrial pressure did not change by > 5 mmHg, then the ASD was closed completely; however, if the pressure increased by > 5 mmHg, a fenestration was created in the device and the device was deployed according to a protocol described previously.^7,9 One dose of cephalexin was administered during the procedure and 2 doses were administered 8 hours apart after the procedure. Aspirin (81 mg) was started 48 hours before the procedure and continued for 6 months. In addition to aspirin, clopidogrel 75 mg per day was added in the last 3 years for a 2-month period postclosure. This was done in an effort to reduce the incidence of headaches associated with device closure. Subacute bacterial endocarditis precautions were observed for 6 months after the procedure until complete closure was documented.
Follow up. Patient history and physical examination, electrocardiography and transthoracic echocardiography (TTE) were performed 24 hours after the procedure, at 6 months and yearly thereafter to assess symptoms and to look for any complications and residual shunt. The residual shunt was defined as a leak traversing or passing between the 2 discs of the ASO or around the device edges to the right atrium and detected by two-dimensional color-flow Doppler. The residual shunt was classified according to the color-jet width described by Boutin and her colleagues¹⁰ as trace < 1 mm, small > 1 mm and < 2 mm, moderate > 2 mm and < 4 mm, and large if > 4 mm.
Statistics. Results are presented as median and range. Differences between parameters pre- and postclosure were compared using the Student’s t-test. Values were considered significantly different when p-values were < 0.05. In patients with multiple ASDs, the largest defect size was used for analysis.

Results
Thirty-eight patients had single ASDs and 3 patients had multiple ASDs. The hemodynamic data and related conditions obtained in the catheterization laboratory are listed in Table 1.

A single device was placed in 38 patients (93%). Three patients (7%) with multiple defects had 2 devices placed in the same procedure. The smaller device was first deployed and sequential release of the devices was performed starting with the smaller device so that 2 devices were overlapping each other.^11,12 The median size of ASDs as measured by ICE (n = 38) or TEE (n = 3) was 18.9 mm (range, 8–40 mm), and the median ASD balloon-stretched diameter (stop-flow technique) (n = 32) was 23.5 mm (range, 12–40 mm). The median mean pulmonary artery pressure was 26 mmHg (range 11–52 mmHg). The median Qp:Qs ratio as calculated using the Fick principle¹³ was 2.3:1 (range 1–7.5:1) The median device size used for all patients was 24 mm (range 12–40 mm). The 40 mm ASO was successfully used for ASD closure in 2 patients with large defects during the U.S. Food and Drug Administration (FDA)-sponsored clinical trial. A fenestrated ASO was placed in 2 patients (5%) and a small fenestration (6 mm) was left open in 2 patients (5%) to serve as a protective interatrial communication, reducing the left ventricular preload by left-to-right shunt and preventing the development of pulmonary edema.
Pulmonary artery hypertension (mean > 20 mmHg) was present in 23 patients (56%). Six patients had significant pulmonary hypertension (mean pulmonary artery pressure was > 40 mmHg); of these, 5 had complete closure of the ASD without any events, and a small defect was left open in the sixth patient due to evidence of left ventricular diastolic dysfunction.
Complications encountered during or within 24 hours from the procedure included: hematoma at the site of venous puncture occurred in 4 patients, with no long-term sequelae; a small pericardial effusion in 5 patients requiring observation only, and in 1 patient, the pacemaker lead was dislodged and required reimplantation.
The time course of residual atrial shunt disappearance after ASO placement is represented in Table 2. The complete closure rate as assessed by ICE or TEE immediately after the procedure was 82%. In this assessment, immediately after closure, 2 patients who had a fenestration created (96 mm) were excluded from the analysis. This left 32 patients with complete closure, 3 with a trivial shunt, 3 with a small residual shunt, and 1 with a moderate residual shunt. However, as assessed by transthoracic echocardiography (TTE) at 24 hours and 6–24 months from closure, the complete closure rate was 82% and 97%, respectively. Two patients were judged by ICE to have a trivial shunt, and TTE showed that the residual shunt was small. Two patients did not return for follow up and 4 patients were known to have expired for reasons unrelated to ASD closure (1 due to chronic liver disease, 1 due to ischemic heart disease and 2 because of a severe cardiovascular comorbidities). Device closure was associated with a statistically significant decrease in the right ventricular end-diastolic dimension (RVEDD) as measured by TTE in the short-axis view. The median RVEDD decreased from 38.9 mm (range, 20–55)[n-37] before ASD closure to 26.6 mm (range 14–38) at a median interval of 6 months (p < 0.001, n = 31). The RVEDDs for the 4 patients who expired were not included in the analysis preclosure or postclosure. Therefore, we believe that the reduction represents a real decrease in the individual measurement. Furthermore, 4 patients did not undergo measurement of their right ventricle at the time of their follow-up visit (Figure 1). The mean ± standard deviation (SD) follow-up interval was 28 ± 23.7 months (range 6–79 months). New York Heart Association functional classification was used to assess symptoms (Table 3). The majority of the patients showed improvement in their symptoms during follow up. One patient in NYHA cardiac function class III who had a moderately large ASD with reduced left ventricular diastolic elasticity underwent successful ASD closure using a fenestrated ASO and subsequently improved by 1 functional class during follow up. However, he developed acute congestive heart failure 6 years after his ASD closure due to elevated blood pressure. Atrial arrhythmias were documented in 24 of 41 patients (59%) before ASD closure and in 5 of 41 patients (12%) following the interventional procedure. Of the former group, 13 patients had atrial fibrillation or flutter; 3 of whom were successfully treated by radiofrequency ablation before ASD closure, and the remainder of whom were managed with antiarrhythmic medications. Only 1 patient had new onset of persistent atrial fibrillation during follow up 4 years after ASD closure.

One patient was noted to have a femoral pseudoaneurysm at 1 year follow up that required surgical repair. However, this patient underwent another cardiac catheterization 2 weeks prior to the closure procedure, thus we were unable to determine which procedure was implicated. At the latest follow up, none of the patients had developed any other complication.

Discussion
Transcatheter closure of secundum ASDs with ASO implantation in pediatric and adult patients has a high success rate and excellent results that have been documented in several studies.1–5 However, little data are available about the results of this procedure in the elderly population (> 60 years of age) with prolonged shunts. We have previously published our own results in 113 patients over the age of 40 years3 who underwent device closure of their ASDs. Since publication of that paper, an additional 15 patients over the age of 60 years underwent closure of their defects at our center.
This retrospective study was performed to determine the immediate- and short-term effects of ASD closure with ASO on symptoms, RVEDD, and to identify associated complications. The procedure was successful in all patients with minimal complications, and a complete ASD closure rate of 97% at follow up in 34 of 41 patients who continued regular clinic visits and did not have a fenestrated device.
From this study, a statistically significant decrease in right ventricular size has been documented in the short term after ASD closure in elderly patients. The loss of a decompressive ASD can result in serious acute effects on left heart hemodynamics which have been reported after surgical repair of ASDs.¹⁴ In elderly patients, the possible explanation of this pathophysiologic mechanism is evidence of restrictive left ventricular diastolic dysfunction that results in left atrial hypertension and subsequent pulmonary edema.¹⁵ The ASD serves as a protective interatrial communication reducing the left ventricular preload by left-toright shunting. Therefore, a fenestrated ASO was placed in 2 patients and a small defect was left open in 2 other patients who had multiple ASDs. Therefore, careful hemodynamic assessment of elderly patients with moderate-to-large ASDs for this potential left ventricular dysfunction is recommended. We recommend temporary balloon occlusion of the defect in any patient with a baseline left atrial pressure ≥ 18 mmHg for 15–20 minutes, then left atrial pressure measurement using the end-hole of the balloon catheter after removing the wire. If the pressure increases by more than 5 mmHg, then our recommendation is to either pretreat with diuretics and afterload-reducing agents if the patient was not receiving such medications, or to close the defect leaving a small fenestration as we described previously.¹⁶ We choose 18 mmHg as a cutoff to test for left ventricular dysfunction. In adults, the left atrial pressure normally should be < 15 mmHg.
In this study, we used ICE in 38 out of 41 of the patients. The right femoral vein was punctured in 2 separate sites, 1 for the ICE catheter and the other for the device delivery. The Acu- Nav 10.5 Fr catheter (Acuson, a Siemens Company, Mountain View, California) was used for imaging without any complication. ICE should replace TEE as an imaging guidance tool for ASD and PFO device closure, thus eliminating the need for endotracheal intubation and general anesthesia, as we previously reported.^17,18 For multiple ASD closure, the left femoral vein was also punctured for a second device implantation. Thirty-five patients were followed for a median interval of 2 years, and of these, 31 (89%) improved by at least 1 NYHA functional class, and 4 remained in NYHA class I. Two patients who were in NYHA class IV before device closure had significant comorbidities including ischemic heart disease, hypertension, cor pulmonale and ventricular arrhythmia. Both patients died because of severe cardiovascular comorbidities 1 and 6 months after ASD closure.
Our study results demonstrate that device closure of ASDs in the elderly is technically easy, safe and effective with minimal complications. We did not encounter any serious complications such as erosion, device migration, thrombus formation and embolic events during the procedure or at follow up. Surgical repair of ASDs in patients > 60 years of age results in significant mortality and morbidity. Harjula et al¹⁹ reported an operative mortality rate of 6% and a postoperative morbidity rate of 24% in the form of major complications. 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).²⁰ On the other hand, device closure of ASDs has a low morbidity rate and shorter hospital stays compared to postoperative surgical complications and admission to the intensive care unit.¹ Morbidity is related to the possible risks of blood transfusions required for surgery, which were not required in our patients undergoing percutaneous ASD closure. However, there have been no reports comparing results, closure rates, morbidity rates and complications of transcatheter and surgical closure of ASDs at the same institution among patients > 60 years of age.
In this study, 32% of the patients had documented atrial fibrillation or flutter prior to ASD closure. Device closure did not influence cardiac rhythm in any patient in chronic atrial fibrillation or flutter. The occurrence of arrhythmias in this population could be explained by prolonged right atrial dilatation caused by an interatrial shunt that results in structural changes and the presence of arrhythmogenic foci in the region of the pulmonary veins and vena caval junctions.^21,22
Study limitations. Limitations to our study include its retrospective nature and the inherent biases in such studies. Furthermore, 4 patients did not undergo right ventricular size measurement at their follow-up visit.

Conclusion
The immediate high success rate and follow-up results of our study demonstrate the safety and feasibility of ASO use for ASD closure in elderly patients. Right-heart remodeling can occur in patients > 60 years of age after device closure of an ASD.

References

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