Autopsy Findings of Amplatzer Septal Occluder at 5 Months After Closure of Atrial Septal Defect: How Long Does it Take to be Endothelialized

ABSTRACT: An 83-year-old man died of aspiration pneumonia 5 months after closure of atrial septal defect (ASD) with an Amplatzer atrial septal defect occluder (ASO). At autopsy, the device was scarcely covered by the endothelium. After percutaneous ASD closure, 6-month course of antiplatelet therapy and prophylaxis for endocarditis are recommended. However, the 6-month duration may not be sufficient for some patients. More data are required to clarify how long it takes for the ASO device to be endothelialized in the human body and to determine predictors of poor endothelialization.

J INVASIVE CARDIOL 2013;25(8):E167-E168

Key words: Amplatzer septal occluder, atrial septal defect

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Case Report. An 83-year-old frail gentleman with atrial septal defect (ostium secundum), chronic atrial fibrillation, and bladder cancer was referred to our hospital for transcatheter closure of the defect. The patient was complaining of shortness of breath with minimal exertion and was bedridden. The patient underwent transcatheter closure with a 32 mm Amplatzer septal occluder (ASO) device (AGA Medical) successfully. At the time of implantation, the atrial septal defect (ASD) was completely closed by transesophageal echocardiogram (TEE) evaluation. Seven days and 1 month after the procedure, follow-up transthoracic echocardiogram (TTE) showed complete closure of the ASD. He had been on warfarin for atrial fibrillation, and aspirin 100 mg/day was newly introduced. Two months later, the patient underwent transurethral resection of a bladder tumor. Aspirin was stopped 1 week before the operation, and warfarin was switched to heparin perioperatively. The operation was non-eventful, and the patient was discharged home in stable condition. The patient continued to take aspirin and warfarin. Unfortunately, however, the patient died of aspiration pneumonia 5 months after the closure of the ASD. 

Autopsy was performed, and the ASO device was examined. On gross examination, no thrombi were found on the surface of the device. Both discs were intact without fracture. The polyester patch inside the disc was covered by fibrous tissue, but only a limited part of the metallic mesh was endothelialized (Figure 1). 

Discussion. In animal models, most ASO devices are reported to be endothelialized in 3 months.¹ However, a paucity of data is available for human models. Several authors have reported cases of incomplete endothelialization of the device complicated by endocarditis >6 months after implantation.^2,3 Chessa et al reported a case of no endothelialization found incidentally at valve operation 18 months after ASD closure.⁴ Moreover, Chen et al reported incomplete endothelialization and late dislocation of the device even after 7 years.⁵ On the other hand, a histopathological case report showed complete endothelialization of the device 15 months after implantation.⁶ Although only 5 months had passed after device implantation in our case, almost no endothelialization was identified on the surface of the metallic mesh at autopsy. In our case, old age and relatively poor nutritional state might be related to the poor endothelialization. In addition, although the ASD seemed to be completely closed by cardiac ultrasound, microscopic evaluation was not done. Therefore, it is possible that not all of the rims of the device were in close contact with atrial septal tissue, and that this contributed to incomplete endothelialization of the device. 

Currently, antiplatelet therapy and prophylaxis for endocarditis are recommended for 6 months following device implantation. Typically, aspirin is prescribed at a dose of 3-5 mg/kg daily for children and 81-325 mg daily for adults for 6 months. Clopidogrel (75 mg/day) is sometimes added to aspirin for 1 month following the procedure. However, these therapies may not be sufficient for some patients. In our case, no thrombotic complication occurred under aspirin and warfarin even with a minimally endothelialized device. Therefore, it would be of special interest to find out the significance of complete coverage of the device. More data are needed to clarify the time frame for the ASO device to be endothelialized in the human body and to determine predictors of poor endothelialization.  

References

1. Lock JE, Rome JJ, Davis R, et al. Transcatheter closure of atrial septal defects. Experiment studies. Circulation. 1989;79(5):1091-1099.
2. Images in cardiovascular medicine. Slensick TC, Nugent AW, Fraser CD Jr, Cannon BC. Incomplete endothelialization and late development of acute bacterial endocarditis after implantation of an Amplatzer septal occluder device. Circulation. 2008;117(18):326-327.
3. Zahr F, Katz WE, Toyoda Y, Anderson WD. Late bacterial endocarditis of an Amplatzer atrial septal defect occluder device. Am J Cardiol. 2010;105(2):279-280.
4. Chessa M, Butera G, Frigola A, Carminati M. Endothelialization of ASD devices for transcatheter closure: possibility or reality? Int J Cardiol. 2004;97(3):563-564.
5. Chen F, Zhao X, Zheng X, Chen S, Xu R, Qin Y. Incomplete endothelialization and late dislocation after implantation of an Amplatzer septal occluder device. Circulation. 2011;124(6):e188-e189. 
6. Sigler M, Jux C, Ewert P. Histopathological workup of an Amplatzer septal occluder after surgical removal. Pediatr Cardiol. 2006;27(6):775-776.

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From the ¹Department of Cardiology, Keio University School of Medicine, Tokyo, Japan and the ²Department of Pathology, Kyorin University School of Medicine, Tokyo, Japan.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript submitted November 21, 2012, provisional acceptance given December 21, 2012, final version accepted February 25, 2013.

Address for correspondence: Akio Kawamura, MD, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Email: kawamura@cpnet.med.keio.ac.jp