Left atrial appendage obliteration: mechanisms of healing and intracardiac integration.
OBJECTIVE
The objectives of this study were: 1) to delineate the temporal course of histopathologic healing as the left atrial appendage (LAA) is obliterated by a mechanical device; and 2) to compare this process with other intravascular and intracardiac implanted technologies.


BACKGROUND
Intracardiac device healing is incompletely understood. We thus studied the histopathology of device-based LAA obliteration.


METHODS
Nine dog hearts were examined over time after LAA device placement and results were compared with human hearts with prior LAA obliteration using the same device.


RESULTS
At 3 days in dogs, atrial surfaces were covered by fibrin, which sealed gaps between the LA wall and the device and filled the LA appendage cavity. At 45 days, endothelial cells covered the endocardial surface with underlying smooth muscle cells that sealed the device-LA interface. Regions with prior thrombus were replaced by endocardium surrounding the device membrane. Disorganized thrombus remained in the LAA body and at the periphery near the appendage walls. Mild inflammation was observed as thrombus resorbed. By 90 days, a complete endocardial lining covered the former LAA ostium. Organizing thrombus had become connective tissue, with no residual inflammation. The human necropsy hearts had similar findings. In these 4 hearts (139, 200, 480, and 852 days after implant), the ostial fabric membrane was covered with endocardium. The appendage surface contained organizing thrombus with minimal inflammation. Organizing fibrous tissue was inside the LAA cavity, prominent near the atrial wall. The LAA interior contained organizing thrombus.


CONCLUSIONS
This intracardiac device integration study delineated healing stages of early thrombus deposition, thrombus organization, inflammation and granulation tissue, final healing by connective tissue, and endocardialization without inflammation. These observations may yield insight into cellular healing processes in other cardiac devices.
Schwartz
Robert S
RS
Minneapolis Heart Institute and Foundation, Minneapolis, Minnesota 55407, USA. rss@rsschwartz.com
Holmes
David R
DR
Van Tassel
Robert A
RA
Hauser
Robert
R
Henry
Timothy D
TD
Mooney
Michael
M
Matthews
Ray
R
Doshi
Shephal
S
Jones
Russell M
RM
Virmani
Renu
R
D000818:Animals; D020517:Atrial Appendage / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D006348:Cardiac Surgical Procedures / Q000295:instrumentation*; D004285:Dogs; D004699:Endocardium / Q000473:pathology; D042783:Endothelial Cells / Q000473:pathology; D005337:Fibrin / Q000378:metabolism; D006097:Granulation Tissue / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000473:pathology; D011474:Prosthesis Design; D013908:Thoracotomy; D013927:Thrombosis / Q000473:pathology; D013997:Time Factors; D014945:Wound Healing
D005337:Fibrin