A History of Left Atrial Appendage Occlusion.

A new era in antiembolic therapy has been initiated by the growing numbers of device-based therapies. Early concerns surrounding eliminating this enigmatic structure have not proven true. Other benefits are being further evaluated. Many other questions remain, such as whether there is a device-specific outcome effect or whether it is a class effect. Other questions include other devices, what head-to-head studies will show, and the impact of residual leak. Left atrial appendage using the Watchman ablation strategy can reduce cardioembolic stroke, with comparable or fewer adverse effects by device technology than obtained by long-term anticoagulation with its attendant bleeding risks.

Left atrial appendage obliteration: mechanisms of healing and intracardiac integration.

OBJECTIVES: 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.

Is the left atrial appendage more than a simple appendage?

The left atrial appendage (LAA) is a cardiac structure with unique anatomic and functional features. It is significantly more than a simple chamber appended to the left atrium (LA), differing from the LA in structure, function, and hormonal activity. Unfortunately, it is the source of more than 90% of cardiac-based emboli, particularly in atrial fibrillation, mandating lifelong anticoagulation. Percutaneous LAA exclusion was developed to limit or eliminate cardioembolic events in patients with atrial fibrillation. Benign healing of the appendage occurs without adverse hemodynamic effects, and with no residual surface thrombus or tissue damage. The feasibility of this treatment is now established, suggesting that percutaneous therapy is safe, practical and possibly effective to eliminate the need for anticoagulation and significantly reduce cardioembolic events.

Patent foramen ovale closure by radiofrequency thermal coaptation: first experience in the porcine model and healing mechanisms over time.

BACKGROUND: Percutaneous transcatheter patent foramen ovale (PFO) closure is now standard practice and may limit embolic complications for at least 10 years. Implantable PFO closure devices may be complicated by thrombosis, infection, device fracture, or embolization. A novel strategy uses radiofrequency-based thermal energy to seal PFO membranes, with no implanted device. We successfully used this method and examined histopathologic events in swine to characterize safety and efficacy. METHODS AND RESULTS: Thirteen domestic swine were examined over time after thermal PFO closure. Three animals were euthanized within 1 hour of treatment, 5 after 7 days, and 5 at 28 days. Gross and histopathologic findings were examined. Radiofrequency energy was delivered successfully in all cases, and PFOs were closed in 12 of 13 cases. One case was not suitable for histological examination because of laceration at euthanasia, and the other PFO was clinically closed, with no shunt at 7 days, but was histologically open. All of the other PFOs were confirmed closed histologically. Acute histological results showed edema, hemorrhage, and myocyte necrosis. Minimal thrombus formation occurred on the left atrial endocardial surface. At day 7, transmural thermal effects occurred through the atrial wall that extended to the epicardial surface. At day 28, thermal effects showed excellent scar formation. Collagen, matrix, and neovascularization were present in all cases. No animal experienced adverse events. CONCLUSIONS: Thermal PFO closure is feasible, safe, and effective in swine. Thermal healing is nearly complete by 4 weeks and consists of collagen formation and tunnel closure. This technique may allow substantial reduction in PFO closure risk over current device-based therapy.

Feasibility of transcatheter intervention for severe aortic stenosis in patients >or=90 years of age: aortic valvuloplasty revisited.

OBJECTIVES: The goals of this study were to determine the feasibility, safety, and early outcomes of balloon aortic valvuloplasty (BAV) for severe aortic stenosis in a nonagenarian population. BACKGROUND: This very elderly population is expanding rapidly, has a high incidence of aortic stenosis, and uncommonly undergoes surgical aortic valve replacement. These patients may best be treated with a transcatheter approach due to comorbidities, surgical risk, and personal preference. METHODS: We reviewed 31 consecutive patients >or=90 years of age who underwent BAV at our institution from July 2003 to August 2006 for data pertinent to patient characteristics, procedural techniques, and 30-day outcomes. RESULTS: Our patients had a mean age of 93 +/- 3.0 years (90-101). The society of thoracic surgery risk score was 18.5 (+/-10.2) and logistic Euroscore was 35.8 (+/-19.3). Twenty-five patients (81%) underwent retrograde BAV and 6 (19%) antegrade BAV. Five patients (16%) underwent combined BAV and coronary stenting. Overall mean aortic valve area increased from 0.52 cm2 (+/-0.17) to 0.92 cm2 (+/-0.22) and mean New York Heart Association (NYHA) functional class improved from 3.4 to 1.8. Intraprocedural mortality occurred in one patient (3.2%) and 30-day mortality in three patients (9.7%). CONCLUSIONS: BAV can be carried out in high risk nonagenarian patients with an acceptable complication rate, low perioperative mortality, and early improvement in NYHA functional class.

Radiation following percutaneous balloon aortic valvuloplasty to prevent restenosis (RADAR pilot trial).

OBJECTIVES: We wished to determine the feasibility and early safety of external beam radiation therapy (EBRT) used following balloon aortic valvuloplasty (BAV) to prevent restenosis. BACKGROUND: BAV for calcific aortic stenosis (AS) has been largely abandoned because of high restenosis rates, i.e., > 80% at 1 year. Radiation therapy is useful in preventing restenosis following vascular interventions and treating other benign noncardiovascular disorders. METHODS: We conducted a 20-patient, pilot study evaluating EBRT to prevent restenosis following BAV in elderly patients with calcific AS. Total doses ranging from 12-18 Gy were delivered in fractions over a 3-5 day post-op period to the aortic valve. Echocardiography was performed pre and 2 days post-op, 1, 6, and 12 months following BAV. RESULTS: One-year follow-up is completed (age 89 +/- 4). There were no complications related to EBRT. Eight patients died prior to 1 year; 5 of 10 (50%) in the low-dose (12 Gy) group and 3 of 10 (30%) in the high-dose (15-18 Gy) group. None of these 8 patients had restenosis, i.e., > 50% loss of the initial AVA gain, and only three deaths were cardiac in origin. One patient underwent aortic valve replacement and none repeated BAV. By 1 year, 3 of the initial 10 (30%) in the low-dose group and 1 of 9 (11%) in the high-dose group demonstrated restenosis (21% overall). CONCLUSIONS: EBRT following BAV in elderly patients with AS is feasible, free of early complications, and holds promise in reducing the 1 year restenosis rate in a dose-dependent fashion.