Fig. 9.1
PLAATO device composed of a nitinol collapsible cage structure covered with ePTFE. The device is shown in the lateral view (a) and frontal view (b). Adapted from Nakai et al. [14] with permission from Circulation
Preclinical Studies
The seminal proof of principle study was completed at the University of California, San Francisco [14]. This study was the first demonstration that a LAA occlusion device could be successfully implanted into the LAA with endothelialization of the PLAATO device (Fig. 9.2). The study objectives were to demonstrate feasibility, safety, and healing characteristics of the percutaneous transseptal delivery of the PLAATO device to occlude the LAA.
Fig. 9.2
Preclinical postmortem analysis. The top panel of figures are the gross anatomy at 1 and 3 months, demonstrating the snug fit of the implant into the LAA orifice. Adapted from Nakai et al. [14] with permission from Circulation
Twenty-five dogs underwent successful implantation of the PLAATO device into the LAA. Conformation of proper placement of the PLAATO device was confirmed with both LA angiography and intracardiac echocardiography. There were no complications associated with the implant of the device with the exception of a small pericardial effusion that did not need treatment. Animals were sacrificed for histological examination on day 2, 2 weeks, 1 and 3 months. In one animal, there was evidence of a small perforation of the tissue anchor with no other abnormality noted. At 1 and 3 months, there was complete closure of the LAA with demonstration of endothelialization of the atrial surface of the implant (Fig. 9.3). It was concluded that the LAA occlusion with the PLAATO device was feasible, safe, and led to complete sealing of the LAA.
Fig. 9.3
Confirmation of PLAATO positioning within the LAA. Contrast fluoroscopy is shown in the left panel. The initial LA angiogram delineating the LAA (a) and after the implantation of PLAATO device (b) demonstrating complete occlusion of the LAA. Corroboration of the contrast fluoroscopy is provided by TEE imaging. The top upper left figure (c) is the pre-implant image of the LAA. (d) It is the visualization of the PLAATO device seated in the LAA. (e, f) Shows the same TEE views 1 and 6 months after the implantation. Adapted from Nakai et al. [24] with permission from Pacing Clin Electrophysiology
Clinical Results
Based on the favorable preclinical studies, Horst Sievert performed the first LAA occlusion intervention in man in August, 2001. The early clinical experience was reported by Sievert and colleagues in 15 patients with chronic AF at high risk for stroke, who were poor candidates for long-term warfarin therapy [15]. The PLAATO device was successfully implanted in all 15 patients with only one non-device complication of hemopericardium resulting from LAA access. LA angiography and TEE were typically used to confirm the PLAATO device sealing the LAA (Fig. 9.4). The authors concluded that the PLAATO was feasible and safe to occlude the LAA.
Fig. 9.4
Postmortem analysis from a patient with AF. TEE imaging (a) demonstrating a well-seated PLAATO device in the LAA. Gross anatomy dissection showing the PLAATO device occluding the LAA (b) covered by endothelium (c). Adapted from Omram et al. [21] with permission from Journal of Interventional Cardiac Electrophysiology
The initial multicenter observational study was the International Multi-Center Feasibility Trials that assessed the primary end point of incidence of major adverse events (MAEs), a composite of stroke, cardiac or neurological death, myocardial infarction, and requirement for procedure-related cardiovascular surgery within the first month [16]. This study was performed in 111 patients with a contraindication for anticoagulation therapy and at least one additional risk factor for stroke. Following PLAATO implantation into the LAA, patients were treated with ASA or ASA plus clopidogrel. The PLAATO device was successfully implanted in 108 of 111 patients (97 %). During the first 30 days, there were 3 patients with hemopericardium requiring surgery and 1 patient that needed cardiovascular surgery and eventually expired. No thrombi were noted on TEE at 1 and 6 months. However, there were 2 patients sustaining strokes and 3 patients with TIAs. The observed annual stroke rate was 2.2 %, but did not include the TIAs that would have brought the neurological event rate to 5.5 %.
In a subsequent follow-up European PLAATO study, LAA occlusion was successful in 162/180 patients (90 %) [17]. There were 2 procedural deaths (1.1 %), 6 cardiac tamponades with 2 requiring surgical drainage (3.3 %), and 1 device embolization (0.6 %). Three strokes occurred (2.9 %) which was lower than the CHADS2 score predicted 6.6 % per year. The study was stopped prematurely due to financial considerations.
There have been several other small single center or multicenter observational studies suggesting the benefits of LAA occlusion in preventing strokes with acceptable adverse events [18–21]. The annual event rate of stroke ranged from no strokes during a 2-year follow-up of 73 PLAATO implanted patients to 3.8 % annual stroke/TIA rate after a 5-year follow-up period [18, 19]. All of the studies had small number of patients with no independent adjudication or monitoring. In general, only antiplatelet therapy was used after the LAA implantation of the PLAATO device, supporting the notion that an implant could potentially be used in patients with contraindications to oral anticoagulation therapy.
Postmortem Analysis of the PLAATO Device
Postmortem analysis of the PLAATO device has demonstrated both the desired effect and potential concerns with any LAA occlusion device (Fig. 9.5). The design of the PLAATO device incorporated ePTFE to allow for healing and occlusion of the LAA. A postmortem analysis of the PLAATO device 1 year after implantation demonstrated that the atrial surface of the device was completely covered by neo-endothelium and the device occludes the appendage completely [21]. This finding corroborated the preclinical studies that also demonstrated a complete endothelial layer over the device. In contrast, a different postmortem analysis of a PLAATO device implanted for 2 years demonstrated thrombotic deposition on the atrial-side surface of the PLAATO system [22]. The patient did not experience any embolic events, but the detection of thrombotic deposition on the atrial surface of the device presents the potential for future thromboembolic events.
