Left atrial appendage (LAA) closure as a prophylactic strategy for thromboembolic
events in patients with atrial fibrillation (AF) has been performed for decades; initially
during mitral valve repair surgeries
1
and, more recently, in nonvalvular AF patients at high risk of embolism who do not
tolerate the use of oral anticoagulants (OACs).
The idea of LAA occlusion as an alternative to chronic warfarin use emerged from observations
of anatomopathological studies and during cardiac surgery that disclosed the LAA as
the main site of thrombus formation in patients with nonvalvular atrial fibrillation.
2,3
The evolution of cardiac access interventionist techniques, together with the development
of specific prostheses for LAA occlusion, allowed the appendage closure to be performed
percutaneously, using a minimally invasive procedure, making it simpler and not restricted
to patients who would have undergone heart surgery.
The first prosthesis developed for this purpose, called PLAATO, was tested early in
the last decade by Horst Sievert et al.
4
and consisted of a nitinol structure, covered by an expanded polytetrafluoroethylene
(ePTFE) occlusive membrane. The clinical study published in 2002 showed that the concept
of percutaneous LAA occlusion was feasible; however, the prosthesis use was discontinued
in 2005, due to the considerable number of complications such as cardiac tamponade,
residual leaks, prosthesis protrusion towards the atrial cavity and, in some cases,
lack of neo-endothelization of the prosthesis with formation of local thrombi.
5
On the other hand, the experience obtained with the implantation of this prosthesis
was important for the development of more effective devices.
Currently, two prostheses with different profiles are being used in clinical practice:
the Watchman prosthesis sold by Boston Scientific and the Amplatzer Amulet device
(evolution of the Amplatzer Cardiac Plug) sold by ABBOTT. Of these, only the Watchman
prosthesis has been evaluated in two prospective, multicenter, and randomized clinical
trials. The PROTECT-AF study (Watchman Left Atrial Appendage Closure Technology for
Embolic Protection in Patients With Atrial Fibrillation),
6
evaluated the effectiveness and safety of percutaneous LAA occlusion with the Watchman
prosthesis, compared with oral anticoagulation with warfarin in 707 patients (463
in the intervention group) with nonvalvular AF and CHADS2 ≥ 1. The LAA occlusion (3
events per patient-year) met the noninferiority criterion compared to warfarin (4.9
events per patient-year) in the efficacy criterion; however, the LAA occluder implantation
was associated with a higher number of adverse events, especially the occurrence of
hemopericardium (4.8%), which was related to the interventionist’s learning curve
in the prosthesis placement.
Due to safety concerns, the study was repeated (Watchman LAA Closure Device in Patients
With Atrial Fibrillation Versus Long Term Warfarin Therapy - PREVAIL trial)
7
with the same characteristics as the previous one, except for the greater experience
of the operators. A total of 407 patients (269 in the intervention group) were included
and at 18 months of follow-up, efficacy event rates (stroke, systemic embolization,
and cardiovascular or unexplained death) of 0.064 were observed in the intervention
group and 0.063 in the warfarin group, thus not meeting the pre-specified non-inferiority
criteria previously obtained in the PROTEC-AF study, due to the very low number of
events in the control group, a fact not observed in the previous and subsequent studies
using warfarin.
However, the noninferiority criterion was met in the analysis of the second primary
efficacy endpoint related to the event rate after 7 days of randomization. Also positive
was the lower rate of prosthesis implant complications compared with the PROTECT AF
study.
A complicating factor for the clinical implementation of the LAA occlusion strategy
was the emergence of four new direct-acting oral anticoagulants (DOACs), supported
by potent clinical studies showing no inferiority or even superiority of these new
drugs over warfarin in patients with nonvalvular AF.
8,9
Due to the practical use of DOACs, the indication of appendage occlusion devices has
been postponed and considered only in patients who are intolerant to oral anticoagulants,
or in those who experienced embolic events while using these drugs, although the effectiveness
of the device has not been studied in randomized controlled trials.
Therefore, due to this heterogeneity of indications and the lack of randomized controlled
trials, the records have become important. Reddy et al.
10
evaluated 3822 consecutive cases of LAA occluder implantation based on Medicare data,
showing a cardiac tamponade rate of 1.02%, most of them adequately treated with pericardiocentesis;
however, the tamponade resulted in death in three cases. These rates were lower than
those observed in clinical studies, although most devices were implanted by less experienced
operators. Another European registry (EWOLUTION)
11
also demonstrated a low complication rate, showing 34 (3.3%) adverse events among
1021 patients included in the study.
Two Brazilian registries have been recently published and suggested the safety of
appendage occlusion device implantation. Guerios et al.,
12
performed a multicenter registry and evaluated the results of 91 patients with nonvalvular
AF (62% ineligible for anticoagulation) and high risk of stroke (CHA2DS2VASc 4.5 ±
1.5), submitted to the implantation of 96 prostheses, with the ACP (Amplatzer Cardiac
Plug) being implanted in 94.6%. The implant success rate was 97.8%, with 7.2% of complications,
with five pericardial effusions requiring pericardiocentesis, one non-dedicated device
embolization and one gas embolism without sequelae. In this series, during a median
follow-up of 346 days (128.6 patient-years), three non-procedure-related deaths were
observed, as well as five cases of peri-prosthesis leakage, with thrombus formation
next to the prosthesis in two, resolved with the return of anticoagulation and only
two patients had stroke at the follow-up.
In the second registry, Marcio Costa et al.,
13
evaluated 15 patients with nonvalvular AF and high risk of bleeding, submitted to
implantation of the ACP prosthesis. In this small series, the procedure was successfully
performed in all cases with no reports of hemopericardium or prosthesis displacement.
In this issue of the Brazilian Archives of Cardiology, Şahiner et al.
14
disclose retrospective data from a center in Turkey, which included 60 patients submitted
to implantation of the Amplatzer Amulet device. The main indication for the procedure
was the occurrence of bleeding (usually gastrointestinal) in the presence of oral
anticoagulation. The authors demonstrated that the implantation procedure was successful
and safe in most patients. One patient had pulmonary artery rupture due to a probable
direct injury by the prosthesis struts. In most patients, antiplatelet therapy consisted
of ASA (100 mg) and clopidogrel (75 mg) for 6 months after the procedure, being maintained
on single therapy after transesophageal echocardiography demonstrated the absence
of periprosthetic leaks or thrombi. During a mean follow-up of 21 ± 15 months, none
of the patients had a stroke but two patients had clinical symptoms of transient ischemic
attack.
Thus, due to the lack of robust evidence, the most recent guideline on atrial fibrillation
recommends the implantation of appendage occlusion devices as a IIb indication, level
of evidence B-NR, in patients with non-valvular AF at high risk for stroke and with
contraindications for long-term oral anticoagulation use.
8
An ongoing randomized trial (ASAP-TOO)
15
is seeking to demonstrate the effectiveness of the Watchman prosthesis in this clinical
condition, but the study is estimated to be completed in 2023.
Apparently, we are reaching a stage of clinical knowledge and experience in optimizing
the use of warfarin and direct-acting anticoagulants in patients with non-valvular
AF at high risk of stroke and systemic embolization, recognizing and establishing
the safe limits for their use. This opens up a new phase for the consideration of
LAA occlusion devices. Therefore, additional prospective, multicenter, controlled
clinical trials are needed to clarify the effectiveness and safety of the implantation
of the devices in these new clinical situations, such as patients with absolute contraindication
to OACs and antiplatelet use, even for a short period of time; patients that had a
stroke while receiving apparently effective oral anticoagulation; LAA occlusion as
an alternative to chronic use of NOACs; occlusion device implantation simultaneously
with AF ablation; in addition to establishing the need and safe handling of short-term
anticoagulant therapy and minimal antiplatelet therapy, which should be maintained
after the implantation of different prostheses.