Left Atrial Appendage Closure for Prevention of Stroke: A Meta-Analysis of Device Comparison on Random Clinical Trials

This meta-analysis compares the safety and efficacy of Amplatzer and Watchman left atrial appendage closure devices for stroke prevention in patients with atrial fibrillation. The study includes a search of PubMed, EMBASE, and the Cochran library for studies up to February 2022. Findings show higher rates of major procedure-related complications with Amplatzer, while Watchman is associated with higher rates of PDL and DRT. No significant difference was found in ischemic stroke and bleeding.

Left atrial appendage closure for
prevention of stroke

Table of Contents
LIST OF FIGURE AND TABLES..................................................................................................1
LIST OF ABBREVIATIONS..........................................................................................................2
ACKNOWLEDGEMENT...............................................................................................................3
ABSTRACT.....................................................................................................................................4
Background.............................................................................................................................4
Method....................................................................................................................................4
Result......................................................................................................................................4
Conclusion..............................................................................................................................4
INTRODUCTION (1500)................................................................................................................5
What is strokes.......................................................................................................................5
Why stroke should be researched...........................................................................................5
What are the causes of strokes?..............................................................................................6
Effect of left atrial appendages closure for prevention of stroke...........................................7
Aim.........................................................................................................................................8
Objective.................................................................................................................................8
Research questions.................................................................................................................8
Alternative Hypothesis...........................................................................................................8
Null hypothesis.......................................................................................................................8
METHODOLOGY (2500)...............................................................................................................9
Criteria for eligibility..............................................................................................................9
Source of information...........................................................................................................11
Screening of studies..............................................................................................................12
Quality assessment and data extraction................................................................................13
Heterogeneity.......................................................................................................................14
Statistics................................................................................................................................15
RESULTS (2000)...........................................................................................................................17
PRISMA flowchart...............................................................................................................17
Quality assessment...............................................................................................................19
Data extraction table.............................................................................................................21

DISCUSSION (2500)....................................................................................................................24
Risk of bias: ethics................................................................................................................24
Summary of finding..............................................................................................................25
Raw data...............................................................................................................................26
Similar studies......................................................................................................................26
Follow up period...................................................................................................................27
Method based on follow up..................................................................................................28
Limitation.............................................................................................................................28
Future research implication..................................................................................................29
CONCLUSION (500)....................................................................................................................31
REFERENCES..............................................................................................................................33
APPENDICS..................................................................................................................................38
APPENDIX A: MeSH term..................................................................................................38
APPENDIX B: Data extraction process...............................................................................38

LIST OF FIGURE AND TABLES
Table 1 Eligibility criteria (Inclusion and exclusion criteria)
Table 2 PICO search term that is used to search PubMed, Cochran and EMBASE
Table 3 Inclusion and exclusion key term that is associated with Covidence.
Table 4 Data extraction process of included studies
Table 5 Difference between included studies
Appendix A MeSh term used
Appendix B Data extraction process
Chart 1 PRISMA flowchart
1

LIST OF ABBREVIATIONS
TIA Transient ischaemic attack
AVM Arteriovenous malformations
ECG Electrocardiogram
WHO World Health Organisation
LAA Left atrial appendage
LAAC Left atrial appendage closure
RCT Randomised control trials
AF Atrial fibrillation
CI Confidence interval
2

ACKNOWLEDGEMENT
I would like to express my special thanks of gratitude to my teacher …… who gave me such
golden opportunity to do project that is related with investigation of Left atrial appendage closure
for prevention of stroke.
While conducting the research on title, I came to know about various of thing that I never
achieved without support to teacher and family. Secondly, I would also like to thank my parents
and friends who help me a lot of finalising this project within the limited time frame.
3

ABSTRACT
Background
The associated ablation and left atrial appendage closure is substitute for atrial fibrillation among
the patient with the high risk of stroke and other issue. Therefore, the paper covers the stroke
prevention. However, the long term outcome of this combined process which is always elusive.
In addition, paper also cover the Amplatzer and Watchman left atrial appendage closure device
that is focus on the two most frequently used based on device for LAAC device on the world
wide. The meta analysis used to show the compare the safety and efficacy of the two decide.
Method
In addition, searched is based on PubMed, EMBASE and the Cochran library that is based on
studies up to February, 2022 that show comparison the safety and efficacy the Amplatzer and
Watchmen device. Therefore, they are work as search strategy that used to manage the data and
information. The PubMed is official in order to extract the data that is required for the paper
which is based on topic.
Result
As per the study and proper review of article, it is well analysed that patient which is selected for
the study is undertaken to process of randomised control trial where patient is selected. Overall,
the studies are based on observational studies which is included in the term of meta-analysis.
Amplatzer device was associated with higher rates of major procedure related complicated that
show the odd ratio that is 1.99, 95 percent of confidence interval.
Conclusion
Ampatzer LAAC device was well associated with the higher rate of major procedure that is
related with complication which is based on device embolization. The Watchmen LAAC device
is well associated with the higher rates of PDL and DRT. There are various no significant
difference between two devices in ischemic stroke and bleeding.
4

INTRODUCTION
What is strokes
A stroke can be characterised as one of the serious life threatening medical circumstances
that occurs when anything obstructs blood supply to the cells of brain or when a blood vessel
bursts in the brain. A stroke can cause long term disability, brain damage and even death.
According to the perspective of James (2020), there are basically three main types of stroke
(Alfadhel, and et. al., 2021). They stated these were ischaemic stroke; in this blood clots create
disturbance in blood and oxygen from reaching a region of the brain, haemorrhagic stroke; it
occurs due to rapture blood vessels and these stroke are usually outcome of arteriovenous
malformations (AVMs) or aneurysms, Transient ischaemic attack (TIA); a type of mini stroke
due to inadequate blood flow to brain. Charles (2022) suggests that atrial fibrillation, heart valve
disease and patent foramen ovale can be the effective cause of stroke. Morgan & Claypool
(2010) specified that there are four major arteries in human body, which supply the brain with
blood. That arteries are left and right carotid arteries are found in the front side of the neck and
by the assist of fingers their pulse can be felt. The left and right vertebral arteries are enlaced in
the bone as they run in the neck through vertebrae. When fibrillation and obstruction occurs due
to any circumstances in these arteries then it causes blockage to brain flow with blood. It can be
recognised by an electrocardiogram (ECG) having irregular interval between QRS complexes
and no P wave (Cruz-Gonzalez, and et. al., 2018).
Why stroke should be researched
As per the report of world health organisation (WHO), stroke can be upcoming pandemic
in future. According to Anita et. Al (2017), it was determined that at least “£48 million” was
spent per stroke patient. It was also evaluated that the whole spending could increase to 10%
from 0.7% over the next 10 to 12 years. With the heavy disbursement on treatable situations such
as stroke, this is becoming progressively harder to fund too vital areas of the NHS that need aid.
Raphael Wittenberg states (2015) states that annual National health safety cost of strokes could
enhance to £10.2 billion in 2035 from £3.4 in 2015. As per the perspective of Anita (2017), the
estimated yearly number of the stroke cases ranges from 113400 – 119100 in United Kingdom.
Derek king et. al. (2017) estimates that by 2035, approximately 187,000 human being may have
stroke in United Kingdom alone (Ibrahim, and et. al., 2019). The other main reason which is also
5

show their relevance in order to develop and formulate the research is based on purpose of left
atrial appendage in the heart that refer as small pouch extending off the side of left atrium in the
heart that can act as decompression chamber when the pressure that associated with atrial is high.
The risk of developing stroke is proportional to age. Which means, there is an enhancement in
their risk of evolving stroke at one age. As the world develops, it has become too observable that
human being are living more which means higher number of human being are at risk of evolving
stroke and will therefore enhance load or burden and dependency on the national health safety
(NHS) (Perez and et. al., 2019).
Risk of stroke is commonly associated with the atrial fibrillation. As per the view of
Starek et. al. (2017), in adults in their 50s the risk of stroke is 1.5% but this enhances to 23.5% in
adults in their 80s. This is due to the a poorly contraction of atria causing in the pooling of blood
within the arteries. Currently NINDS funded stroke research involves; antithrombin
interventions, thrombolytic interventions, restoring blood flow, risk factors and health disparities,
and others. These all aspect that studies deeply rise the context to make the in-depth study which
is beneficial for creating the understanding and also show the sense of knowledge that is
productive for gathering information and data that is well related with atrial fibrillation.
Overall, majority of embolic stroke among the patient with the nonvalvular atrial
fibrillation which is well caused by thrombi in the left atrial appendage. It is well projected that
the stroke is always related with atrial fibrillation which is enhanced the risk and complication
among the patient. It is important to investigated and understand the medical need and their
relevance in future (Dobrev and et. al., 2019).
What are the causes of strokes?
Starek et. al. (2017) suggests that a stroke can occurs as:
 An ischaemic stroke which is caused through atherosclerosis - an artery may become
obstructed through gradual thickening of artery walls.
 An ischaemic stroke due to embolism – a blood clot obstructs an artery and blocks blood
getting to the cells of the human brain.
 A haemorrhagic stroke – it is also known as cerebral haemorrhage. It is due to an artery
may damage and result bleeding into the tissue of brain (Masjuan, and et. al., 2019).
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The brain tissue is killed in the immediate area since brain's cells are deprived of O2. The dead
are being known as infract, that cause from stroke. As per the perspective of Derek king et. al.
(2017), there are several lifestyles related factors which enhances the risk of stroke involve:
 High blood pressure; is the very vital risk factors to stroke. Due to the high blood
pressure a stress occurs on the lateral wall of arteries result weakness and damages of
arteries inner walls. Therefore, it can lead to stroke, especially cerebral haemorrhage.
 Carotid artery stenosis; thickening and hardening of the arteries in the neck region can be
lead to high risk for brain stroke. It causes narrowing of blood vessels.
 Atrial fibrillation; persons with atrial fibrillation have special kind of irregular heartbeat,
are at enhanced risk of ischaemic stroke. This is due to the less pumping of the chambers
of heart (atria).
Effect of left atrial appendages closure for prevention of stroke
Atrial fibrillation is the most prevalent cardiac arrhythmia where the people are usually
diagnosing that show roughly calibration about 2 to 3 percent among the general population. It
usually shows the causes blood to stagnate in the atrial chamber which show the concept that is
well related with thrombus formation. The risk of stroke is to 4 to 5 times higher in person with
the AF than in those without (Linz and et. al., 2019). In addition, the risk of stroke is usually
show 3 and 4 time is higher with the person who is dealing with arterial fibrillation as
comparison to those who is living without any AF. It is also analysing that it more than 90
percent of thrombus accumulation occur in the left atrial appendage. Therefore, the left atrial
appendage closure is referring as the treatment which is alternative and it is more useful in order
to prevent the stroke in high risk patient with the non-valvar AF who are not candidate for the
oral anticoagulation therapy or in whom OAC therapy is usually failed. In addition, there are
number of endocardial LAA closure is used and developed where the first generation device,
percutaneous LAA trans-catheter occlusion system which is never reached as a commercial
production (Yasuda and et. al., 2019).
The left arterial appendages are the source of atrial antidiuretic peptide. There is some
assumption that, elimination of the appendages might disturb the renal clearance of water and
salt so, enhancing the risk of cardiac failure. As per the point of view of Richard et. al. (2021),
surgical closure of the left atrial appendages decreases the risk of stroke by ways of a various
procedures from that of anticoagulants, and their impacts reflect to be additive to that of oral
7

anticoagulation (Andrade and et. al., 2019). This procedure which is also known as left atrial
appendage closure LAAC usually responsible in order to make the barrier that prevent the risk of
stroke by mechanism that follow the sealing of small, unessential section of the heart which is
also called as left atrial appendages. For the population with atrial fibrillation, the number of
stroke are usually get started in their LAA because that is all about blood clot tend to form new
aspect of treatment which is done by using the medication or use of LAA (Severino and et. al.,
2019).
As per the view of Matthew (2014), left atrial appendages removal or closures is a process
that closes or blocks the opening to the left atrial appendages to clots of blood from leaving there
and travelling into the bloodstream. Without blood thinners, this stops stroke in persons
associated with atrial-fibrillation (Nguyen, and et. al., 2019).
Aim
The main aim of this research is “To identify the importance of left atrial appendage
closure in preventing stroke: A meta and systematic analysis of device comparison on random
clinical trials
Objective
 To develop basic understanding about the left atrial appendage closure
 To analyse the role of left atrial appendage closure for the prevention of stroke.
 To evaluate the mechanism and pathophysiological notion of left atrial appendage closure
for prevention of stroke.
Research questions
Is left atrial appendage closure is beneficial for prevention of stroke?
Meta-analysis comparison between " Watchman, Amplatzer & Amulet"
Alternative Hypothesis
The mechanism of left atrial appendage closure is reducing chances of stroke.
Null hypothesis
The mechanism of left atrial appendage closure is not reducing chances of stroke.
8

METHODOLOGY
Criteria for eligibility
The criteria for eligibility within the research section help to define protocol which is used
by researcher while conducting research. In reference to clinical trials, requirement that must be
met for the person is well include in the trial. In context to this research process, meta-analysis
and systematic analysis is used to take that must configure essential component that is related
with research work (Boersma and et. al., 2019). In addition, every review has protocol which is
followed inappropriate manner that create ethical consideration for the selection of information
and data. The criteria for eligibility is well include inclusion and exclusion criteria which show
detail or protocol for the selection and qualification for research work. Therefore, the below table
is about inclusion criteria and exclusion criteria that elaborate qualified context that is undertaken
within research process and procedure. The Table 1 defined as inclusion and exclusion criteria
(Yaghi and et. al., 2020).
Table 1: Eligibility criteria
Inclusion criteria Exclusion criteria
 English language is mandatory while
taking the study or review that is based
on meta-analysis and systematic
review.
 Studies is also including systematic
review that is related with literature and
configure to meet the following
inclusion criteria. It is meta-analysis
and systematic review where the risk of
bias is higher which is must be
neglected within each study.
 The patient with stroke is undertaken
within the study for the research work
in order to evaluate the mechanism and
effectives of left atrial appendage
closure.
 Rather than English language is not
undertaken within the study for the
research work. Therefore, other
languages are taken within exclusion.
 There are some studies that were freely
available as this is require money and
proper fund to initiate which is
excluded from the study and also not
available for the reviewer.
 Apart from Left atrial appendage
closure, no other intervention is used to
taken RCT (Randomised control trial).
 Cohort study, experimental study and
so on is also excluded from the study
because the major of review process is
based on meta-analysis and systematic
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 Therefore, the stroke is generally
common among the age group of 35 to
50 years old people. Therefore, the
major of data and information is
collected from such article or reviews
that consider such age group for their
study.
 The intervention which is taken for the
stroke is left atrial appendage closure
where motive to measure the
effectiveness and importance is studies
in appropriate manner.
 Stroke among the people is arise as
issue from last 10 to 15 years which
show high mortality rate and
complication. In this, population with
stroke is participated into the study for
the study of basic mechanism that how
pathophysiological function are render
during stroke to know working of left
atrial appendage. Apart from this, no
other patient with any complication is
taken under the study, the inclusion is
persistent on stroke patient.
 The study is usually taken from
secondary source where article,
journals, peer reviewed paper, grey
literature and so on is outline as per
published in the last 10 years to ensure
the data and information which is up to
date and data is well appropriate to the
literature review.
 The mechanism that follow non
pharmacological method or intervention
is not undertaken within the review or
research work. The main reason behind
the exclusion is that they are inaccurate
and generate aspect which is focus on
traditional aspect that have less
probability of action potential.
 Above 10 years of published literature
that is related with topic is not
undertaken within the process of review
(Volkov and et. al., 2021).
10

tool that is currently implemented in
hospital for the treatment in stroke.
 Finally, each study which have been
show the information and data that is
well related with PICO framework
implemented in this review.
These above discussions create relevance regards with understanding of inclusion criteria
and exclusion criteria for gathering the attention to know about the research that what
information is undertaken while conducting research. Although, eligibility criteria allow the
researcher to make protocol while conducting research to avoid the gathering of such data or
information which is not relevant to research question or topic which is chosen for research work
(Pacha and et. al., 2019).
Source of information
The source of information is reliable to provide the information regarding the resource that
used during the research work to extract or gather the data. In reference to this research work, the
database is used which work as searched fraction to obtain the validated article for systematic
review. The database named as PubMed, Cochrane library and EMBASE. These are most
reliable and trusted source to gather the information from article especially for medical research.
While collecting the data or information from PubMed, the filter is applied which is associated
with published article in the last 10 years and also RCT. This is essential to apply filter with
reason that it is part of inclusion criteria (Albaghdadi and et. al., 2020). Above 10 years and more
published article is excluded from the study so the while finding the article for information, filter
is applied to follow the inclusion criteria. Therefore, it helps to provide proper data and
information that is relevant as per study to make the comprehensive information which is
evidence based with the elucidation from PubMed. Similarly, Cochran as a database use for
extraction of data and information where reliable article is present. Same as PubMed, filter is
applied for the years that is 2012 to 2022. Therefore, searches must be relevant so that they are
made under trail section. While conducting the screening process, the major of studies is not
refer where RCT is excluded. With this, EMBASE is also used as appropriate database to extract
11

the article which is linked with topic for collection of information, filter is applied and article is
selected especially systematic literature review (van den Berg and et. al., 2019).
The last search on the PubMed, Cochran and EMBASE is usually occurred in 28 July
2022. The PICO term is the major configuration as diabolical search though the two database
which is shown is Table 2. The MeSH term is created and well searched in PubMed for the
proper data collection and selection. The MeSh term is present in Appendix A.
Table 2: PICO search term that is used to search PubMed, Cochran and EMBASE
Patient Patient more than 35 years with issue of stroke.
Intervention Left atrial appendage closure
Comparison None
Outcome Patient recovery and enhance level of comfort after Left atrial appendage
closure.
Screening of studies
After searching through the various of determined source which is predominantly identified as
database which is PubMed, Cochran and EMBASE. Therefore, the search result is well imported
with the use of paid systematic review software named Covidence (Xue and et. al., 2018) In
addition, while elucidation of data when the duplication is removed, screening of the title and
abstract start to begin there is only review per reviewer is worked in independent way to screen
through the all the result. Moreover, the list of keyword is drop below in table 3 that show the
screen through the abstract and title. Such keyword has potential to configure the data and
information again with the help of using keyword which is identified below. Therefore,
Covidence is also show their potential ability that highlight the words which can made the thing
as well reading faster and applicable that is efficient (Kosturakis, and Price, 2018).
Table 3: Inclusion and exclusion key term that is associated with Covidence.
Inclusion criteria Exclusion criteria
Adults
Left atrial appendage
Left atrial appendage closure.
Stroke
Non pharmacological
Older people.
Causes
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Heart stroke.
Random
Randomised control trial
The title and abstract which is reviewed and show the relevancy which is assessed, full text
screening is also began with the start of studies. During the research work, the method and
outcome is major focus which is suitable in order to make proper studies for elucidation of data
and information. In addition, trials are required some report which is associated with patient
suffering from stroke. The study has some basic requirement where inclusion is used to made
and included within the study. It is also experience that the data extraction section is well show
the relevance where proper information regarding the study is extracted as per the vision of
different author. This is usually undertaken for all studies that is identified to meet the inclusion
criteria or has component of exclusion criteria, then it was excluded and show the reason which
is well provided for the topic or hypothesis which is essential to prove (Fujita and et. al., 2022).
Quality assessment and data extraction
The quality assessment is referring as tool or technique which is undertaken in order to
show the devise structure that is diabolical in term where they support the data in adequate and
evaluate the quality after the review. The review is usually initiated with literature and article
that is articulated for the gathering of information and data (Masci and et. al., 2019). The quality
assessment as well as extraction process that relevant with data is began when the screening of
studies is completed. The screening and other tactics is used by software which is above
mentioned named Covidence (Dudzińska-Szczerba and et. al., 2021).
It is also evaluated that the use of PubMed and Cochran is more reliable in order to show
the risk that is formulated from Cochran for the criteria of bias. Therefore, quality of each study
that included in research work is well assessed. Moreover, when the review is outline, the whole
complete assessment is transmitted to review manager. It is allowed for the formulation of
summarised figure which well indicated with the context to colour which provided instruction for
bias (The green one indicated low risk, yellow indicate unsure and at last red is well show
reference of high risk.). In this, the data extraction process is found with elucidated article from
database i.e. PubMed, Cochran and EMBASE. The data extraction process seen within Appendix
B (Kurzawski and et. al., 2020).
13

In below Table 4, the data extraction process from the selected study is well taking into
consideration where the outcome and data is plotted. In this, the reviewer used to review the data
and analyse the missing data or information which lacked while conducting the process of review
(Caliskan and et. al., 2018).
Table 4: Data extraction process of included studies.
General Payam and Abdi, 2018. Country chosen for study is United states.
Participants 100 participant were taken in study, mean age is approx. 40 and the
ratio of male and female is 1:1.
Intervention/comparison Left atrial appendage closure for treatment of left main coronary
artery disease.
Outcome The initial outcome of LAA closure and their ligation process help
to prevent the stroke which is encouraging.
Overall, the study shows the data extraction process that is reliable and validated for
included studies. In addition, the process helps to provide detailed structure of research topic
where participant, age, mean age, constructed age, diabolical age and many more. The risk of
biasness is the major threat while conducting the research, in this, the data extraction process is
well reliable in order to provide the data regards with bias studies which is outline within the
study and overall process of research work. In addition, they also provide context that help to
create proper aspect which is well related biasness that linked with hypothesis majorly alternative
hypothesis rather than null hypothesis (Masoud and et. al., 2018).
Heterogeneity
The studies that is undertaken within the process is well provide the aspect which show the
importance of left atrial appendage closure for the treatment of left coronary artery disease.
Therefore, initial result which is well evaluated with the Left atrial appendage and ligation work
as process that is useful in order to prevent the AF-related stroke that is encouraging. Among the
participants with atrial fibrillation which has been undergone towards the cardiac surgery, most
of the continued to gain or receive ongoing antithrombotic therapy, therefore, risk of stroke or
systematic embolism which is lower with concomitant left atrial appendage which show the
occlusion that is well performed during the surgery than without it (Granier and et. al., 2018).
14

Moreover, the difference which is associated between selected studies that have been noted in
Table 5 below.
Table 5: Difference between included studies
Participants Left atrial appendage closure Anti-platelet therapy
The primary analysis
population is well included
2379 participant which is
outline for study in the
occlusion group and 2391 in
non-occlusion group. The
mean age of the participant is
about 71 years.
The surgical occlusion of the
left atrial appendage which
has been hypothesized to
prevent ischemic stroke in
patient with the issue of atrial
fibrillation. Therefore,
procedure is well performed
during cardiac surgery which
is undertaken for other reasons
(Korhonen and et. al., 2018).
Antiplatelet is refer as group
of medicine that stop of blood
cell which is also called as
platelet from sticking together
and forming the blood clot. It
is also analysed that the injury
in the body, platelet is used to
send to the site of the injury.
Whereas, they can clump
together to the form of blood
clot.
Statistics
Using the proper tool that help to provide the data and information which is well related with
research topic. The topic is focus on importance of left atrial appendage in treatment of stroke.
The statistic is plotted with the help of forest plot (Kawakami and et. al., 2021). The forest plot is
also called as blobbogram which is useful in order to make the graphical display of estimated
outcome form the number of scientific studies in order to address the same question along with
the outcome which is elucidated. Therefore, in reference with left atrial appendage have some
outcome which defined by various of article in the different way. In this, they are enough in
order to provide data and outcome that show the context for the result that is usually derive by
longer path. Moreover, the pooled incidence rate of the ischemic stroke is well analysed about
1.38 per 100 patient years with the 95% CI 1.08;1.77. Overall, main purpose to use the left atrial
appendage is small pouch extending to the left side of atrium in the heart which can act as
decompression chamber when the pressure that is related with pressure is high (Burysz and et.
al., 2019). In this, patients with non-valvular atrial fibrillation are generally at a 3 to 5-fold
enhanced risk of ischemic stroke, more attributable towards the stagnation of the flow of blood in
15

the left atrial appendage which can encourage the local thrombus formation. An oral
anticoagulation is an effective approach in preventing the thromboembolic events, therefore, its
use is restricted by poor adherence as well as are required for the long terms treatment, its side
effects consisting bleeding and the interactions of drug as well. In addition to this, the
percutaneous left atrial appendages occlusion (LAAO) can specifically prevent the thrombus
embolization. In the year 2015, Food and Drug Administration approved a single seal mechanism
Watchman device for the occlusion of Left atrial appendages which generally need six weeks of
a post procedural anticoagulation. Furthermore, the Left Atrial Appendages Occlusion with
involving a single seal procedure can be incomplete, it is because of a complex as well as
variable anatomy of the Left Atrial Appendages Occlusion. Moreover, a dual seal device with
consisting an outer disc can specifically overcome the limitations of an anatomic heterogeneity,
given an enhanced seal of a Left Atrial Appendages Occlusion ostium as well as can decrease the
possible risk of leakage.
Figure 1 Efficacy and safety comparison at different follow up period.
Source: https://www.researchgate.net/figure/Forest-plot-of-cardiac-neurological-mortality-The-
marker-size-represented-the-weight-of_fig1_306046613
16

RESULTS
PRISMA flowchart
In order to understand the PRISMA flowchart and their importance, primarily get an
outlook of systematic review in the literature which act as component to draw a flowchart that
contain various elements. Therefore, the systematic review in the literature have become more
essential as mean of keeping the clinician’s up to date on the various advance in the field and as
method of developing clinical guideline. Systematic review is also important in order to
determine research question and making the proper justifying to grants agencies that further
research in the specific area is required. In addition to this, PRISMA statement is help to improve
the transparency and the merit which is based on scientific level that reported systematic review
or meta-analysis. There are number of article and journals used to enrol the statement and
reference it in their guideline for the authors. For nursing, attention to make the proper guideline
by the researcher, clinicians, authors and reviewers that help to improve the nursing practice by
enhancing quality of the evidence (Qian and et. al., 2018).
In the research work, the PRISMA is essential tool or framework that is used which is stand
for the preferred reporting item for Systematic review. It is well suitable to gather the attention
toward the data and information which by showing the evidence based minimum set of item that
reported in systematic review and meta-analysis. The PRISMA statement consist of a 27
checklist and the 4 phase flow diagram. Such item has been showing the adapted for use of by
student conducting systematic review which is refer as the part of KIN 4400. In this, PRISMA is
well recognised standard for reporting the evidence in systematic review and meta-analysis. The
standard which is selected for the report foster by article and journals in the health science. There
are some of benefits which is gain as per adoption of PRISMA flowchart or framework.
 It has ability to demonstrate the quality of review which is outline within research work.
 Allow the reader to get the knowledge in depth with the assess of strength and weakness.
 It also allows the user to take the permit of replication of the review method and so on.
 In this, the structure and format are used to show the review with help of using PRISMA
heading (Yu and et. al., 2019).
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18
Records identified from*:
Databases (n = 240)
Registers (n = 110)
Records removed before
screening:
Duplicate records removed (n
= 120)
Records marked as ineligible
by automation tools (n = 90)
Records removed for other
reasons (n = 60)
Records screened
(n = 110)
Records excluded**
(n = 25)
Reports sought for retrieval
(n = 90) Reports not retrieved
(n = 20)
Reports assessed for eligibility
(n = 45)
Reports excluded:
Reason 1 (n = 25)
Reason 2 (n = 15)
Reason 3 (n = 10)
etc.
Studies included in review
(n = 30)
Reports of included studies
(n = 10)
Identification of studies via databases and registers
I
d
e
n
ti
fi
c
a
ti
o
n
S
c
r
e
e
ni
n
g
I
n
c
l
u
d
e
d

Quality assessment
In order to conduct the quality assessment of topic that is derived in research work is
predominantly focus on the acquired factor that is relative to provide wide range of data and
information. The systematic review that is focused on consideration in order to provide the most
reliable form of evidence for decision makers. The formal assessment of the quality of included
studies which is undertaken within the research is useful to generate creative aspect and act as
component of systematic review. Quality assessment is used to taken from the diverse tool and
technique that support the qualities of report that is based on data collect and information.
Therefore, they provide context of reliability and validity that support the research work in term
of evidence based data. Moreover, the main reason in order to conduct the quality review as
assessment to consider the three component that is internal validity which is also called as risk of
bias, external validity and reporting quality. The quality of included studies usually depend on
the sufficient design and conducted to able to provide reliable result. In this, the poor design,
conduct or evaluation can create biasness and systematic error that affect the overall study result
and conclusion. Therefore, it is also known as internal validity which help to access the quality
of research work. External validity or applicability of the study is help to review the question
which is important in order to share the component of study quality. It is also difficult to make
the assess with the other component of study that focus on quality of study which is not reported
with the level of appropriate data (Zhang and et. al., 2020).
In addition to research work, there are wide range of tool are used in order interpret the
quality of work. For this work, compared with quantitative studies, assessment tool for
qualitative studies are less. The CASP qualitative research checklist is most frequent use tool for
the quality assessment where author and their aim with proper study design is evaluated. In the
context with quality assessment tool, it is well analysing that the systematic review is refer as
important factor which is help to analyse the data within the project. In addition, it is also
evaluated as per the poor conduction of study that can skewed the biases from the methodology
which is avail in research and also show the proper interpretation with proper caution. Therefore,
such studies should be acknowledged as such in the form of systematic review which is outright
excluded. There is an appropriate tool is taken in order to analyse and evaluate strength of
evidence and imbedded biases within each paper which is also essential. In addition to this, the
use of systematic review manuscript development tool for example the major tool to analyse the
19

strength of evidence and review of paper that may be used to build the proper software. In this
research work, the major software that is used under research process are RevMan, a checklist
may be also available into software which create descriptive form of analyse data. There is other
software which may help with the process of screening search result and discarding the irrelevant
studies. In this, the following tools are well used which is suitable in order to make the
proportional of quality studies and put a form of critical appraisal that create aspect to understand
the data that chosen for the research question in order to prove hypothesis of research work.
Other validated software is also used to taken in order to provide alternative for quality
assessment such as Rayyan that may help with the process of screening search result and
discarding the irrelevant studies where some of the tool are well used to in order to determine the
study assessment and critical appraisal (Auf, and et. al., 2018).
 They are usually assessable towards the section of methodological quality of systematic
review that is also named as AMSTAR 2 that is broad and helpful in order to analyse the
data with aspect to critical appraisal systematic review.
 Therefore, the centre for evidence based medicine that is also called CEBM usually
consist collection of critical appraisal tool which is well suitable for studies with all type
and example and their usage.
 Cochran risk of bias which is mentioned with the name of RoB 2 that is tool which is
well suitable to recommended tool within research work to assess quality and risk of bias
in the randomised control trail in the Cochran submitted systematic review.
 In addition, one of the major plot which is undertaken within research for quality review
or assessment is by using of critical appraisal skills programme that is CASP which have
25 years of experience and expertise in the critical appraisal and offer the wide level of
checklist that bring the coordinated study.
These all are well used in order to interpret the quality and study assessment of article or
resource which is used to collect the data. Overall, the information and data is usually
configuring aspect that is relevant and based on proper evidence. In this, study allow reader to
understand the concept and model which is used within the research work which may create
relevance in the process of study and quality assessments. As per this, the study and quality
evaluation with the tool is helpful in order to provide support the study in wide manner.
20

Data extraction table
Data extraction is also a part of research work where the article from different author is
review and outline that information which is essential for research question in order to prove the
hypothesis. In other word, the review of the article is taken and collected some data and
information for the assign research process where hypothesis is usually proved. The extraction of
data is usually connected with the study quality in that both process is usually untaken at the
same time. The standardised data extraction form is help to improve the persistent flow of work.
Moreover, systematic review is usually undertaken within process to make the meta-analysis for
hypothesis that may intervene or to prove relevance in research question (Akkasaligar, and
Biradar, 2020).
Below the author are chosen with tool that configure the study design as well all
information which create study assessment and quality review. The quality review is the main
focus on data extraction table where the author aim and outcome is derived that is provide
potential to make the hypothesis true and worthy as per research work. In addition, the data
extraction table is plotted in order to review the quality as per based on study. Therefore, there
are various of study which allow the researcher to make competent review for study and quality.
It is also derived that article is selected as per study design which create final draft for review
which is worthy and adequate for conducting the process of review which configure wide range
of data. As per this, study allow to make the proper review which show the aspect where sample
size is also undertaken that derive a wide range of study among the participant and they have
prominent view to gather the information which allow the researcher to carry the research with
relevant outcome that is extracted as per trial or analysis of article or journals (Wang, Cui, and
Zhu, 2020).
Title Author Years Country Patient
age
Study
design
Sample
size
Outcome
Meta-Analysis
Comparing
Watchman and
Amplatzer
Devices for
Stroke
Indranill
et. al.,
2020 United
state
Not
defined
Systematic
review
614
patients are
selected on
random
basis.
In this, the
LAA closure
device has low
complication
rate and low
events rate.
21

Prevention in
Atrial
Fibrillation
Peri-device
leakage in the
Watchmen
device is
analysed.
Comparison
between
Amulet and
Watchman left
atrial
appendage
closure
devices: A
real-world,
single center
experience
Saad et.
al.,
2021 Germany Unknown Systematic
study
design
Unknown Amulet LAAC
device was well
associated with
enhanced peri-
procedural
complication as
compared to
make the
Watchman
LAAC device.
A meta-
analysis for
efficacy and
safety
evaluation of
transcatheter
left atrial
appendage
occlusion in
patients with
nonvalvular
atrial
fibrillation
Wei et.
al.,
2015 Nanjing Unknown Systematic
review
and meta-
analysis.
3585
patient
The trans
catheter LAA
occlusion was
effective and
safe among the
patient.
Comparison
between
Qiao et.
al.,
2022 China Unknown Systematic
review
2150
patient is
Amplatzer
LAAC device
22

Amplatzer and
Watchman
Left Atrial
Appendage
Closure
Devices for
Stroke
Prevention in
Atrial
Fibrillation: A
Systematic
Review and
Meta-Analysis
undertaking
for
research.
is well
associated with
the higher rate
of major
procedure
related
complication.
There is no any
change which
may show the
difference
between tow
device in
stroke.
Systematic
review on left
atrial
appendage
closure with
the LAmbre
device in
patients with
non-valvular
atrial
fibrillation
Ali et.
al.,
2020 Germany Unknown Systematic
review
Unknown RCT require
scrutinize the
value of
LAmbre
compared with
LAAC device.
23

DISCUSSION
Risk of bias: ethics
Several different term that is used to talk about the assessment of the studies underpinning
the guideline that is appropriate the research work and process. The hypothesis is usually
underpinning that allow to make proper research on the justified research question. Therefore,
the critical appraisal, quality assessment, internal validity in which they are showing various of
module use of concept of risk of bias. The concept of risk of bias in ethical consideration allow
the use to make the proper interpretation which allow the user to make the data and information
appropriate. Bias is referring as the facto which is well associated with the systematically affect
the observation and conclusion of the study and also cause harm which is based on different from
the truth (Afsari, Abbosh, and Rahmat-Samii, 2018). Therefore, the additional data which is
analyse as per the studies that they are usually affected by the bias that is showing inaccuracy.
For example, finding false positive or false negative effect which is well associated by over or
under estimating the true effect. In addition, it helps to show and lead to create inappropriate
guideline recommendation. The risk of bias is usually likelihood that show the feature of the
study design or conduct the study which usually mislead outcome. This can show the result
which is wasted resource, lost opportunities for effective intervention or harm to consumer. Risk
of bias assessment where degree is well associated with methodological expertise and may be
conducted with proper guidelines that is formulated or by experienced through researcher as the
part of evidence review. In addition, risk of bias assessment is completed, it can be use inform
the formulation of studies which is about finding and integrate the overall assessment (Kaur and
et. al., 2020).
There are several of factor that can introduce bias are common to many region of research,
including:
 The issue with comparability of participant of specific population which is selected for
research work. For example: Selection bias.
 Issue with measurement or division of exposure or relevant result such as detection bias.
 There is some factor which is rather than intervention or exposure of interest that affect
the estimation such as performance bias or confounding.
 Missing information such as attrition bias or reporting bias.
24

The specific factor which is well depend on the kind of studies that is meant to considered in the
guideline. For example, clinical trials, cohort studies and more. It is analysed that impossible to
measure that whether they are not depending on particular study which has been affected by
biasness (Yang and et. al., 2020).
In addition, the process of conducting systematic review may introduce the aspect of
biasness and so on. The review process that is assessed separately as well as in addition to the
risk of bias of their included studies which is undertaken for the process of research. review is
usually creating high risk of bias might for example, they have issue with completeness of the
search for relevant studies that is associated with inclusion or with following their planned
analysis has been available in result.
Summary of finding
After several years of evaluating and monitoring, outcomes from the predicted
randomized trail displayed that left atrial appanages occlusion or closure is equivalence to the
therapy of warfarin single in stopping death related with cardiovascular, systemic embolism or
stroke in sufferers with non valvular atrial fibrillation. The researcher or investigator selected
707 sufferers at 59 sites, split 244 patients to warfarin therapy and 463 patients for the left atrial
closure groups. The pace of the unwanted events as stroke and transient ischaemic attack was 3.1
events hundred patient year in the warfarin group and versus 3.6 in the left atrial closure group
(Turagam, and et. Al., 2020). This report raised few concerns, although the high starting pace of
complications related to the procedure, failure for implanting the left atrial closure appendages in
few sufferers, and a very low score of CHADS2 of the sufferers after the treatment of stroke.
According to the evaluation of the meta-analysis of the 23 studies recorded that 57 per 100 of
sufferers with the valvular atrial fibrillation had thrombi situated in the left atrial appendages and
expanded in the cavity of left atrial (Dilibal and et. al., 2021). In divergence, in sufferers with
non-rheumatic atrial fibrillation, 91 per 100 of thrombi were situated in the left atrial appendages
only (p< 0.0001). This vital observation separates the management of non-rheumatic (non-
vascular) and rheumatic (vascular) atrial fibrillation assigned to the thrombus site specific
location which led to stroke. According the several research, to patients suffer with atrial
fibrillation, a general cardiac pace or rhythm diseases, closing some part of the heart recognising
as the left atrial as an additional process at the time of surgery of heart related with a 40 %
decrement in the risk of a condition when a blood clot forms and obstructs an artery, that can be
25

a reason of stroke or many other issues (thromboembolism) as per an observational research
(Toale, and et. Al., 2019).
Raw data
The term of raw data is referred as information which is gathered for research study before
that information which has been transition or analysed in any way. Therefore, term can usually
have applied to the data as soon as they gathered or after that have been scoured but not in any
way which is further transformed or analysed. In addition to this, raw data within the research
work is associated with participants, observational group and so on which is undertaken within
the research work (Choudhary and et. al., 2021). Therefore, the research work usually covers
wide range of data that provide the brief attention towards the words that is undertaken within
raw data. Raw data is referring as those data which may provide wide range of study that provide
proper elaboration as suffix which focus on study and allow the use to interpret the data. The
major of raw data are participants and other data. Moreover, study allow to make sense for the
reader as well researcher when they are investigated the topic in wide manner. Raw data within
this project is act as initial stage form which data is extracted are well nominated and provide the
wide range of data that support data and information which chosen for the research work. As per
this, it is also analysed that the study has the broad range of data which make the sense to keep
the information updated and prepare in such a form which is accessible and create better
understanding for the research work (Aluculesei and et. al., 2021).
Sometime, the raw data is associated with search factor and keywords which is used in
order to manage the data and information that is undertaken for research work. the research work
started with interpretation of raw data that is further taking as the core part of research work that
is based on research question where hypothesis is well used. In this, study allow the researcher to
follow research guideline where initial material as raw data is collected which provide baseline
to conduct the research process. Moreover, raw is more suitable in order to provide initial
information that is focus on the research question as well hypothesis which is used proved within
the research work. Overall, raw data provide wide range of study process that configure
information in elaborative form (Hassanin and et. al., 2019).
Similar studies
In the modern day’s stroke continue to be a principles cause of the mortality and
morbidity in the case of atrial fibrillation patients. Some of the oral anticoagulation gives
26

protection against peripheral embolization and stroke in atrial fibrillation but a maximum
numbers of sufferers could not be initiated on anticoagulation due to the complication associated
with bleeding. According to the perspective of the Payam Safavi- Naeini, atrial fibrillation (AF),
is the most occurred cardiac arrhythmia, are diagnosed in 2 percent to 3 percent of the common
population. It is responsible for the stagnate of blood in the atrial chamber of heart, which directs
to the formation of thrombus in the blood vessels of human heart. The risk of the stroke is four to
five times higher in the human beings associated with the atrial fibrillation in compare to those
persons who are not suffered with AF. There are more than 90% of accumulation of thrombus
present in the LAA (left atrial appendages). Left atrial appendages occlusion or closure is the
other treatment for preventing the strokes in the patient who are at high risk with non valvular
atrial fibrillation who are not suitable to the OAC (oral anticoagulant) therapy. In the modern
years, several endocardial left atrial appendages closure devices have been evolved. PLAATO
(the percutaneous left atrial appendages transcatherter occlusion system) is a first generation
device, which never reached commercial production. Watchman is the second generation
devices which used by implanting in the heart to the closure of left atrial appendages. The
another device is AMPLATZER cardiac plug is also not used commercially till now (Nguyen,
and et. al., 2019).
Follow up period
Activity/Weeks January February March April May June July
Introduction
Aim and
objective
Literature
review
Research
methodology
Result
Discussion
Conclusion
Submission
27

Method based on follow up
The method which is generally used for the follow up is large randomised control trial. The
method is common where proper monitoring is used to taken in order to create aspect that is
productive for research work. In addition, study is all based on review of article and journals
where the major of article or process of review configure the systematic review or meta-analysis
that allow the researcher to make comprehensive study as a part of research work to gather more
and more information which is based on research question. Therefore, it is also analysed that
there are wide range of study that is taking within the research process where maximum 5 to 10
article is reviewed that is systematic review. The meta-analysis is all to develop and create the
aspect which is showing the large scale of randomise control trials. The randomised control trial
is helpful to seek the review towards the intervention which is mentioned for the research
questions. The hypothesis is well generalised where intervention is described as the part of LAA
which is used in order to treat the strokes. The stroke is become of the common disease which
enhance the mortality rate among UK. As per this, the widely used intervention which is
prescribed for the control and manage of condition is LAA which is also known as Left Atrial
Appendage that work in order to improve the condition (Simona Răboacă and et. al., 2020).
Limitation
This study has some limitations. It is a retrospective single centre study with a too little
sample size because of the very low morbidity of hypertrophic cardiomyopathy (HCM), this is
one of the main limitations of the left atrial appendages closure to prevent stroke. At the same
time, taking into consideration to the deficiency of investigating studies of left atrial appendages
closure in the case of stroke prevention in the hypertrophic cardiomyopathy (HCM) and atrial
fibrillation (AF) populations, this type of investigating studies provides some valuable and
essential evidences on the utilisation of left atrial appendages closures techniques for secondary
and primary prevention of the stroke (Masjuan, and et. Al., 2019). Persons with the hypertrophic
cardiomyopathy and atrial fibrillation are completely heterogenous. Instant cardiac arrest and
death is very general in younger adults of aged 10 to 35 years old, death due to heart failure is
very general in the patients of middle aged, and stroke because of the Atrial fibrillation and
Hypertrophic cardiomyopathy is too common in the old age human beings. Human beings with
hypertrophic cardiomyopathy and atrial fibrillation in this topic were highly selective, majorly
with very old age, mild or non-obstruction and ventricular aneurysm and without previous
28

surgery. So, all these selected human beings had very low risk of instant cardiac arrest or death
but an enhanced risk of stroke, and therefore did not display the whole population human beings
with atrial fibrillation and hypertrophic cardiomyopathy. Apart from the manifestation to most
sufferers in the current study having a huge risk of bleeding and were unwanted to take the oral
anticoagulation therapy (OAC). How to elect the sufferers with atrial fibrillation and
hypertrophic cardiomyopathy who can get benefits from left atrial appendages closure treatment
to prevent stroke rest-overs an open question. Limitation of this study include the deficiency of
appropriate information about the comparative efficacy of the left atrial appendages closures as
contrast with the oral anticoagulation (Martin Gutierrez, and et. Al., 2020).
Future research implication
Left atrial appendages closure protect clot in approximately 90 percent cases of non
valvular Atrial fibrillation. More research in this field can provide more idea or knowledge about
the treatment via left atrial appendages closure for stroke prevention which occur due to
blockage of heart blood vessels. Further research on the prevention of stroke through left atrial
appendages can assist to decrease the number of cases of cardiac death and mortality rate due to
the cardiac obstructive disease. Further research can improve the techniques of the instalment of
the devices in human body which prevent the formation of blood clot and prevent the obstruction
in the blood vessel of human heart. There are number of cases where oral anticoagulant
techniques cannot be used due to the several bleeding problems and also not suitable for the
surgery to the closure of left atrial appendages (Diwakar and et. al., 2022). Therefore, through
the further the research surgery of left atrial closure can be made too easy in terms of surgery.
Atrial fibrillation is a main risk factor for ischaemic stroke in case of various age groups patients.
Anticoagulation are the effective techniques to prevent the stroke in patients with atrial
fibrillation and hypertrophic cardiomyopathy, but there are larger number of patients who are not
able to take or handle chronic therapy by anticoagulant like warfarin. So, further studies in terms
of left atrial appendages closure enhance decrement in the blood clothing process in the heart and
prevent the flow of clot with the blood flow which results improvement to the quality of
treatment and decrease the number of cases of stroke. Further research can decrease the risk
associated with the left atrial appendages closures techniques like decrease the blood clots
around the installed device. Decrease the fluid build-up surrounding to the heart in the
membranes (Hutt, and et. Al., 2019).
29

CONCLUSION
According to the above discussion, it has been concluded that a stroke can be defined as one
of the major life threatening medical circumstances which occurs when anything obstructs
supply of blood to the cells of brain or when the brain's blood vessel bursts. The findings of the
Left atrial appendage closure for prevention of stroke meta-analysis of device comparison on
random clinical trial suggested that it is superior to APT (anti platelet therapy) and placebo, and
comparable for non-vitamin K antagonist oral anti coagulants (NOAC) to prevent stroke and
mortality or systemic embolism (SE), with same risk of bleeding in sufferers with Non-valvular
atrial fibrillation (AF). Although, these outcomes should be explained with awareness and many
more studies are required to develop support this advantage, in perspective of the broad Cls with
another variable in the latest meta-analysis. The meta analysis network of leftatrial appendages
closures consists 19 recent randomised controlled trails (RCTs) with a large numbers of sufferers
with atrial fibrillation taking anti platelet therapy (APT), anticoagulants, left atrial appendages
closures (LAAC) or placebo. In the above study it has been also discussed that the impact of
Vitamin K antagonist (VKA) vs anti platelet therapy and placebo is well accepted to prevention
of stroke in case of atrial fibrillation. In intracranial bleeding prevention and stroke vitamin K
antagonist is less superior to the non-vitamin K antagonist oral anticoagulants. Vitamin K
antagonist inferiority over percutaneous left atrial appendages closure is suggested by the recent
randomised controlled trail. In the premises of non valvular atrial fibrillation with enhanced
stroke risk, cardio vascular death or embolism sufferers who are diagnosed and treated with the
help of Watchman device to left atrial appendages closure have denoted decrement in CV death,
major procedural related bleeding, haemorrhagic stroke compared to sufferers treated with long
term warfarin. It is balanced through a small magnitude enhance in ischaemic stroke in
watchman device treated suffers which may show the different cause of stroke in the population.
The left atrial closure devices as watchman devices had low event rates and low
complication rates. After the follow up of 3.8 years in sufferers with non valvular atrial
fibrillation at high risk to stroke, percutaneous left atrial closure fulfils the standard to both
superiority and non-superiority, with compare to warfarin therapy, to prevent the joint results of
systemic embolism, cardiovascular death and stroke, as well as superiority to all cause of
mortality and cardiovascular mortality. To a prophylactic process like left atrial appendages
closure, there is a very well balance between the continued risk of anti-coagulations and upfront
30

risk of the process. The device panel FDA Circulatory examine the data of Watchman 3 time
prior finally giving the approval. Although, with the development of this process, the risk of post
procedural has been importantly decreased to all the devices. This meta evaluation makes the
case and confirms these findings to wider providing of left atrial appendages occlusion, so as a
supplement to anti coagulation to sufferers with very high bleeding risk and stroke related with
the atrial fibrillation. In addition to this, Amplatzer LAAC devices was mainly linked with an
increased rates of major process associated complications, more specifically among device
embolization’s. In context with Watchman LAAC device was generally linked with greater rates
of DRT and PDL. Within this, there is generally no specific variation among the two devices in
an ischemic stroke/ TIA, all cause deaths, haemorrhagic, bleeding and cardiovascular deaths as
well. As compared with the first generation Watchman device, Left Atrial Appendages
Occlusion with involving a dual seal procedure by using an Amulent occluder exhibited a non-
inferior safety as well as an effectiveness, with involving a superior Left Atrial Appendages
occlusion rates but greater device associated complications. Furthermore, the medical
significance of differences among Left Atrial Appendages closure will required to be ascertained
via the longer term follow-ups.
31

REFERENCES
Books and Journals
Alfadhel, M., Nestelberger, T., Samuel, R., McAlister, C. and Saw, J., 2021. Left atrial
appendage closure–Current status and future directions. Progress in Cardiovascular
Diseases.
Cruz-Gonzalez, I., Fuertes-Barahona, M., Moreno-Samos, J.C., Gonzalez-Ferreiro, R., Lam,
Y.Y. and Sanchez, P.L., 2018. Left Atrial Appendage Occlusion: The Current Device
Landscape and Future Perspectives. Interventional cardiology clinics, 7(2), pp.253-265.
Ibrahim, A.M., Tandan, N., Koester, C., Al-Akchar, M., Bhandari, B., Botchway, A.,
Abdelkarim, J., Maini, R. and Labedi, M., 2019. Meta-analysis evaluating outcomes of
surgical left atrial appendage occlusion during cardiac surgery. The American journal of
cardiology, 124(8), pp.1218-1225.
Masjuan, J., Salido, L., DeFelipe, A., Hernández‐Antolín, R., Fernández‐Golfín, C., Cruz‐
Culebras, A., Matute, C., Vera, R., Pérez‐Torre, P. and Zamorano, J.L., 2019. Oral
anticoagulation and left atrial appendage closure: a new strategy for recurrent
cardioembolic stroke. European Journal of Neurology, 26(5), pp.816-820.
Nguyen, A., Gallet, R., Riant, E., Deux, J.F., Boukantar, M., Mouillet, G., Dubois-Rande, J.L.,
Lellouche, N., Teiger, E., Lim, P. and Ternacle, J., 2019. Peridevice leak after left atrial
appendage closure: incidence, risk factors, and clinical impact. Canadian Journal of
Cardiology, 35(4), pp.405-412.
Dobrev, D., Aguilar, M., Heijman, J., Guichard, J.B. and Nattel, S., 2019. Postoperative atrial
fibrillation: mechanisms, manifestations and management. Nature Reviews
Cardiology, 16(7), pp.417-436.
Perez, M.V., Mahaffey, K.W., Hedlin, H., Rumsfeld, J.S., Garcia, A., Ferris, T.,
Balasubramanian, V., Russo, A.M., Rajmane, A., Cheung, L. and Hung, G., 2019. Large-
scale assessment of a smartwatch to identify atrial fibrillation. New England Journal of
Medicine, 381(20), pp.1909-1917.
Linz, D., Elliott, A.D., Hohl, M., Malik, V., Schotten, U., Dobrev, D., Nattel, S., Böhm, M.,
Floras, J., Lau, D.H. and Sanders, P., 2019. Role of autonomic nervous system in atrial
fibrillation. International Journal of Cardiology, 287, pp.181-188.
Yasuda, S., Kaikita, K., Akao, M., Ako, J., Matoba, T., Nakamura, M., Miyauchi, K., Hagiwara,
N., Kimura, K., Hirayama, A. and Matsui, K., 2019. Antithrombotic therapy for atrial
fibrillation with stable coronary disease. New England Journal of Medicine, 381(12),
pp.1103-1113.
Andrade, J.G., Champagne, J., Dubuc, M., Deyell, M.W., Verma, A., Macle, L., Leong-Sit, P.,
Novak, P., Badra-Verdu, M., Sapp, J. and Mangat, I., 2019. Cryoballoon or
radiofrequency ablation for atrial fibrillation assessed by continuous monitoring: a
randomized clinical trial. Circulation, 140(22), pp.1779-1788.
Severino, P., Mariani, M.V., Maraone, A., Piro, A., Ceccacci, A., Tarsitani, L., Maestrini, V.,
Mancone, M., Lavalle, C., Pasquini, M. and Fedele, F., 2019. Triggers for atrial
fibrillation: the role of anxiety. Cardiology Research and Practice, 2019.
Boersma, L.V., Ince, H., Kische, S., Pokushalov, E., Schmitz, T., Schmidt, B., Gori, T., Meincke,
F., Protopopov, A.V., Betts, T. and Mazzone, P., 2019. Evaluating real-world clinical
outcomes in atrial fibrillation patients receiving the WATCHMAN left atrial appendage
closure technology: final 2-year outcome data of the EWOLUTION trial focusing on
32

history of stroke and hemorrhage. Circulation: Arrhythmia and Electrophysiology, 12(4),
p.e006841.
Yaghi, S., Chang, A.D., Akiki, R., Collins, S., Novack, T., Hemendinger, M., Schomer, A., Mac
Grory, B., Cutting, S., Burton, T. and Song, C., 2020. The left atrial appendage
morphology is associated with embolic stroke subtypes using a simple classification
system: a proof of concept study. Journal of cardiovascular computed
tomography, 14(1), pp.27-33.
Volkov, D., Gorbunov, D., Anohina, A., Shulga, E., Rygalov, D., Gulniashkina, K., Buyankov,
D. and Sakovich, V., 2021. Analysis of postoperative strokes in patients after resection or
suturing of the left atrial appendage. EP Europace, 23(Supplement_3), pp.euab116-121.
Pacha, H.M., Al-Khadra, Y., Soud, M., Darmoch, F., Pacha, A.M. and Alraies, M.C., 2019.
Percutaneous devices for left atrial appendage occlusion: a contemporary review. World
Journal of Cardiology, 11(2), p.57.
Albaghdadi, M., Kadlec, A., Adler, A., Siddiqui, U., Romanov, A., Kuck, K.H., Sievert, H.,
Leon, M.B. and Vahl, T., 2020. Peri-device leaks after percutaneous left atrial appendage
closure: Clinical significance and unmet diagnostic needs. Structural Heart, 4(6), pp.475-
481.
van den Berg, N.W., Neefs, J., Berger, W.R., Boersma, L.V., van Boven, W.J., van Putte, B.P.,
Kaya, A., Kawasaki, M., Driessen, A.H. and de Groot, J.R., 2019. PREventive left atrial
appenDage resection for the predICtion of fuTure atrial fibrillation: design of the
PREDICT AF study. Journal of Cardiovascular Medicine, 20(11), pp.752-761.
Xue, X., Jiang, L., Duenninger, E., Muenzel, M., Guan, S., Fazakas, A., Cheng, F., Illnitzky, J.,
Keil, T. and Yu, J., 2018. Impact of chronic kidney disease on Watchman implantation:
experience with 300 consecutive left atrial appendage closures at a single center. Heart
and vessels, 33(9), pp.1068-1075.
Kosturakis, R. and Price, M.J., 2018. Current state of left atrial appendage closure. Current
Cardiology Reports, 20(6), pp.1-9.
Fujita, K., Kajiyama, S., Noguchi, H. and Arita, T., 2022. Percutaneous left atrial appendage
closure for stroke prevention in patients with atrial fibrillation: Current status and future
perspective. Journal of Biorheology, 36(1), pp.31-37.
Masci, A., Barone, L., Dedè, L., Fedele, M., Tomasi, C., Quarteroni, A. and Corsi, C., 2019. The
impact of left atrium appendage morphology on stroke risk assessment in atrial
fibrillation: a computational fluid dynamics study. Frontiers in physiology, 9, p.1938.
Dudzińska-Szczerba, K., Michałowska, I., Piotrowski, R., Sikorska, A., Paszkowska, A.,
Stachnio, U., Kowalik, I., Kułakowski, P. and Baran, J., 2021. Assessment of the left
atrial appendage morphology in patients after ischemic stroke—The ASSAM
study. International Journal of Cardiology, 330, pp.65-72.
Kurzawski, J., Janion-Sadowska, A., Zandecki, L., Piatek, L., Koziel, D. and Sadowski, M.,
2020. Global peak left atrial longitudinal strain assessed by transthoracic
echocardiography is a good predictor of left atrial appendage thrombus in patients in
sinus rhythm with heart failure and very low ejection fraction–an observational
study. Cardiovascular ultrasound, 18(1), pp.1-11.
Caliskan, E., Sahin, A., Yilmaz, M., Seifert, B., Hinzpeter, R., Alkadhi, H., Cox, J.L., Holubec,
T., Reser, D., Falk, V. and Grünenfelder, J., 2018. Epicardial left atrial appendage
AtriClip occlusion reduces the incidence of stroke in patients with atrial fibrillation
undergoing cardiac surgery. Ep Europace, 20(7), pp.e105-e114.
33

Masoud, A., Bartoletti, S., Fairbairn, T., Khurana, A., Velavan, P., Morrison, W.L., Khalatbari,
A., Aggarwal, S., Sharma, N., Kirchhof, P. and Gupta, D., 2018. Outcome of left atrial
appendage occlusion in high-risk patients. Heart, 104(7), pp.594-599.
Granier, M., Guillaume Laugaudin, M.D., Franßois Massin, M.D., Stephane Cade, M.D., Pierre
Franßois Winum, M.D., Cornelia Freitag, M.D. and Pasquie, J.L., 2018. Occurrence of
incomplete endothelialization causing residual permeability after left atrial appendage
closure. Journal of Invasive Cardiology, 30(7).
Kawakami, H., Nolan, M.T., Phillips, K., Scuffham, P.A. and Marwick, T.H., 2021. Cost-
effectiveness of combined catheter ablation and left atrial appendage closure for
symptomatic atrial fibrillation in patients with high stroke and bleeding risk. American
Heart Journal, 231, pp.110-120.
Burysz, M., Litwinowicz, R., Burysz, A., Ogorzeja, W. and Bartuś, K., 2019. Causes of death
and morbidity in patients with atrial fibrillation after left atrial appendage
occlusion. Kardiologia Polska (Polish Heart Journal), 77(11), pp.1047-1054.
Korhonen, M., Mustonen, P., Hedman, M., Vienonen, J., Onatsu, J., Vanninen, R. and Taina, M.,
2018. Left atrial appendage morphology and relative contrast agent concentration in
patients undergoing coronary artery CTA. Clinical Radiology, 73(11), pp.982-e17.
Hutt, E., Wazni, O.M., Saliba, W.I., Kanj, M., Tarakji, K.G., Aguilera, J., Barakat, A.F.,
Rasmussen, P., Uchino, K., Russman, A. and Hussain, S., 2019. Left atrial appendage
closure device implantation in patients with prior intracranial hemorrhage. Heart
Rhythm, 16(5), pp.663-668.
Martin Gutierrez, E., Castano, M., Gualis, J., Martínez-Comendador, J.M., Maiorano, P.,
Castillo, L. and Laguna, G., 2020. Beneficial effect of left atrial appendage closure during
cardiac surgery: a meta-analysis of 280 585 patients. European Journal of Cardio-Thoracic
Surgery, 57(2), pp.252-262.
Masjuan, J., Salido, L., DeFelipe, A., Hernández‐Antolín, R., Fernández‐Golfín, C., Cruz‐
Culebras, A., Matute, C., Vera, R., Pérez‐Torre, P. and Zamorano, J.L., 2019. Oral
anticoagulation and left atrial appendage closure: a new strategy for recurrent
cardioembolic stroke. European Journal of Neurology, 26(5), pp.816-820.
Nguyen, A., Gallet, R., Riant, E., Deux, J.F., Boukantar, M., Mouillet, G., Dubois-Rande, J.L.,
Lellouche, N., Teiger, E., Lim, P. and Ternacle, J., 2019. Peridevice leak after left atrial
appendage closure: incidence, risk factors, and clinical impact. Canadian Journal of
Cardiology, 35(4), pp.405-412.
Toale, C., Fitzmaurice, G.J., Eaton, D., Lyne, J. and Redmond, K.C., 2019. Outcomes of left
atrial appendage occlusion using the AtriClip device: a systematic review. Interactive
cardiovascular and thoracic surgery, 29(5), pp.655-662.
Turagam, M.K., Osmancik, P., Neuzil, P., Dukkipati, S.R. and Reddy, V.Y., 2020. Left atrial
appendage closure versus oral anticoagulants in atrial fibrillation: a meta-analysis of
randomized trials. Journal of the American College of Cardiology, 76(23), pp.2795-2797.
Afsari, A., Abbosh, A.M. and Rahmat-Samii, Y., 2018. Modified born iterative method in
medical electromagnetic tomography using magnetic field fluctuation contrast source
operator. IEEE Transactions on Microwave Theory and Techniques, 67(1), pp.454-463.
Kaur, S., Singla, J., Nkenyereye, L., Jha, S., Prashar, D., Joshi, G.P., El-Sappagh, S., Islam, M.S.
and Islam, S.R., 2020. Medical diagnostic systems using artificial intelligence (ai)
algorithms: Principles and perspectives. IEEE Access, 8, pp.228049-228069.
34

Yang, Y., Feng, C. and Wang, R., 2020. Automatic segmentation model combining U-Net and
level set method for medical images. Expert Systems with Applications, 153, p.113419.
Dilibal, C., Davis, B.L. and Chakraborty, C., 2021, June. Generative design methodology for
internet of medical things (IoMT)-based wearable biomedical devices. In 2021 3rd
International Congress on Human-Computer Interaction, Optimization and Robotic
Applications (HORA) (pp. 1-4). IEEE.
Aluculesei, A.C., Nistoreanu, P., Avram, D. and Nistoreanu, B.G., 2021. Past and Future Trends
in Medical Spas: A Co-Word Analysis. Sustainability, 13(17), p.9646.
Hassanin, A.A.I.M., Shaaban, A.S.E. and Abd El-Samie, F.E., 2019, June. Medical applications
of image reconstruction using electromagnetic field in terahertz frequency range. In 2019
International Symposium on Networks, Computers and Communications (ISNCC) (pp. 1-
4). IEEE.
Simona Răboacă, M., Dumitrescu, C., Filote, C. and Manta, I., 2020. A New Adaptive Spatial
Filtering Method in the Wavelet Domain for Medical Images. Applied Sciences, 10(16),
p.5693.
Diwakar, M., Shankar, A., Chakraborty, C., Singh, P. and Arunkumar, G., 2022. Multi-modal
medical image fusion in NSST domain for internet of medical things. Multimedia Tools
and Applications, pp.1-21.
Choudhary, N., Kumar, A., Sharma, V. and Kumar, P., 2021. Barriers in adoption of additive
manufacturing in medical sector supply chain. Journal of Advances in Management
Research.
Qian, Y., Han, Q., Yuan, W. and Fan, C., 2018. Insights into medical humanities education in
China and the West. Journal of International Medical Research, 46(9), pp.3507-3517.
Yu, X., Hu, W., Lu, S., Sun, X. and Yuan, Z., 2019, August. BioBERT based named entity
recognition in electronic medical record. In 2019 10th international conference on
information technology in medicine and education (ITME) (pp. 49-52). IEEE.
Zhang, J., Hu, Q., Wang, S., Tao, J. and Gou, M., 2020. Digital light processing based three-
dimensional printing for medical applications. International Journal of Bioprinting, 6(1).
Auf, A.I., Awadalla, H., Ahmed, M.E. and Ahmed, M.H., 2018. Perception, barriers, and
practice of research among teaching staff at five Sudanese medical faculties. Journal of
Public Health and Emergency, 2(22), pp.1-8.
Akkasaligar, P.T. and Biradar, S., 2020. Selective medical image encryption using DNA
cryptography. Information Security Journal: A Global Perspective, 29(2), pp.91-101.
Wang, Z., Cui, Z. and Zhu, Y., 2020. Multi-modal medical image fusion by Laplacian pyramid
and adaptive sparse representation. Computers in Biology and Medicine, 123, p.103823.
Online
The Cerebral Circulation, 2010, [Online] available through:
<https://www.ncbi.nlm.nih.gov/books/NBK53086/>
Stroke, 2022, [Online] available through:
<https://www.medicinenet.com/stroke_symptoms_and_treatment/article.htm>
35

APPENDIX
APPENDIX A: MeSH term
Population “Young people” [MeSH Terms] OR “young” [All Fields] OR “young” [All
Field] OR “young’s” [All Field]
“Stroke” [MeSH Terms] OR “Strokes” [All Fields] OR “Stroke’s” [All field]
Intervention “Left atrial appendage closure” [MeSH Terms] OR “left atrial appendage
closure” [All Field]
Comparison None
Outcome “Prevent stroke” [MeSH Terms] OR “prevent stroke” [All Field] OR “Patient
recovery” [All field] OR “patient recovery” [All field] OR “Comfort patient”
[All field] OR “comfort patient” [All field]
APPENDIX B: Data extraction process
Criteria/Author Payam et. al.,
2018
Fareed et. al.,
2021
Richard et. al.,
2021
Mathew et. al.,
2014
Random
sequence
formulation
Allocation
Blinding of
participants
Incomplete
outcome data
Selection bias
Other risk of bias
36

37