Can Left Atrial Strain Measurements, and Correlating Changes in Left Atrium Area and Volume Size, be Used as an Early Predictor of Atrial Fibrillation?
Conditions: Atrial Fibrillation, Hypertension
Sponsor: Hywel Dda Health Board

1 
Protocol: Left Atrial Strain Values as an Early Predictor of Atrial Fibrillation, V6 17/05/2023 
 
PROTOCOL 
Title Page 
 
Study Title: Can left atrial strain measurements, and correlating changes in left 
atrium area and volume size, be used as an early predictor of atrial fibrillation?   
 
Acronym/Short Title: Left Atrial Strain Values as an Early Predictor of Atrial Fibrillation  
 
Protocol/Study ID: IRAS 324893 
 
 
REC Reference: 
 
 
 
 
Version Number: 6.0 , 17/05/2023 
 
 

2 
Protocol: Left Atrial Strain Values as an Early Predictor of Atrial Fibrillation, V6 17/05/2023 
 
Study Summary 
 
 
Study Outline 
Atrial fibrillation (AF) is the most prevalent type of arrhythmia within 
an adult population and is characterised by disorganised, chaotic, 
electrical activity and thus, ineffective atrial contraction causing 
irregular ventricular contraction.  AF can be categorised into three 
different groups: paroxysmal, persistent and permanent. The 
prevalence of AF increases with age and is associated with a range 
of risk factors including: hypertension, obesity and alcohol 
consumption. There is a plethora of both cardiac and non-cardiac 
causes of AF and the cause is not always clear for each patient. 
Furthermore, causes of AF can also present as the by-product of AF, 
this increases the difficulty in determining the individual patient’s 
cause of onset. A diagnosis of AF can be incidental as not all patients 
are symptomatic. If AF goes undetected, this puts the patient at an 
increased risk of blood clot formation and stroke.  
Patients suspected of having AF are routinely referred for a 
transthoracic echocardiogram (TTE). It is common for AF patients to 
have a dilated left atrium (LA). This can be visually confirmed, and 
the LA area and volume can be measured during a TTE. LA strain 
measurements are not routinely measured during TTEs but may be 
able to detect subtle changes in longitudinal strain patterns of the 
myocardium. By comparing the strain patterns in patients with normal 
sinus rhythm (control) to those with AF, a scale can be created to 
suggest and predict whether a patient is likely to develop AF in the 
future based on these subtle changes before any changes in LA size 
occur. Furthermore, this can then be further developed to determine 
whether there are any significant differences in strain patterns 
between the three AF groups. 
Lay Summary 
Atrial fibrillation (AF) is the most common type of abnormal heart 
rhythm. This occurs as the chambers of the heart pump irregularly, 
often resulting in a fast heart rate and symptoms of irregular pounding 
and fluttering. There are many risk factors predisposing to AF, 
however, the cause cannot always be easily determined. 
Additionally, not all AF patients experience symptoms and 
consequently, this abnormal rhythm may go undetected and may be 
discovered accidentally. This is detrimental to patients, as untreated 
AF patients are at an increased risk of stroke.  
Patients that are suspected of having AF are referred for an 
ultrasound scan of the heart (echocardiogram). It is expected to see 
structural changes to the heart's chambers. However, structural and 
electrical changes of the heart may be the cause of AF but may also 
be a result of AF, resulting in a chicken and egg situation. It may be 
possible that a different type of measurement can be used during an 
echocardiogram to detect subtle changes in heart muscle patterns. 
This measurement may then serve to be an early predictor of AF. 
This would be determined by comparing the patterns in patients with 
a normal, regular rhythm to those with AF. 
Potential candidates are initially screened based on their 
echocardiogram referral. If deemed suitable for this study, the study 

3 
Protocol: Left Atrial Strain Values as an Early Predictor of Atrial Fibrillation, V6 17/05/2023 
process is explained to the patient and written informed consent is 
invited and received. The echocardiogram will be performed as 
normal with a focus on the area and volume measurements taken of 
one of the top chambers of the heart. An additional measurement will 
be taken to observe any subtle changes in the arrangement of heart 
cells within this same heart chamber. These measurements can be 
compared to each other to establish any relationship as well as 
compared to patients with and without AF.  
Objectives 
To determine whether there is a significant difference in atrial strain 
values between patients that are in normal sinus rhythm (NSR, 
control group) to patients that are known to have atrial fibrillation 
(disease group). A disease-control group of controlled hypertensive 
patients in NSR will also be utilised as hypertension is a known risk 
factor for atrial fibrillation.  
 
Providing that there is a significant difference in the values between 
NSR and AF patients, a further comparison will be conducted on 
patients in different type of AF: paroxysmal AF, persistent AF and 
permanent AF to determine if there is a deterioration in atrial strain 
values within AF patients. 
 
Left atrial area and volume size will also be measured in all patients 
and this can then be compared to atrial strain values.  
Sample Size  
234 
Duration 
1 year – project end date of March 2024 
 

4 
Protocol: Left Atrial Strain Values as an Early Predictor of Atrial Fibrillation, V6 17/05/2023 
 
Statement of Compliance 
The study as detailed within this protocol (Version 6, 17/05/2023) or any subsequent 
amendments will be conducted in accordance with the International Conference on 
Harmonization guidelines for Good Clinical Practice (ICH E6), the UK Policy Framework for 
Health and Social Care Research (2017), the World Medical Association Declaration of 
Helsinki (1996) and the current applicable regulatory requirements and any subsequent 
amendments of the appropriate regulations. 
 

5 
Protocol: Left Atrial Strain Values as an Early Predictor of Atrial Fibrillation, V6 17/05/2023 
Signature Page 
The signature below constitutes the approval of this protocol and the Patient Information 
Sheet, Informed Consent Form, Case Report Form for Research, Good Clinical Practice 
Certificate, Curriculum Vitae, Gantt Chart and Power Calculations attached and provides the 
necessary assurances that this study will be conducted according to all stipulations of the 
protocol, including all statements regarding confidentiality, and according to local legal and 
regulatory requirements. 
 
Principal Investigator: 
 
Signed: 
L. M. Hwozdyk 
Date: 
17/05/2023 
 
Name: Lucy Hwozdyk  
 
Title: Trainee Clinical Scientist – Cardio-Respiratory Department, Withybush 
General Hospital, Hywel Dda University Health Board 
 
 
 
 
 
 
 
 

6 
Protocol: Left Atrial Strain Values as an Early Predictor of Atrial Fibrillation, V6 17/05/2023 
Contact Details 
 
Chief Investigator 
Name: Miss Lucy Hwozdyk  
Role: Trainee Clinical Scientist – Cardio-Respiratory Department 
Site: Withybush General Hospital, HDUHB 
Email: lucy.hwozdyk@wales.nhs.uk 
Tel: 07704032344 
 
Co Investigators 
Name: Dr. Nikolaos Anatoliotakis  
Role: Consultant Cardiologist 
Site: Withybush General Hospital, HDUHB 
Email: nikolaos.anatoliotakis@wales.nhs.uk 
Tel: 01437773892 
 
Co Investigators 
Name: Mrs Teleri Cudd 
Role: Advanced Cardiac Physiologist  
Site: Withybush General Hospital, HDUHB 
Email: teleri.cudd@wales.nhs.uk 
Tel: 01437773410 
 
 
Collaborators 
Name: Mr. Rehan Junejo 
Role: Academic Supervisor  
Site: Manchester Metropolitan University 
Email: r.junejo@mmu.ac.uk 
 
Name: Dr. Gareth Davies 
Role: Statistical Support & Research Assistant   
Site: Prince Phillip Hospital, HDUHB 
Email: gareth.davies14@wales.nhs.uk 
Tel: 01554899048 
 
 

7 
Protocol: Left Atrial Strain Values as an Early Predictor of Atrial Fibrillation, V6 17/05/2023 
Contents 
Title Page ................................................................................................................... 1 
Study Summary .......................................................................................................... 2 
Statement of Compliance ........................................................................................... 4 
Signature Page .......................................................................................................... 5 
Contact Details ........................................................................................................... 6 
Abbreviations and Glossary of Terms……………………………………………………..9 
1.Introduction ........................................................................................................... 10 
1.1Background ..................................................................................................... 11 
1.2Research Question .......................................................................................... 12 
2.Study Outline ......................................................................................................... 13 
2.1Aims and Objectives ........................................................................................ 13 
2.2Method ............................................................................................................. 13 
2.2.1 Study Type ............................................................................................... 14 
2.2.2 Study Overview ........................................................................................ 14 
2.2.3 Study Populations, Subject Selection, Recruitment and Study Schedule 14 
2.2.4 Eligibility Criteria ....................................................................................... 15 
2.2.5 Power Calculation .................................................................................... 15 
2.2.6 Statistical Analysis Plan ........................................................................... 16 
2.3 Study Outcomes ............................................................................................. 16 
2.4 Timescale ....................................................................................................... 17 
2.5 Publication Policy ............................................................................................ 17 
3.Screening, Consent and Withdrawal ..................................................................... 18 
3.1Screening Duties ............................................................................................. 18 
3.2 Informed Consent Procedures ........................................................................ 18 
3.3 Study withdrawal ............................................................................................. 19 
4.Risk, Ethical Considerations and Confidentiality ................................................... 20 
4.1 Risk and Benefits ............................................................................................ 20 
4.2 Ethical Considerations .................................................................................... 20 
4.3 Patient & Public Involvement .......................................................................... 20 
4.4 Confidentiality ................................................................................................. 20 
4.5 Premature Termination or Suspension of Study ............................................. 20 
4.6 Future Use of Stored Specimens and Other Identifiable Data ........................ 21 
4.7 Record Retention, Storing and Archiving ........................................................ 21 
4.8 Study Oversight .............................................................................................. 21 
4.9 Study Reporting .............................................................................................. 21 
4.10 Safety Reporting ........................................................................................... 21 

8 
Protocol: Left Atrial Strain Values as an Early Predictor of Atrial Fibrillation, V6 17/05/2023 
5.References ............................................................................................................ 22 
Appendix .................................................................................................................. 24 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

9 
Protocol: Left Atrial Strain Values as an Early Predictor of Atrial Fibrillation, V6 17/05/2023 
Abbreviations: 
 
AF 
 
= 
 
atrial fibrillation 
AFI 
 
= 
 
automated function imaging 
ANOVA 
= 
 
analysis of variance 
BSE  
= 
 
British Society of Echocardiography 
CI 
 
= 
 
Chief Investigator 
EF 
 
= 
 
ejection fraction 
GDPR  
= 
 
general data protection regulation 
GLS  
= 
 
global longitudinal strain 
HRA  
= 
 
Health Research Authority  
ICF 
 
= 
 
Informed Consent Form 
LA 
 
= 
 
left atrium/atria 
LV 
 
= 
 
left ventricle 
NHS  
= 
 
National Health Service 
NSR  
= 
 
normal sinus rhythm 
PACS  
= 
 
picture archiving system 
PAF  
= 
 
paroxysmal atrial fibrillation 
PALS  
= 
 
peak atrial longitudinal strain 
PI 
 
= 
 
Principal Investigator 
PIS 
 
= 
 
Participant Information Sheet 
REC  
= 
 
Research Ethics Committee 
R&D  
= 
 
Research & Development 
STE  
= 
 
speckle tracking echocardiography 
TTE 
 
= 
 
transthoracic echocardiogram 

10 
Protocol: Left Atrial Strain Values as an Early Predictor of Atrial Fibrillation, V6 17/05/2023 
1. Introduction  
 
Atrial fibrillation (AF) is the most prevalent type of arrhythmia within an adult population 
and is characterised by disorganised, chaotic, electrical activity and thus ineffective 
atrial contraction causing irregular ventricular contraction (Wyndham, 2000).  AF can 
be categorised into three different groups: paroxysmal, persistent, and permanent. 
The prevalence of AF increases with age and is associated with, but not limited to, a 
range of risk factors including hypertension, obesity, and alcohol consumption (Staerk, 
et al., 2017). There is a plethora of both cardiac and non-cardiac causes of AF and 
the cause is not always clear for each patient. Furthermore, causes of AF can also 
present as the by-product of AF, this increases the difficulty in determining the 
individual patient’s cause of onset. A diagnosis of AF can be incidental as not all 
patients are symptomatic. If AF goes undetected, this puts the patient at an increased 
risk of blood clot formation and stroke (Markides and Schilling, 2003).    
  
Patients suspected of having AF are routinely referred for a transthoracic 
echocardiogram (TTE). It is common for AF patients to have a dilated left atrium (LA) 
and this can be visually confirmed in addition to the LA area and volume 
measurements (Van De Vegte, et al., 2021). However, as LA measurements are 
limited to area and volume size, LA strain measurements may be taken but these are 
not routinely performed during standard TTEs. LA strain is measured using a type of 
speckle-tracking echocardiography (STE) technique which focuses on the subtle 
longitudinal changes within the myocardium to analyse myocardial deformation (Gan, 
et al., 2018). Strain imaging of the LA produces three functional strain values 
(contractile, conduit and reservoir) which correspond to different stages of the cardiac 
cycle (Jarasunas, et al., 2018). As patients in AF lack normal atrial contraction and 
have a loss of atrial kick, it is expected that the contractile strain, associated with LA 
contraction, is not present. However, the conduit and reservoir functions can still be 
compared across all three study groups to create a scale to suggest and predict 
whether a patient is likely to develop AF in the future; prior to any changes in LA size. 
Furthermore, this can then be further compared to determine whether there are any 
significant differences in strain patterns between the different groups of AF.   
  
The correlation between AF and a dilated LA are widely recognised, however, LA 
enlargement may be both a cause and consequence of AF. Dilation of the LA has 
been largely suggested to be due to atrial remodelling as a result of a change in atrial 
function and structure – as seen in the case of AF. However, there are other factors 
which affect atrial function and structure which ultimately result in atrial remodelling. 
This includes pathologies such as mitral valve disease (mitral stenosis, regurgitation, 
or a mixed disease), structural cardiac disease (such as heart failure, 
cardiomyopathies, and congenital disease) and hypertension (Van De Vegte, et al., 
2021). As hypertension can also cause atrial remodelling and is a risk factor for AF, 
patients that are in normal sinus rhythm (NSR) that have controlled hypertension are 
included in this study as a disease-control group. It is expected that the atrial strain 
values of these patients will fall between those of the control group (NSR) and of those 
in the disease group (chronic AF).  
  
Existing available literature (see document Literature Review Table) suggests that 
there is a significant difference in the strain values between patients in NSR to those 
in AF. However, limited studies have included hypertensive patients or investigated 

11 
Protocol: Left Atrial Strain Values as an Early Predictor of Atrial Fibrillation, V6 17/05/2023 
the differences in strain values between AF patients. Furthermore, previous studies 
have been limited by method technique. This is because many studies have either 
used external STE software to create atrial strain values or have adopted global 
longitudinal strain (GLS) methods to track the LA. This is a significant limiting factor as 
GLS methods are intended to assess longitudinal function of the left ventricle. 
 
 
1.1 
 Background 
 
From the current literature available (see document Literature Review Table), it has 
been suggested that there is a correlation between AF and LA strain values. Existing 
literature suggests that patients in AF have a reduced LA strain value compared to 
patients in NSR. However, there are limited studies which also include controlled 
hypertensive patients despite collecting data regarding blood pressure. Furthermore, 
the majority of literature reviewed appears to focus on patients that have other co-
morbidities, and it could be argued that these can affect the parameters measured 
and analysed. This includes studies involving patients with valvular pathologies such 
as aortic stenosis and aortic valve replacements as well as studies involving patients 
with potential structural heart deformations such as those seen with heart failure or 
following a myocardial infarction. These factors may alter strain patterns and LA size 
as a result. By listing these factors as exclusion criteria, this study should minimise 
any external and uncontrollable factors which may affect LA strain value and LA size. 
 
Furthermore, some studies do not have a standardised zero-reference point as some 
studies used the P wave for NSR and the R wave for AF patients which may cause a 
discrepancy in results. In this study, it has been agreed that the zero-reference point 
will be the R wave to create R-R cycles. This is because the P wave is not present in 
AF and thus cannot be used as a definitive reference point within the AF group. Both 
groups will have R waves present and therefore, the reference-point can be 
standardised across all three groups.  Additionally, many of the studies reviewed 
appear to focus on only one LA strain and phase within the cardiac cycle. However, 
some do include all three. This study will include all three strain values as well as 
peak atrial longitudinal strain (PALS) values. However, statistical analysis may not 
be doable for the contractile phase as this is not present in patients with AF. The 
biggest pitfall that is common to most, if not all, studies reviewed is that the methods 
used to calculate LA strain were originally designed to measure global longitudinal 
strain (GLS) of the left ventricle (LV). This study utilises the automated function 
imaging (AFI) LA atrial strain tool provided by GE Healthcare which is specific to the 
LA as opposed to GLS methods to track the LV.  
 
The key outcomes from this study will be whether there is a significant difference in 
atrial strain values between NSR patients, controlled hypertensive patients and 
patients with either persistent or permanent AF. These electrical changes should 
correlate with structural changes within the LA as the LA becomes more dilated in AF 
patients. Furthermore, subtle differences in LA strain values may be observed 
between patients with paroxysmal atrial fibrillation (PAF), persistent and permanent 
AF to suggest a decline in atrial strain patterns with a worsening and prolongation of 
AF.  
  

12 
Protocol: Left Atrial Strain Values as an Early Predictor of Atrial Fibrillation, V6 17/05/2023 
This will have a significant impact to the general population as AF is the most common 
arrhythmia. Left atrial enlargement and dilation can occur, either as a cause or 
complication of AF. However, the detection of this structural change and cardiac 
remodelling by measuring LA area and volume is often only detected when the patient 
has been in AF for a prolonged period of time. The utilisation of speckle-tracking 
echocardiography (STE) and atrial strain measurements may be able to detect subtle 
changes in LA strain pattern which may occur before any significant cardiac 
remodelling and LA dilation, and thus serve as an early predictor of AF. This will allow 
for closer monitoring and the correct administration of anticoagulants. Furthermore, 
the results from this study will also be generalisable and transferrable and may 
suggest that LA strain measurements should be more routinely performed during 
TTEs.  
 
 
1.2 
 Research Question  
 
Can measurements of left atrial strain, along with correlating changes in left atrium 
area and volume size, be used as an early predictor of atrial fibrillation? 
 
 
 
 
 
 
 
 
 
 
 
 
 

13 
Protocol: Left Atrial Strain Values as an Early Predictor of Atrial Fibrillation, V6 17/05/2023 
 
2. Study Outline 
 
2.1 Aims and Objectives 
 
The aims of this research project are split into two sets of comparisons. The first is to 
determine whether there is a statistically significant difference between atrial strain 
values in normal sinus rhythm (NSR) patients (control group), to controlled 
hypertensive patients (disease-control group) and patients with established, chronic 
AF (disease group). Atrial strain values from these groups will also be compared to 
left atrium (LA) area and volume to determine correlation. Furthermore, providing there 
is a significant difference, atrial strain values between AF groups PAF, persistent, and 
permanent can also be compared to potentiate deterioration of atrial strain. 
 
Null hypothesis: There is no significant difference between the atrial strain 
measurements in patients with normal sinus rhythm to patients with chronic atrial 
fibrillation and no correlation between atrial strain measurements and left atrium are 
and volume size. 
 
Research / alternative hypothesis: There is a statistically significant difference 
between atrial strain values between patients with normal sinus rhythm and patients 
with atrial fibrillation and this correlates with changes seen in left atrium area and 
volume size.  
 
2.2 Method  
 
Patient selection: 
Potential candidates for this study will have been referred for a TTE by a healthcare 
professional. The referrals will be reviewed and if the patient meets the initial eligibility 
criteria, they will be considered as part of this study. The initial eligibility criteria consist 
of being over the age of 50 (although patients will be age-matched across the three 
groups) and falling within the control (normal sinus rhythm), disease-control (controlled 
hypertension) or disease groups (chronic AF). 
 
Data collection: 
The images obtained from the TTE scan will be stored on the ultrasound machine as 
well as the picture archiving systems (PACS) on the computer. The measurements to 
be compared are: 
- 
Left atrium area 
- 
Left atrium volume 
- 
Left atrium strain measurement and analysis using the R wave 
 
The first two measurements are routinely performed during TTEs, but atrial strain 
measurements are not routinely performed. This additional measurement will not 
affect or delay the TTE results and report from being sent back to the referrer or delay 
any further correspondences with other healthcare professionals. Atrial strain 
measurements will be conducted using the AFI LA atrial strain tool provided by GE 
Healthcare. These three measurements will be compared across the three groups and 
tested for a statistically significant difference. Providing that there is a significant 

14 
Protocol: Left Atrial Strain Values as an Early Predictor of Atrial Fibrillation, V6 17/05/2023 
difference, particularly between the control and disease groups, a subsequent 
comparison will be conducted between the three groups of AF using the existing data. 
 
 
2.2.1 Study Type 
Single centre case-control study, quantitative and a prospective study.  
 
2.2.2 Study Overview 
• Study design – quantitative, observational, case-control study. 
• Patients will be assigned to one of three groups: control group (normal sinus 
rhythm), disease-control group (controlled hypertension) and disease group 
(chronic atrial fibrillation). 
• Patients will be required to visit the department on one occasion. This will be 
as part of either a routine or urgent referral for a transthoracic echocardiogram 
(TTE).  
• TTEs are stored on both the ultrasound machines and computer picture 
archiving systems (PACS). Measurements can be taken on either the 
ultrasound machine or on the PACS following the patient’s scan. The data 
obtained from these scans that will be utilised include patient demographics, 
heart rate and rhythm, LA area and volume measurements as well as LA strain 
measurements. This will be pseudo-anonymised using two Excel spreadsheets 
and the document will be password encrypted on a NHS OneDrive account 
• Study site: within the Cardio-Respiratory department at Withybush General 
Hospital, there are five sonographers. This creates a throughput of 
approximately 60 TTE scans per week. With an expected data collection period 
of five months, this would equate to approximately 1200 outpatient scans – 
factoring in annual leave and sickness. Additionally, inpatient scans can boost 
this number, but is dependent on current demand.  
 
2.2.3 Study Populations, Subject Selection, Recruitment and Study Schedule 
Sampling design – only patients that have been referred for a transthoracic 
echocardiogram will be included as part of this study. Patient referrals will be screened 
to assess whether the patients fit into either of the three study groups. On patient 
arrival, patients that are deemed to be eligible thus far will be provided with an 
explanation of the study, patient information documents, and written informed consent 
is to be invited and received. Departmental sonographers may initiate Research 
discussion with patient either pre- during or post- scan, prior to the CI explaining the 
study in full and obtaining written informed consent. Providing that the transthoracic 
scan images are of a good enough quality to obtain strain measurements, the patient 
will be included as part of the study. Recruitment options will be tailored to the 
participant and may be either remotely or at time of clinic visit. Once potential 
candidates have been screened, it is envisaged that the invitation letter, Participant 
Information Sheet (PIS), Informed Consent Form (ICF) and a template ICF will be 
posted to the participant along with their appointment letter for an echocardiogram. 
This will allow plenty of time for potential participants to read over the PIS. The patient 
then may be contacted prior to their appointment via telephone to discuss the study 
and participant involvement and give verbal consent. If this is not feasible, the study 
should be discussed with patient during their appointment visit and written consent 
can be obtained. If the CI is not able to discuss the study with the patient at either of 

15 
Protocol: Left Atrial Strain Values as an Early Predictor of Atrial Fibrillation, V6 17/05/2023 
these times, the patient may be telephoned following their scan to discuss and provide 
verbal consent. 
 
 
2.2.4 Eligibility Criteria  
Patients must be in one of the following categories to be included: normal sinus 
rhythm, normal sinus rhythm with controlled hypertension and chronic atrial fibrillation 
(persistent or permanent). Patients with paroxysmal AF may also be included but only 
as part of subsequent analysis when comparing strain measurements between AF 
groups. Additionally, eligible patients must conform to the following inclusion and 
exclusion criteria.  
 
Inclusion criteria:    
- 
Criterion 1: subjects will be included in the study if they are within one of the 
following groups: 
o Known to be in normal sinus rhythm, are normotensive and have no 
underlying health problems. 
o Known to be in normal sinus rhythm and have controlled hypertension. 
This must have been diagnosed by a healthcare professional and the 
patient should be taking appropriate antihypertensive medication. 
o Known to have chronic atrial fibrillation (persistent or permanent AF). 
This must have been diagnosed by a healthcare professional and the 
patient should be appropriately anticoagulated.  
- 
Criterion 2: subjects should ideally be ≥ 50 years, but subjects will be age 
matched across all three groups. 
- 
Criterion 3: patients should have an EF ≥ 50%. 
- 
Criterion 4: good quality TTE images. 
- 
Criterion 5: No valvular pathologies.  
o Patients with AF that have < moderate valvular pathologies may be 
considered (as per the British Society of Echocardiography Guidelines). 
 
Exclusion criteria:  
- 
Criterion 1: subjects with any valvular pathologies in the control and disease-
control groups. 
- 
Criterion 2: subjects with AF that have ≥ moderate valvular pathologies (as per 
the British Society of Echocardiography Guidelines).  
- 
Criterion 3: subjects with an EF < 50%. 
- 
Criterion 4: subjects < 50 years old. 
- 
Criterion 5: poor quality TTE images. 
- 
Criterion 6: inability to provide informed consent. 
- 
Criterion 7: permanent atrial / ventricular pacing. 
- 
Criterion 8: previous cardiac surgery. 
- 
Criterion 9: unsatisfactory tracking of the LA endocardial border. 
- 
Criterion 10: patients unwilling to have their results potentially published 
 
 
2.2.5 Power Calculation 
 
The study aims to investigate significant differences in atrial strain values between 
subjects with atrial fibrillation (AF), hypertension (no AF), and healthy volunteers. To 

16 
Protocol: Left Atrial Strain Values as an Early Predictor of Atrial Fibrillation, V6 17/05/2023 
achieve statistical power for this study, a large enough sample size must be obtained. 
This will be achieved via the use of power calculations utilising G*Power 3.1 Statistical 
support has been provided and a sample size calculation was based on data found 
within the literature and involved detecting the smaller difference of left atrium 
contractile % between subjects with atrial fibrillation and healthy volunteers. The 
following criteria will be utilised: alpha level of 0.05, beta level of 15% and statistical 
power of 85%. Hence using this minimum value to determine our sample size 
(expected difference of 4.0, power = 0.85 and SD ± 7.5) and one-way ANOVA at three 
levels, a minimum sample size of at least 78 subjects in each group will be required 
for this study, total of 234 participants required. See Appendix Figures 1 & 2 for power 
calculation plots. 
 
 
2.2.6 Statistical Analysis Plan 
Continuous data normality will be assessed utilising the Shapiro-Wilk test. Non-
parametric data will be analysed via Mann-Whitney U tests and Kruskal-Wallis one-
way ANOVA tests. If data shows a normal distribution, to compare the LA strain values 
between the control (NSR) and disease (AF) groups an independent T-test can be 
performed; this will establish whether there is an initial statistically significant 
difference between the two. Following this, to compare the mean strain values for each 
phase between the three groups, a one-way ANOVA must be performed. A one-way 
ANOVA can also be performed to determine any significant differences between the 
strain values between AF groups. These data analysis methods will also be repeated 
to analyse LA area and volume. To assess whether LA area and volume size correlate 
with LA strain, a Pearson correlation coefficient must also be performed. Furthermore, 
to determine whether LA strain may be used as an early predictor of AF, linear 
regression models must be adapted. For categorical data, such as gender, chi-
squared tests will be performed to determine any significant difference between 
groups. All statistical tests will be performed using the Prism GraphPad software. 
  
It is expected that there will be a significant difference in strain values between NSR 
and AF participants. It is also expected that an increase in LA area and volume size 
will correlate with a decrease in LA strain values. 
 
2.3 Study Outcomes 
The key outcomes from this study will be whether there is a significant difference in 
atrial strain values between NSR patients, controlled hypertensive patients and 
patients with either persistent or permanent AF. These electrical changes should 
correlate with structural changes within the LA as the LA becomes more dilated in AF 
patients. Furthermore, subtle differences in LA strain values may be observed 
between patients with PAF, persistent and permanent AF to suggest a decline in atrial 
strain patterns with a worsening and prolongation of AF. 
 
This will have a significant impact to the general population as AF is the most common 
arrhythmia. Left atrial enlargement and dilation can occur, either as a cause or 
complication of AF. However, the detection of this structural change and cardiac 
remodelling by measuring LA area and volume is often only detected when the patient 
has been in AF for a prolonged period. The utilisation of speckle-tracking 
echocardiography (STE) and atrial strain measurements may be able to detect subtle 
changes in LA strain pattern which may occur before any significant cardiac 

17 
Protocol: Left Atrial Strain Values as an Early Predictor of Atrial Fibrillation, V6 17/05/2023 
remodelling and LA dilation, and thus serve as an early predictor of AF. This will allow 
for closer monitoring and the correct administration of anticoagulants. 
 
2.4 Timescale 
The project completion date is estimated to be March 2024 with the possibility of 
publishing following this. An overview of the entire project timescale can be visualised 
in the Gantt Chart – see Appendix Figure 3. The project has been split into three 
phases: project planning, data collection and analysis and dissertation write up and 
submission. The planning stage includes sponsorship and ethics approval and has an 
estimated completion date of May 2023. Following this, data collection and analysis 
may commence and in order to allow for sufficient data collection, a deadline of the 
end of November 2023 has been set. Furthermore, the end of January 2024 has been 
set to complete data analysis. The final stage consists of the write up of results, 
discussion and conclusion. Some of which may commence alongside data analysis 
and should be complete at the end of February 2024, ready for March submission. 
The date of the last visit for the patient will denote the end of the study. There are no 
follow-ups post echocardiogram required for this study, only data collection and 
analysis after this point. 
 
2.5 Publication Policy  
 
As findings from this study may be applicable in a much wider setting, it is important 
that any significant findings and benefits to patients are widely disseminated 
throughout research. Patients will be informed as part of the participant information 
document as well as verbally during their appointment regarding the intentions to 
possibly publish study findings. The participants are welcome to access and receive a 
copy of the findings and publication if they wish to do so post-study. It will be reiterated, 
and patients should be assured that any publishable findings will be completely 
anonymised and that no identifiers will be present in the publication which can link 
back the results to individual participants. Subjects who are not happy to have their 
results potentially published will be excluded from the study.  

18 
Protocol: Left Atrial Strain Values as an Early Predictor of Atrial Fibrillation, V6 17/05/2023 
 
3. Screening, Consent and Withdrawal 
 
3.1 
 Screening Duties  
The Chief Investigator will be responsible for screening potential participants. This will 
be done by reviewing both in-patient and out-patient referrals to look for patients that 
are in one of the following categories: normal sinus rhythm, normal sinus rhythm with 
controlled hypertension and chronic atrial fibrillation. Subsequently, this can be further 
refined by excluding patients based on age, valvular pathologies and ventricular 
dysfunction.  
 
3.2 
 Informed Consent Procedures  
The CI will be responsible for inviting and receiving informed consent. Once potential 
candidates have been screened, it is envisaged that the invitation letter, PIS, ICF and 
a template ICF will be posted to the participant along with their appointment letter for 
an echocardiogram. The study team will telephone participants after they have 
received this information and prior to their TTE to explain the study details and to 
confirm whether they are interested in participating. Verbal, telephone consent can be 
given and recorded at this time. Written consent can also be given if the patient wishes 
to complete the received ICF, following the template ICF. Additionally, written consent 
may be given if the research team are unable to contact the patient prior to their 
appointment. This can be completed during the echocardiogram appointment via 
written informed consent. If patients are not contactable prior to their appointment, or 
patients contacted during their appointment wish to have more time to think about their 
decision, the patient may be contacted following their scan to obtain verbal, telephone 
consent. Similarly, if the patient is not contactable prior to their scan, and the CI is 
unable to discuss the study with the patient during their appointment, then again, the 
patient may be contacted via telephone following the TTE to obtain verbal, telephone 
consent. Furthermore, if a potential candidate for the study is an in-patient, after the 
referral has been screened, the CI will go to the appropriate ward and provide the 
patient with the PIS, ICF and template ICF. The study may be explained to the patient 
at this time or at the time of the scan and only written informed consent can be given 
in this instance. Participants will be enrolled into the study once verbal or written 
consent have been given. If telephone consent is obtained, a copy of the signed 
consent form will be provided to the participant – either during their appointment visit 
or via post following the scan.  
 
It will be explained to patients that they have been identified as potential candidates 
for this study and a lay summary will be provided to outline the research project. The 
patient should be reassured that the scan will not differ because of their involvement 
in the study and there will be no delay in the results and TTE report as a result. The 
patient should also be informed that if they choose not to participate in the research 
study, this will not affect their standard of care in any way. Participants will be 
encouraged to ask questions and they will have the right to decline to take part in the 
study without providing any reasons. It should be explained to the patient that it is 
highly unlikely that there will be any incidental findings. However, any incidental 
findings would be dealt with accordingly, as they usually would as per standard of care, 
and would be reported back to the referring clinician. Unless GPs are the initial 
echocardiogram refer, they will not be directly contacted regarding incidental findings 

19 
Protocol: Left Atrial Strain Values as an Early Predictor of Atrial Fibrillation, V6 17/05/2023 
but should have access to patient information and testing using the Welsh Patient 
Administration System and Welsh Clinic Portal system. The cardio-respiratory 
department does not have any direct contact or involvement with life insurance 
companies, however, if a patient has already been referred for an echocardiogram, it 
could be argued that they are currently awaiting investigations regardless of their 
involvement in the study. 
 
 
 
3.3 
 Study Withdrawal  
Not all patients that provide written informed consent to be involved in this study will 
be deemed to be suitable and thus will not be included. If it is deemed that the quality 
of the TTE images obtained are not of a high enough quality (LA and LA walls must 
be fully visible and clear), then the subject will not be included in the study. This is 
because unclear images make it very difficult to accurately measure the LA area and 
volume. Clear LA wall borders are required to obtain atrial strain measurements. 
Including unclear images in the study will not provide an accurate measurement of LA 
strain for comparison. This will be explained to the patient prior to receiving consent 
and in the participant information sheet. The patient should be reassured that if their 
images are deemed to be of an inadequate standard for LA strain analysis, this does 
not mean that they do not have a diagnostic use as per referral request.  
 
Participants have a right to withdraw their consent at any point in the study. As the 
data will have been pseudo-anonymised, if consent withdrawal is following data 
collection, the data obtained thus far must be uncovered to match the patient identifiers 
which are to be kept separately from patient data. Once the patient's data has been 
correctly identified, this will be removed from records and not included in any data 
analysis. However, if the participant chooses to withdraw following any processing of 
data, it may not be possible to remove this data from the analysis. 

20 
Protocol: Left Atrial Strain Values as an Early Predictor of Atrial Fibrillation, V6 17/05/2023 
 
4. Risk, Ethical Considerations and Confidentiality 
 
4.1 
 Risks and Benefits  
 
This research study is very low risk. TTEs have no known associated risks. Some 
pressure is applied during the scan to obtain images, and this may be sensitive for 
some patients, however, this is the case regardless of the study. The potential benefit 
of this study is that participants may be identified as having atrial strain patterns which 
are similar to those seen in patients with AF or may be an early predictor of AF. If this 
is the case, the patient can be monitored more closely and appropriately medicated if 
required.  
 
4.2 
 Ethical Considerations  
 
Joint Health Research Authority (HRA) and NHS Research Ethics Committee (REC) 
approvals are required for this project to uphold standards surrounding confidentiality, 
anonymity and informed consent. This is primarily due to the transferable and 
generalisable nature of the study outcomes and the identification of potential 
candidates as a result of previous NHS service use.  
 
4.3 
 Patient and Public Involvement  
 
Patients will not be involved in the development of the study and will only be involved 
as part of the conduction of data collection from TTEs. Patients will be informed prior 
to providing informed consent that there may be a possibility of publication and 
dissemination and will have been reassured that there will be no identifiable 
information present within any potential publications. 
 
4.4 
 Confidentiality  
 
For patients that wish to participate in this study, all signed Informed Consent Forms 
will be securely stored in the Investigator Site File within the Cardio-Respiratory 
Department and must not leave the department under any circumstances. The 
participant data will undergo pseudo-anonymisation via the use of two password-
protected excel spreadsheets. One spreadsheet will contain participant numbers and 
corresponding hospital ID numbers. The second spreadsheet will include participant 
numbers along with patient demographics (i.e., sex, age, participant group, reason for 
patient referral, etc.). This data will be encrypted and the folder it resides in will also 
be encrypted and password protected. This will be stored on an NHS OneDrive 
account on a departmental computer. General data protection regulation (GDPR) will 
be maintained and followed throughout. 
 
4.5 
 Premature Termination or Suspension of Study 
 
In the unlikely event that the study was to be prematurely terminated or suspended 
(potentially due to insufficient adherence to protocol requirements or perhaps 
insufficient data availability), written notification will be provided to all parties involved 
in the study (REC, sponsor, participants, clinical supervisors and academic 

21 
Protocol: Left Atrial Strain Values as an Early Predictor of Atrial Fibrillation, V6 17/05/2023 
supervisor). This notice will document the reasons for premature termination or 
suspension and outline the steps to be taken regarding collected data. 
 
4.6 
 Future Use of Stored Specimens and Other Identifiable 
Data 
 
There are no current plans to use the data collected post study. However, the data will 
be securely stored and encrypted as it may be deemed to be necessary that the 
pseudo-anonymisation is uncovered in the patients' best interests.  
 
 
4.7 
 Record Retention, Storing and Archiving  
 
TTE scans are stored on both the ultrasound machine and on the computer through 
PACS. Scans stored on the machine are routinely archived after 3 months; clinical 
guidelines suggest than scans should be accessible on PACS server for 7 years post-
investigation. These are to be accessible to healthcare professionals throughout 
following the patient scan for clinical progression external to the research project. Data 
which has been obtained from these scans will be stored in two locations. The first of 
which is across two excel spreadsheets to maintain pseudo-anonymisation. Both 
spreadsheets will be password protected and folders encrypted on an NHS OneDrive 
account. These will be located on a single departmental computer.  
 
4.8 
 Study Oversight  
 
The CI will be responsible for study oversight, including monitoring safety, ensuring 
that the study is conducted according to the protocol and ensuring data integrity.  The 
CI will review the data obtained and will also perform a reproducibility study. Any 
issues that arise (unanticipated problems, protocol deviation, and significant events) 
will be promptly reported to the REC, the sponsor, clinical supervisors and academic 
supervisor. 
 
4.9 
 Study Reporting  
 
Regular updates will be provided to the clinical supervisors and academic supervisor 
involved in this project as well as to the Sponsor. Regular meetings will be held 
between all parties to ensure the project is on track and progressing as planned. This 
may be in person, via Teams or through email updates.  
  
4.10 Safety Reporting  
 
No adverse events are anticipated during this study. Subjects included in this study 
will have either been urgently or routinely referred for a TTE. The extra measurements 
taken from the patient’s scan occur after the patient has left, thus there is no alteration 
to the scan itself for patient experience.  
 
 

22 
Protocol: Left Atrial Strain Values as an Early Predictor of Atrial Fibrillation, V6 17/05/2023 
 
5. References 
Alhakak, A. S., Biering-Sørensen, S. R., Møgelvang, R., Modin, D., Jensen, G. B., Schnohr, P., Iversen, A. Z., 
Svendsen, J. H., Jespersen, T., Gislason, G. and Biering-Sørensen, T. (2022) 'Usefulness of left atrial strain for 
predicting incident atrial fibrillation and ischaemic stroke in the general population', Eur Heart J Cardiovasc 
Imaging, 23(3), pp. 363-371. 
 
Beyls, C., Hermida, A., Bohbot, Y., Martin, N., Viart, C., Boisgard, S., Daumin, C., Huette, P., Dupont, H., Abou-
Arab, O. and Mahjoub, Y. (2021) 'Automated left atrial strain analysis for predicting atrial fibrillation in severe 
COVID-19 pneumonia: a prospective study', Ann Intensive Care, 11(1), pp. 168. 
 
Choi, H. M., Yoon, Y. E., Oh, I. Y., Cho, Y. and Cho, G. Y. (2018) 'Global Left Atrial Strain as a Predictor of Silent 
Atrial Fibrillation Following Dual Chamber Cardiac Implantable Electronic Device Implantation', JACC Cardiovasc 
Imaging, 11(10), pp. 1537-1539. 
 
Gan, G. C. H., Ferkh, A., Boyd, A. and Thomas, L. (2018) 'Left atrial function: evaluation by strain analysis', 
Cardiovasc Diagn Ther, 8(1), pp. 29-46. 
 
Guo, C., Liu, J., Zhao, S., Teng, Y. and Shen, L. (2016) 'Decreased left atrial strain parameters are correlated 
with prolonged total atrial conduction time in lone atrial fibrillation', Int J Cardiovasc Imaging, 32(7), pp. 1053-61. 
 
Hauser, R., Nielsen, A. B., Skaarup, K. G., Lassen, M. C. H., Duus, L. S., Johansen, N. D., Sengeløv, M., Marott, 
J. L., Jensen, G., Schnohr, P., Søgaard, P., Møgelvang, R. and Biering-Sørensen, T. (2021) 'Left atrial strain 
predicts incident atrial fibrillation in the general population: the Copenhagen City Heart Study', Eur Heart J 
Cardiovasc Imaging, 23(1), pp. 52-60. 
 
Her, A. Y., Kim, J. Y., Kim, Y. H., Choi, E. Y., Min, P. K., Yoon, Y. W., Lee, B. K., Hong, B. K., Rim, S. J. and 
Kwon, H. M. (2013) 'Left atrial strain assessed by speckle tracking imaging is related to new-onset atrial 
fibrillation after coronary artery bypass grafting', Can J Cardiol, 29(3), pp. 377-83. 
 
Hsu, P. C., Lee, W. H., Chu, C. Y., Lee, H. H., Lee, C. S., Yen, H. W., Lin, T. H., Voon, W. C., Lai, W. T., Sheu, 
S. H. and Su, H. M. (2016) 'Prognostic role of left atrial strain and its combination index with transmitral E-wave 
velocity in patients with atrial fibrillation', Sci Rep, 6, pp. 17318. 
 
Jarasunas, J., Aidietis, A. and Aidietiene, S. (2018) 'Left atrial strain - an early marker of left ventricular diastolic 
dysfunction in patients with hypertension and paroxysmal atrial fibrillation', Cardiovasc Ultrasound, 16(1), pp. 29. 
 
Ma, X. X., Zhang, Y. L., Hu, B., Zhu, M. R., Jiang, W. J., Wang, M., Zheng, D. Y. and Xue, X. P. (2017) 'The 
usefulness of global left atrial strain for predicting atrial fibrillation recurrence after catheter ablation in patients 
with persistent and paroxysmal atrial fibrillation', Arch Cardiovasc Dis, 110(8-9), pp. 447-455. 
 
Markides, V. and Schilling, R. J. (2003) 'Atrial fibrillation: classification, pathophysiology, mechanisms and drug 
treatment', Heart, 89(8), pp. 939-43. 
 
Mochizuki, A., Yuda, S., Fujito, T., Kawamukai, M., Muranaka, A., Nagahara, D., Shimoshige, S., Hashimoto, A. 
and Miura, T. (2017) 'Left atrial strain assessed by three-dimensional speckle tracking echocardiography predicts 
atrial fibrillation recurrence after catheter ablation in patients with paroxysmal atrial fibrillation', J Echocardiogr, 
15(2), pp. 79-87. 
 
Motoc, A., Luchian, M. L., Scheirlynck, E., Roosens, B., Chameleva, H., Gevers, M., Galloo, X., von Kemp, B., 
Ramak, R., Sieira, J., de Asmundis, C., Chierchia, G. B., Magne, J., Weytjens, C., Droogmans, S. and Cosyns, B. 
(2021) 'Incremental value of left atrial strain to predict atrial fibrillation recurrence after cryoballoon ablation', 
PLoS One, 16(11), pp. E0259999. 
 
Motoki, H., Negishi, K., Kusunose, K., Popović, Z. B., Bhargava, M., Wazni, O. M., Saliba, W. I., Chung, M. K., 
Marwick, T. H. and Klein, A. L. (2014) 'Global left atrial strain in the prediction of sinus rhythm maintenance after 
catheter ablation for atrial fibrillation', J Am Soc Echocardiogr, 27(11), pp. 1184-92. 
 
Olsen, F. J., Christensen, L. M., Krieger, D. W., Højberg, S., Høst, N., Karlsen, F. M., Svendsen, J. H., 
Christensen, H. and Biering-Sørensen, T. (2020) 'Relationship between left atrial strain, diastolic dysfunction and 
subclinical atrial fibrillation in patients with cryptogenic stroke: the SURPRISE echo substudy', Int J Cardiovasc 
Imaging, 36(1), pp. 79-89. 
 
Pagola, J., Juega, J., Francisco-Pascual, J., Bustamante, A., Penalba, A., Pala, E., Rodriguez, M., De Lera-
Alfonso, M., Arenillas, J. F., Cabezas, J. A., Moniche, F., de Torres, R., Montaner, J., González-Alujas, T., 

23 
Protocol: Left Atrial Strain Values as an Early Predictor of Atrial Fibrillation, V6 17/05/2023 
Alvarez-Sabin, J., Molina, C. A. and group, C.-A. s. (2021) 'Predicting Atrial Fibrillation with High Risk of 
Embolization with Atrial Strain and NT-proBNP', Transl Stroke Res, 12(5), pp. 735-741. 
 
Park, J. J., Park, J. H., Hwang, I. C., Park, J. B., Cho, G. Y. and Marwick, T. H. (2020) 'Left Atrial Strain as a 
Predictor of New-Onset Atrial Fibrillation in Patients With Heart Failure', JACC Cardiovasc Imaging, 13(10), pp. 
2071-2081. 
 
Parwani, A. S., Morris, D. A., Blaschke, F., Huemer, M., Pieske, B., Haverkamp, W. and Boldt, L. H. (2017) 'Left 
atrial strain predicts recurrence of atrial arrhythmias after catheter ablation of persistent atrial fibrillation', Open 
Heart, 4(1), pp. E000572. 
 
Pathan, F., Sivaraj, E., Negishi, K., Rafiudeen, R., Pathan, S., D'Elia, N., Galligan, J., Neilson, S., Fonseca, R. 
and Marwick, T. H. (2018) 'Use of Atrial Strain to Predict Atrial Fibrillation After Cerebral Ischemia', JACC 
Cardiovasc Imaging, 11(11), pp. 1557-1565. 
 
Pessoa-Amorim, G., Mancio, J., Vouga, L., Ribeiro, J., Gama, V., Bettencourt, N. and Fontes-Carvalho, R. (2018) 
'Impaired Left Atrial Strain as a Predictor of New-onset Atrial Fibrillation After Aortic Valve Replacement 
Independently of Left Atrial Size', Rev Esp Cardiol (Engl Ed), 71(6), pp. 466-476. 
 
Petre, I., Onciul, S., Iancovici, S., Zamfir, D., Stoian, M., Scărlătescu, A., Diaconeasa, A., Acatrinei, C. and 
Dorobanțu, M. (2019) 'Left Atrial Strain for Predicting Atrial Fibrillation Onset in Hypertensive Patients', High 
Blood Press Cardiovasc Prev, 26(4), pp. 331-337. 
 
Rasmussen, S. M. A., Olsen, F. J., Jørgensen, P. G., Fritz-Hansen, T., Jespersen, T., Gislason, G. and Biering-
Sørensen, T. (2019) 'Utility of left atrial strain for predicting atrial fibrillation following ischemic stroke', Int J 
Cardiovasc Imaging, 35(9), pp. 1605-1613. 
 
Shaikh, A. Y., Maan, A., Khan, U. A., Aurigemma, G. P., Hill, J. C., Kane, J. L., Tighe, D. A., Mick, E. and 
McManus, D. D. (2012) 'Speckle echocardiographic left atrial strain and stiffness index as predictors of 
maintenance of sinus rhythm after cardioversion for atrial fibrillation: a prospective study', Cardiovasc Ultrasound, 
10, pp. 48. 
 
Shin, D. G., Kang, M. K., Han, D., Choi, S., Cho, J. R. and Lee, N. (2022) 'Enlarged left atrium and decreased left 
atrial strain are associated with atrial fibrillation in patients with hyperthyroidism irrespective of conventional risk 
factors', Int J Cardiovasc Imaging, 38(3), pp. 613-620. 
 
Singh, A., El Hangouche, N., McGee, K., Gong, F. F., Lentz, R., Feinglass, J. and Akhter, N. (2021) 'Utilizing left 
atrial strain to identify patients at risk for atrial fibrillation on ibrutinib', Echocardiography, 38(1), pp. 81-88. 
 
Staerk, L., Sherer, J. A., Ko, D., Benjamin, E. J. and Helm, R. H. (2017) 'Atrial Fibrillation: Epidemiology, 
Pathophysiology, and Clinical Outcomes', Circ Res, 120(9), pp. 1501-1517. 
 
Svartstein, A. W., Lassen, M. H., Skaarup, K. G., Grove, G. L., Vyff, F., Ravnkilde, K., Pedersen, S., Galatius, S., 
Modin, D. and Biering-Sørensen, T. (2022) 'Predictive value of left atrial strain in relation to atrial fibrillation 
following acute myocardial infarction', Int J Cardiol, 364, pp. 52-59. 
 
Uziębło-Życzkowska, B., Krzesiński, P., Jurek, A., Krzyżanowski, K. and Kiliszek, M. (2021) 'Correlations 
between left atrial strain and left atrial pressures values in patients undergoing atrial fibrillation ablation', Kardiol 
Pol, 79(11), pp. 1223-1230. 
 
van de Vegte, Y. J., Siland, J. E., Rienstra, M. and van der Harst, P. (2021) 'Atrial fibrillation and left atrial size 
and function: a Mendelian randomization study', Sci Rep, 11(1), pp. 8431. 
 
von Roeder, M., Blazek, S., Rommel, K. P., Kresoja, K. P., Gioia, G., Mentzel, L., Lurz, J. A., Besler, C., Fengler, 
K., Hindricks, G., Desch, S., Thiele, H. and Lurz, P. (2022) 'Changes in left atrial function in patients undergoing 
cardioversion for atrial fibrillation: relevance of left atrial strain in heart failure', Clin Res Cardiol, 111(9), pp. 1028-
1039. 
 
Wyndham, C. R. (2000) 'Atrial fibrillation: the most common arrhythmia', Tex Heart Inst J, 27(3), pp. 257-67. 
 
Yasuda, R., Murata, M., Roberts, R., Tokuda, H., Minakata, Y., Suzuki, K., Tsuruta, H., Kimura, T., Nishiyama, 
N., Fukumoto, K., Aizawa, Y., Tanimoto, K., Takatsuki, S., Abe, T. and Fukuda, K. (2015) 'Left atrial strain is a 
powerful predictor of atrial fibrillation recurrence after catheter ablation: study of a heterogeneous population with 
sinus rhythm or atrial fibrillation', Eur Heart J Cardiovasc Imaging, 16(9), pp. 1008-14. 
 
 
 

24 
Protocol: Left Atrial Strain Values as an Early Predictor of Atrial Fibrillation, V6 17/05/2023 
Appendix 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

25 
Protocol: Left Atrial Strain Values as an Early Predictor of Atrial Fibrillation, V6 17/05/2023