Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000639921
Ethics application status
Approved
Date submitted
8/05/2020
Date registered
1/06/2020
Date last updated
30/08/2022
Date data sharing statement initially provided
1/06/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Characterising Left Atrial Function and Compliance in Atrial Fibrillation
Scientific title
The Impact of Left Atrial Function and Compliance in patients with paroxysmal and persistent Atrial Fibrillation undergoing Catheter Ablation
Secondary ID [1] 301086 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atrial Fibrillation 317156 0
Condition category
Condition code
Cardiovascular 315305 315305 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
All patients recruited to the study will have symptomatic atrial fibrillation (AF) planned for AF ablation. AF ablation is an interventional treatment for AF recommended for patients with symptomatic AF refractory to at least 1 anti-arrhythmic drug. Participants will be recruited when both patient and physician have decided to proceed with AF ablation. These patients will undergo AF ablation regardless of recruitment to the study.

Within 4 weeks prior to their AF ablation, enrolled participants will undergo a series of non-invasive testing including baseline echocardiogram, stress echocardiogram, cardiopulmonary exercise testing and blood sampling for NT-pro BNP. They will also complete an AF symptom questionnaire and the Minnesota Living with Heart Failure questionnaire.

AF ablation will then be undertaken as per standard institutional protocols. LA pressure will be
measured via trans-septal puncture, as occurs routinely during such procedures. LA dimensions will be measured by transoesopageal echocardiography (TOE). TOE is also part of the standard procedure to exclude left atrial thrombus and guide transeptal puncture. Following baseline assessment of LA dimensions and LA pressure, the LA will be directly infused with isotonic saline through the standard LA sheath. The volume to be infused will be 15 mL/kg of body weight over 8 minutes. LA volume via TTE and LA pressure will be recorded every 2 minutes during the infusion using TTE. During infusion, LA pressure and respiratory parameters will be measured and infusion will be stopped if there is any evidence of fluid overload. LA compliance will be calculated from the LA volume pressure curve provided by these measurements.

Procedure duration will be variable depending on the ablation procedure itself and can last anywhere between 1-4 hours. The study protocol will add only 10 minutes to the overall procedure. Following the procedure, patients will be followed up for a period of 12 months and in addition to standard follow-up protocols, will undergo repeat stress echocardiogram and CPET and 6 and 12 months post-procedure.
Intervention code [1] 317394 0
Not applicable
Comparator / control treatment
Within the recruited cohort, comparisons will be made between participants with persistent and paroxysmal AF.
Control group
Active

Outcomes
Primary outcome [1] 323546 0
Left atrial stiffness assessed by measuring left atrial pressure changes with direct infusion of isotonic saline into the left atrium. Left atrial pressure will be assessed by using the standard pressure transducer used for transeptal puncture during the AF ablation procedure.
Timepoint [1] 323546 0
At the time of catheter ablation
Secondary outcome [1] 382207 0
Left atrial dimensions assessed using transthoracic echocardiography.
Timepoint [1] 382207 0
Within 4 weeks prior to AF ablation procedure
Secondary outcome [2] 382209 0
Left atrial ejection fraction using transthoracic echocardiography
Timepoint [2] 382209 0
Within 4 weeks prior to AF ablation
Secondary outcome [3] 382212 0
Left ventricular global longitudinal strain assessed using transthoracic echocardiography
Timepoint [3] 382212 0
Within 4 weeks prior to AF ablation
Secondary outcome [4] 382213 0
Symptoms of atrial fibrillation using AF symptom severity (AFSS) questionnaire score
Timepoint [4] 382213 0
Prior to AF ablation and 12 months after ablation
Secondary outcome [5] 382214 0
Minnesota Living with Heart Failure Questionnaire score
Timepoint [5] 382214 0
4 weeks prior to AF ablation and 12 months after ablation
Secondary outcome [6] 382215 0
Aerobic exercise capacity using the 6 minute walk test.
Timepoint [6] 382215 0
Within 4 weeks prior to AF ablation and 12 months after AF ablation
Secondary outcome [7] 382216 0
Exercise capacity assessed using Peak VO2 measured during cardiopulmonary exercise test
Timepoint [7] 382216 0
4 weeks prior to AF ablation and 12 months after AF ablation
Secondary outcome [8] 382217 0
Left ventricular diastolic function during exercise with cycle ergometer exercise stress echocardiogram (E/e' and TR velocity)
Timepoint [8] 382217 0
Within 4 weeks prior to AF ablation and 12 months after AF ablation
Secondary outcome [9] 382218 0
Pulmonary capillary wedge pressure assessed using Swan-Ganz catheter
Timepoint [9] 382218 0
During AF ablation procedure
Secondary outcome [10] 382219 0
AF ablation success/failure with Holter monitor or implantable cardiac device monitoring assessing for AF recurrence
Timepoint [10] 382219 0
3,6 and 12 months following AF ablation
Secondary outcome [11] 382220 0
Natriuretic peptides assessed using blood sampling (BNP and nt-pro-BNP)
Timepoint [11] 382220 0
Within 4 weeks prior to AF ablation
Secondary outcome [12] 382223 0
Composite of markers of thrombogenesis via blood sampling from the left atrium, right atrium and peripheral circulation:
Platelet activation
Thrombin generation
Endothelial dysfunction
Platelet derived inflammation
Timepoint [12] 382223 0
At time of AF ablation procedure
Secondary outcome [13] 382224 0
Left and right atrial voltage assessed using electroanatomic mapping catheters
Timepoint [13] 382224 0
At time of AF ablation
Secondary outcome [14] 383141 0
Left ventricular systolic function (ejection fraction measured using Simpson's biplane method not transthoracic echocardiography)
Timepoint [14] 383141 0
Within 4 weeks prior to AF ablation
Secondary outcome [15] 383142 0
Left ventricular diastolic function using transthoracic echocardiography
Timepoint [15] 383142 0
Within 4 weeks prior to AF ablation
Secondary outcome [16] 383148 0
Left atrial strain and strain rate assessed using transthoracic echocardiography
Timepoint [16] 383148 0
Within 4 weeks prior to AF ablation
Secondary outcome [17] 383149 0
Left and right atrial conduction velocity assessed using electroanatomic mapping catheters
Timepoint [17] 383149 0
At time of AF ablation
Secondary outcome [18] 383150 0
Atrial effective refractory periods assessed using standard electrophysiologiocal diagnostic catheters
Timepoint [18] 383150 0
At time of AF ablation
Secondary outcome [19] 383151 0
Sinus node recovery time assessed using standard electrophysiologiocal diagnostic catheters
Timepoint [19] 383151 0
At time of AF ablation
Secondary outcome [20] 413432 0
We will assess the prevalence of HFpEF in this cohort of patients with atrial fibrillation, diagnosing HFpEF when mean left atrial pressure is greater than 15mmHg at baseline. We will compare all the above paramters of left atrial function and hemodynamics between patients with HFpEF and without HFpEF.
Timepoint [20] 413432 0
Diagnosis of HFpEF will be made at AF ablation procedure

Eligibility
Key inclusion criteria
Symptomatic AF with scheduled AF ablation procedure and failed >1 antiarrhythmic drug therapy
Capable of providing written consent
Ability to perform an exercise stress test on a cycle ergometer
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Ejection fraction <50% by transthoracic echocardiography (TTE) determined by Simpsons biplane method at the time of enrolment
Previous diagnosis of a cardiopmyopathy
Moderate to severe valvulopathy
Prior diagnosis of pulmonary hypertension
Active malignancy
Musculoskeletal diseases or injuries limiting exercise capacity
Severe chronic obstructive pulmonary disease
Moderate to severe valvulopathy
Unable to provide written consent
Unable to exercise

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
A previous study has reported that mean LA stiffness is 0.5mmhg/ml in a cohort of patients with paroxysmal AF. In order to detect a 0.3mmHg/ml difference in LA stiffness between patients with paroxysmal and persistent AF with 80% power, we would require a total of 29 patients in each group.

Early data after recruitment of 40 patients showed that 50% of patients with AF have raised LA pressure at baseline and therefore have a diagnosis of HFpEF. We would like to compare AF patients with paroxysmal AF with those with those with persistent AF. The primary outcome is change in left atrial compliance which is calculated by dividing change in left atrial diameter by change in left atrial pressure with saline infusion. Our data so far shows that the ratio of change in diameter to change in pressure in paroxysmal AF is 220 compared to 250 (standard deviation 70) in persistent AF. In order to observe a significant difference between the 2 groups with 80% and alpha error of 0.5, we will need a total of 85 patients in each group.

We have also powered the study to assess the prevalence of HFpEF in this cohort of patients with AF. We calculated that a sample size of 93 would be required to determine a prevalence of 40% with a desired precision of ±10% at the 95% confidence level.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/06/2020
Actual
1/06/2020
Date of last participant enrolment
Anticipated
31/12/2022
Actual
Date of last data collection
Anticipated
2/01/2023
Actual
Sample size
Target
170
Accrual to date
115
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 16516 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 16518 0
Ashford Community Hospital - Ashford
Recruitment postcode(s) [1] 30072 0
5000 - Adelaide
Recruitment postcode(s) [2] 30074 0
5035 - Ashford

Funding & Sponsors
Funding source category [1] 305522 0
Hospital
Name [1] 305522 0
In-kind support from Centre for Heart Rhythm Disorders, Royal Adelaide Hospital
Country [1] 305522 0
Australia
Primary sponsor type
University
Name
University of Adelaide
Address
University of Adelaide,
Adelaide, 5005
South Australia
Country
Australia
Secondary sponsor category [1] 305932 0
None
Name [1] 305932 0
Address [1] 305932 0
Country [1] 305932 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305834 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 305834 0
Royal Adelaide Hospital
Clinical Trial Centre
Level 3, Wayfinder 3D460.02
Port Road
ADELAIDE SA 5000
Ethics committee country [1] 305834 0
Australia
Date submitted for ethics approval [1] 305834 0
Approval date [1] 305834 0
15/10/2019
Ethics approval number [1] 305834 0

Summary
Brief summary
This study will investigate the association between left atrial compliance on AF type (paroxysmal versus persistent), patient symptoms, exercise tolerance, left ventricular function and long-term prognosis. The hypothesis is that left atrial compliance will be increased in patients with persistent AF compared with those with paroxysmal AF and may be correlated with patient symptoms, exercise tolerance and long-term outcomes of AF ablation. This will be the first study to assess left atrial compliance using direct measurements of the left atrial dimensions and pressure and direct infusion of saline into the left atrium.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 101758 0
Prof Prash Sanders
Address 101758 0
Centre for Heart Rhythm Disorders | University of Adelaide
Cardiovascular Investigation Unit | Royal Adelaide Hospital
Adelaide SA 5000
Australia
Country 101758 0
Australia
Phone 101758 0
+61 883139000
Fax 101758 0
Email 101758 0
[email protected]
Contact person for public queries
Name 101759 0
Miss Ellen Lyrtzis
Address 101759 0
South Australian Health and Medical Research Institute
PO Box 11060
Adelaide 5001
South Australia
Country 101759 0
Australia
Phone 101759 0
+61 8 8128 4000
Fax 101759 0
Email 101759 0
[email protected]
Contact person for scientific queries
Name 101760 0
Dr Adrian Elliott
Address 101760 0
Centre for Heart Rhythm Disorders | University of Adelaide
Cardiovascular Investigation Unit | Royal Adelaide Hospital
Adelaide SA 5000
Australia
Country 101760 0
Australia
Phone 101760 0
+61 883139000
Fax 101760 0
Email 101760 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseIdentification of Subclinical Heart Failure With Preserved Ejection Fraction in Patients With Symptomatic Atrial Fibrillation.2023https://dx.doi.org/10.1016/j.jchf.2023.07.019
EmbaseExercise echocardiography to assess left atrial function in patients with symptomatic AF.2024https://dx.doi.org/10.1016/j.ijcha.2023.101324
N.B. These documents automatically identified may not have been verified by the study sponsor.