Paroxysmal Atrial Fibrillation
Conditions
Keywords
Paroxysmal atrial fibrillation, Pulmonary vein isolation, Ganglionated plexus, Radiofrequency ablation, Pulmonary vein ectopy, High frequency stimulation, autonomic nervous system, Ganglionated plexi, atrial fibrillation
Brief summary
Atrial fibrillation (AF) is a common heart rhythm disorder which can significantly affect a patient's quality of life and cause strokes. Abnormal electrical activity from the pulmonary veins are thought to be the most common cause of this condition. Current ablative strategy in drug refractory AF is pulmonary vein isolation (PVI), where the pulmonary veins are electrically isolated from the body of the left atrium. However, success rate of this procedure remain \ 50-70% for a single procedure despite advances in mapping and ablation techniques. Ganglionated plexuses (GP) are dense clusters of nerves in the atria that are implicated in AF. Endocardial high frequency stimulation (HFS) delivered within the local atrial refractory period can trigger ectopy and AF from specific GP sites (ET-GP). The aim of this study was to understand the role of ET-GP ablation in the treatment of AF by comparing two different strategies: 1. Pulmonary vein isolation alone 2. GP ablation alone
Detailed description
This is a prospective, multi-centre study recruiting patients with paroxysmal AF indicated for AF ablation. 180 patients will be recruited. Patients are randomised to either GP ablation alone or to PVI. All antiarrhythmics are stopped for at least 48 hours prior to their procedures. All have general anaesthesia and CARTO system (Biosense Webster, inc.) are used for 3D electroanatomical mapping of the left atrium. Patients randomised to GP ablation will have high frequency mapping performed within the atrial refractory period to identify ectopy or AF triggering GP (ET-GP) sites in the left atrium. Patients in this group will only have GP ablation and will not have pulmonary veins isolated. The primary endpoint is any documented atrial arrhythmia 30 seconds or more after a 3 month blanking period. This will be assessed for up to 12 months post-procedure, using 48hr Holter monitors at 3, 6, 9 and 12 month intervals. Secondary endpoints include mortality, major complications and redo procedures.
Interventions
PROCEDUREPulmonary vein isolation
Conventional endocardial radiofrequency catheter ablation for pulmonary vein isolation.
PROCEDUREGanglionated plexus ablation
Endocardial radiofrequency catheter ablation of ganglionated plexus in the left atrium
Sponsors
Imperial College London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Males or females eighteen (18) to eighty five (85) years old * Paroxysmal atrial fibrillation * Suitable candidate for catheter ablation * Signed informed consent
Exclusion criteria
* Contraindication to catheter ablation * Presence of a cardiac thrombus * valvular disease that is grade moderate or greater * Any form of cardiomyopathy * On amiodarone therapy * Severe cerebrovascular disease * Active gastrointestinal bleeding * Renal failure (on dialysis or at risk of requiring dialysis) * Active infection or fever * Life expectancy shorter than the duration of the trial * Allergy to contrast * Intractable heart failure (NYHA Class IV) * Bleeding or clotting disorders or inability to receive heparin * Serum Creatinine \>200umol/L * Uncontrolled diabetes (HbA1c ≥73mmol/mol or HbA1c ≤64mmol/mol and Fasting Blood Glucose ≥9.2mmol/L) * Malignancy needing therapy * Pregnancy or women of childbearing potential not using a highly effective method of contraception * Patients in current research or have recently been involved in any research prior to recruitment will not be included in the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With no Evidence of >30s Recurrent Atrial Arrhythmia Post-index Procedure | 3 to 12 months post-ablation. | That is documented recurrent atrial arrhythmia lasting 30 seconds or more after a blanking period of 3 months; the outcome measure will be assessed up to 12 months of follow-up with 48hr halter monitors arranged every 3 months to investigate Arrhythmia recurrence . |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Presenting a Reduction in the Usage of Antiarrhythmics Post-ablation | 3 to 12 months post-ablation. | The reduction was defined as either a decrease of dose or a cessation of a drug over a 12 month follow-up period post ablation. |
Countries
United Kingdom
Participant flow
Recruitment details
The enrolement of participants was between 2017 and 2020
Participants by arm
| Arm | Count |
|---|---|
| Pulmonary Vein Isolation Conventional endocardial radiofrequency catheter ablation for pulmonary vein isolation.
Pulmonary vein isolation: Conventional endocardial radiofrequency catheter ablation for pulmonary vein isolation. | 50 |
| Ganglionated Plexus Ablation Endocardial radiofrequency catheter ablation of ganglionated plexus in the left atrium
Ganglionated plexus ablation: Endocardial radiofrequency catheter ablation of ganglionated plexus in the left atrium | 52 |
| Total | 102 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | 4 withdrawndue to non-identifiable GPs during HFS mapping in the GPA group. | 0 | 4 |
| Overall Study | Withdrawal by Subject | 3 | 7 |
Baseline characteristics
| Characteristic | Pulmonary Vein Isolation | Ganglionated Plexus Ablation | Total |
|---|---|---|---|
| Age, Continuous | 62 years STANDARD_DEVIATION 11 | 64 years STANDARD_DEVIATION 11 | 63 years STANDARD_DEVIATION 11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 50 Participants | 52 Participants | 102 Participants |
| Sex: Female, Male Female | 14 Participants | 17 Participants | 31 Participants |
| Sex: Female, Male Male | 36 Participants | 35 Participants | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 53 | 0 / 63 |
| other Total, other adverse events | 1 / 53 | 7 / 63 |
| serious Total, serious adverse events | 0 / 53 | 1 / 63 |
Outcome results
Primary
Number of Patients With no Evidence of >30s Recurrent Atrial Arrhythmia Post-index Procedure
That is documented recurrent atrial arrhythmia lasting 30 seconds or more after a blanking period of 3 months; the outcome measure will be assessed up to 12 months of follow-up with 48hr halter monitors arranged every 3 months to investigate Arrhythmia recurrence .
Time frame: 3 to 12 months post-ablation.
Population: Number of patients with no evidence of Atrial arrhythmia recurrence, \>30s, on a 48 hour Holter monitor during the initial 12 months post procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pulmonary Vein Isolation | Number of Patients With no Evidence of >30s Recurrent Atrial Arrhythmia Post-index Procedure | 32 Participants |
| Ganglionated Plexus Ablation | Number of Patients With no Evidence of >30s Recurrent Atrial Arrhythmia Post-index Procedure | 26 Participants |
p-value: <0.05Log Rank
Secondary
Number of Participants Presenting a Reduction in the Usage of Antiarrhythmics Post-ablation
The reduction was defined as either a decrease of dose or a cessation of a drug over a 12 month follow-up period post ablation.
Time frame: 3 to 12 months post-ablation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pulmonary Vein Isolation | Number of Participants Presenting a Reduction in the Usage of Antiarrhythmics Post-ablation | 12 Participants |
| Ganglionated Plexus Ablation | Number of Participants Presenting a Reduction in the Usage of Antiarrhythmics Post-ablation | 16 Participants |
Post Hoc
Extended Follow up to Assess Freedom From Atrial Arrhythmia Over a Prolonged Duration
evidence of \>30s atrial arrhythmia or symptoms consistent with arrhythmia recurrence, during routine clinical care, over an extended follow up period of 40 months.
Time frame: 40 months post procedure.