Left Atrial Arrhythmia Substrate Identification After Confirmed durABLE Pulmonary Vein Isolation

Not Applicable

• Conditions: Persistent Atrial Fibrillation; Atrial Fibrillation
• Interventions: Procedure: Radiofrequency pulmonary vein isolation; Procedure: Cryoballoon pulmonary vein isolation; Procedure: Repeat electrophysiological study; Procedure: Left atrial posterior wall isolation

• Registration Number: NCT04111731
• Lead Sponsor: Liverpool Heart and Chest Hospital NHS Foundation Trust

Brief Summary

Under current practice, patients with persistent atrial fibrillation, can be offered one of two types of ablation treatment. Both of these treatments are aimed at electrically isolating the 4 pulmonary veins (PVs) at the back of the heart which connect it to the lungs. These PVs have been identified to serve as the sites where the abnormal heart rhythm is generated. One of the treatments is called radiofrequency (RF) catheter ablation, where 'heat energy' is delivered through the tip of a catheter to make tiny burns (ablation lesions) around the outlines of the 4 PVs at their bases. The other treatment technique utilises a 'cold balloon' (Cryoenergy or cryoballoon ablation) to freeze the bases of the 4 PVs to achieve the electrical isolation. Sometimes the treated tissues develop reconnections that can lead to a recurrence of the abnormal heart rhythm, and thus the need for a repeat procedure.

In this study, participants will receive a second treatment 2 months after the first one. During the second treatment, investigators will check to identify areas that have developed reconnections since the first treatment; these will be treated again. This will increase the chances of all participants having a complete treatment.

In order to improve understanding of how best to treat this condition, investigators will also carry out some further measurements within the heart during the repeat procedure. During these measurements, investigators will check to see if treatment has succeeded in reducing the occurrence of an abnormal heart rhythm. In the group of participants in whom RF energy is used for the initial procedure, investigators will also treat the back wall of the heart, and repeat these measurements.

Detailed Description

Persistent atrial fibrillation (PeAF) is defined as continuous atrial fibrillation for 7 days or more. Approximately 10% of people are diagnosed with atrial fibrillation (AF) by age 80 years; and among people of European descent, 26% of men and 23% of women have a lifetime risk of developing AF after age 40.

Catheter ablation by pulmonary vein isolation is the usual approach employed for PeAF. This involves making lesions within the pulmonary veins to achieve electrical isolation. Electrical isolation cuts off abnormal electrical triggers originating from the pulmonary veins. However, treatment outcomes are less than optimal with a lot of variability in success rates for different techniques. Hence, the optimal treatment strategy for patients with PeAF is not clear.

In this pilot study, investigators aim to study two different treatment modalities of catheter ablation: cold balloon (cryoballoon, Group 1) and hot tip (radiofrequency ablation, Group 2) used in (electrically) isolating the pulmonary veins. There will be 1:1 randomisation to either of the two modalities. All participants will subsequently undergo a repeat procedure 2 months later to identify reconnections and to re-isolate the veins using the hot tip (radiofrequency ablation) guided by an ultra-high density mapping technology. During the repeat procedure, investigators will perform further electrophysiological studies including assessing arrhythmia inducibility and measuring the extent of isolated areas. For participants in Group 2, investigators will also make some lesions in the back wall of the heart (posterior wall isolation) and recheck arrhythmia inducibility.

All participants will be given a handheld ECG recording (Omron) device. Participants will be shown how to use the device to make daily 30-second recordings and when they have symptoms, to be reviewed. Follow up will be at 3, 6 and 12 months.

Study Timeline

• Study First Submitted: 2019-04-03
• Study First Submitted QC: 2019-09-30
• Study First Posted: 2019-10-01
• Study Start: 2020-03-03
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-26
• Last Update Posted: 2022-08-29
• Primary Completion: 2022-12-30
• Study Completion: 2022-12-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Age 18 to 80 years
2. Evidence of persistent Atrial Fibrillation

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Exclusion Criteria

1. Any previous catheter (or surgical) ablation for atrial fibrillation or cryoballoon pulmonary vein isolation
2. An indwelling atrial septal defect (ASD) occluder device or anatomical structure that pre-vents free access to the left atrium
3. Left atrial diameter on transthoracic echo (Parasternal long axis, M-mode) > 5.5cm
4. Recent stroke/Transient Ischaemic Attack within 3 months
5. Inability, unwillingness or absolute contraindication to taking oral anticoagulant medication
6. Severe kidney impairment (estimated Glomerular Filtration Rate < 30ml/min)
7. Morbid obesity (Body Mass Index ≥40)
8. Extreme frailty
9. Severe valvular heart disease of any kind as assessed by the investigator, with or without prosthetic valve in place
10. Pregnancy

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group one	Repeat electrophysiological study	Cryoballoon pulmonary vein isolation
Group two	Repeat electrophysiological study	Radiofrequency pulmonary vein isolation
Group two	Radiofrequency pulmonary vein isolation	Radiofrequency pulmonary vein isolation
Group two	Left atrial posterior wall isolation	Radiofrequency pulmonary vein isolation
Group one	Cryoballoon pulmonary vein isolation	Cryoballoon pulmonary vein isolation

Primary Outcome Measures

Name	Time	Method
Number of late pulmonary vein re-connections	Up to 2 months after index ablation procedure	Number of late pulmonary vein re-connections at repeat electrophysiological study as identified by ultra-high density mapping: comparison between the 80 pulmonary veins in each group

Secondary Outcome Measures

Name	Time	Method
Incidence of peri-procedural complications	From index procedure to after repeat procedure	Incidence of peri-procedural complications such as tamponade, major bleeding, myocardial infarction, requirement for permanent pacemaker, stroke, death
Clot formation and fibrinolysis assessment using turbidimetric analyses	At baseline, 2 months and 12 months	Clot formation (lag time, rate of clot formation, maximum absorbance) and rate of fibrinolysis
Area of low voltage	2 months after the index ablation procedure	Area of left atrial low voltage at start of repeat electrophysiological study under ultra-high density mapping guidance in each group
Incidence of arrhythmia inducibility before and after left atrial posterior wall isolation	2 months after the index ablation procedure	Incidence of arrhythmia inducibility after complete posterior wall isolation as compared to after pulmonary vein isolation alone assessed during an electrophysiological study
Quality of life assessment: validated questionnaire	At the index procedure and at the 6th month and 12th month follow-up appointments	At baseline, 6 months and at 12 months using a validated questionnaire with 2 components: descriptive system and visual analogue scale. Descriptive system has 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each has 5 levels: no problems (level 1), slight problems (2), moderate problems (3), severe problems (4), and extreme problems (5). The digits for the 5 dimensions will be combined into a 5-digit number describing the participant's health state - a total of 3125 possible health states. The health state will be converted to a single index value using conversion tables, and summarised as means or medians. Visual analogue scale records the participant's self-rated health on a 20 cm vertical scale with endpoints 'the best health you can imagine' and 'the worst health you can imagine'. It will be summarised as means or medians.
Fibrin permeation testing	At baseline, 2 months and 12 months	Permeation constant (Ks)
Amount of radiofrequency energy needed to re-isolate the veins	2 months after the index ablation procedure	Amount of radiofrequency energy needed at repeat electrophysiological study to re-isolate the pulmonary veins
Total length of time free from atrial arrhythmia estimated with the Omron device	At the 12th month follow-up visit	Freedom from atrial arrhythmia at 12 months following the 2 procedures: comparison between groups. Time period free from atrial arrhythmia in minutes/hours/days
Incidence of renal function impacting on left atrial electrical properties	At the index procedure and 2 months after the index procedure	Incidence of renal function impacting on electrical properties of the left atrium and arrhythmic substrate: assessed at baseline and during repeat electrophysiological study

Trial Locations

Locations (3)

Liverpool Heart and Chest Hospital NHS Foundation Trust; 🇬🇧 Liverpool, United Kingdom

Manchester University NHS Foundation Trust; 🇬🇧 Manchester, United Kingdom

The Newcastle Upon Tyne Hospital NHS Foundation Trust, Freeman Hospital; 🇬🇧 Newcastle Upon Tyne, United Kingdom