Clinical trial NCT04111731: Left Atrial Arrhythmia Substrate Identification After Confirmed durABLE Pulmonary Vein Isolation
Official title: Left Atrial Arrhythmia Substrate Identification by Ultra-high Density Mapping After Confirmed durABLE Pulmonary Vein Isolation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Atrial Fibrillation
Persistent Atrial Fibrillation
Keywords: Radiofrequency catheter ablation
Cryoballoon pulmonary vein isolation
Rhythmia
Orion catheter
Posterior wall isolation
Electrophysiological study
Omron device
Lead sponsor: Liverpool Heart and Chest Hospital NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Boston Scientific Corporation
First posted: 2019-10-01
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomised, controlled multi-centre pilot study. Forty participants with persistent atrial fibrillation will have an equal chance of being randomised to receive either of two treatment techniques of pulmonary vein isolation:

Cryoballoon (Group 1) or Radiofrequency ablation (Group 2). Subsequently, all patients will undergo a repeat procedure 2 months later to assess for reconnections requiring further treatment.

In Group 2 participants, there will also be lesions made to the back wall of the heart (left atrial posterior wall isolation).
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

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

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

Primary outcomes:
measure: Number of late pulmonary vein re-connections
timeFrame: Up to 2 months after index ablation procedure
Secondary outcomes:
measure: Amount of radiofrequency energy needed to re-isolate the veins
timeFrame: 2 months after the index ablation procedure
measure: Area of low voltage
timeFrame: 2 months after the index ablation procedure
measure: Incidence of arrhythmia inducibility before and after left atrial posterior wall isolation
timeFrame: 2 months after the index ablation procedure
measure: Incidence of peri-procedural complications
timeFrame: From index procedure to after repeat procedure
measure: Incidence of renal function impacting on left atrial electrical properties
timeFrame: At the index procedure and 2 months after the index procedure
measure: Total length of time free from atrial arrhythmia estimated with the Omron device
timeFrame: At the 12th month follow-up visit
measure: Quality of life assessment: validated questionnaire
timeFrame: At the index procedure and at the 6th month and 12th month follow-up appointments
measure: Clot formation and fibrinolysis assessment using turbidimetric analyses
timeFrame: At baseline, 2 months and 12 months
measure: Fibrin permeation testing
timeFrame: At baseline, 2 months and 12 months
Other outcomes:
Locations:
city: Liverpool
country: United Kingdom
facility: Liverpool Heart and Chest Hospital NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Newcastle Upon Tyne Hospital NHS Foundation Trust, Freeman Hospital
Study officials:
affiliation: Liverpool Heart and Chest Hospital
name: Dhiraj Gupta, MBBS MD FRCP
role: STUDY_CHAIR
References: