CHILLY-AF
Research type
Research Study
Full title
Randomised Controlled Trial of Cryo Ablation versus Cardioversion in Persistent Atrial Fibrillation
IRAS ID
226368
Contact name
James McCready
Contact email
Sponsor organisation
Brighton & Sussex University Hospitals NHS Trust
Duration of Study in the UK
1 years, 11 months, 31 days
Research summary
Research Summary
Persistent atrial fibrillation is the most common sustained heart rhythm disorder and is associated with a variety of symptoms including lethargy and breathlessness. This can be treated with cardioversion (electric treatment) with long term medication, or a more definitive treatment with ablation .
The usual first line treatment for Persistent AF is cardioversion but recurrence rates following this are up to 90%. A Cardioversion involves a controlled electric shock to the chest wall under general anaesthesia or heavy sedation. This is usually performed as a day case procedure.
Cryo ablation is a minimally invasive cardiac procedure and has a success rate of between 57-69% in treating persistent AF. The procedure involves passing two tubes into a vein from the groin. After crossing to the left chamber of the heart (atrium), a balloon is used to engage the pulmonary veins which are then frozen. The procedure lasts around 90 minutes.
The aim of this study is to determine whether cryo ablation is more effective than cardioversion at preventing recurrence of persistent AF.
Summary of Results
Background and study set up The sponsor of this study was Brighton and Sussex University Hospitals NHS Trust (now known as University Hospitals Sussex NHS Foundation Trust), and they would like to thank everyone who took part and made this study possible.
The study took place, between 2019 and 2021, at 5 sites: Eastbourne, Leeds, Portsmouth, Southampton and the lead site which was Brighton. These sites recruited 150 patients and it was funded by Medtronic International who had no competing interests in the study.
Atrial fibrillation (AF) is the most common heart rhythm disturbance where the heart does not beat in a regular rhythm. It affects around 1.4 million people in the UK and can cause symptoms such as palpitations and breathlessness while also increasing the likelihood of the person experiencing a stroke.
AF is generally categorised into one of 4 types which depends on the duration of the abnormal rhythm:
• paroxysmal AF – episodes come and go, and usually stop within 48 hours without any treatment.
• persistent AF – each episode lasts for longer than 7 days (or less when it's treated).
• permanent AF –present all the time with no plans to restore normal rhythm.
• long-standing AF – where you've had atrial fibrillation for over 1 year.
Persistent AF can be treated in 2 ways:
• Electric treatment (cardioversion), which is a procedure where the heart is shocked back into normal rhythm. The procedure is performed under a short general anaesthetic and takes around 5 minutes. . Success with cardioversion at 1 year is 30-40%.
• Catheter ablation is a procedure performed through blood vessels at the top of the right leg. Catheters (long tubes) are introduced inside the heart and the areas inside the heart that cause AF are ablated (killing cardiac tissue) using a freezing balloon (cryoablation). It is performed with either local or general anaesthetic and takes around 60 minutes. Success with ablation at 1 year is 50-60%.
Patients that maintain normal rhythm after treatment have:
• Improved symptoms (less breathlessness, improved exercise ability, increased energy levels, less palpitations)
• A decreased risk of heart failure, heart attacks, stroke and death
There are no studies comparing the success of cardioversion to cryoablation.
The purpose of this study was to help establish whether cardioversion or cryoablation was better at preventing AF recurrence in patients with persistent AF. The goal was to add to the scientific evidence for the management of this condition.
The main measure for assessing which procedure was most effective was differences in the time to recurrence of AF following treatment. Other measures were adverse effects and evaluating the participants experience of their condition using the Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) questionnaire.
The protocol (which is equivalent to a study instruction manual) was developed by clinicians, but its appropriateness and all the information that was provided to patients was reviewed by a multi-disciplinary panel that included patient representatives.
Statisticians at the Brighton & Sussex Clinical Trials Unit calculated that the number of patients that needed to be recruited to the study to assess if there were any differences in outcomes to the patients, depending on which treatment they had, was 150. It was also decided that it should be a randomised study, which meant that patients would be randomly allocated to one of the treatments.
Blinding, which means not knowing which treatment a patient receives, is not possible in a trial such as this as it is evident which procedure the patient has had.
Results
All patients entering the study had a period of at least 4 weeks on medication to stabilise their heart rhythm which is standard practice. A total of 149 patients with proven persistent AF were randomised. Of these 75 patients were randomised to, and received, cryoablation.74 patients were randomised to cardioversion therapy, but of these only 55 underwent the procedure because 19 had returned to normal rhythm on medication.
Recurrence of atrial arrhythmia occurred in 46 patients (63.9%) of those in the cardioversion group and 39 patients (52.0%) in the cryoablation group. The median (middle) time to recurrence in the cardioversion group was 45.5 days and in the cryoablation group 84.0 days. After adjusting for multiple factors, such as the duration of AF prior to treatment which affects the likelihood of AF recurrence, AF recurrence was reduced in the cryoablation group by a factor of 0.64.. All these differences were statistically significant.
Serious adverse events are any event that results in the below:
• death
• hospitalisation
• prolongation of existing hospitalisation
• persistent or significant disability/incapacity
• congenital anomaly or birth defect
These events were similar between the two groups with procedural related complications following cryoablation recorded in 2 patients: phrenic nerve palsy (injury to the phrenic nerve that helps control the diaphragm and therefore affects breathing) and post procedure fluid retention, both of which resulted in prolongation of hospital stay. Both of these complications resulted in no long-lasting injury.
There was weak evidence from the completed Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) questionnaires that symptoms following the procedure were improved in the participants who had cryoablation compared to cardioversion. However, 28% of patients who had cardioversion subsequently had cryoablation which may have affected these results. This is because results were analysed according to which treatment the patient was randomised (so 28% of the cardioversion group went on to have cryoablation).
Conclusion
The study demonstrated that cryoablation compared to cardioversion as a rhythm control strategy for persistent atrial fibrillation led to a greater time to atrial arrhythmia recurrence without an increase in serious adverse events and therefore provides further evidence that cryoablation is an effective first-line treatment for persistent atrial fibrillation. The advantage for patients being that patients may require less interventions if they undergo a cryoablation compared to cardioversion.REC name
East of England - Essex Research Ethics Committee
REC reference
17/EE/0448
Date of REC Opinion
1 Dec 2017
REC opinion
Further Information Favourable Opinion