The BRIGHT study

• Research type

  Research Study

• Full title

  Safety and efficacy of shorter ablation times to the posterior wall during pulmonary vein isolation with a multielectrode radiofrequency balloon catheter

• IRAS ID

  328017

• Contact name

  John Silberbauer

• Contact email

  john.silberbauer@nhs.net

• Sponsor organisation

  University Hospitals Sussex NHS Foundation Trust

• Clinicaltrials.gov Identifier

  NCT06271967

• Duration of Study in the UK

  1 years, 7 months, 31 days

• Research summary

  Research Summary

  Atrial fibrillation (AF) is the most common clinical cardiac rhythm disturbance affecting 1 in 200 people regardless of age. At present, standard care involves a procedure called an ablation. Small burn marks are made inside
  the heart in an attempt to correct the irregular heart beat. The main goal of AF ablation is isolating the electrical signals from the pulmonary veins that enter the left upper heart chamber (atrium). Delivering this energy with balloon catheters have demonstrated a shorter learning curve and reduced procedural time. The new multi pole ablation balloon (Heliostar) has demonstrated to be a safe and effective tool for AF abation. The posterior wall of the left atrium is adjacent to the oesophagus and a rare and severe complication is a connection between both structures (fistula). Bylimiting energy to the posterior wall and hence to the oesophagus there should be a reduced chance of fistula formation. This study will assess a new reduced energy delivery time, to the posterior wall, to achieve pulmonary vein isolation and assess safety by monitoring for any oesophageal injury through temperature monitoring and a post procedural gastroscopy.

  Summary of Results

  Abbreviations AF – Atrial Fibrillation ECG – Electrocardiogram EDEL - Endoscopically Detected Oesophageal Lesions LA – Left Atrium PV – Pulmonary Vein PVI – Pulmonary vein isolation ST – The ST-segment of an ECG Background and study set up NB. This summary was reviewed by three lay members of the public, through the University Hospitals Sussex NHS Foundation Trust, Research Champions.
  Atrial fibrillation (AF) is the most common sustained arrhythmia (heart beat irregularity) encountered in clinical practice, resulting in significant associated illness and death. In 2010, an estimated 20.9 million men and 12.6 million women were suffering with AF. With an ageing population, significant growth in this number is predicted. By 2030 within Europe alone, it has been estimated that there will be 14-17 million AF patients, with 120,000-215,000 newly diagnosed patients per year. Patients afflicted with AF, have between a 10 and 40% probability of being admitted to hospital each year and, at present, the direct cost of AF approximates to 1% of the total healthcare spending in the UK. Furthermore, around 20-30% of all strokes are due to AF, while other complications such as heart failure (inadequate pump function of the heart to meet the body’s demand), decreased quality of life, depression, cognitive decline and dementia remain strongly associated. AF is also independently associated with a 1.5-fold increased risk of all-cause death in men, and 2-fold increased risk in women.

  A significant advance in the understanding of AF came two decades ago, when pulmonary vein ectopy (electrical activation of the heart muscle from the pulmonary veins which attach from the lungs into the left upper chamber of the heart) was found to initiate AF. Historically management of AF was by using drugs or with electrical cardioversion (a specially timed electric shock to restore the normal heart rhythm). The discovery of pulmonary vein ectopy as a possible cause of AF prompted the development of a technique to identify and create ablation marks (scars), over which false electrical signals cannot pass, to attempt to cure patients with AF.

  These ablation marks have traditionally been created by using specialized wires (catheters) that either freeze or burn the muscle of the heart. One rare but potentially life-threatening complication still remains which is where the small burn or freezing marks create a connection between the heart chamber where the ablation is performed (left atrium) and the food pipe (oesophagus). At present, this occurs in about 1 in 500 patients. This complication can occur because the food pipe is just behind the area of the heart where the ablation needs to be performed; however, due to its vicinity, the food pipe can occasionally also be inadvertently affected. Across many centres around the world, it is common practice to monitor the temperature in the food pipe during the ablation and, a few days after the procedure, to check the food pipe with a camera that is advanced through the mouth (endoscopy) to ensure there has been no damage.

  The study, whose design was reviewed by a pre-sponsorship review panel that included lay members of the public, aimed to see whether ablation using a new specialised wire in the shape of a balloon (the HelioStar balloon catheter) and reducing the amount of burning performed close to the food pipe (from the standard 20 seconds to only 15 seconds), could further improve the safety of these procedures whilst achieving the same successful results in treating AF. To do this, we planned to monitor the food pipe temperature during ablation with a temperature probe and, in addition, within 7 days after the ablation we planned to perform an endoscopy (camera advanced through the mouth into the food pipe) to ensure that no damage had been caused to the food pipe. Patients would then be followed up for 1 year after the ablation to assess the success of the procedure in preventing the atrial fibrillation happening again.
  Patients were identified as having atrial fibrillation that would be treated by the research team from specialist referrals, outpatient clinics, and procedure waiting lists at participating centres. These patients were then given a Patient Information Sheet that explained the study and had at least two weeks to consider if they wished to take part. If they did not wish to participate ablation was performed using the treatment sites usual method.

  For the sample size, given the expected high rate of acute success during the ablation (hence, requiring a very small sample size for the primary efficacy endpoint) the sample size was calculated based on a reduction of at least one third of the rate of expected Endoscopically Detected Esophageal Lesions (EDEL) to the food pipe. These occurred in 12.8% of the study population within the RADIANCE study, which used the same catheter but 20 seconds of ablation close to the food pipe). Therefore, for an expected incidence of EDEL of 8.3%, a confidence level of 95% and a 0.05 margin of error, the required sample size would be of 114 patients. Considering a 5% drop out rate, the total required number of patients was calculated to 120.

  In this multicentre study all participants received the same intervention and only 32 patients were included before a decision was made to stop the study early due to the company manufacturing the catheter making the decision to stop making the product. The decision of the company to stop making catheter was not for any safety reasons, but the study investigators and management teams felt it would be unethical to continue recruiting patients into a study for a device that would not be available in the future.
  The study was run at the Department of Cardiology, University of Athens Medical School, Greece and the Royal Sussex County Hospital, UK and conducted by the heart specialists (cardiologists) who would be involved in the patient’s standard of care.
  The 32 patients (72% male; median age 66 years [60-70]) were planned for an ablation procedure between December 2023 and March 2024, for recurrent symptomatic atrial arrhythmias (75% paroxysmal (occasional) atrial fibrillation and 25% persistent atrial fibrillation (AF episodes lasting more than 7 days)). The temperature probe was introduced and tolerated in all patients at the beginning of the case. Ablation was not performed in one patient due to failure to achieve venous access. All ablations were performed as planned by means of the HelioStar catheter. The primary outcome was the percentage of acutely isolated pulmonary veins. The main safety endpoint was the number of significant lesions documented in the food pipe during the endoscopy (EDEL). Secondary outcomes included the rate of isolation after a single application, any significant rise in the temperature registered by the monitor placed in the food pipe during ablation and the reoccurrence of atrial fibrillation during the 12 months follow up.
  Within the 31 patients receiving ablation, 27 (87%) presented a normal pulmonary vein (PV) configuration, whilst 4 (13%) presented a left common ostium (fusion of the 2 left PVs). Out of the 120 pulmonary veins treated, all of them were successfully isolated at the end of the procedure. 119 (99.1%) were successfully isolated by means of the Heliostar catheter, whilst 1 vein (0.9%) required ablation with a smaller catheter to achieve isolation. Isolation after the first application was achieved in 100/120 (83%) of those pulmonary veins. A significant rise in temperature over 42 degrees was only observed during ablation in 3/120 pulmonary veins treated

  Out of the 31 patients receiving ablation, 28 underwent their endoscopy within the first 7 days. The three remaining patients decided that they did not want to go ahead with the endoscopy and withdrew from the study. Only 1/28 patient (3.6%) presented an EDEL type 1 (the mildest form of lesion, that almost always resolve without treatment). This had no clinical significance, and the patient presented no symptoms or complications related to it.
  At 12 months follow up, 6/31 (19.4%) patients had experienced a recurrence of their arrhythmia. When stratifying by the type of atrial fibrillation, 2/24 (8.3%) patients with paroxysmal AF presented a recurrence at 12-month follow up, whilst in the persistent AF subset 4/7 (57.1%) did.
  During follow up, 5 patients presented with Serious adverse effects, definite or probably related with the study protocol:
  - One patient presented with ST elevation (a tracing of the heart activity which often indicates one of the coronary arteries is blocked) during the ablation procedure, which resolved with nitrates; a coronary angiogram performed did not show any abnormalities and the patient did not present any sequels.
  - Two patients presented with pericarditic chest pain after ablation, attending the Emergency department; no abnormalities were detected in either of these cases and the patients were discharged with conventional pain killers.
  - One patient presented with persistent gastric discomfort after his endoscopy. Cardiac investigations (bloods, ECG, echocardiogram) were unremarkable. His case was discussed with the endoscopy team, who was convinced that these symptoms related to the manipulation of the endoscopy probe in this patient, who had underlying significant hiatus hernia. Symptoms did resolve completely within 6 weeks.
  - One patient presented with a significant skin burn in his back, close to the area where the ablation patches were located. This resolved on his own without sequels.

  Summarizing, this study was prematurely terminated due to the manufacturer of the catheter deciding not to continue producing it. Although the number of patients required to achieve significant conclusions was not reached, the acute results of the ablation (99.1% success) were equivalent to the ones achieved with other technologies. The long-term success in terms of freedom of atrial fibrillation (91.7% in patients with paroxysmal AF and 42.9% in those with persistent AF) were also similar to the ones published in the literature. Regarding the number of food pipe lesions documented during the endoscopy (EDEL), there was only a very mild one that had no clinical significance. When comparing this to the standard 20-seconds application with the same HelioStar catheter, the ablation protocol used in the study showed a lower proportion of food pipe lesions (3.6% vs 12.8%).

• REC name

  London - Harrow Research Ethics Committee

• REC reference

  23/PR/1010

• Date of REC Opinion

  26 Oct 2023

• REC opinion

  Further Information Favourable Opinion