Cryoballoon (CB) catheter ablation is a treatment for atrial fibrillation (AF), the most common type of arrhythmia. It has been reported to have a short procedure time and low complication rate, and its effectiveness and safety have been confirmed in several global clinical studies.

Clinical studies have recently been published from various angles on cryoballoon ablation, confirming its effectiveness and safety in paroxysmal AF and persistent AF (PeAF). At the European Society of Cardiology Congress 2023, held in late August, a study comparing the effectiveness and safety of therapies using CB in patients with persistent A-fib was presented, attracting attention.

The study, titled "A Study of Patients Undergoing Additional Right Atrial Linear Ablation After Cryoballoon Ablation" (CRALAL Trial), compared the efficacy and safety of cryoballoon ablation with additional right atrial linear ablation in 339 Korean patients with persistent atrial fibrillation scheduled for pulmonary vein ablation for at least seven days.

The primary endpoint was the rate of recurrence of any type of atrial arrhythmia (atrial fibrillation, atrial flutter, and atrial tachycardia) after a three-month washout period during a minimum 12-month follow-up.

Secondary endpoints included:

Atrial arrhythmia recurrence.

Use of antiarrhythmic drugs after a three-month washout period.

Procedure duration.

Complications.

Rate of need for cardioversion.

As the primary endpoint, atrial arrhythmia recurrence was 39.9 percent in the CB alone group and 28.8 percent in the right atrial linear ablation group, indicating an about 11 percentage point lower rate of atrial arrhythmia recurrence with the addition of right atrial linear ablation.

Among the secondary endpoints, the rates of atrial arrhythmia recurrence and antiarrhythmic drug use after a three-month washout period were 70.6 percent in the CB alone group and 56.8 percent in the right atrial linear ablation group, indicating about 14 percent lower rate of atrial arrhythmia recurrence with the addition of right atrial linear ablation.

In patients with persistent atrial fibrillation who underwent pulmonary vein ablation for the first time, the right atrial ablation plus treatment arm, which included both Superior Vena Cava- Right Atrial (SVC-RA) septal line and Cavo Tricuspid Isthmus (CTI) ablation, reduced the risk of arrhythmia recurrence by 35 percent compared to the cryoballoon ablation alone.

Korea Biomedical Review sat down with the study's principal investigator, Dr. Park Hee-nam, professor of cardiology at Severance Heart and Vascular Hospital, to learn about treating persistent atrial fibrillation and the CRALAL study.

Question: Recently, there seem to be a lot of studies focusing on patients with persistent atrial fibrillation. What are the characteristics of persistent atrial fibrillation?

Answer: Persistent atrial fibrillation is defined as atrial fibrillation that persists for more than a week despite medication, and many patients have long-term persistent atrial fibrillation that has been present for more than a year or two. The problem is that the more severe the condition, the more difficult it is to return to a normal rhythm and the more likely it is to recur. As AF becomes chronic, with or without symptoms, the risk of complications, such as stroke, dementia, and heart failure, increases. Currently, paroxysmal atrial fibrillation is well-treated and responds well to medical procedures. However, persistent AF remains a challenging condition in modern medicine.

Q: How is persistent AF treated in Korea?

A: Patients with atrial fibrillation that has not been present for a long time are treated with antiarrhythmic drugs or electrical cardioversion to maintain a normal rhythm. About 40 percent of patients with atrial fibrillation that is not very old can maintain a normal rhythm with medication. However, patients are candidates for radiofrequency (RF) ablation if atrial fibrillation remains uncontrolled despite medication. In recent years, there has been an increase in the number of patients with atrial fibrillation under 60. Increased awareness and diagnosis rates are one reason for this, but another is the increasing number of patients with risk factors, including obesity. This is likely to be an important issue in the future.

Q: Your study of patients with persistent atrial fibrillation was recently presented at ESC. Can you give us an overview of the study, including its background and design?

A: Cryoballoon ablation, a part of cardiac catheter ablation as the treatment of AF, has become an important procedure for patients with paroxysmal atrial fibrillation who do not have severe disease due to its short procedure time and simple treatment method. The CRALAL study, presented at the ESC Late Breaking Clinical Trial (LBCT), confirmed the efficacy of cryoballoon ablation in moderately advanced AF and is the first LBCT presented at the European Society of Cardiology among Korean arrhythmia studies.

In LBCT, four pulmonary veins connected to the left atrium are frozen like a stamp using a 28mm cryoballoon to block the path of the arrhythmia downstream. It is less time-consuming and more comfortable than radiofrequency (RF) ablation, which involves point-by-point vascular necrosis. However, it depends on anatomy and atrial size, so it has only been studied in patients with paroxysmal atrial fibrillation without a large atrium. This study shows that it can be applied to persistent atrial fibrillation.

Q: What is particularly noteworthy in this study?

A: The CRALAL study was a randomized, comparative study conducted by six Korean institutions and included 289 patients with AF who had a left atrial size of 45 mm or less and were resistant to antiarrhythmic medications. It was designed to exclude patients with AF who had progressed too far. The median time from diagnosis to the procedure was 18 months.

The study was divided into two treatment groups: one underwent cryoballoon ablation alone, and the other underwent cryoballoon ablation and right atrial linear ablation. After 18 months of follow-up in both groups, the recurrence rate of atrial arrhythmias was 39.9 percent in the cryoballoon ablation alone group and 28.8 percent in the right atrial linear ablation plus cooling balloon ablation group. Most patients who underwent the procedure remained in normal rhythm, with a slightly smaller proportion of patients experiencing atrial fibrillation or atrial tachycardia for more than 30 seconds with the addition of right atrial linear ablation.

The treatment area for cryoballoon ablation is limited to the periphery of the pulmonary veins (left atrium). It is more effective when combined with linear ablation in the right atrium. Procedural complications were not different between the two treatment groups, ranging from 2 to 3 percent. Contrary to popular belief that cryoballoon ablation may be an insufficient treatment for patients with persistent AF, this study shows that additional procedures can improve outcomes. The data also show that cryoballoon ablation with additional right atrial treatment is as successful as conventional radiofrequency ablation in patients with persistent AF. However, this is not a 1:1 study comparing cryoballoon ablation to radiofrequency ablation, and further randomized comparative studies are warranted.

Q: Are there any risks associated with adding right atrial ablation?

A: There was no difference in the incidence of post-procedure complications, and although the procedure time is about 10 minutes longer when performing right atrial ablation, it is acceptable to improve the treatment effect. However, it is still difficult to apply realistically (in Korea) regarding insurance coverage and securing supporting data.

It may be premature to proceed with left atrial therapy alone for persistent AF. Since the cryoballoon electrode conductivity is highly influenced by the size and anatomy of the patient's atrium, I think it is possible to treat patients with persistent AF with cryoballoon ablation alone if the atrium is not very large and not very old. In the future, as more data on Korean patients are accumulated, I think the guidelines will change to allow for a wider range of applications for cryoballoon ablation in persistent atrial fibrillation.

Q: What does this study mean for medical professionals and patients?

A: New treatment options for persistent AF are welcome, especially if they are effective with a shorter procedure time. It will be welcomed by patients and healthcare providers and help ensure the efficient utilization of healthcare resources. However, further research to identify the optimal indications and structural characteristics is essential instead of taking a one-size-fits-all approach.