Left atrial functions in the early period after cryoballoon ablation for paroxysmal atrial fibrillation

In patients with paroxysmal atrial fibrillation (PAF), functional changes are observed in the left atrium (LA) after pulmonary vein isolation (PVI) procedure. Although previous studies have investigated the altered mechanical functions of the LA with radiofrequency (RF) ablation, changes in the LA functions in the early period after cryoablation (CB‐2) have not been clearly demonstrated. This study aims to explore the early periodical changes in mechanical functions of the LA in patients with PAF who underwent CB‐2 based ablation through the help of echocardiographic methods which contain Doppler and strain parameters.


INTRODUCTION
While atrial fibrillation (AF) is related to increased mortality and morbidity in patients, it also places a heavy burden on global health systems. AF through various pathophysiologic mechanisms leads to atrial dilatation, dysfunction, and fibrosis. 1 Being one of the most common reasons for increased volume and mechanical dysfunction of the left atrium (LA), AF also distorts the mechanical function of the heart globally. Mechanical remodeling takes place when the increased compliance of the atria leads to decreased contractility and increased tension on the atrial myocardium. 2 Restoration of the normal sinus rhythm has become a significant target in the treatment of patients with AF since the studies showed that controlling the AF leads to improvement in the mechanical functioning of the LA. 3 Pulmonary vein isolation (PVI) is the established therapy of invasive management of AF, considered as the cornerstone step of AF. The "Fire and Ice" trial proved the non-inferiority of cryoballoon ablation (CB-2) to RF-PVI in patients with paroxysmal AF (PAF). 4 CB-2 has been found to have high procedural success and shorter procedural duration, high durability of PVI and convincing clinical results in various clinical conditions. [5][6][7][8] Preferred ablation pathway and the degree of ablation to control the AF are vital and can contribute to the disruption of the mechanical functioning of the LA. 9 There are many studies in which the effects of PVI modality with radiofrequency catheter ablation (RF) on the LA function of patients with AF are evaluated. 10,11 Especially in the early periods following RF ablation, disrupted mechanical functions of the LA in patients with PAF have been shown through cardiac magnetic resonance imaging (MRI) and echocardiographic methods which also contains Doppler parameters. [12][13][14] Although former studies have explored the impacts of RF ablation on the function of the LA, they lack a clear illustration of the altered LA functions in early periods after a CB-2 procedure is done. This prospective study aims to explore the early periodical changes in mechanical functions of the LA in patients with PAF who underwent CB-2 based PVI through the help of echocardiographic methods which contain Doppler and strain parameters.

Preprocedural management
Transesophageal echocardiography and baseline echocardiography were performed in all patients on the morning of the day of the procedure. Apart from echocardiography, no additional preprocedural imaging was performed. In patients on vitamin K antagonists, anticoagulation was continued throughout the procedure aiming at an INR of 2-3. In patients treated with novel oral anticoagulants (NOACs), the drug was discontinued ≥24 h prior to the procedure and re-initiated 6 h post-ablation at half the regular dose, and at full dose the following day.

Procedural management
All procedures were performed under deep sedation using midazolam, Application of cryo-energy was terminated immediately upon attenuation or loss of phrenic nerve capture. The procedural endpoint was defined as persistent PVI verified by spiral mapping catheter recordings 30 min after the last energy application. All the PVs were isolated during the procedure. In cases where AF occurred during the procedure, when not terminated by ablation, sinus rhythm was restored by cardioversion (CV). The duration of the procedures was nearly 60 min.

Postprocedural management
Following ablation, all patients underwent transthoracic echocardiography to rule out a pericardial effusion. All patients were treated with proton-pump inhibitors twice daily for 6 weeks. Anticoagulation was continued for at least 3 months and thereafter based on the individual CHA DS-VASC score. To prevent early recurrence, an antiarrhythmic drug was administered throughout the 3 months blanking period.

Echocardiographic acquisition
All was measured as the difference between peak reservoir and peak contractile strain, representing the atrial mechanics during the passive LA filling phase, after the opening of the mitral valve, and before LA contraction. Paired t-test was used to compare the measurements before and after the ablation procedure. A two-tailed p-value equal to or less than .05 was accepted to be significant.

RESULTS
A total of 77 patients with PAF underwent PVI by CB-2. All patients were included and completed initial echocardiography and followed up 3 months after the procedure with a control echocardiogram. All patients were in sinus rhythm at the time of ablation and after the procedure. No major complications were observed.

Baseline characteristics
Patient demographics and clinical characteristics were presented in Table 1. The mean age was 57.5 ± 11.2 years and 44 patients were men (57%). None of the patients had undergone a prior ablation procedure.

2D-ECHOCARDIOGRAPHIC PARAMETERS
The LA dimension, measured from the long apical axis, was 41.3 ± 6 mm before the procedure and 41.4 ± 6 mm (p = .25) 3 months after the procedure. LAVI, measured using the biplane method and corrected for body surface area, was non-significant. E and A wave velocities were measured by using Doppler method and although velocities before TA B L E 2 Comparison echocardiographic parameters of the patients before and 3 months after the procedure. the procedure were shown to be increased in the 3rd-month control echocardiography, the difference was not statistically significant. Likewise, there were no significant differences in lateral and septal E/é values, indicators of diastolic dysfunction. Prolongation, observed in the electromechanical delay time of lateral and medial mitral annular tissues was found to be statistically non-significant. Details of echocardiographic data was presented in Table 2.

Speckle tracking echocardiography analysis
The LA and the LV strain parameters at baseline and at 3 months after the procedure are listed in Table 2 There were no significant differences observed between the values of the LV endocardial average strain before and after the procedure.

DISCUSSION
The Among the patients with PAF who were followed after RF ablation therapy, left atrial functions failed to improve in some of them while in the others reverse remodeling took place only after 6 months. 19 Our study is unique in the sense that it has serially assessed the left atrial In a previous study which is performed using 2D-STE method and includes the patients with persistent and paroxysmal AF, peak atrial longitudinal strain parameter which is measured before the procedure has been shown to be effective in predicting the AF recurrences occurring 3 months after the procedure in both patients with LA size in normal ranges and patients with an enlarged LA. 21 The results of our study detected no significant change in the parameters of diastolic functions. Despite the non-significant increase in the left atrial dimension, a significant improvement was detected in the parameters, LAsr and LAsct which shows the ability of compliance and contractility of the LA through the 2D-STE method. The average value of LA reservoir and contractile strain parameters were found to be lower than the normal reference range, but it subsequently recovered to the slightly lower limit of normal average value. This can be considered clinically significant. 22 The use of angiotensin-converting enzyme inhibitor (ACEi), ARBs, and ARNIs may have an effect on atrial remodeling. When compared between patients included in the study before and after cryoballoon treatment, there was no difference found between the use of these drugs, which suggests that the improvement in parameters related to left atrial function may be due to the effect of the treatment rather than the drugs used. This result is in compliance with the former studies which have also pointed out that left atrial mechanical function is an independent variable, regardless of the left atrial dimension. Although significant improvement in left atrial mechanical functions was observed, no improvement was detected in the LV endocardial average strain values.

Limitations
The major limitation of the present study is relatively small sample size.
Additionally this study lack of conclusion on persistent or long standing persistent AF patients, due to enrollment of PAF. In four of the patients who were included in the study, the 2D-STE measures were taken after