Influence of Left Atrium Volume Index on effectiveness of Thoracoscopic Ablation in the Treatment of Atrial Fibrillation

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Atrial fibrillation (AF) is the most common arrhythmia, the prevalence in the population is on average 0,4-2% [1,2].Number of patients with AF will double by 2050 [3].
AF is associated with high risks of thromboembolic events (12-31% of all ischemic strokes), heart failure (2.9-26%) and significantly reduces the quality of life of patients [4].Progression of arrhythmia leads to remodeling of the chambers of the heart, in particular the left atrium (LA).
Patients with symptomatic AF and refractory to drug therapy are recommended to perform catheter ablations (CA) and/or Maze procedures [5,6].However, the effectiveness of CA decreases with the progression of AF from 80 to 60%, and during the 10-year follow-up period is 52% [7,8,9].
The surgical strategy for the treatment of nonparoxysmal AF, presented by the Cox-Maze IV procedure and its modifications, demonstrates the best results in the early and long-term period with freedom from AF up to 93%, remaining the "gold standard" of treatment [10,11,12,13].Early number of previously published studies have shown that an increase in the size of the LA can affect the effectiveness of the Maze procedure [14,15,16,17].
Increased LA increases the propensity to AF as a consequence of structural remodeling of the atrium due to fibrosis and deposition of extracellular matrix proteins [20,21].Despite the high efficiency of surgical treatment of progressive forms of AF, these procedures are highly traumatic and involve a high risk of perioperative complications, which is undesirable for patients with isolated AF, and therefore epicardial ablation methods using endovideosurgical equipment have been introduced into clinical practice.Thoracoscopic ablation (TSA), as an isolated procedure, demonstrated promising results, with 65-96% free of AF [22,23,5,21].The influence of LA size on TSA has not yet been studied [24].
The purpose of this study was to establish the influence of LAVI on effectiveness of TSA of AF and determine the risk factors for manifestation of supraventricular arrhythmias in the long-term follow-up results.

Study population
Prospective cohort study enrolled 121 consecutive patients performed TSA with drug-refractory AF at A.V. Vishnevskiy National Medical Research Center of Surgery (Moscow, Russia) between 2018 to 2021.
All patients were divided into two groups: group I included patients with LAVI > 34 ml/m 2 , group II patients with LAVI ≤ 34 ml/m 2 [18].
Design study is shown in Fig. 1.

Follow-up
All patients were followed up at 3 months, 6 months, and every 6 month thereafter.At each visit, 12-lead ECG or 24-h Holter monitoring ECG was performed to evaluate rhythm and atrial activity.Recurrence was defined as symptomatic or asymptomatic episodes of AF lasting longer than 30 seconds and identified on 12-lead ECG or 24-h Holter monitoring ECG after a blanking period of 3 months (HRS/EHRA/ECAS guidelines) [17].Antiarrhythmics drugs (AADs) were discontinued at 6 months or up to 12 months.
The main adverse cardiovascular events (MACE) in the early and long-term follow-up result were also taken into account.

Surgery ablation technique
Procedures were performed thoracoscopically under general anaesthesia with sequential single lung ventilation using either a double-lumen tube or bronchial blocker.Patients were positioned supine.
The features of the modified TSA technique suggested in our center are the provision of simultaneous bilateral approaches and electrophysiological control of bidirectional block.In case of incomplete isolation, the possibility of applying additional ablution set critical points remains.This makes it possible to complete the creation of a "Box lesion" along the back wall of LA with high reliability.
Right-sided and left-sided stages of the operation were represented by performing isolation of the pulmonary veins (PVs) with a bipolar electrode for 10 ablations with a gradual displacement of the branches to increase the isolation zone and the formation of the upper and lower lines of LA with a monopolar electrode (Fig. 2, 3).When registering a signal from superior vena cava (SVC), additional ablation was performed using a bipolar electrode (Fig. 4).
Exclusion of left atrium appendage (LAA) is performed from the left-sided access using an endospler (Fig. 5-7).
An electrophysiological study was performed intraoperatively, the transmurality and achievement of bidirectional block of conduction through the ablation lines (exit and entrance block) were estimated.With the help of high-frequency stimulation, the start of AF was caused, its spontaneous blocking within 30 seconds was considered the norm.When registering a stable AF at the end of the procedure, electropulse therapy was performed.

Left atrial volume index
Compliance with the clinical guidelines on imaging methods of the cardiovascular system (EACVI), asymmetric LA remodeling is more accurately evaluated when measuring its volume.LA volume varies throughout the cardiac cycle.
Measurement of LA volumes can be performed by many methods, but two are used in clinical practice.The first is the calculation of the LA area along the long axis from the four-chamber and two-chamber positions, after which calculations are made using a special formula.
Considering that AF was registered in many patients included in the study at the time of the TEE study, we performed LAVI measurements using the Simpson's method [18].This measurement is carried out similarly to the measurement of left ventricle (LV) volumes, in 2D echocardiography mode from apical access.At the same time, the mouths of PVs and LAA should be excluded from the measurements.ACE/ EACVI specialists recommend indexing LA volumes to body surface area (BSA) [18,19].For an accurate assessment of LA, it is necessary to obtain 3 main volume indicators.The maximum LA size at the end of the LV isovolumic relaxation phase before the opening of the mitral valve is the measurement point of the maximum LA volume.The minimum LA volume is measured at the end of the LV diastole when mitral valve closes.The presystolic LA volume (mean LA volume) is measured before the atrial systole (before the P wave on the ECG).
Normal LAVI values are considered 22 ± 6 ml/m 2 .LA dilatation is defined as LAVI>28 ml/m 2 (one standard deviation from the mean value), however, to determine LV diastolic dysfunction, a value of LAVI > 34 ml/m 2 (two standard deviations from the mean) is proposed as the upper bound [22,25,19].The ASE/EACVI recommendations indicate that the upper limit of the LAVI norm is 34 ml/m 2 [18].Method of measuring the volume of LA with PVs using MCT was similar in the previously published work of M Sangsriwong et al. [16].

Statistical analysis
Statistical data processing was carried out using the built-in Excel 2016 spreadsheet processor analysis package and the SPSS 24.0 spreadsheet application package.
Descriptive statistics are represented by arithmetic averages (M) ± standard deviation (SD).
When assessing the statistical reliability of differences (p) in groups for quantitative features (with normal distribution), a comparison of averages (M) was used using parametric criteria -the Student's two-sample t-criterion -homoscedastatic with equal variances, heteroscedastic with inequality (variance difference was evaluated using the Fisher criterion (F-test), in the absence of a normal distribution, U-the Mann-Whitney criterion.The differences were considered significant at a significance level of p < 0.05.
Correlation analysis was carried out using Spearman rank correlation coefficient, the values were considered significant at p < 0.05.

Results
All patients in the two groups were comparable in terms of the main clinical parameters: age, gender, and concomitant diseases.The AF duration prevailed in the group of patients with LAVI > 34 ml/m 2 6.71 ± 3.14 y, compared 5.41 ± 5.19 y in group with normal LAVI (p = 0.062).Baseline characteristics and examinations data are shown in Table 1 and Table 2 No correlation was established between the history of AF duration and LAVI.
Before surgery the differences in the groups were in previous catheter ablations (CA) and anticoagulants.
The distribution of type AF in the groups is presented in Table 1, patients with non-paroxysmal AF prevailed in two groups (p > 0.05).
Spearman rank correlation coefficient showed that there is a relationship between LAVI and LVEF.
All patients underwent bilateral isolation of the PVs, excepted of 1 (1.6%) patient from II group, whom isolation of the left PVs wasn't performed due to a expressed commissural process.Intraoperatively, the sinus rhythm was restored at the right-stage of surgery in 4 (6.9%) and 7 (11.1%), at the left-stage of surgery in 4 (6.9%) and 3 (4.8%) in I and II groups, respectively for patients only with non-paroxysmal AF.Additional VCS circular ablation was performed 4 (6.8%)patients in I group.
At the end of the operation, electrical cardioversion was required in I group -63.8%, in II group -1.6% (p = 0.08).The sinus rhythm at the end of the procedure in I was 89.7%, in II -90.5% (p = 0.039).
The ventilation time was 719.66 ± 464.05 min and 617.41 ± 535.0 min, blood loss in the early postoperative period was 191.55 ± 105.88 ml and 229.37 ± 150 ml for I and II groups, respectively.
The time of hospitalization was comparable for patients with LAVI > 34 ml/m 2 was 5.8 ± 4.5 and with a normal LAVI was 5.4 ± 6.2 days (p = 0.82) Table 3.

Follow-up
At the follow-up of 36 months the freedom from atrial arrhythmia was 80.8% in I group (for nonparoxysmal AF 78.6% and for paroxysmal AF 88.9%).In II group, sinus rhythm was recorded in 81.5%, mainly in patients with paroxysmal AF -88.9%, versus 77.8% with non-paroxysmal AF (Fig. 8, 9).Spearman rank correlation coefficient showed the dependence of sinus rhythm recovery and reten-tion on the LAVI indicator (Table 4).LAVI is the only factor that affects the effectiveness of TSA in our study.
Figure 10 shows a positive correlation between the history of atrial fibrillation (years) and LAVI (ml/m 2 ) in patients with sinus rhythm in the long-term follow-up period.It is worth noting that it is an increase in the LAVI more than 40 ml/m 2 that may be a risk factor in the return of AF after TSA.AADs was discontinued after 1 year in 74.4% patients.
Just 3 months after TSA, 20 CA were performed, 6 months later one patient (II group) underwent repeated CA, and another patient (I group) performed CA of arrhythmogenic zones of the right atrium.

Complications
Complications associated with the procedure and MACE were not registering within 30 days after surgery.
Implantation pacemaker device, paralysis diaphragmatic nerve, bleeding in the early postoperative period that required conversion were not registered.

Discussion
The choice of optimal methods for the treatment of various forms of AF remains one of the advanced problems of contemporary arrhythmology.The pro-gression of AF is accompanied not only by clinical manifestations with subsequent deterioration in the quality of life of the patient, but also leads to morphological changes in LA.To date, it has not been studied what is the primary arrhythmia or LA remodeling [12,35,26,27].
According to published data, an increased LAVI worsens the results of CA and surgical treatment of AF.The impact of LAVI on TSA outcomes is presented to date only in the work of J. Neefs et al. [24] in relation to giant LA (LAVI > 50 ml/m 2 ).Therefore interest remains for further study of this problem [28][29][30][31][32].
The ASE/EACVI guidelines indicate that the upper limit of normal for LAVI is 34 ml/m 2 [24], an increase in this indicator is a predictor of adverse cardiovascular events [7,22,3,29].All patients included in the study underwent TSA (Figure 1).Before surgery, patients in the two groups were comparable in almost all clinical characteristics (p > 0.05) (Table 1), with the exception of previous CA and anticoagulants (p < 0.05).
Spearman rank correlation coefficient showed that there is a relationship between LAVI and LVEF, that is consistent with the research data on the contribution of LA to LV function [33,34].According to our study, only LAVI > 34 ml/m 2 is a risk factor for arrhythmia after TSA (Table 4).In I group, the effectiveness of TSA was 77.8%, that is significantly lower than the recovery of sinus rhythm compared to II group -88.9%. 3 months after the TSA, 20 (17%) additional CA were required, mainly in patients of I group [7,14,22].
Long-term development of MACE events was not registered in any of the groups, even after discontinuation of anticoagulants and AADs.The findings confirm that LA remodeling and volume expansion reduces the effectiveness of TSA.It is possible that the presence of excess fibrous tissue (more than 20-30%) in the left and right atrium, as well as the presence of epicardial fat in the left atrium, affect the effectiveness of TSA [20,29,33,34].We will present the results of research in this area in subsequent publications.
Thus, the LAVI score should be taken into account before the CA and the TSA.

Conclusion
Research results showed that an increase in LAVI significantly reduces the effectiveness of TSA in the long-term period by 11.1% compared with LAVI < 34 ml/m 2 .That are conform with other data of previously submitted researches.