Factors Influencing Stereotaxic Pulmonary Vein Isolation

Background – Catheter ablation of atrial fibrillation (AF) is performed to restore and maintain a sinus rhythm. Remote magnetic navigation system (RMNS) allows an efficient and safe procedure. Left atrial (LA) anatomic barriers of this device are not well known. Aims – This study was aimed to evaluate clinical, echocardiographic and cardiac computed tomography (CCT) anatomic LA characteristics as predictors of stereotaxic AF procedure duration. Methods – From February 2015 to April 2016, 102 symptomatic and drug refractory AF patients were consecutively enrolled in an observational, prospective trial when first AF ablation. AF Radiofrequency (RF) was performed with a RMNS using Niobe  ES. Clinical endpoints and LA characteristics were reported, prospectively by a transthoracic and transesophageal echocardiography, and CCT scan. Results – Mean patient age was 59  12 years old, 77% male, mean CHA2DS2VASc of 1.3  1.3 and mean LA surface of 23  6.5cm2. Procedure duration of 97.2  32.9 minutes and fluoroscopy duration of 13.4  7.9 minutes were recorded. Persistent versus paroxysmal AF (p<0.05), previous flutter ablation (p<0.01), LA dilation (p<0.05), narrow LA ridge (p=0.01), small surface area and high eccentricity of the left inferior pulmonary vein (LIPV) (p<0.01) are correlated to an increased procedure duration. Previous flutter ablation (p<0.01), persistent AF (p<0.05), LIPV eccentricity (p<0.05) and ridge width (p=0.05) were found to be independently associated with procedure duration. Conclusion – Our study is the first analyzing predictors of stereotaxic procedure duration. Narrow LA ridge, small and flattened LIPV were independently correlated with an increased procedure duration. Yet neither co-morbidity nor


Introduction
Radiofrequency ablation (RF) is a treatment of choice for atrial fibrillation (AF) because of a positive risk/benefit ratio compared to antiarrhythmic drugs [1][2][3].
Even if significant advances have been made over the past years regarding RF, pulmonary vein isolation (PVI) notably, several limitations remain to be overcome, such as the management of recurrences usually due to pulmonary veins (PV) reconduction, the high level of X-ray exposure and a significant risk of complications [4][5][6].
AF ablation is carried out in expert centers with high patient volumes. It is one of the most common procedures in electrophysiology departments (30 to 50% of total procedures) due to its prevalence and the recent guidelines [1][2][3]. The management of end cavity ablation in challenging clinical settings may lead to tedious and risky procedures [6,7]. and the evolvement of AF ablation indications lead to increased procedures per operator [8].
The aim of this study was to itemize clinical and anatomical factors influencing stereotaxic PVI duration when AF ablation.

Study population
The current trial was an observational, prospective, and The following data were prospectively collected: demographic patients data, comorbidities, AF background and AF therapeutic management.

Pre procedure imaging
Conventional transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) were systematically performed 24-72 hours before the ablation procedure with a commercially available system (Vivid E9, GE Healthcare, France).
During TEE study, LAA was carefully analyzed to detect left atrial thrombi and spontaneous echo contrast [21].

Ablation procedure
The procedure is detailed in the supplementary appendix. LA mapping was performed using CartoÒ 3 System (Carto® 3 system, Bio sense Webster, CA), an electromagnetic system allowing realtime Advanced Catheter Location™ and visualization of both ablation and circular mapping catheters (NaviStar® and Lasso catheters®).
Once the map was completed, 3D computed tomography scan was performed in order to optimize LA reconstruction.

Procedure and fluoroscopy parameters
Skin to skin total duration was recorded for all patients. The following parameters were also recorded: X-ray duration (sec), X-ray (Gy) and indexed X-ray (Gy x cm²) procedure time. These parameters were divided in different periods: setting up, mapping and ablation period (including left and right PVI).

Statistical analysis
Continuous variables were presented as mean±SD, or median+IQR as appropriate. Categorical variables were expressed as percentage. Linear uni and multi-variate models were generated to predict procedure duration. Characteristics of each model were given at the regression parameter for each variable (b), with its 95% confidence intervals and p-value. The multiple linear regression model was built in a backward stepwise manner, selecting theoretically impacting covariates (defined by p<0.05 in the univariate analysis) to predict procedure times and X-ray patient exposure, to maximize the goodness of fit expressed as R². All analyses were performed using R (R Foundation for Statistical Computing, Vienna, Austria, http://www.R-project.org).

Procedure features
Procedure parameters are summarized in (  Continuous variables are presented as mean±SD. AF=atrial fibrillation.

Univariate analysis
Clinical characteristics impacting the ablation duration No co-morbidity was associated with an increase of the AF ablation procedure or X-ray exposure duration (Table 3). On the other hand, persistent versus paroxysmal AF (p<0.05), and previous flutter ablation (p<0.01) were both risk factors associated with a with procedure duration. The left ventricular function was not associated with a change in ablation procedure duration parameters (Table 3): neither LVEF (p=0.2) nor sAoTVI (=0.6). Furthermore, mitral valve disease, whether mitral regurgitation (p=0.9) or stenosis (p=0.4), was not correlated to longer procedures. Anatomical characteristics impacting the ablation duration LA dilation, assessed by LA area (p<0.05) and LA volume (p<0.05), was associated to an increased procedure duration (Table 3). This association was found during the mapping poeriod of the procedure (p<0.01), but not for the setting up and ablation ones (

Multivariate analysis
Through multivariate linear regression analysis with relevant clinical and echocardiographic features, a previous flutter ablation (p<0.01) and persistent AF (p=0.03) were found to be independently associated with total procedure duration. Furthermore, left LA fluoroscopy duration was independently influenced by LIPV eccentricity (p<0.05) and LA ridge width (p=0.05).

Major findings
This prospective observational study suggests that no comorbidity and cardiomyopathy was associated to longer stereotaxic PVI procedures. LA dilation was correlated with increased setting up but not ablation duration. Persistent AF and previous atrial flutter are independently associated to an increased procedure duration.
Only LA ridge width and LIPV anatomy influenced significantly and independently the ablation duration.

Stereotaxic procedure duration
Due to the improving indications of AF ablation, all dedicated EP departments deal with an increased daily ablation procedure.

Volume 3 -Issue 3 Adv Card Res.
Thereby, different challenges appear: [1] decrease procedure duration leading to reduce physician fatigue and X-ray exposure and [2] optimize the management of consecutive daily procedures. As an indicator shown in (Figure 1), the procedure duration seems to be significantly shorter in the current study using stereotaxic system, compared to cry balloon and manual RF ablation in FIRE and ICE trial [23]. Indeed, manual RF ablation seems to approximately 50% longer than stereotaxic procedure, while fluoroscopy duration is 75% longer with cry balloon and 33% longer with manual RF than stereotaxic ablation. In addition to a shorter procedure, stereotaxic ablation reduces the operator tiredness and increases its accuracy by allowing a seated and comfortable procedure. However, it is important to keep in mind that all ablations were performed with an experienced operator, after a usual learning curve.

Figure 1:
Procedure and fluoroscopy duration with stereotaxic ablation compared to cryoballoon and radiofrequency ablation in FIRE and ICE trial [23].
Factors influencing procedure duration (Figure 2) Clinical characteristics impacting the ablation duration. Age, sex, diabetes mellitus, vascular disease and obesity are not correlated with an increased manual RF procedure duration [24], which is consistent with our trial. Our study was the first highlighting the lack of association between body weight and procedure duration. In addition, AF radiofrequency seems to be safe despite of overweight: there is not a higher hemorrhagic and infectious complications incidence reported [25]. Yet several AF risk factors such as obesity and sleep apnea, seems to be important to maintain a sinus rhythm after AF ablation [26]. Persistent AF was associated to a longer PVI procedure, suggesting the presence of more severe LA architectural abnormalities when persistent AF. Indeed, persistent AF seems to be associated to a much more severe atrial cardiomyopathy compared to paroxysmal AF [27]. Furthermore, previous ablation of atrial flutter RF was an independent risk factor of longer ablation procedure. The interrelationship between AF and atrial flutter is still unclear [28]. But this finding suggests that patients with previous atrial flutter get a complex atrial cardiomyopathy including fibrosis [24] and atrial dilation. It could lead to a longer and less efficient IVP procedure [29]. Hemodynamic characteristics impacting the ablation duration neither systolic left ventricular dysfunction nor mitral disease were correlated to a longer procedure. Since 50% of AF patients get heart failure and 25% of heart failure patients get AF [30], the efficacy and safety of the AF ablation has to be proved. Indeed, antiarrhythmic drugs fail AF patients with heart failure [31], and AF ablation could be a therapeutic key, as suggested by CASTLE-AF trial [32]. In this study, catheter ablation decreased hospitalization rate and mortality, increased left ventricular function, over midterm follow up [33]. The stereotaxic ablation seems to be an interesting strategy when heart failure, regarding the safety of the procedure and the absence of LV dysfunction and LA dilation impact in procedure duration.
Left atrial architectural features impacting the ablation duration In our study, LA dilation led to a longer procedure, with an increased mapping duration, yet no effect on stereotaxic ablation duration was reported. Stereotaxic procedure seems to overcome anatomical difficulties such as LA dilation, preventing technical difficulties because of an efficient navigation.
On the other side, a narrow ridge was a predictor of longer ablation using RMNS. The left lateral ridge is known as a uniform width or muscular thickness being narrower and thicker at the antero-superior level [34]. This area acts as a fibrillary process due to the presence of the vein of Marshall, an electrical gap between left PV and LA [35]. This area constitutes a preferential zone of PVs reconnection [36]. Manual RF procedures often fail to complete ablation line in LA ridge [37]. This study also pointed out a tough ablation in this area despite stereotaxic accurate navigation.

Clinical implications
AF catheter ablation is an efficient treatment to achieve a rhythm control strategy, regarding recent guidelines [8]. But this procedure is still challenging and needs to be more efficient and safer. RMNS may be an interesting way to achieve this goal. In this study, all procedures allow an acute PV isolation, associated to a short procedure and fluoroscopy time. Furthermore, RMNS allows an efficient navigation during PVI, regardless LA dilation and left ventricular dysfunction.
But RMNS accuracy could be improved. The Stereotaxis Magnetic Navigation System allows precise navigation with a spatial resolution of 1 degree of omni-directional deflection and 1 mm for catheter advancement and retraction, as opposed to the manual catheter manipulation and catheter movements which highly depends on the operator. RMNS leads to a stable cathetertissue contact during cardiac motion, unlike manual RF ablation [38]. This study suggests that a narrow LA ridge and a small and flattened LIPV increase overall procedure time. The knowledge of these anatomical limitations ta achieve IVP may help the engineers to work on RMNS improvements.

Study limitations
The major limitation of this observational study was its lack of randomization. However, this study included consecutive patients, prospectively, in order to prevent bias analysis. In addition, this monocentric trial was based on IVP procedures performed by a single operator. It avoids the inter-observer variability but limits the exptrapolability of the data. Finally, a new trial should be designed to test LA anatomical predictors of AF recurrences and PVs reconnection with RMNS compared to manual RF and cry balloon procedures.

Conclusion
Our study proposed to highlight predictors of stereotaxic procedure duration. Both narrow LA ridge, small and flattened left inferior PV are independently correlated with increased procedure duration. But no co-morbidity and cardiomyopathy were linked to a procedure change.