**2. Brief literature review of landmark trials on benefits of rhythm control**

Initial RCTs [5, 6] failed to show superiority of rhythm control on mortality [4], however maintenance of sinus rhythm did show improvement in quality of life and exercise capacity [7, 8]. These particular studies did not include patients with catheter ablation and most patients underwent rhythm control with repeated cardioversions and Antiarrhythmic drugs. Bunch et al. [9] published AF ablation patients have a significantly lower risk of death, stroke, and dementia in comparison to AF patients without ablation. Various experimental studies [10] and scientific position papers [11, 12] have indicated that early intervention with a rhythm-control strategy to prevent progression of AF may be beneficial [4] which eluded to the fact that "AF begets AF" due to electrical and structural myocardial left atrial remodeling. Subsequently, several RCTs have tested the strategy of catheter ablation vs. medical management as discussed below.

MANTRA PAF [13] was one of the initial trials that enrolled 294 patients (June 2005 through 2009) with symptomatic Paroxysmal Atrial Fibrillation (PAF) with no history of antiarrhythmic drug use. These patients were treated with either radiofrequency catheter ablation (146 patients) or therapy with Class IC or Class III antiarrhythmic agents (148 patients) [13]. This trial found no significant difference in cumulative AF burden between both treatment groups over a follow up of 24 months but the burden of symptomatic atrial fibrillation and any atrial fibrillation was significantly lower in the ablation group than in the drug-therapy group. These findings suggested that the efficacy of catheter ablation may be more durable than

#### *Recent Advances in Catheter Ablation for Atrial Fibrillation and Non-pharmacological Stroke… DOI: http://dx.doi.org/10.5772/intechopen.106319*

that of currently available antiarrhythmic drugs. There was no difference in quality of life between both treatment arms, but a perception of more improvement in physical well-being was seen in the ablation group which authors admitted that this may be attributable in part to a placebo effect. There were 36% of patients who were initially assigned to AAD arm who subsequently required ablation for recurrent atrial fibrillation, a finding signaling that though an initial rhythm control strategy with AAD may be initiated, a minority of such patients may subsequently require catheter ablation for adequate rhythm control. A major limitation of this trial was definition of goal of ablation for atrial fibrillation. At the time of the study, this was defined as elimination of complex high frequency electrograms inside encircled areas around the Pulmonary Veins (PV), but with rapid development of ablation techniques, this end point was no longer valid. A general agreement on end point of ablation is considered complete electrical isolation of pulmonary veins. A change in ablation strategy based on this end point may have potentially changed the outcome of the study.

RAAFT 2 [14]. was another contemporary RCT to MANTRA PAF enrolling 127 patients with symptomatic PAF from Europe and North America between July 2006 to January 2010 and then patients were followed up for 2 years till 2012. Patients were randomized to ablation vs. anti arrhythmic treatment arms. Ablation was performed with circumferential pulmonary vein isolation with demonstration of entrance block into pulmonary vein, with additional ablation such as linear lines in Left Atrium (LA), ganglionic plexi, targeting complex fractionated electrogram, superior vena cava (SVC) isolation, cavotricuspid isthmus (CTI) ablation all at the investigator's discretion [14]. With change in ablation goal when compared to MANTRA PAF, RAAFT 2 trial demonstrated catheter ablation resulted in significantly lower rate of recurrent atrial tachyarrhythmia at 2 years, and reduced the frequency of repeated episodes of AF and thus improvement in quality of life however, recurrence was documented in approximately 50% of patients. Ablation extends the time free of both symptomatic and asymptomatic AF and significantly reduced the recurrence of repeated episodes, potentially having an effect on AF progression [14]. This study was limited by small sample size, and findings restricted to mostly young people with PAF. So authors suggested that when offering ablation as a therapeutic option to patients with paroxysmal AF naive to antiarrhythmic drugs, the risks and benefits need to be discussed and treatment strategy individually recommended.

Rhythm control vs. rate control for AF in patients with heart failure (HF) were studied in multiple studies. In a multi center RCT [15], 1376 patients who had congestive heart failure with EF ≤ 35% were enrolled. Maintenance of sinus rhythm with Antiarrhythmic drugs did not reduce the rate of death from cardiovascular causes, as compared with a rate-control strategy. Role of catheter ablation was however not studied in this RCT. Significant proportion of patients do not tolerate anti arrhythmic drugs due to various side effects, is not responsive to AAD, or has difficulty in medication adherence or compliance. Catheter ablation is a suitable alternative for rhythm control. There have been several studies that has shown positive effect of ablation in AF and CHF patients [16–20]. CASTLE AF was a landmark large multi center open labeled randomized control trial [21] where 398 patients were enrolled with symptomatic Paroxysmal or Persistent AF who failed, had unacceptable side effects, or had an unwillingness to take antiarrhythmic drugs. These patients also had New York Heart Association (NYHA) Class II, III, or IV heart failure and a left ventricular ejection fraction (LVEF) of 35% or less. As compared to multiple previous trials showing benefit of catheter ablation [16–20], this was the first trial that tested the effectiveness of catheter ablation in improving rates of hard primary end points such as death

or the progression of heart failure. Primary end point which was a composite of death from any cause and lower rates of hospital admission for heart failure was significantly fewer in the ablation group. In addition there were other secondary outcomes seen such as increase in LVEF and reduction in AF burden.

CABANA trial [1] (published in 2019) was a landmark trial that enrolled 2204 symptomatic AF patients (paroxysmal, persistent and long persistent) from 126 centers over 10 countries and tested catheter ablation vs. medical management with antiarrhythmic and/or rate control medications. Catheter ablation did not significantly reduce the primary composite end point of death, disabling stroke, serious bleeding, or cardiac arrest, but secondary end point of mortality or CV hospitalization showed a significant 17% relative lower event rate for the catheter ablation group [1]. Post 90 day blanking period, patients were monitored for time to first AF recurrence defined as AF/AFl/AT for ≥30 s. Catheter ablation was associated with a lower AF recurrence rate than drug therapy (50% vs. 69% at 3 years post blanking follow-up). Another significant observation in this study was low rate of procedure related complication seen in catheter ablation group indicating that ablation is feasible. The trial had several limitations [1] such as higher rate of patient withdrawal in drug therapy group, catheter ablation and drug therapy may have changed over the long course of the trial, small percentage of patients may have received only rate control drugs. Comparisons of the intention to treat (ITT) results with the treatment received and per-protocol analyses suggest that the combined effect of crossovers and withdrawals reduced the estimated treatment effect and the precision of the effect size estimates as assessed by ITT. Additionally, potential introduction of bias due to unblinded site adjudication of cause of hospitalization etc. might have affected the results of the study. Authors concluded that the estimated treatment effect of catheter ablation was affected by lower-than-expected event rates and treatment crossovers, which should be considered in interpreting the results of the trial.

With initial belief that rhythm control strategy is not superior over rate control, based on AFFIRM study published in early first decade of twenty-first century, we have witnessed through several trials discussed above, the evolution of scientific evidence demonstrating efficacy of ablation strategy in improving quality of life, improvement of heart failure symptoms, improvement of exercise tolerance, survival benefits, reduce hospitalization etc. A monumental trial that brought a paradigm shift is EAST AFNET 4 [22]. This study was published in 2020 and sought to compare early rhythm control vs. usual care. This was a multi center randomized trial that enrolled over 2700 patients from 135 sites in 11 countries. Early rhythm control required antiarrhythmic drugs or atrial fibrillation ablation, as well as cardioversion of persistent atrial fibrillation, to be initiated early after randomization. Usual care arm patients were initially treated with only rate control therapy and rhythm-control therapy was used only to mitigate uncontrolled atrial fibrillation–related symptoms during adequate rate-control therapy. The trial was stopped for efficacy at the third interim analysis after a median of 5.1 years of follow-up per patient. The first primary outcome was a composite of death from cardiovascular causes, stroke (either ischemic or hemorrhagic), or hospitalization with worsening of heart failure or acute coronary syndrome [22]. First primary outcome event was found to have occurred less often in patients assigned to early rhythm control than in patients assigned to usual care achieving a conclusion that early rhythm control was beneficial that was associated with lower risk of adverse cardiovascular outcomes [22]. The results of this study

*Recent Advances in Catheter Ablation for Atrial Fibrillation and Non-pharmacological Stroke… DOI: http://dx.doi.org/10.5772/intechopen.106319*

was different from previously published studies comparing rhythm vs. rate control because of incorporation of catheter ablation which is a powerful tool for restoring sinus rhythm.

Another recent study, STOP-AF First [23] was published in 2021 which compared the efficacy of cryoboalloon ablation over AAD in patients with symptomatic paroxysmal AF. Cryoballoon ablation as initial therapy was superior to drug therapy for the prevention of atrial arrhythmia recurrence in patients with paroxysmal atrial fibrillation with low procedure related adverse events.

There are three modes for rhythm control: Electrical (direct current cardioversion), Pharmacological (Antiarrhythmic mediation) and catheter ablation. With the scope of this chapter we will focus more on evolution and rapid advent of catheter ablation strategy over past few years (**Figure 1**).

Current AHA/ACC/HRS Atrial Fibrillation guidelines [4] and 2017 HRS/EHRA/ ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation recommend catheter ablation in patients with symptomatic PAF (COR Class I) who are intolerant or refractory to Class I or Class III AAD, or ablation as initial strategy before trial of AAD (COR Class IIa). In recent 2019 focused update new recommendation have been added as AF catheter ablation may be reasonable in selected patients with symptomatic AF and HF with reduced left ventricular (LV) ejection fraction (HFrEF) to potentially lower mortality rate and reduce hospitalization for HF based on evidence from CASTLE AF data (COR Class IIb, LOE B-R) (**Table 1**) [24].

#### **Figure 1.**

*Strategies for rhythm control in patients with paroxysmal\* and persistent AF† . \*Catheter ablation is only recommended as first-line therapy for patients with paroxysmal AF (Class IIa recommendation). † Drugs are listed alphabetically. ‡ Depending on patient preference when performed in experienced centers. § Not recommended with severe LVH (wall thickness > 1.5 cm).* ‖ *Should be used with caution in patients at risk for torsades de pointes ventricular tachycardia. ¶ Should be combined with AV nodal blocking agents. AF indicates atrial fibrillation; AV, atrioventricular; CAD, coronary artery disease; HF, heart failure; and LVH, left ventricular hypertrophy. Adopted from [4].*


**Table 1.**

*Professional society guideline recommendations for atrial fibrillation catheter ablation.*

### **3. Catheter ablation of atrial fibrillation**

Pathogenesis of AF is incompletely understood. Broadly generalized, there is a trigger that initiate AF and there is a perpetuating factor that sustain the arrhythmia. Usually a PAC or a focal atrial tachycardia triggers atrial fibrillation that further creates a rapid irregular multiple wavelets of depolarization.

Dr. Cox in 1987 first described surgical ablation of atrial fibrillation [25] by creating multiple scars by "cut and sew" technique to create lines of conduction block to prevent atrial reentry and allow sinus impulses to activate the entire atrial myocardium, thereby preserving atrial transport function postoperatively. However, application of the maze III operation has been limited by the morbidity and risk associated with sternotomy-thoracotomy and cardiopulmonary bypass, as well as by limited adoption by cardiothoracic surgeons [26]. Seminal publication by Dr. Michel Haïssaguerre [27] in 1998 that pulmonary vein ectopics are frequent triggers for AF and ablation of these foci can treat AF laid the initial foundation for catheter ablation of AF. With the success of surgical lines, catheter ablation was tried with different curve sheaths but procedure was fraught with high complication rates and exceedingly high fluoroscopic times. Initial catheter ablations tried to target Right Atrium (RA) by creating Intercaval lines along the interatrial septum and Cavotricuspid isthmus line and target Left Atrium (LA) by creating three or four lines. Pappone and Co workers published Circumferential Radiofrequency Ablation of Pulmonary Vein Ostia with electroanatomic guidance is safe and effective in either paroxysmal or permanent AF [28].

Since then, different approachs for catheter ablation for atrial fibrillation have evolved such as segmental ostial PV Isolation, circumferential antral Pulmonary vein isolation (PVI), wide area circumferential LA ablation, catheter Maze (lines to connect the ipsilateral pairs of the PVs and a line to link the left PV encircling lesion to the mitral annulus), complex fractionated electrogram ablation (CFAE), Box lesion sets with linear lines ("floor line" and "roof line") to isolate posterior wall, Left atrial Appendage (LAA) isolation, Superior Vena Cava (SVC) isolation, autonomic ganglionated plexi ablation or Cardioneural ablation, alcohol ablation of vein of Marshal etc. There is no clear consensus about efficacy of one approach over another,

*Recent Advances in Catheter Ablation for Atrial Fibrillation and Non-pharmacological Stroke… DOI: http://dx.doi.org/10.5772/intechopen.106319*

**Figure 2.**

*Schematic diagram of various approaches of catheter ablation shown. Red circles are ablation lesions. Picture adopted from [26].*

but approaches often vary between paroxysmal Atrial Fibrillation and persistent Atrial Fibrillation. In PAF targeting the trigger for Atrial Fibrillation with wide antral circumferential ablation of bilateral PVs may prove sufficient in freedom from recurrent AF/AFl/AT. In contrast, patients with persistent Atrial Fibrillation, both trigger and substrate needs to be ablated and ablation may be necessary beyond routine PVI which may include posterior wall isolation or additional linear lines in left atrium depending on operator's discretion (**Figure 2**).

#### **3.1 Substrate based ablation for persistent/long persistent atrial fibrillation: targeting pulmonary and non pulmonary vein triggers**

Though PV are most frequent triggers for AF, investigators have shown several non PV triggers, incidence ranging between 3.2% and 47%, especially in Persistent/ Long standing Persistent AF. Triggers have been demonstrated in SVC (common in female patients), LA posterior wall, (common in patients with enlarged LA), Crista terminals, Left atrial appendage, Coronary sinus, Ligament of Marshall, Interatrial septum. Additionally, SVTs such as AVN reentrant tachycardia (AVNRT) and AV reentrant tachycardia (AVRT) can be identified in up to 4% in unselected patients referred for AF ablation and can serve as a triggering mechanism for AF [26]. Previous studies have suggested a benefit to intervention with ablation before drug failure, because a shorter "diagnosis-to-ablation" time is associated with lower rates of arrhythmia recurrence or repeat procedures and fewer hospitalizations [29–31].

STAR AF II [32] was a randomized trial that compared efficacy of three different approaches to catheter ablation of AF in patients with Persistent AF. They randomized patients into three arms: (1) PVI alone (2) PVI with CFAE (3) PVI and Linear ablation lines along the LA roof and Mitral Isthmus. Primary outcome of the study was to see any documented episode of atrial fibrillation lasting longer than 30 s and occurring after the performance of a single ablation procedure, with or without the use of antiarrhythmic medications. Clinical assessments, 12-lead electrocardiograms, and 24-h Holter-monitor recordings were obtained at baseline and at 3, 6, 9, 12, and 18 months after the initial ablation. Study showed no reduction in the rate of recurrent atrial fibrillation when either linear ablation or ablation of complex fractionated electrograms was performed in addition to pulmonary-vein isolation. Recurrence of atrial arrhythmia despite extensive ablation on a substrate based approach with targets beyond PV such as CFAE, linear lines probably created iatrogenic areas of arrhythmogenesis potentially from incomplete ablation of areas with complex electrograms or conduction gaps in linear lines.

A meta-analysis of 113 studies including 18,657 patients examined the impact of ablation approach on outcomes associated with Persistent or Long standing persistent AF [33]. Findings of this meta-analysis supports the findings of the STAR AF II trial, with collated results indicating that a simpler PVI approach (57% success) yields at least equivalent single-procedure results (or potentially better) compared with more complex substrate ablation techniques including PVI + Linear ablation lines (46%), PVI + CFAE (46%), and PVI + Linear ablation lines + CFAE (33%) as currently performed and reported. This study also concluded that the efficacy of a single-AF ablation procedure for Persistent or Long standing persistent AF is 43%; however, can be increased to 69% with the use of multiple procedures and/or anti-arrhythmic drug.

#### **3.2 Left atrial appendage electrical isolation/vein of marshall alcohol ablation**

BELIEF trial [34] is an RCT that included 173 patients with long standing persistent atrial fibrillation that were randomized into two arms: (1) Standard ablation arm that comprised of an extended PV antrum ablation plus non-PV trigger ablation (2) standard ablation plus empirical electrical left atrial appendage isolation. Primary end point of the study was freedom from atrial arrhythmia (AF, A Fl, AT) defined as >30 s after initial 12 weeks blanking period while off anti arrhythmic drugs, secondary end points were 12-month post-procedure incidence of stroke, death, and rehospitalization. Trial results showed that in patients with Long standing Persistent

### *Recent Advances in Catheter Ablation for Atrial Fibrillation and Non-pharmacological Stroke… DOI: http://dx.doi.org/10.5772/intechopen.106319*

AF, empirical isolation of LAA improved long-term freedom from atria arrhythmia without increasing complications. An important finding to consider however is life long need for uninterrupted anticoagulation in patients who underwent LAA isolation as post procedure lack of proper mechanical function in the LAA may contribute to stroke.

Recently, Alcohol ablation of Vein of Marshall (VoM) has gained significant attention. This method of ethanol infusion into VoM in addition to catheter ablation was investigated in VENUS [35] RCT. 343 patients with Persistent AF were randomized into catheter ablation alone vs. catheter ablation with VoM ethanol infusion. Primary end point was freedom from AF/AT > 30 s without AAD at 6 and 12 months, several secondary endpoints including AF burden, freedom from AF after multiple procedures, perimitral block, and others were studied. VoM is the embryological remnant of left superior vena cava is implicated as AF trigger, parasympathetic and sympathetic innervation contributing to AF, located in the mitral isthmus contributing to perimitral atrial tachycardia. Results of this study concluded that addition of VoM ethanol infusion to catheter ablation increased the likelihood of remaining free of AF or atrial tachycardia at 6 and 12 months. Adverse events were not significantly different between both group: intraprocedural pericardial effusion occurred in two patients in VoM ethanol infusion group (one in ablation only group), subacute pericardial effusion requiring drainage occurred in four patients (two in each group), symptomatic inflammatory pericarditis not requiring drainage occurred in 11 patients in the VoM ethanol infusion group and in 6 in the catheter ablation group. The benefits of VoM ethanol infusion in addition to


**Table 2.**

*Professional society recommendations for catheter and surgical ablation strategies and endpoints.*

catheter ablation was attributed to elimination of AF trigger, achieving more reliable perimitral block, enhanced atrial denervation (**Figure 3**).

2017 HRS/EHRA/ECAS/APHRS/SOLAECE Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation recommends following Atrial fibrillation ablation strategies, techniques, and endpoints (**Table 2**).

#### **3.3 High power short duration (HPSD) ablation**

High power short duration (HPSD) ablation strategy is a newer approach in effective lesion formation. Conventionally AF ablation has been performed with low power long duration (LPLD) at 25–35 W power delivery for 30–60 s per lesion. Success of AF ablation is dependent on durability of lesions that in turn is influenced by several variables like catheter stability, orientation of ablation catheter (perpendicular vs. parallel), time duration, effective power and current delivered at catheter tip, transmurality of lesion etc. HPSD (50–80 W power for 5 s) was initially described by Bhaskaran et al. [36] in 2016 as safe and effective as the conventional ablation. Current definition of HPSD varies between power of 50–90 s and time duration of 2–20 s. Based on principles of biophysics of Radiofrequency (RF) ablation, HPSD is believed to cause majority of tissue death via resistive heating and, as a result, theoretical advantages have been proposed, including optimized lesion geometry, reduced collateral tissue damage and increased durability of electrical isolation, in addition to obvious benefits in reduction in procedural duration [37]. Winkle et al. [38] reported very low complication rates with HPSD (45–50 W for 2–10 s) compared to LPLD (35 W for 20 s) in total of 13,974 ablations performed in 10,284 patients, of these, 11,436 ablations performed in the posterior wall. They also found HPSD ablations shorten procedural and total RF times and create more localized and durable lesions. Recently, Very High Power Short

*Recent Advances in Catheter Ablation for Atrial Fibrillation and Non-pharmacological Stroke… DOI: http://dx.doi.org/10.5772/intechopen.106319*

Duration (vHPSD) with 90 W for 4 s with a novel catheter design (THERMOCOOL SMARTTOUCH SF-5D System) was studied in Q DOT FAST trial [39] where 52 patients with PAF underwent ablation with no deaths, stroke, atrioesophageal fistula, pulmonary vein stenosis, or unanticipated adverse device effects. This study showed safety, feasibility and short term efficacy of vHPSD ablation along with substantial reduction in procedural and fluoroscopic time. Currently there is an ongoing prospective clinical trial (HIPAF) comparing two strategies: HPSD-PVI (70 W over 5 s posterior and 7 s anterior) ablation vs. Cryo PVI [40].

#### **3.4 Pulsed Field Ablation (PFA)**

So far, RF or Cryo ablation has been the only two available technologies for endocardial ablation of Atrial Fibrillation. In recent years, clinical research on an emerging modality for cardiac ablation has demonstrated significant advantages over existing thermal ablation modalities. Irreversible Electroporation is a non thermal modality with emerging application in the field of cardiology with more selective and effective ablation with minimal surrounding tissue damage. Dr. Steven Mickelsen at University of Iowa developed Pulsed Field Ablation (PFA) system and adapted catheters to deliver pulsed field electricity to the tissue for treating AF with his start up called "IOWA APPROACH" in 2012 later known as FARAPULSE Inc., which was later acquired by Boston Scientific in 2020.

Pulsed Field Ablation (PFA) is based on the premise of irreversible electroporation, where trains of high voltage, short duration energy are pulsed to create an electric field of substantial strength to injure tissue. The principle of electroporation has been used in a wide variety of practices ranging from gene therapy to tumor ablation but has only recently been applied to cardiac ablation. It is the unique properties of the cell membrane that are manipulated during electroporation. Cell membrane is composed of a phospholipid bilayer that is stabilized by Van der Waals forces that allow for aqueous pores to form in the membrane due to molecular water interactions across the cell membrane. The application of an electric field amplifies the molecular interaction of the water molecules across the cell membrane disrupting the Van der Walls forces of the phospholipid bilayer to create aqueous pores. If an electric field of substantial strength and duration is applied to the cell, these aqueous pores can become stabilized resulting in permanent disruption to the permeability of the cell membrane resulting in an apoptotic like cell death, which is termed irreversible electroporation or PFA (**Figure 4**).

RF ablation is associated with very low rate of complications but include pulmonary vein stenosis, atrio-esophageal fistula. Similarly Cryoablation is associated with low rate of complications as well but include phrenic nerve palsy. In contrast during PFA ultra rapid (microseconds to nanoseconds) electrical energy is delivered to destabilize cell membrane by forming irreversible nanoscale pores resulting in ell death, however threshold field strength for tissue necrosis is different for different tissues such as myocardium, blood vessels, nerve fibers thus rendering a great advantage of tissue selectivity. This differential tissue sensitivity to pulsed electrical fields is believed to decrease collateral damage. This single shot ablation technology in addition to being associated with clinical safety, success and durability has significantly reduced procedural time [41].

So far there have been three Multicenter studies three multicenter studies with PFA system: (IMPULSE [A Safety and Feasibility Study of the IOWA Approach Endocardial Ablation System to Treat Atrial Fibrillation], PEFCAT [A Safety

#### **Figure 4.**

*Figure adopted from Reddy [41].*

and Feasibility Study of the FARAPULSE Endocardial Ablation System to Treat Paroxysmal Atrial Fibrillation], and PEFCAT II [Expanded Safety and Feasibility Study of the FARAPULSE Endocardial Multi Ablation System to Treat Paroxysmal Atrial Fibrillation]). Reddy et al. [41] reported 1 year outcome of PFA in patients with PAF from these three trials. In a patient cohort of 121 patients, acute PVI with PFA was achieved in 100% of patients, primary adverse event occurred in 2.5% of patients (2 pericardial effusion, 1 transient ischemic attack, 1 hematoma), Freedom from recurrence of any atrial arrhythmia at 1 year was around 78%. In >100 patients and with 5 operators, the mean procedure times were only 96.2 ± 30.3 min, inclusive of ∼20 min of voltage mapping time after PVI which is faster than procedure times with other technologies. With increased operator experience and elimination of voltage mapping, procedure times should improve further. PVI with a "single-shot" PFA catheter results in excellent PVI durability and acceptable safety with a low 1-year rate of atrial arrhythmia recurrence ushering in a new era in the front of modern day advanced Atrial Fibrillation management.

#### **3.5 Cryoablation for atrial fibrillation**

An alternative mode of PAF ablation is Cryoablation. STOP AF [42] trial compared Cryoablation and AAD and demonstrated the safety and effectiveness of Cryoablation therapy as an alternative to antiarrhythmic medication for the treatment of patients with symptomatic PAF, for whom at least one AAD has failed. RF ablation requires operator skill and training and longer time for catheter navigation to complete point by point ablation around the pulmonary veins. In contrast, cryoballoon is a balloon catheter which is positioned inside pulmonary vein and with good occlusion, with a single Cryo application pulmonary vein isolation can be achieved rather simply with short procedure time. FIRE and ICE trial [43] compared both technologies (RF vs. Cryo ablation) and found Cryoablation was non inferior to radiofrequency ablation with respect to efficacy, no significant difference in overall safety between two methods. The mean total procedure time was shorter in the cryoballoon group than in
