Cardiac Rhythm Management
Articles Articles 2017 November

Catheter Ablation of Atrial Fibrillation: A Review of the Current Status and Future Directions

DOI: 10.19102/icrm.2017.081101

DANIEL P. MELBY, MD1

1Minneapolis Heart Institute at Abbott Northwestern Hospital, Minneapolis, MN, USA.

PDF Download PDF

 

ABSTRACT. Atrial fibrillation (AF) is one of the most common arrhythmias encountered in clinical practice today. Over the last 20 years, the frequency of use of catheter ablation to treat AF has grown, commensurate with the rise in arrhythmia burden and via a number of technical advancements. These developments can be divided into new techniques for myocardial ablation, improvements in the understanding of AF trigger mechanisms, and advancements in atrial mapping. Progress in these fields has led to a fundamental change in daily practice, and has contributed to a rise, for ablation, from a procedure performed infrequently at select centers to one that is commonplace worldwide. In this article, the data and methods leading to this fundamental change will be presented and discussed.

KEYWORDS. Atrial fibrillation, catheter ablation, review.

Dr. Melby reports the reception of personal fees from Biosense Webster, outside the scope of the submitted work.
Manuscript received July 27, 2017. Final version accepted August 19, 2017.

Address correspondence to: Daniel P. Melby, MD, Minneapolis Heart Institute at Abbott Northwestern Hospital, 800 E. 28th St., Heart Hospital, Minneapolis, MN 55407, USA. E-mail: daniel.melby@allina.com.

Introduction

Atrial fibrillation (AF) is one of the most common arrhythmias encountered in clinical practice. Population studies have revealed an increase in AF prevalence over the past 30 years, with projections for the observed growth to continue.16 Over the last 20 years, the frequency of catheter ablation for AF has also increased, commensurate with the rise in arrhythmia burden and via a number of technical advancements.7,8 These developments can be divided into three fields: new techniques for endocardial ablation, improvements in the understanding of AF trigger mechanisms, and advances in electroanatomical mapping. Progress in these areas has led to a fundamental change in daily practice, and has contributed to the evolution in ablation from a procedure performed infrequently at select centers to one that is commonly relied upon worldwide.

The current 2014 American College of Cardiology/American Heart Association guidelines for the treatment of AF position ablation as a class I option for the treatment of symptomatic drug-refractory persistent AF. Primary ablation of paroxysmal AF prior to drug failure is a class IIa recommendation.9 With further technical advancements, it is reasonable to anticipate expanded procedural indications, as well as improved procedural outcomes and techniques. This review will discuss the history, current status, and anticipated future developments of myocardial ablation and AF mapping techniques.

Ablation techniques for AF

Catheter ablation for AF was first described in 1994 in combination with several ongoing endeavors, including attempts to replicate a surgical MAZE lesion set,10 the performance of isolated right atrial linear lesions,11 and the ablation of focal right atrial triggering mechanisms.12 Further efforts to reproduce MAZE surgical outcomes with less linear ablations were made with some success using progressively more complex linear ablations within the right and left atria.13 These techniques, apart from identifying triggers within the right atrium, were essentially attempts to reproduce the MAZE surgical outcomes.14 These methods also, however, only had limited success due to associated technical difficulties in achieving adequate transmural lesion formation with available ablation catheters, and in completely addressing AF triggers.

Many of the above early approaches stemmed from evidence indicating that linear lesions eliminated reentrant regions within the atrium that were responsible for sustained fibrillatory activity. By creating multiple linear lesions within the left and right atria, small anatomic regions were subsequently established, which were not capable of sustaining reentry.15 This theory was further supported by multiple lines of evidence that demonstrated that a critical myocardial mass, as well as single and multiple wave fronts of propagation, were necessary for sustained fibrillatory activity.1620 However, the seminal advancement in the field of AF occurred when spontaneous, focal initiation of human AF was documented in 1997, and confirmed in 1998, with the observation that ectopic beats from pulmonary veins triggered paroxysmal AF.21,22 This discovery ushered in the modern era of performing pulmonary vein isolation (PVI) for the treatment of paroxysmal, and later, persistent, AF.23 Furthermore, this methodology has been firmly elucidated to allow for longer-term freedom from AF in a majority of patients, without the need for extensive linear atrial ablation.

AF ablation was performed historically using non-irrigated 4-mm and 8-mm catheters. This catheter technology had several limitations, including the risk for tissue or electrode overheating, which could result in catheter char, coagulum formation, or steam pop. The development of char and coagulum posed a risk to lead to thromboembolic complications, while steam pop could result in cardiac perforation. In attempts to improve catheter safety, ablation was most commonly performed in a temperature control mode, which allowed for a reduction in power output to maintain a maximum allowed electrode temperature. Unfortunately, this restriction manifested as a suboptimal single-procedure freedom from AF of approximately 50%.24,25 In part, these outcomes were likely related to insufficient lesion formation resulting from inadequate power delivery. In addition, several factors fundamental to lesion formation could not be assessed or modified with early-generation catheters, such as convective heat loss, the above-mentioned coagulum formation (which would further limit power delivery), and catheter-tissue contact force. As a result, ablation time was often the only parameter under direct and measurable control of the electrophysiologist. Such was often insufficient to secure an optimally successful procedure, as biophysical studies of radiofrequency (RF) ablation have demonstrated that lesion formation is nonlinearly dependent on four critical factors: ablation time, power, catheter myocardial contact force, and convective heat loss.26,27 Only allowing for the control of ablation time leaves these other factors not well-addressed, thus potentially resulting in inadequate lesion formation and procedural failure.

Efforts to address factors affecting lesion formation

The development of externally irrigated ablation catheters was a significant advancement and obviated several of the deficiencies inherent to standard, non-irrigated catheters. Initial irrigation was predominantly accomplished via irrigation holes within the distal aspect of the ablation electrode. Despite affecting only this segment of the electrode, there was significantly improved cooling at the electrode–tissue interface, where overheating is most common. This reduction in catheter overheating led to improved power delivery, as well as reduced char and coagulum formation at the distal electrode.28,29 Consequently, improved lesion formation was possible, and was associated with improved procedural success, in comparison with that seen with the use of standard 4-mm catheters.30

Limitations, however, remained with first-generation externally irrigated catheters. To achieve adequate electrode cooling, these catheters required substantial fluid delivery, a stipulation often leading to clinical volume overload states following long procedures. Additionally, first-generation designs cooled only the distal portion of the ablation electrode, leaving them vulnerable to char formation at the proximal portion. Second-generation externally irrigated ablation catheter designs improved on both these deficiencies by increasing the number of irrigation holes and spreading them more completely over the entire electrode surface area. This technology decreased the risk of char formation at the proximal portion of the electrode and allowed for a reduction in the needed amount of fluid delivery, due to improved electrode cooling.31 These advancements in external irrigation allowed for consistent power delivery even in myocardial locations such as the coronary sinus, where first-generation catheters often received only limited power delivery due to overheating.

Despite the improved design, the measurement of contact force (an important biophysical measure) was not addressed and, without this knowledge, lesion formation was neither consistent nor reproducibly achieved. Surrogate methods to assess lesion formation, such as impedance drop and electrogram elimination, were therefore commonly employed and were found to be helpful.32,33 However, these measures were not reliable predictors of lesion development, as they often correlated with the unmeasured contact force, or were dependent on confounding factors such as catheter orientation. This shortcoming led to the next significant advance in catheter design: the advent of contact force-sensing catheters allowed for the direct measurement of catheter-myocardial contact and directionality. More recently, this important development has translated to an improved success rate for ablation of AF,34,35 likely due to an improvement in lesion formation. Additional evidence from two contact force-sensing trials, SMART-AF and TOCCASTAR, demonstrated that when optimal contact force is used a significantly improved freedom from AF rate occurs, in comparison with that seen with the use of suboptimal contact force (81% versus 66% in SMART-AF; 75.9% versus 58.1% in TOCCASTAR).36 Using a combination of ablation time, consistent power delivery via second-generation irrigated catheters, and contact force measurement, adequate lesion formation was more reliably achieved.

In spite of this improvement, however, lesion formation continues to be inadequate in certain circumstances, and there remains an unmet need for accurate lesion measurement or software-based prediction methods. Evidence from the chronic assessment of PVI has demonstrated that even with the use of contact force catheters, frequent pulmonary vein recovery still occurs.37,38 To better improve chronic PVI outcomes, the direct measurement of lesion formation, including depth and diameter, would be optimal, although it is somewhat technically challenging, and there is no method that is clinically available or United States Food and Drug Administration (FDA)-approved at this time.3945 Methods to achieve practical lesion measurement are under active research, but have not reached a level at which they are suitable for deployment in an electrophysiology laboratory. This absence has led to interest in software algorithm methods to predict or estimate lesion formation. These include nonlinear algorithms that utilize contact force, ablation time, and power settings.46 Such methods have been shown to predict lesion size in animal models,47,48 and are under investigation for their applicability to humans. Perhaps the use of such technology may allow for the accurate prediction of lesion formation, and could offer a consistent and operator-independent method to improve procedural success rates.

The final element affecting lesion formation is convective head loss and its effect on ablation-induced tissue temperature. Current-generation catheters are unable to monitor for heat loss or to measure tissue temperature in any form. A surrogate for convective heat loss may be the accurate measurement of myocardial tissue temperature during RF ablation. As myocardial cell death occurs above 50°C, the evaluation of tissue temperature would allow for the electrophysiologist to measure convective heat loss in a surrogate manner. The next step in catheter development is likely to focus on such measurements.

An alternative method to achieve lesion formation is ablation based on tissue cooling, or cryoablation, which leads to myocardial cell death due to both a direct cryothermal affect and microvascular destruction.4953 This methodology was originally developed in the form of a 4 mm ablation catheter, where the ablation electrode was cooled to achieve sufficient myocardial tissue destruction. Originally used for the ablation of the atrioventricular node slow pathway for atrioventricular nodal reentrant tachycardia, this technology was later deployed for PVI for AF. Cryoablation was deemed less likely than RF ablation to lead to atrioesophageal or esophageopericardial fistula formation, although these conditions have since been described in case reports. The use of 4- or 5-mm electrode cryoablation catheters for PVI was adopted at several centers that were attempting to minimize fistula formation. Ultimately, however, this method proved too time-consuming for incorporation as standard use, and the efficacy for PVI achieved was not optimal in comparison with that of externally irrigated RF ablation. Next-generation cryoablation for PVI was achieved through the development of balloon-based technology during which the balloon was positioned at the pulmonary vein ostium and PVI was performed in a single step. This led to an improved procedure efficiency rate in certain centers.54 Of note, the STOP-AF trial evaluated the efficacy of cryoablation and demonstrated a 12-month freedom from AF rate of 69.9%.55 In this study, 11.2% of patients had phrenic nerve paralysis, with 1.5% of cases persisting beyond 12 months. A comparison of RF ablation using externally irrigated catheters versus cryoablation in the FIRE AND ICE trial demonstrated non-inferiority of cryoablation.56 However, notably, for the RF ablation arm, this trial used a mix of first-generation noncontact force and second-generation contact force catheters, a potential study limitation. Freedom from AF was observed in 64.1% of subjects undergoing RF ablation and in 65.4% of those undergoing cryoablation. This is somewhat lower than the rates observed in the SMART-AF trial using contact force-sensing catheters alone, in which an overall freedom from AF rate of 72.5% was demonstrated.38 Additional 30-month freedom from AF data supported the non-inferiority of cryoablation, in comparison with that of RF ablation.

Optimal use of either cryoablation or RF ablation is important to achieve a higher procedural success rate. When contact force was kept within an operator-selected range ≥ 80% of the time, 12-month freedom from AF in the SMART-AF trial improved to 81%, in comparison with 66% when the contact force was within range ≤ 80% of the time.38 In several studies, the use of second-generation cryoablation has also demonstrated a higher success rate and improved procedural efficiency than did first-generation cryoballoon ablation.54,57,5961 Specifically, in a meta-analysis of 2,363 patients undergoing ablation using a second-generation cryoballoon, the one-year freedom from AF rate was 82%.61 Cryoablation though has a potential economic barrier due to the increased cost that results when additional catheters are used to treat concurrent atrial tachycardias.

Alternative methods for achieving PVI have been developed, but are investigational in nature and are not currently FDA approved. These include balloon-based technologies that incorporate laser or RF energy or circular multielectrode ablation catheters. In the HotBalloon study, a prospective multicenter study of balloon RF ablation, freedom from AF was observed in 59% of the ablation group.62 However, complications of pulmonary vein stenosis were observed in 5.2%, and transient phrenic nerve paralysis in 3.7%. The HeartLight® (CardioFocus, Marlborough, MA, USA) laser-based balloon ablation system was also evaluated in a multicenter study of 353 patients.63 This study demonstrated a promising freedom from AF rate at one year of 61.1%, which was equivalent to that seen in the RF ablation arm. Diaphragm paralysis was observed in 3.5% of patients, though no pulmonary vein stenosis was noted. In regards to circular multielectrode catheters, there were safety concerns regarding non-irrigated catheters, as an analysis that compared the performance of either external irrigated RF ablation or cryoballoon demonstrated a 1.48 times higher risk of silent cerebral ischemic lesions (identified via post-procedural magnetic resonance imaging (MRI)).64 Next-generation catheters have effectively reduced this risk. The nMARQ™ catheter (Biosense Webster, Diamond Bar, CA, USA) is an irrigated circular ablation catheter that has demonstrated a one-year success rate ranging from 46% to 87% (with the three largest trials yielding rates of 65%, 73%, and 75%, respectively).6576 Another example, the pulmonary vein ablation catheter (PVAC; Medtronic, Minneapolis, MN, USA) sports a non-irrigated design with an improved safety profile for thromboembolic events. This catheter has demonstrated one- to two-year success rates ranging from 38% to 86% (with the three largest trials yielding rates of 47%, 65%, and 75%, respectively).7791 There is some, though limited, data available on the achievement of improved procedural success rates using multielectrode ablation in comparison with using single-electrode irrigated ablation.92,93

Importantly, despite the early mixed success rates for these emerging technologies, these studies typically represented first- or early-generation devices that had likely not reached full maturity or efficacy. The goal of performing longer or larger contiguous lesions with a single ablation procedure remains attractive, especially for its potential to improve procedural efficiency.

Another method to improve outcomes with ablation has focused on electrical isolation of the left atrial appendage (LAA). There has been interest particularly involving this subject and longstanding persistent AF, where the LAA may be a source of AF rotors or focal drivers. This concept was tested in the BELIEF trial, an open-label randomized trial of 168 patients with longstanding persistent AF.94 In this study, patients underwent either extensive atrial ablation alone, or such in combination with electrical LAA recurrence following a single procedure, in comparison with 28% in patients with no isolation performed. This improved outcome was replicated and expanded in a study comprised of 90% non-longstanding persistent AF, where 200 consecutive patients underwent cryoballoon PVI alone or in combination with LAA isolation.95 Following 12 months of follow-up and an average 1.2 procedures, the group who underwent PVI alone had a 67% freedom from atrial tachycardia, versus 86% when appendage isolation was also performed. Further studies will be needed to assess whether these results are widely applicable, and whether the potential increased risk for appendage thrombus formation following isolation is acceptable.

The superior vena cava (SVC) is another potential trigger for AF, and in a seminal study, was found to account for 6% of paroxysmal AF trigger sites.96 In one study, SVC isolation was evaluated as an adjunct to PVI in a group of 320 consecutive patients consisting of both paroxysmal and persistent AF.97 Patients with either longstanding persistent or persistent AF had no improvement in freedom from atrial tachycardia. However, in paroxysmal patients, 90% of those with SVC isolation were free of atrial tachycardia, versus 77% of those without isolation. This result, however, could not be replicated in other randomized studies.98 In addition, SVC isolation has the potential to lead to complications such as SVC stenosis and sinus node injury. Therefore, currently recommendations are to proceed with SVC isolation only when tachycardia, frequent ectopy, or AF is documented to originate from this structure.

The intrinsic cardiac autonomic system located in the ganglionated plexuses (GP) has also been shown to participate in the initiation and maintenance of AF.99 Stimulation of the GP results in parasympathetic stimulation leading to early after depolarizations, calcium transient triggered firing in the pulmonary veins, and initiation of AF. The GP are located near the left superior and inferior pulmonary veins, the right superior and inferior pulmonary veins, and the Marshall tract. In a randomized study of paroxysmal AF, pulmonary vein isolation alone or in combination with GP ablation was performed. In this study, single-procedure freedom from recurrence was 46% with PVI alone versus 73.5% with PVI and GP ablation.100 This strategy was particularly beneficial when PVI was performed ostially. Current ablation techniques focus on pulmonary vein antrum isolation, which encompasses the ablation of the GP locations inadvertently. This additional GP ablation may account for why antral ablation has a higher success rate than ostial PVI. As a result of the wider ablations performed, most centers no longer ablate the GP as a separate step in the procedure.

Mapping developments for non-pulmonary vein AF drivers

PVI remains the cornerstone in the ablation of both paroxysmal and persistent AF. In paroxysmal AF, PVI alone can achieve reasonable success rates, as mentioned above, of approximately 80% with contact force RF ablation, or second-generation cryoballoon ablation. PVI alone in persistent AF has not proven as successful. For this reason, intensive research has been performed for methods to map non-pulmonary vein drivers. Ablation of these additional sites holds promise to improve ablation in persistent AF, as well as to identify the subset of paroxysmal patients with non-pulmonary vein triggers in whom additional ablation may be helpful. Prior studies have indicated the importance of several non-pulmonary vein triggers arising from locations such as the SVC, the vein of Marshall, the coronary sinus, the crista terminalis, and the posterior left atrium. The incidence is as high as 20% in paroxysmal AF and 35% in persistent AF, respectively.101103 The identification of these triggers has proven to be important, and is currently the preferred approach over substrate ablation alone.

Basic electrophysiology research has demonstrated the presence of a variety of non-pulmonary vein AF driver types, including microreentry, spiral rotors, and focal triggers, among others.104112 These mechanisms have also been modeled with software capable of accurately reproducing the observations in high-density tissue and animal studies. The translation of these mechanistic findings into an effective ablation strategy that improves freedom from AF has been challenging. One of the largest randomized multicenter studies of persistent AF, the STAR-AF II trial, evaluated PVI only versus PVI plus linear ablation or complex fractionated atrial electrogram (CFAE) ablation. This study did not determine the occurrence of any significant improvement in freedom from AF with the addition of ablation beyond PVI. The overall single-procedure success rate in these persistent patients, however, was suboptimal at 59%, indicating a need for alternative ablation strategies to improve outcomes. Additional evidence has supported that ablation of CFAE has not produced consistent improvements in ablation outcomes.113120 Further studies have indicated that multielectrode mapping may identify critical CFAE regions with greater accuracy than single-electrode catheter mapping by allowing for the separation of CFAE regions into either passive or driver regions.121125 The use of multielectrode mapping has also been utilized to identify alternative non-pulmonary vein drivers such as regions of high spatiotemporal dispersion, with ablation leading to improved freedom from AF.126,127

Two additional methods to map non-pulmonary vein drivers include surface electrocardiogram arrays and the FIRM mapping system (Topera Medical, Palo Alto, CA, USA). Studies evaluating these methods have identified sites consistent with spiral rotors and focal drivers of AF in humans for the first time without the need for incorporating surgically placed electrodes.22 There is significant interest in such methods, especially regarding their potential to identify critical electrophysiology-based sites.

The FIRM mapping system (Topera Medical, Palo Alto, CA, USA) utilizes a balloon catheter with 64 electrodes to map the entire atrium. This method involves using pacing to initiate AF, if it is not present at baseline, and placing the mapping balloon catheter within the left atrium. Proprietary software analysis of the electrograms through phase mapping, and analysis of repolarization and conduction dynamics, have been used to map patient-specific sources.128 Specific sites of non-pulmonary vein AF mechanisms are identified through electrogram analysis and marked on a corresponding map. This information is then extrapolated to an existing electroanatomic map, which has been created using an alternate mapping system. The ablation procedure typically would then involve isolation of the pulmonary vein antrum using standard contact force-sensing externally irrigated catheters, followed by ablation of the FIRM-identified non-pulmonary vein sites. Procedural endpoints include AF termination or average AF cycle length slowing.

Initial study results achieved with FIRM mapping were positive. The pivotal CONFIRM trial was a 92-patient multicenter study that found an intermediate six- to 12-month procedural success rate of 82% in a mixed cohort of paroxysmal and persistent AF.129 A follow-up multicenter study involving 78 patients demonstrated a single-procedure success rate of 87.5% again for a mixed paroxysmal and persistent cohort.130 In the initial studies, local rotors or focal impulses were detected in 97% of patients with an average of 2.1 sources. The sources identified were within the left atrium in 76%, which included pulmonary vein locations and disparate locations such as posterior, inferior, roof, and anterior regions. The remaining 24% of locations were within the right atrium in the inferolateral, posterior, and septal regions. Unfortunately, the reported positive initial results could not be replicated in other studies, including in a longer-term 18-month multicenter study involving 43 patients, of whom 37% had freedom from AF.131 The precise reason for these disparate results is not definitively established. Possibilities include either poor basket electrode-myocardial contact, leading to inadequate electrogram resolution sufficient for rotor site identification, or the presence of an underlying technical software deficiency that is limiting accurate identification of driver sites.

The CardioInsight mapping system (Medtronic, Minneapolis, MN, USA), a noninvasive body surface mapping analysis device, uses 252 external electrocardiogram electrodes in combination with computed tomography (CT) to create simultaneous biatrial three-dimensional maps. Specific algorithms, including wavelet transformation and phase mapping, are then applied to allow for the identification of AF driver sites.132 This system is currently available, but is in need of multicenter randomized-based evaluation to further assess its abilities. Additionally, non-invasive body surface mapping suffers from a potential hurdle in that it is not capable of precise localization to millimeter accuracy, as is standard when typical maps are created (eg, when using intracardiac catheters and current mapping systems).

Advancements in the accuracy of the left atrial map, from which AF triggers are identified and the ablation lesion set is planned, have been made as well. Historically, the left atrial anatomical map was created using a single-electrode ablation catheter and point-by-point mapping. This was an effective method, but was also time-consuming; a lack of a high-density anatomic point cloud also limited the completeness of the map. Progress in software and multielectrode catheters allowed for a progression to occur, from the use of point-by-point maps obtained with single-electrode catheters to multielectrode mapping, with multiple simultaneously acquired points. Additionally, the increasingly widespread use of preprocedural atrial CT or MRI, and maps derived from intracardiac echo, have improved atrial anatomic mapping. One method to improve procedure efficiency and accuracy is to merge a preprocedure left atrial CT scan or MRI scan onto a basic and incomplete left atrial anatomy image acquired via use of a mapping catheter.133135 This technique allows for a complete left atrial map to be generated in a relatively efficient manner.

Beyond map creation, preprocedural imaging has also proven useful to ensure that complete anatomic mapping is accomplished. Reducing inaccurate anatomy has led to improved circumferential PVI.136 Other benefits to imaging include evidence for reduced radiation dosing and improved outcomes, in comparison with those achieved using standard point-by-point mapping.137,138 A second method for imaging the left atrial anatomy is by intracardiac echo.139 Using echo images, the endocardial contours are traced within the mapping system, allowing for a complete left atrial anatomy map to be developed without the need for catheter manipulation within the chamber of interest. Intracardiac echo, as well as the CT and MRI merge technique, can provide a complete left atrial anatomy when the mapping catheter cannot be maneuvered to achieve such a result.

Multielectrode mapping of the cardiac chambers using rapid and automatically acquired anatomic points has proven to be accurate and effective for rendering a complete model of a patient’s atrial anatomy.140 This technique is currently one of the most commonly utilized, as it provides accurate mapping in a relatively efficient manner. This can be performed using either a circular or multispline catheter. In addition to anatomy, this technique can generate high-density voltage maps, which provide additional useful information about the substrate for AF drivers and other scar-mediated arrhythmias.141

Future directions in the ablation of AF

There has been intense research done into mapping non-pulmonary vein drivers to improve procedural efficiency and outcomes. PVI alone has proven to be reasonably effective for the treatment of paroxysmal AF, but remains somewhat suboptimal in cases of persistent AF. Methods to map non-pulmonary vein sources of AF will likely prove important in the future to achieve single-procedure success rates for both paroxysmal and persistent AF, similar to other atrial arrhythmias. Technologies such as FIRM or body surface mapping to identify AF drivers hold great promise but also potential technological deficiencies. A lack of spatial accuracy, and difficulty with electrogram resolution due to inadequate electrode contact, may account for the mixed results achieved using these methods. Basic research has been consistent in identifying that such drier sites should be present in humans, and therefore there is reason to believe such mechanisms can be identified and ablated to improve procedural outcomes. The next phase in AF mapping will depend on developing mapping techniques that are accurate in all aspects, temporally, spatially, and with high electrogram resolution.

Heterogeneous lesion formation remains another potential key limitation, and has likely confounded studies like STAR-AF II, and techniques such as FIRM-based ablation. Until methods are developed to assess lesion formation, either through software or direct measurement, PVI and ablation of non-pulmonary vein sites are subject to interoperator variability. This variability often manifests as disparate results between centers, as has been observed in many trials to date. These findings do not definitively negate the importance of such non-pulmonary vein sites, but likely underline a fundamental technologic impediment. Ultimately, reproducible mapping of alternative AF driver sites, in addition to consistent, non-heterogeneous lesion formation, will be necessary to achieve higher single-procedure freedom from AF.

Successful ablation of AF ultimately relies on three fundamental and equally important factors. First, (1) a reproducible and measurable method to achieve lesion formation in the desired location must exist. Additionally, (2) an ability to map and understand the basic mechanisms and optimal ablation sites to eliminate AF, and (3) an accurate anatomic map from which to perform electrogram and ablation localization, are also ideal. Current mapping systems using multielectrode catheters can produce anatomically accurate cardiac chambers. RF ablation lesions have improved with the current generation of contact force external irrigation catheters. Further methodology to predict lesion formation through software-based algorithms is the next generational step in achieving consistent and reliable lesions. Catheter development, which will lead to accurate measurement of tissue temperature as a surrogate method to assess for convective heat loss, will likely further improve consistent lesion formation. Mapping of non-pulmonary vein driver sites is under active development, with several methods currently available, but with limitations that prevent widespread utility. Ultimately, future success of any such strategy depends heavily on advancing fundamental knowledge of these mechanisms in humans, and the existence of the ability to accurately map such sites with both high spatial and electrogram resolution. With further advancement in these three areas, the ablation of both paroxysmal and persistent AF will become a reliable, reproducible, and electrophysiologic-guided, rather than anatomically based, procedure.

Conclusions

Significant advancements have been achieved in the ablation of AF over the past 20 years. Current state-of-the-art ablation technology can achieve a high success rate for ablation and paroxysmal AF. Further technological advancements such as lesion prediction and catheter developments that accurately measure tissue temperature will further improve the rate of success. These developments will be especially important for the ablation of persistent AF where all elements—from accurate AF driver mapping to consistent lesion formation—are fundamental to a successful result.

References

  1. Miyasaka Y, Barnes ME, Gersh BJ, et al. Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation. 2006;114(2):119–125. [CrossRef] [PubMed]
  2. Wolf PA, Benhamin EJ, Belanger AJ, et al. Secular trends in the prevalence of atrial Fibrillation: The Framingham study. Am Heart J. 1996;131(4):790–795. [CrossRef] [PubMed]
  3. Wattigney WA, Mensah GA, Croft JB. Increasing trends in hospitalization for atrial fibrillation in the United States, 1985 through 1999: implications for primary prevention. Circulation. 2003;108(6):711–716. [CrossRef] [PubMed]
  4. Naccarelli GV, Varker H, Lin J, Schulman KL. Increasing prevalence of atrial fibrillation and flutter in the United States. Am J Cardiol. 2009;104(11):1534–1539. [CrossRef] [PubMed]
  5. Freeman JV, Wang y, Akar JG, Desai N, Krumholz H. National trends in atrial fibrillation hospitalization, readmission, and mortality for Medicare beneficiaries, 1999-2013. Circulation. 2017;135(13):1227–1239. [CrossRef] [PubMed]
  6. Deshpande S, Catanzaro J, Wann S. Atrial fibrillation: prevalence and scope of the problem. Card Electrophysiol Clin. 2014;6(1):1–4. [CrossRef] [PubMed]
  7. Kneeland PP, Fang MC. Trends in catheter ablation for atrial fibrillation in the United States. J Hosp Med. 2009;4(7):e1–5. [CrossRef] [PubMed]
  8. Kumar s, Walters TE, Halloran K, et al. Ten-year trends in the use of catheter ablation for treatment of atrial fibrillation vs. the use of coronary intervention for the treatment of ischaemic heart disease in Australia. Europace. 2013;15(12):1702–1709. [CrossRef] [PubMed]
  9. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation. 2014;130(23):2071–2104. [CrossRef] [PubMed]
  10. Elvan A, Pride HP, Zipes DP. Replication of the “Maze” procedure by radiofrequency catheter ablation reduces the ability to induce atrial fibrillation. Pacing Clin Electrophysiol. 1994;17(4):774. [CrossRef]
  11. Haïssaguerre M, Gencel L, Fischer B, et al. Successful catheter ablation of atrial fibrillation. J Cardiovasc Electrophysiol. 1994;5(12):1045–1052. [CrossRef] [PubMed]
  12. Haïssaguerre M, Marcus FI, Fischer B, et al. Radiofrequency catheter ablation in unusual mechanisms of atrial fibrillation: report of three cases. J Cardiovasc Electrophysiol. 1994;5(9):743–751. [CrossRef]
  13. Haïssaguerre M, Jaïs P, Shah DC, et al. Right and left atrial radiofrequency catheter therapy of paroxysmal atrial fibrillation. J Cardiovasc Electrophysiol. 1996;7(12):1132–1144. [CrossRef] [PubMed]
  14. Cox JL, Schuessler RB, D’Agostino HJ, Jr, et al. The surgical treatment of atrial fibrillation. III. Development of a definitive surgical procedure. J Thorac Cardiovasc Surg. 1991;101(4):569–583. [PubMed]
  15. Cox JL, Canavan TE, Schuessler RB, et al. The surgical treatment of atrial fibrillation. I. Intraoperative electrophysiologic basis of flutter and atrial fibrillation. J Thorac Cardiovasc Surg. 1991;101(3):406–426. [PubMed]
  16. Garrey WE. The nature of fibrillatory contraction of the heart. its relation to tissue mass and form. Am J Physiol. 1914;33:397–414.
  17. West TC, Landa JF. Minimal mass required for induction of a sustained arrhythmia in isolated atrial segments. Am J Physiol. 1962;202:232–236. [CrossRef] [PubMed]
  18. Moe GK, Rheinboldt WC, Abildskov JA. A computer model of atrial fibrillation. Am Heart J. 1964;67:200–220. [CrossRef] [PubMed]
  19. Konings KTS, Kirchhof CJHJ, Smeets JRLM, et al. High-density mapping of electrically induced atrial fibrillation in humans. Circulation. 1994;89(4):1665–1680. [PubMed]
  20. Allessie MA, Rensma PL, Brugada J, et al. Pathophysiology of atrial fibrillation. In: Zipes DP, Jalife J, eds. Cardiac electrophysiology: from cell to bedside. Philadelphia: W.B. Saunders, 1990:548–59.
  21. Jaïs P, Haïssaguerre M, Shah DC, et al. A focal source of atrial fibrillation treated by discrete radiofrequency ablation. Circulation. 1997;95(3):572–576. [CrossRef] [PubMed]
  22. Haïssaguerre M, Jaïs P, Shah DC, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med. 1998;339(10):659–666. [CrossRef] [PubMed]
  23. Oral H, Knight BP, Tada H, et al. Pulmonary vein isolation for paroxysmal and persistent atrial fibrillation. Circulation. 2002;105(9):1077–1081. [CrossRef] [PubMed]
  24. Ouyang F, Tilz R, Chun J, et al. Long-term results of catheter ablation in paroxysmal atrial fibrillation lessons from a 5-year follow-up. Circulation. 2010;122(23):2368–2377. [CrossRef] [PubMed]
  25. Ganesan AN, Shipp NJ, Brooks AG, et al. Long-term outcomes of catheter ablation of atrial fibrillation: a systematic review and meta-analysis. J Am Heart Assoc. 2013;2(2):e004549.[CrossRef] [PubMed]
  26. Shah DC, Lambert H, Nakagawa H, et al. Area under the real-time contact force curve (force-time integral) predicts radiofrequency lesion size in an in vitro contractile model. J Cardiovasc Electrophysiol. 2010;21(9):1038–1043. [CrossRef] [PubMed]
  27. Thiagalingam A, D’Avila A, Foley L, et al. Importance of catheter contact force during irrigated radiofrequency ablation: evaluation in a porcine ex vivo model using a force-sensing catheter. J Cardiovasc Electrophysiol. 2010;21(7):806–811. [CrossRef] [PubMed]
  28. Demazumder D, Mirotznik MS, Schwartzman D. Biophysics of radiofrequency ablation using an irrigated electrode. J Interv Card Electrophysiol. 20015(4):377–389. [CrossRef] [PubMed]
  29. Yokoyama K, Nakagawa H, Wittkampf FH, Pitha JV, Lazzara R, Jackman WM. Comparison of electrode cooling between internal and open irrigation in radiofrequency ablation lesion depth and incidence of thrombus and steam pop. Circulation. 2006;113(1):11–19. [CrossRef] [PubMed]
  30. Thomas SP, Aggarwal G, Boyd AC, Jin Y, Ross DL. A comparison of open irrigated and non-irrigated tip catheter ablation for pulmonary vein isolation. Europace. 2004;6(4):330–335. [CrossRef] [PubMed]
  31. Park C, Lehrmann H, Keyl C, et al. Enhanced efficiency of a novel porous tip irrigated RF ablation catheter for pulmonary vein isolation. J Cardiovasc Electrophysiol. 2013;24(12):1328–1335. [CrossRef] [PubMed]
  32. Knecht S, Reichlin T, Pavlovic N, et al. Contact force and impedance decrease during ablation depends on catheter location and orientation: insights from pulmonary vein isolation using a contact force-sensing catheter. J Interv Card Electrophysiol. 2015;43(3):297–306. [CrossRef] [PubMed]
  33. Reichlin T, Knecht S, Lane C, et al. Initial impedance decrease as an indicator of good catheter contact: insights from radiofrequency ablation with force sensing catheters. Heart Rhythm. 2014;11(2):194–201. [CrossRef] [PubMed]
  34. Natale A, Reddy VY, Monir G, et al. Paroxysmal AF catheter ablation with a contact force sensing catheter: results of the prospective, multicenter SMART-AF trial. J Am Coll Cardiol. 2014;64(7):647–656. [CrossRef] [PubMed]
  35. Marijon E, Fazaa S, Narayanan K, et al. Real-time contact force sensing for pulmonary vein isolation in the setting of paroxysmal atrial fibrillation: procedural and 1-year results. J Cardiovasc Electrophysiol. 2014;25(2):130–137. [CrossRef] [PubMed]
  36. Reddy VY, Dukkipati SR, Neuzil P, et al. A randomized controlled trial of the safety and effectiveness of a contact force sensing irrigated catheter for ablation of paroxysmal atrial fibrillation: results of the TOCCASTAR study. Circulation. 2015;132(10):907–915. [CrossRef] [PubMed]
  37. Neuzil P, Reddy VY, Kautzner J, et al. Electrical reconnection after pulmonary vein isolation is contingent on contact force during initial treatment: results from the EFFICAS I study. Circ Arrhythm Electrophysiol. 2013;6(2):327–333. [CrossRef] [PubMed]
  38. Kautzner J, Neuzil P, Lambert H, et al. EFFICAS II: optimization of catheter contact force improves outcome of pulmonary vein isolation for paroxysmal atrial fibrillation. Europace. 2015;17(8):1229–1235. [CrossRef] [PubMed]
  39. Muselimyan N, Swift LM, Asfour H, et al. Seeing the invisible: revealing atrial ablation lesions using hyperspectral imaging approach. PLoS ONE. 2016;11(12):e0167760. [CrossRef] [PubMed]
  40. Gil D, Swift LM, Asfour H, et al. Autofluorescence hyperspectral imaging of radiofrequency ablation lesions in porcine cardiac tissue. J Biophotonics. 2017;10(8):1008–1017. [CrossRef] [PubMed]
  41. Mercader M, Swift L, Sood S, et al. Use of endogenous NADH fluorescence for real-time in situ visualization of epicardial radiofrequency ablation lesions and gaps. Am J Physiol Heart Circ Physiol. 2012;302(10):2131–2138. [CrossRef] [PubMed]
  42. Swift L, Gil D, Jaimes R, Kay M, Mercader M, Sarvazyan N. Visualization of epicardial cryoablation lesions using endogenous tissue fluorescence. Circ Arrhythm Electrophysiol. 2014;7(5):929–937. [CrossRef] [PubMed]
  43. Swartling J, Pålsson S, Platonov P, Olsson SB, Andersson-Engels S. Changes in tissue optical properties due to radio-frequency ablation of myocardium. Med Biol Eng Comput. 2003;41(4):403–409. [CrossRef] [PubMed]
  44. Thomsen S, Jacques S, Flock S. Microscopic correlates of macroscopic optical property changes during thermal coagulation of myocardium. Proc SPIE. 1990;1202:2–11.
  45. Dana N, Di Biase L, Natale A, Emelianov S, Bouchard R. In vitro photoacoustic visualization of myocardial ablation lesions. Heart Rhythm. 2013;11(1):150–157. [CrossRef] [PubMed]
  46. Das M, Loveday JJ, Wynn GJ, et al. Ablation index, a novel marker of ablation lesion quality: prediction of pulmonary vein reconnection at repeat electrophysiology study and regional differences in target values. Europace. 2017;19(5):775–783. [CrossRef] [PubMed]
  47. Nakagawa H, Ikeda A, Govari A, et al. Prospective study using a new formula incorporating contact force, radiofrequency power and application time (Force-Power-Time Index) for quantifying lesion formation to guide long continuous atrial lesions in the beating canine heart [Abstract]. Circulation. 2013;128:A12104.
  48. Nakagawa H, Ikeda A, Govari A, et al. Prospective study to test the ability to create RF lesions at predicted depths of 3, 5, 7 and 9 mm using a new formula incorporating contact force, radiofrequency power and application time (Force-Power-Time Index) in the beating canine heart [Abstract]. Heart Rhythm. 2013;10:S481.
  49. Mazur P. Cryobiology: the freezing of biological systems. Science. 1970;168(3934):939-949. [CrossRef] [PubMed]
  50. Takamatsu H, Zawlodzka S. Contribution of extracellular ice formation and the solution effects to the freezing injury of PC-3 cells suspended in NaCl solutions. Cryobiology. 2006;53(1):1–11. [CrossRef] [PubMed]
  51. Gill W, Da Costa J, Fraser J. The control and predictability of a cryolesion. Cryobiology. 1970;6(4):347–353. [CrossRef] [PubMed]
  52. Gill W, Fraser J, Da Costa J, et al. The cryosurgical lesion. Am Surg. 1970;36(7):437–445. [PubMed]
  53. Kreyberg L. Development of acute tissue damage due to cold. Physiol Rev. 1949;29(2):156-167. [PubMed]
  54. Liu J, Kaufmann J, Kriatselis C, Fleck E, Gerds-Li JH. Second generation of cryoballoons can improve efficiency of cryoablation for atrial fibrillation. Pacing Clin Electrophysiol. 2015;38(1):129–135. [CrossRef] [PubMed]
  55. Packer DL, Kowal RC, Wheelan KR, et al. Cryoballoon ablation of pulmonary veins for paroxysmal atrial fibrillation: first results of the North American Arctic Front (STOP AF) pivotal trial. J Am Coll Cardiol. 2013;61(16):1713–1723. [CrossRef] [PubMed]
  56. Kuck KH, Brugada J, Fürnkranz A, et al. Cryoballoon or radiofrequency ablation for paroxysmal atrial fibrillation. N Engl J Med. 2016;374(23):2235–2245. [CrossRef]
  57. Di Giovanni G, Wauters K, Chierchia GB, et al. One-year follow-up after single procedure cryoballoon ablation: a comparison between the first- and second-generation balloon. J Cardiovasc Electrophysiol. 2014;25(8):834–839. [CrossRef] [PubMed]
  58. Conti S, Moltrasio M, Fassini G, et al. Comparison between first- and second-generation cryoballoon for paroxysmal atrial fibrillation ablation. Cardiol Res Pract. 2016;2016:5106127. [CrossRef] [PubMed]
  59. He X, Chen Y, Zhou Y, Huang Y, He J. One-year clinical outcome of pulmonary vein isolation using the second-generation cryoballoon: a meta-analysis. Pacing Clin Electrophysiol. 2016;39(2):182–189. [CrossRef] [PubMed]
  60. Fürnkranz A, Bordignon S, Schmidt B, et al. Improved procedural efficacy of pulmonary vein isolation using the novel second-generation cryoballoon. J Cardiovasc Electrophysiol. 2013;24(5):492–497. [CrossRef] [PubMed]
  61. Aryana A, Singh SM, Kowalski M, et al. Acute and long-term outcomes of catheter ablation of atrial fibrillation using the second-generation cryoballoon versus open-irrigated radiofrequency: a multicenter experience. J Cardiovasc Electrophysiol. 2015;26(8):832–839. [CrossRef] [PubMed]
  62. Sohara H, Ohe T, Okumura K, et al. HotBalloon ablation of the pulmonary veins for paroxysmal AF: a multicenter randomized trial in Japan. J Am Coll Cardiol. 2016;68(25):2747-2757. [CrossRef] [PubMed]
  63. Dukkipati SR, Cuoco F, Aryana A, et al. Pulmonary vein isolation using the visually guided laser balloon: a prospective, multicenter, and randomized comparison to standard radiofrequency ablation. J Am Coll Cardiol. 2015;66(12):1350-1360. [CrossRef] [PubMed]
  64. Gaita F, Leclercq JF, Schumacher B, et al. Incidence of silent cerebral thromboembolic lesions after atrial fibrillation ablation may change according to technology used: comparison of irrigated radiofrequency, multipolar nonirrigated catheter and cryoballoon. J Cardiovasc Electrophysiol. 2011;22(9):961–968. [CrossRef] [PubMed]
  65. Mahida S, Hooks DA, Nentwich K, et al. nMARQ Ablation for Atrial Fibrillation: Results from a Multicenter Study. J Cardiovasc Electrophysiol. 2015;26(7):724–729. [CrossRef] [PubMed]
  66. Scaglione M, Caponi D, Anselmino M, et al. Pulmonary vein isolation with a new multipolar irrigated radiofrequency ablation catheter (nMARQ™): feasibility, acute and short-term efficacy, safety, and impact on postablation silent cerebral ischemia. J Cardiovasc Electrophysiol. 2014;25(12):1299–1305. [CrossRef] [PubMed]
  67. Zellerhoff S, Daly M, Lim HS, et al. Pulmonary vein isolation using a circular, open irrigated mapping and ablation catheter (nMARQ): a report on feasibility and efficacy. Europace. 2014;16(9):1296–1303. [CrossRef] [PubMed]
  68. Laish-Farkash A, Khalameizer V, Fishman E, et al. Safety, efficacy, and clinical applicability of pulmonary vein isolation with circular multi-electrode ablation systems: PVAC® vs. nMARQ™ for atrial fibrillation ablation. Europace. 2016;18(6):807–814. [CrossRef] [PubMed]
  69. Deneke T, Müller P, Halbfa P, et al. Effect of different ablation settings on acute complications using the novel irrigated multipolar radiofrequency ablation catheter (nMARQ). J Cardiovasc Electrophysiol. 2015;26(10):1063–1068. [CrossRef] [PubMed]
  70. Stabile G, DeRuvo E, Grimaldi M, et al. Safety and efficacy of pulmonary vein isolation using a circular, open-irrigated mapping and ablation catheter: A multicenter registry. Heart Rhythm. 2015;12(8):1782–1788. [CrossRef] [PubMed]
  71. Vurma M, Dang L, Brunner-LaRocca HP, Sütsch G, et al. Safety and efficacy of the nMARQ catheter for paroxysmal and persistent atrial fibrillation. Europace. 2016;18(8):1164–1169. [CrossRef] [PubMed]
  72. Rodríguez-Entem F, Expósito V, Rodríguez-Mañero M, et al. Initial experience and treatment of atrial fibrillation using a novel irrigated multielectrode catheter: Results from a prospective two-center study. J Arrhythm. 2016;32(2):95–101. [CrossRef] [PubMed]
  73. Wakili R, Siebermair J, Fichtner S, et al. One-year clinical outcome after ablation with a novel multipolar irrigated ablation catheter for treatment of atrial fibrillation: potential implications for clinical use. Europace. 2016;18(8):1170–1178. [CrossRef] [PubMed]
  74. Rosso R, Chorin E, Levi Y, Rogowski O, Viskin S. Radiofrequency ablation of atrial fibrillation: nonrandomized comparison of circular versus point-by-point “smart” ablation for achieving circumferential pulmonary vein isolation and curing arrhythmic symptoms. J Cardiovasc Electrophysiol. 2016;27(11):1282–1287. [CrossRef] [PubMed]
  75. Burri H, Park C, Poku N, Giraudet P, Stettler C, Zimmermann M. Pulmonary vein isolation for paroxysmal atrial fibrillation using a circular multipolar ablation catheter: safety and efficacy using low power settings. J Cardiovasc Electrophysiol. 2016;27(2):170–174. [CrossRef] [PubMed]
  76. Marai I, Suleiman J, Blich M, Abadi S, Boulos M. Acute and mid-term results after pulmonary veins isolation using a novel circular irrigated multielectrode mapping and ablation catheter (nMARQTM™). World J Cardiovasc Dis. 2016;6(12):477–488. [CrossRef]
  77. Gal P, Buist TJ, Smit JJJ, et al. Effective contact and outcome after pulmonary vein isolation in novel circular multi-electrode atrial fibrillation ablation. Neth Heart J. 2017;25(1):16–23. [CrossRef] [PubMed]
  78. Beukema RP, Beukema WP, Smit JJJ, et al. Efficacy of multi-electrode duty-cycled radiofrequency ablation for pulmonary vein disconnection in patients with paroxysmal and persistent atrial fibrillation. Europace. 2010;12(4):502–507. [CrossRef] [PubMed]
  79. Duytschaever M, Anne W, Papiashvili G, Vandekerckhove Y, Tavernier R. Mapping and isolation of the pulmonary veins using the PVAC catheter. Pacing Clin Electrophysiol. 2010;33(2):168–178.[CrossRef] [PubMed]
  80. Wieczorek M, Hoeltgen R, Brueck M, Bandorski D, Akin E, Salili AR. Pulmonary vein isolation by duty-cycled bipolar and unipolar antrum ablation using a novel multielectrode ablation catheter system: first clinical results. J Interv Card Electrophysiol. 2010;27(1):23–31. [CrossRef] [PubMed]
  81. Bulava A, Haniš J, Sitek D, et al. Catheter ablation for paroxysmal atrial fibrillation: a randomized comparison between multielectrode catheter and point-by-point ablation. Pacing Clin Electrophysiol. 2010;33(9):1039–1046. [CrossRef] [PubMed]
  82. Choo WK, Farwell D, Harris S. Experience of atrial fibrillation ablation in a new cardiac centre using three-dimensional mapping and multielectrode duty-cycled radiofrequency ablation. Arch Cardiovasc Dis. 2011;104(6-7):396–402. [CrossRef] [PubMed]
  83. Bittner A, Mönnig G, Zellerhoff S, et al. Randomized study comparing duty-cycled bipolar and unipolar radiofrequency with point-by-point ablation in pulmonary vein isolation. Heart Rhythm. 2011;8(9):1383–1390. [CrossRef] [PubMed]
  84. Khaykin Y, Zarnett L, Friedlander D, et al. Point-by-point pulmonary vein antrum isolation guided by intracardiac echocardiography and 3D mapping and duty-cycled multipolar AF ablation: effect of multipolar ablation on procedure duration and fluoroscopy time. J Interv Card Electrophysiol. 2012;34(3):303–310. [CrossRef] [PubMed]
  85. Tivig C, Dang L, Brunner-La Rocca HP, Özcan S, Duru F, Scharf C. Duty-cycled unipolar/bipolar versus conventional radiofrequency ablation in paroxysmal and persistent atrial fibrillation. Int J Cardiol. 2012;157(2):185–191. [CrossRef] [PubMed]
  86. Beukema RJ, Elvan A, Smit JJ, Delnoy PP, Misier AR, Reddy V. Pulmonary vein isolation to treat paroxysmal atrial fibrillation: conventional versus multi-electrode radiofrequency ablation. J Interv Card Electrophysiol. 2012;34(2):143–152. [CrossRef] [PubMed]
  87. Mulder A, Wijffels M, Wever E, Boersma LV. Freedom from paroxysmal atrial fibrillation after successful pulmonary vein isolation with pulmonary vein ablation catheter-phased radiofrequency energy. 2-year follow-up and predictors of failure. Europace. 2012;14(6):818–825. [CrossRef] [PubMed]
  88. Nardi S, Argenziano L, Cappato R, et al. Ablation of paroxysmal and persistent atrial fibrillation with multielectrode phased radiofrequency duty-cycled catheters: long-term results from a large cohort of patients. J Cardiovasc Med. 2013;14(12):879–885. [CrossRef] [PubMed]
  89. Malmborg H, Lönnerholm S, Blomström P, Bomström-Lundqvist C. Ablation of atrial fibrillation with cryoballoon or duty-cycled radiofrequency pulmonary vein ablation catheter: a randomized controlled study comparing the clinical outcome and safety; the AF-COR study. Europace. 2013;15(11):1567–1573. [CrossRef] [PubMed]
  90. Looi KL, Gajendragadkar P, Taha T, et al. Long-term outcomes (>2 years) of atrial fibrillation ablation using a multi-electrode ablation catheter in patients with paroxysmal atrial fibrillation. J Interv Card Electrophysiol. 2013;36(1):61–69. [CrossRef] [PubMed]
  91. Gal P, Aarntzen AESM, Smit JJJ, et al. Conventional radiofrequency catheter ablation compared to multi-electrode ablation for atrial fibrillation. Int J Cardiol. 2014;176(3):891–895. [CrossRef] [PubMed]
  92. Spitzer SG, Karolyi L, Weinmann T, et al. Multielectrode phased radiofrequency ablation compared with point-by-point ablation for pulmonary vein isolation – outcomes in 539 patients. Research Reports in Clinical Cardiology. 2014;5:11–20. [CrossRef]
  93. De Greef Y, Buysschaert I, Schwagten B, et al. Duty-cycled multi-electrode radiofrequency vs. conventional irrigated point-by point radiofrequency ablation for recurrent atrial fibrillation: comparative 3-year data. Europace. 2014;16(6):820–825. [CrossRef] [PubMed]
  94. Di Biase L, Burkhardt JD, Mohanty P, et al. Left atrial appendage isolation in patients with longstanding persistent AF undergoing catheter ablation: BELIEF Trial. J Am Coll Cardiol. 2016;68(18):1929–1940. [CrossRef] [PubMed]
  95. Yorgun H, Canpolat U, Kocyigit D, Çöteli C, Evranos B, Aytemir K. Left atrial appendage isolation in addition to pulmonary vein isolation in persistent atrial fibrillation: one-year clinical outcome after cryoballoon-based ablation. EP Europace. 2017;19(5):758–768. [CrossRef] [PubMed]
  96. Tsai CF, Tai CT, Hsieh MH, et al. Initiation of atrial fibrillation by ectopic beats originating from the superior vena cava: electrophysiological characteristics and results of radiofrequency ablation. Circulation. 2000;102(1):67–74. [CrossRef] [PubMed]
  97. Corrado A1, Bonso A, Madalosso M, et al. Impact of systematic isolation of superior vena cava in addition to pulmonary vein antrum isolation on the outcome of paroxysmal, persistent, and permanent atrial fibrillation ablation: results from a randomized study. J Cardiovasc Electrophysiol. 2010;21(1):1–5. [CrossRef] [PubMed]
  98. Wang XH, Liu X, Sun YM, Shi HF, Zhou L, Gu JN. Pulmonary vein isolation combined with superior vena cava isolation for atrial fibrillation ablation: a prospective randomized study. Europace. 2008;10(5):600–605. [CrossRef] [PubMed]
  99. Nakagawa H, Scherlag BJ, Patterson E, Ikeda A, Lockwood D, Jackman WM. Pathophysiologic basis of autonomic ganglionated plexus ablation in patients with atrial fibrillation. Heart Rhythm. 2009;6(12):S26–S34. [CrossRef] [PubMed]
  100. Katritsis DG, Giazitzoglou E, Zografos T, Pokushalov E, Po SS, Camm AJ. Rapid pulmonary vein isolation combined with autonomic ganglia modification: a randomized study. Heart Rhythm. 2011;8(5):672–678. [CrossRef] [PubMed]
  101. Chen SA, Ching-Tai T. Catheter ablation of atrial fibrillation originating from the non-pulmonary vein foci. J Cardiovasc Electrophysiol. 2005;16(2):229–232. [CrossRef] [PubMed]
  102. Chen SA, Tai CT, Yu WC, et al. Right atrial focal atrial fibrillation: electrophysiologic characteristics and radiofrequency catheter ablation. J Cardiovasc Electrophysiol. 1999;10(3):328–335. [CrossRef] [PubMed]
  103. Lin WS, Tai CT, Hsieh MH, et al. Catheter ablation of paroxysmal atrial fibrillation initiated by non-pulmonary vein ectopy. Circulation. 2003;107(25):3176–3183. [CrossRef] [PubMed]
  104. Mandapati R, Skanes A, Chen J, et al. Stable microreentrant sources as a mechanism of atrial fibrillation in the isolated sheep heart. Circulation. 2000;101(2):194–199. [CrossRef] [PubMed]
  105. Berenfeld O, Mandapati R, Dixit S, et al. Spatially distributed dominant excitation frequencies reveal hidden organization in atrial fibrillation in the Langendorff-perfused sheep heart. J Cardiovasc Electrophysiol. 2000;11(8):869–879. [CrossRef] [PubMed]
  106. Arora R, Verheule S, Scott L, et al. Arrhythmogenic substrate of the pulmonary veins assessed by high- resolution optical mapping. Circulation. 2003;107(13):1816–1821. [CrossRef] [PubMed]
  107. Skanes AC, Mandapati R, Berenfeld O, Davidenko JM, Jalife J. Spatiotemporal periodicity during atrial fibrillation in the isolated sheep heart. Circulation. 1998;98(12):1236–1248. [CrossRef] [PubMed]
  108. Zaitsev AV, Berenfeld O, Mironov SF, Jalife J, Pertsov AM. Distribution of excitation frequencies on the epicardial and endocardial surfaces of fibrillating ventricular wall of the sheep heart. Circ Res. 2000;86:408–417. [CrossRef] [PubMed]
  109. Berenfeld O, Zaitsev AV, Mironov SF, Pertsov AM, Jalife J. Frequency-dependent breakdown of wave propagation into fibrillatory conduction across the pectinate muscle network in the isolated sheep right atrium. Circ Res. 2002;90(11):1173–1180. [CrossRef] [PubMed]
  110. Kneller J, Zou R, Vigmond EJ, Wang Z, Leon LJ, Nattel S. Cholinergic atrial fibrillation in a computer model of a two-dimensional sheet of canine atrial cells with realistic ionic properties. Circ Res. 2002;90(9):E73–E87.[CrossRef] [PubMed]
  111. Mansour M, Mandapati R, Berenfeld O, Chen J, Samie FH, Jalife J. Left-to-right gradient of atrial frequencies during acute atrial fibrillation in the isolated sheep heart. Circulation. 2001;103(21):2631–2636. [PubMed]
  112. Sarmast F, Kolli A, Zaitsev A, et al. Cholinergic atrial fibrillation: I(K,ACh) gradients determine unequal left/right atrial frequencies and rotor dynamics. Cardiovasc Res. 2003;59(4):863–873. [CrossRef] [PubMed]
  113. Verma A, Jiang C, Betts TR, et al. Approaches to catheter ablation for persistent atrial fibrillation. N Engl J Med. 2015; 372:1812–1822.
  114. Wong KCK, Paisey JR, Sopher M, et al. No benefit of complex fractionated atrial electrogram ablation in addition to circumferential pulmonary vein ablation and linear ablation: Benefit of Complex Ablation Study. Circ Arrhythm Electrophysiol. 2015;8(6):1316–1324. [CrossRef] [PubMed]
  115. Oral H, Chugh A, Good E, et al. Radiofrequency catheter ablation of chronic atrial fibrillation guided by complex electrograms. Circulation. 2007;115(20):2606–2612. [CrossRef] [PubMed]
  116. Providência R, Lambiase PD, Srinivasan N, et al. Is there still a role for complex fractionated atrial electrogram ablation in addition to pulmonary vein isolation in patients with paroxysmal and persistent atrial fibrillation? Meta-analysis of 1415 patients. Circ Arrhythm Electrophysiol. 2015;8(5):1017–1029. [CrossRef] [PubMed]
  117. Vogler J, Willems S, Sultan A, et al. Pulmonary vein isolation versus defragmentation: the CHASEAF clinical trial. J Am Coll Cardiol. 2015;66:2743–2752. [CrossRef] [PubMed]
  118. Nademanee K, McKenzie J, Kosar E, et al. A new approach for catheter ablation of atrial fibrillation: mapping of the electrophysiologic substrate. J Am Coll Cardiol. 2004;43(11):2044–2053. [CrossRef] [PubMed]
  119. Seitz J, Horvilleur J, Curel L, et al. Active or passive pulmonary vein in atrial fibrillation: is pulmonary vein isolation always essential? Heart Rhythm. 2014;11(4):579–586. [CrossRef] [PubMed]
  120. Seitz J, Bars C, Ferracci A, et al. Electrogram fractionation-guided ablation in the left atrium decreases the frequency of activation in the pulmonary veins and leads to atrial fibrillation termination. J Am Coll Cardiol Clin Electrophysiol. 2016;2(6):732–742. [CrossRef]
  121. Jaïs P, Haïssaguerre M, Shah DC, Chouairi S, Clémenty J. Regional disparities of endocardial atrial activation in paroxysmal atrial fibrillation. Pacing Clin Electrophysiol. 1996;19(11 Pt 2):1998–2003. [CrossRef] [PubMed]
  122. Rostock T, Rotter M, Sanders P, et al. High-density activation mapping of fractionated electrograms in the atria of patients with paroxysmal atrial fibrillation. Heart Rhythm. 2006;3(1):27–34. [CrossRef] [PubMed]
  123. Narayan SM, Wright M, Derval N, et al. Classifying fractionated electrograms in human atrial fibrillation using monophasic action potentials and activation mapping: evidence for localized drivers, rate acceleration, and nonlocal signal etiologies. Heart Rhythm. 2011;8(2):244–253. [CrossRef] [PubMed]
  124. Ganesan P, Cherry EM, Pertsov AM, Bhoraani B. Characterization of electrograms from multipolar diagnostic catheters during atrial fibrillation. BioMed Res Int. 2015;2015:272954. [CrossRef] [PubMed]
  125. Haïssaguerre M, Hocini M, Sanders P, et al. Localized sources maintaining atrial fibrillation organized by prior ablation. Circulation. 2006;113(5):616–625. [CrossRef] [PubMed]
  126. Shivkumar K, Ellenbogen KA, Hummel JD, Miller JM, Steinberg JS. Acute termination of human atrial fibrillation by identification and catheter ablation of localized rotors and sources: first multicenter experience of focal impulse and rotor modulation (FIRM) ablation. J Cardiovasc Electrophysiol. 2012;23(12):1277–1285. [CrossRef] [PubMed]
  127. Julien S, Clément B, Guillaume T, et al. AF ablation guided by spatiotemporal electrogram dispersion without pulmonary vein isolation: a wholly patient-tailored approach. J Am Coll Cardiol. 2017;69(3):303–321.[CrossRef] [PubMed]
  128. Narayan SM, Krummen DE, Rappel WJ. Clinical mapping approach to diagnose electrical rotors and focal impulse sources for human atrial fibrillation. J Cardiovasc Electrophysiol. 2012;23(5):447–454. [CrossRef]
  129. Narayan SM, Krummen DE, Shivkumar K, et al. Treatment of atrial fibrillation by the ablation of localized sources: CONFIRM (Conventional Ablation for Atrial Fibrillation With or Without Focal Impulse and Rotor Modulation) trial. J Am Coll Card. 2012;60(7):628–636. [CrossRef] [PubMed]
  130. Miller JM, Kowal RC, Swarup V, et al. Initial independent outcomes from focal impulse and rotor modulation ablation for atrial fibrillation: multicenter FIRM registry. J Cardiovasc Electrophysiol. 2014;25(9):921–929. [CrossRef] [PubMed]
  131. Buch E, Share M, Tung R, et al. Long-term clinical outcomes of focal impulse and rotor modulation for treatment of atrial fibrillation: a multicenter experience. Heart Rhythm. 2016;13(3):636–641. [CrossRef] [PubMed]
  132. Yamashita S, Shah AJ, Mahida S, et al. Body surface mapping to guide atrial fibrillation ablation. Arrhythm Electrophysiol Rev. 2015;4(3):172–176. [CrossRef] [PubMed]
  133. Malchano ZJ, Neuzil P, Cury RC, et al. Integration of cardiac CT/MR imaging with three-dimensional electroanatomical mapping to guide catheter manipulation in the left atrium: implications for catheter ablation of atrial fibrillation. J Cardiovasc Electrophysiol. 2006;17(11):1221–1229. [CrossRef] [PubMed]
  134. Mikaelian BJ, Malchano ZJ, Neuzil P, et al. Integration of 3-dimensional cardiac CT images with real-time electroanatomical mapping to guide catheter ablation of atrial fibrillation. Circulation. 2005;112:e35–e36. [CrossRef]
  135. Caponi D, Corleto A, Scaglione M, et al. Ablation of atrial fibrillation: does the addition of three-dimensional magnetic resonance imaging of the left atrium to electroanatomic mapping improve the clinical outcome? A randomized comparison of Carto-Merge vs. Carto-XP three-dimensional mapping ablation in patients with paroxysmal and persistent atrial fibrillation. Europace. 2010;12(8):1098–1104. [CrossRef] [PubMed]
  136. Pérez-Castellano N, Villacastín J, Moreno J, et al. Errors in pulmonary vein identification and ostia location in the absence of pulmonary vein imaging. Heart Rhythm. 2005;2(10):1082–1089. [CrossRef] [PubMed]
  137. Kistler PM, Rajappan K, Harris S, et al. The impact of image integration on catheter ablation of atrial fibrillation using electroanatomic mapping: a prospective randomized study. Eur Heart J. 2008;29(24):3029–3036. [CrossRef] [PubMed]
  138. Hunter RJ, Ginks M, Ang R, et al. Impact of variant pulmonary vein anatomy and image integration on long-term outcome after catheter ablation for atrial fibrillation. Europace. 2010;12(12):1691–1697. [CrossRef] [PubMed]
  139. Schwartzman D, Zhong H. On the use of CartoSound for left atrial navigation. J Cardiovasc Electrophysiol. 2010;21(6):656-664. [CrossRef] [PubMed]
  140. Koruth JS, Heist EK, Danik S, et al. Accuracy of left atrial anatomical maps acquired with a multielectrode catheter during catheter ablation for atrial fibrillation. J Inter Card Electrophysiol. 2011;32(1):45–51. [CrossRef] [PubMed]
  141. Anter E, Tschabrunn CM, Josephson ME. High-resolution mapping of scar-related atrial arrhythmias using smaller electrodes with closer interelectrode spacing. Circ Arrhythm Electrophysiol. 2015;8(3):537–545. [CrossRef] [PubMed]

 

Advertisement