Over the past 30 years, some remarkable breakthroughs have been achieved in the treatment of AF. It was only in 1987 that a surgical intervention, the Cox Maze, was developed to prevent AF chaotic electrical signals perpetuating through the heart. James Cox, MD and colleagues discovered that it was possible to achieve an electrical block by cutting and suturing heart tissue. Lesion lines made in both the left and right atria create a “maze” which directs electrical signals to the appropriate path within the heart.1 In addition to creating a channel for electrical impulses, the procedure’s effectiveness stems from the transmurality and irreversibility of the blocks created by the sutures and consequent scar lines. Transmurality, i.e. extending through the entire thickness of the atrial wall, is essential in maintaining a permanent electrical block. The cut-and-sew Maze, also known as the Cox Maze III, has recorded the highest efficacy of all AF interventional treatments, with 98% freedom from AF and anti-arrhythmic drugs (AADs).2 However, it is a technically demanding and highly invasive procedure that is rarely performed on a standalone basis today.
The next breakthrough in the understanding of AF came from Michel Haissaguerre, MD and colleagues, who found that 94% of AF episodes originate in the pulmonary veins (PVs). By applying radiofrequency (RF) energy emitted from a catheter, Haissaguerre and colleagues created scar tissue that “isolated” the PVs and prevented AF from proliferating through the heart. Through this process, AF was eliminated in 62% of patients with paroxysmal AF,3 although it was noted that better ablation or mapping techniques might further improve the treatment success rates.4 Although the efficacy was lower than Cox Maze III, the procedure was performed without subjecting patients to the morbidity and mortality risks associated with open heart surgery. Catheter ablation, specifically PV isolation (PVI), became—and remains—the most commonly used interventional treatment for AF.5
PVI is especially beneficial in patients with early diagnoses of AF. However, many patients are asymptomatic or do not seek immediate treatment when they first experience AF symptoms and, as a result, physicians often need to deal with more progressive longstanding AF cases. Even for patients who do receive a prompt diagnosis of AF, current professional medical guidelines recommend treatment with medication, such as AADs, before most patients are considered for catheter ablation.6 Thus, by the time patients are referred to an interventional electrophysiologist for catheter ablation, AF may have already “remodeled” the left atrium (LA).
Remodeling makes other areas of the atria susceptible to triggering or perpetuating AF.7 Electrical and/or substrate modification, which can occur in paroxysmal AF patients, makes it more difficult to identify appropriate targets for catheter ablation. Thus, PVI must be accompanied by the creation of additional ablation lines in other areas of the LA, or by another ablation strategy, such as complex fractionated atrial electrograms targeting (CFAE).8 Patients with more advanced AF (persistent or longstanding persistent) have more extensive remodeling, which is difficult to treat with simple catheter ablation, even using additional ablation lines or strategies.
The greatest advance in the early years of catheter ablation was the development of three-dimensional (3D) mapping and navigation systems, such as CARTO. Prior to the availability of these electroanatomic mapping (EAM) systems, clinicians had to rely on two-dimensional images using X-ray technology (fluoroscopy), which doesn’t provide enough detail on anatomical structures or catheter location to enable ablation to be performed effectively or safely.9 EAM systems create a near real-time 3D image of anatomical structures and the catheter contact points along them. Iterations such as CARTO Merge enable information captured during the procedure to be overlaid on a 3D MRI or CT scan taken prior to the ablation procedure. EAM systems also generate maps that allow the clinician to visualize the electrograms and voltage used in more complex ablation techniques, such as CFAE ablation.10
While EAM is a tremendous improvement over fluoroscopy, which also minimizes exposure to X-ray and enables a zero-fluoro procedure, the clinician must reconcile the discrepancies between the 3D image at the time of the procedure with the MRI or CT image taken days, and sometimes weeks, before the ablation. This lack of real-time anatomic information is a limitation of current EAM systems that can be overcome by either fluoro integration or the use of cardiac ultrasound (either intra-cardiac or trans-esophageal echocardiography).11 In addition, EAM systems do not provide clinicians with information indicating whether or not the ablation has achieved transmurality.
The majority of catheters used in AF procedures have a single tip that emits RF energy to ablate tissue and create lesion lines, thus preventing the initiation or proliferation of AF. Early iterations of RF catheters added the ability to irrigate the catheter tip to prevent charring or thrombus formation at the ablation site, and to enhance the prospect of a transmural lesion being created.12 Multielectrode RF catheters, some of which include mapping functionality, have also been developed.13
The balloon catheter, which uses cryotherapy or laser energy to ablate tissue, was the next development in AF ablation catheters. Balloon catheters were conceived to ensure that all ablation points were contiguous, as a gap between ablation points can result in AF being triggered. It was also thought that balloon catheters would reduce both the incidence of PV stenosis (a complication of standard RF catheters) and procedure times. The efficacy of second generation cryoballoon catheters may be superior to standard RF catheters, and has reached similar efficacy to that of contact force sensing catheters.14,15,16
The contact force (CF) sensing catheter is considered to be the next breakthrough in AF ablation. It can be difficult to maintain consistent force against tissue during beating-heart procedures. If there is insufficient force applied to tissue, the lesion may not be transmural, potentially allowing electrical reconnection and resumption of AF. If too much force is applied to tissue, complications can occur.17 In addition, the thickness of tissue in the LA varies, requiring different ablation parameters and contact force to achieve transmural lesions.
By adhering to newly introduced indices, such as ablation or lesion indices, it was shown that the use of CF catheters can reduce the number of gaps in PVI lines. Nevertheless, it is critical to note that gaps were by no means eliminated altogether.18,19,20,21
“We perform well over 2,000 ablations a year at the St. George Asklepios Hospital in Hamburg. We believe that a reliable, real-time measurement of the impact of the treatment on the local tissue viability will significantly improve the efficacy and greatly simplify the atrial fibrillation ablation procedure.” ‒ Professor Karl-Heinz Kuck
Catheter ablation has a “success rate” (defined as freedom from AF and AADs) of about 70%. However, up to one third of patients may have to undergo multiple procedures to successfully block AF.22 Despite significant advances in ablation catheters, success rates have stayed roughly the same for some time, with the exception of CF sensing catheters.23 AF recurrence in the first year can occur in 20-40% of patients, requiring an additional catheter ablation.24
Success declines over the longer term. At three years, a single catheter ablation procedure might result in freedom from AF rate for 61% for patients with paroxysmal AF.25 Over time, AF is likely to recur, with only 47% of patients free of AF at 4.8 years. Itis important to note that roughly 95% of recurrence results from reconnection of the PVs, and that for these patients paroxysmal AF may progress to more advanced AF.26
Unlike the highly effective cut-and-sew Maze, catheter ablation procedures may leave gaps in the ablation lines. Since current tools do not directly measure the permanency and transmurality of lesions created by ablation, gaps cannot be spotted and addressed easily. Existing endpoints in the procedure focus on the validation of an electrical isolation, which may not distinguish between temporary block due to tissue edema (the natural immediate consequence of “injury” sustained to the tissue from ablation) and the desired permanent block due to complete tissue death. In addition, clinicians cannot assess whether ablation has successfully created a transmural lesion. If transmurality has not been achieved, a gap in the ablation line will emerge which will allow AF to recur.
At experienced centers, AF catheter ablations can take 2-2.5 hours to perform. In the SMART-AF trial evaluating a CF sensing catheter, the average procedure time was 3.7 hours.22 Procedure times must be reduced—and efficacy enhanced—for more patients to receive treatment and avoid the risks associated with untreated AF.
Currently, only around 1% of AF patients undergo ablation.23 Even if medical guidelines were to elevate catheter ablation to first-line treatment for AF patients, the existing experienced operators and electrophysiology labs could not support a meaningful influx of AF patients, given average procedure times and the need for repeat ablations. Thus, the next breakthrough in AF treatment will come from achieving single-procedure success rates nearing 100% with a substantially reduced procedure time. To attain this, clinicians will need to adopt personalized patient-specific therapeutic strategies, identification of correct targets and real-time validation that the desired permanency, transmurality and continuity is achieved.
About the author: Dr. Yitzhack Schwartz is a pediatrician and structural heart disease specialist (Rambam Health Care Campus, Haifa, Israel) with a special interest in harnessing novel technologies to solve unmet clinical needs. He is a graduate of the Technion Faculty of Medicine and actively practiced medicine for 30 years. He has a proven track record of developing novel medical devices, holding over 40 issued patents and patent applications, and was a member of the Biosense-Webster (Johnson & Johnson) advanced R&D team. His main fields of expertise are intra-body guided navigation and catheter-based therapeutic applications. Dr. Schwartz is Chief Medical Director at EP Dynamics Research.
 Cox JL, Schuessler RB, Lappas DG, Boineau JP. An 8½-year clinical experience with surgery for atrial fibrillation. Ann Surg. 1996;224(3):267-73.
 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):659-66.
 Calkins H, Kuck KH, Cappato R, et al. 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design. J Interv Card Electrophysiol. 2012;33(2):171-257.
 Ibid.  Woods CE, Olgin J. Atrial fibrillation therapy now and in the future: drugs, biologicals, and ablation. Circ Res. 2014;114(9):1532-46.
 Burkhardt JD, Natale A. New technologies in atrial fibrillation ablation. Circulation. 2009;120(15):1533-41.
 Kim D, Ahn K. Current status and future of cardiac mapping in atrial fibrillation. In: Choi JL, ed. Atrial fibrillation – Basic research and clinical applications. InTech. 2012;93-124.
 Burkhardt, 2009.
 Pappone C. Pulmonary vein stenosis after catheter ablation for atrial fibrillation. J Cardiovasc Electrophysiol. 2003;14:165-67.
 Calkins, 2012.
 Wasserlauf J, Pelchovitz DJ, Rhyner J et al. Cryoballoon versus radiofrequency catheter ablation for paroxysmal atrial fibrillation. Pacing Clin Electrophysiol. 2015 Apr;38(4):483-9.
 Ciconte G, Baltogiannis G, de Asmundis C et al. Circumferential pulmonary vein isolation as index procedure for persistent atrial fibrillation: a comparison between radiofrequency catheter ablation and second-generation cryoballoon ablation. Europace. 2015 Apr;17(4):559-65.
 Squara F, Zhao A, Marijon E, et al. Comparison between radiofrequency with contact force-sensing and second-generation cryoballoon for paroxysmal atrial fibrillation catheter ablation: a multicentre European evaluation. Europace. 2015 May;17(5):718-24.
 Burkhardt, 2009.
 Neuzil P, Reddy V, Kautzner J, Petru J, et al. Electrical reconnection following PVI is contingent on contact force during initial treatment – Results from the EFFICAS I study. Circ Arrhythm Electrophysiol. 2013;6:327-33.
 Hoffmayer KS, Gerstenfeld EP. Contact force-sensing catheters. Curr Opin Cardiol. 2015 Jan;30(1):74-80.
 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 Jun 3.
 Kimura M, Sasaki S, Owada S, et al. Comparison of lesion formation between contact force-guided and non-guided circumferential pulmonary vein isolation: a prospective, randomized study. Heart Rhythm. 2014 Jun;11(6):984-91.
 Cappato R, Calkins H, Chen SA, Davies W, et al. Updated worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Circ Arrhythm Electrophysiol. 2010;3:32-38.
 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):647-56.
 Calkins, 2012.
 Ganesan AN, Shipp NJ, Brooks AG, Kuklik P, et al. Long-term outcomes of catheter ablation of atrial fibrillation: A systematic review and meta-analysis. J Am Heart Assoc. 2013;2:e004549.
 Ouyang F, Tilz R, Chun J, Schmidt B. Long-term results of catheter ablation in paroxysmal atrial fibrillation: Lessons from a 5-year follow-up. Circulation. 2010;122:2368-77.
 Natale, 2014.
 Kim, 2012.