br Conflict of interest br Introduction br Baseline
Conflict of interest
Baseline ablation strategies targeting PVs It is well known that PVI was first developed to eliminate the triggers that initiate attacks of paroxysmal atrial fibrillation . Subsequently, the additional function of the PV myocardium to perpetuate atrial fibrillation has been a focus . Now, most approaches for eliminating long-persistent atrial fibrillation include PVI as the baseline procedure to reduce both the trigger and the maintaining factor of persistent AF. Although variations still exist in the procedures that target the PVs, including circumferential PV ablation (CPVA),  extensive encircling PV isolation (EEPVI),  PV antrum isolation (PVAI),  and BOX isolation  (Fig. 1), there is a common consensus among them . To reduce the risk of PV stenosis and eliminate the firing foci around the PV ostium, ablations should be performed in the atrial tissue located in the antrum rather than the PV ostium. If the PVs are targeted, complete electrical isolation should be the goal. Radiofrequency (RF) VEGFR Tyrosine Kinase Inhibitor II can be applied either segmentally, guided by a circular mapping catheter, or by a continuous circumferential ablation lesion created to surround the ipsilateral right or left PVs. Analysis of 4 major articles in which antral encirclement of PVs in cases with long-standing persistent AF underwent a single-procedure, showed a drug-free success rate ranging from 37% to 56% at approximately 1 year (Fig. 2) . Integration of repeat procedures (mean, 1.3 per patient) increased the drug-free success rate to 59%. The combination of drugs and multiple procedures yielded a success rate of approximately 77%.
Adjunctive ablation strategies (electrogram-guided ablation and linear ablation) Although ablation strategies targeting the PVs are the cornerstone of AF ablation procedures for both paroxysmal and persistent AF, continued efforts are underway to establish additive strategies to improve ablation outcome. Currently, one of the most popular methods for AF-substrate modification in the atrium is to apply RF energy and create lesions targeting the areas with complex fractionated atrial electrograms (CFAEs), which was developed by Nademanee et al. (Fig. 3) . CFAEs are believed to represent slow conduction or pivot points where wavelets turn around at the end of arcs of functional blocks, and are defined as atrial electrograms with fractionations, continuous activity, or rapid firings with very short cycle lengths of ≤120ms averaged over a 10-s recording period. The primary endpoint of ablation in their original work was either complete elimination of the area with CFAEs or conversion of AF to sinus rhythm. CFAE ablation terminated AF in 49 of 57 patients with paroxysmal AF (86%) and 40 of 64 patients with chronic AF (63%) without the use of antiarrhythmic drugs. The AF-free rate at 1-year follow-up was 91% in 110 patients, including those who underwent repeat procedures (16%). Although this method is well accepted, its role in ablation has not yet been fully established. CFAE ablation only targets the substrate that perpetuates AF, in fact only a modest effect on chronic AF has been reported thus far . More recently, a general consensus has been established that CFAE ablation is regarded as a combination strategy for modifying the AF substrate as discussed below. A recent meta-analysis of randomized controlled trials on the effectiveness of additional CFAE ablation on PVI [11–13] showed no benefit for CFAE ablation as a single approach. However, a significant benefit was shown for adjunctive CFAE ablation in addition to PVI in persistent AF cases, but not in paroxysmal AF cases (Fig. 4). Based on advancements in 3D mapping systems, CFAEs can be targeted either in a subjective (physician interpretation) or objective (online CFAE detection algorithms) manner. One of the first attempts to objectively quantify (CARTO, Biosense Webster, Diamond Bar, CA, USA) and target CFAE in addition to conventional ablation was reported by Hayward et al. . The algorithms yielded primary CFAE sites in the atrium in an average of 24% of the cases, which were accordingly ablated. PVAI and other line ablations (roof and mitral isthmus) were also performed. During the follow-up period (>1 year), they reported a 68% clinical (drug-free) success rate after a single procedure in long-standing persistent AF patients .