Table 1.

Summary of the different approaches of percutaneous ablation of AF.

References	Population	Ablation technique	Acute results/main findings	Long term outcome
PVI
Haïssaguerre et al., 1998	45 PAF	Earliest site of activation of the ectopic beat initiating AF	69 ectopic sites, 94% originating from the PV	62% AF freedom after 8 ± 6months
Chen et al., 1999	79 PAF	Earliest site of activation of the ectopic beat initiating AF	116 ectopic foci, 88.8% originating from the PV	86% AF freedom after 6 ± 2 months, Focal stenosis in 42.4% of the PVs
Haissaguerre et al., 2000	70 PAF	PV isolation (except RIPV) by targeting atrial breakthroughs		73% AF freedom after 4± 5 months, (29 patients had re-ablation session)
Deisenhofer et al., 2003	• 69 PAF • 6 PsAF	Segmental PVI	PVI achieved in 89% of the veins	51% AF freedom after 230 ± 133 days 40% underwent second procedure: 90% due to PV reconnection + 40% extra-PV foci
Arentz et al., 2003	• 37 PAF • 18 PsAF	Segmental PVI	PVI achieved in 99% of the veins	27 pts underwent a second procedure 62% event free after one-year follow-up 70% for PAF, 44% for PsAF
SMART AF Natale et al., 2014	• 172 PAF	• 160 PVI using contact force sensing catheter additional atrial ablation in 50% of the cases		• Atrial arrhythmia freedom after 1-year follow-up     ◦ 74% = symptomatic arrhythmia     ◦ 69.9% = symptomatic and asymptomatic arrhythmia Contact force within the selected range ≥80% of the time significantly increased the 12 month AF/AT freedom (88% vs. 66%)
STAR-AF study Verma et al., 2015	589 PsAF	67: CPVI, 263: CPVI plus CFAE, 259: CPVI plus linear lesions (roof, mitral isthmus)		CPVI + CFAE and CPVI + lines were not superior to CPVI alone after 18% follow-up (AF freedom = 49,46, 59% respectively, P = 0.15)
CHASE-AF trial Vogler et al., 2015	153 PsAF	78 pts PVI alone, 75 full defragmentation	• PVI group: SR achieved with electrical cardioversion • Full defragmentation group: AF termination in 60% (AT = 60%, SR = 40%)	No difference in the AF freedom after 1-year follow-up: 61.4% in the PVI group, vs. 58.3% in the full-defrag group
FIRE AND ICE trial Kuck et al., 2016a	762 PAF	• 378: PVI using cryoablation 384: Segmental PVI using radiofrequency ablation	• Successful PVI • 97.9% in radiofrequency group • 98.9% in the cryoballoon group	• AF and AT freedom without anti-arrhythmic drugs after a mean of 1.5-year follow-up was not different between the two groups:     ◦ 65.4% in the cryoballoon group     ◦ 64.1% in the radiofrequency group
Alster-Lost-AF Trial Fink et al., 2017	• 69 PsAF 6- 12 months 49 PsAF ≥ 12 months	• 61 pts CPVI-only • 57 pts Substrate-modification group, (CPVI + CFAEs and linear ablation)	• AF termination     ◦ CPVI alone = 3%     ◦ Substrate modificatio n = 19% (P = 0.007)	• AF freedom after 1 year follow-up and a single procedure without AAD:     ◦ 39% in the CPVI group     ◦ 323% in the substrate modification group • AF freedom after 1-year follow-up and a single procedure ± AAD:     ◦ 54% in the CPVI group     ◦ 57% in the substrate modification group • AF freedom after 1-year follow-up and multiple procedures • 69% in the CPVI group • 86% in the substrate modification group
CASTLE AF trial Marrouche et al., 2018	• 363 pts NYHA II,III,IV with PAF or PsAF, LVEF ≤35% and an ICD • 118 PAF • 245 PsAF • 106 PsAF > 12months	• Ablation = 179 pts vs. medical therapy = 184 • Ablation consisted in PVI plus additional lesions at the discretion of the operator		• Ablation significantly reduced death from any cause and hospitalizations for worsening heart failure     ◦ 28.5% after ablation     ◦ 44.6%with medical treatment (hazard ratio, 0.62; 95% confidence interval, 0.43 to 0.87; P = 0.007)
TIlz et al., 2018	161 PAF	CPVI using EAM and double-Lasso technique	• All PVI were isolated during the index procedure • Up to 5 redo procedures were performed • Recurrence were mainly due to PV reconnections	• 10-year AF freedom     ◦ 32.9% after a single procedure     ◦ 62.7% after multiple procedures • 6.2% progression to persistent AF after 10 years
CFAE ABLATION
Nademanee et al., 2004	• 57 PAF • 64 PsAF	CFAE ablation	Acute termination without antiarrhythmic drugs • PAF: 86% • PsAF: 62%	• AF freedom after 1 procedure at 1year follow-up = 76% • Overall 91% AF freedom after 1 year follow-up
Oral et al., 2007	100 PsAF	CFAE ablation	Acute termination without antiarrhythmic drug: 16%	• AF freedom after 14 ± 7 months = 33% • Redo ablation = 44% • Overall AF freedom after 13 ±7 months = 57%
Oral et al., 2009	119 long lasting PsAF	• 19 PVI • 50 CFAE ablation • 50 cardioversion	• AF termination by PVI only = 16% • Acute AF termination during CFAE ablatio n = 18%	AF freedom after 1 procedure: 36% in the absence of CFAE ablation and 34% after CFAE ablation (P = NS) No benefit of additional CFAE ablation
SELECT-AF study Verma et al., 2014	• 48 PsAF • 28 PAF	• 38 pts: CPVI and all CFAE • 39 pts: CPVI and selective CFAE with continuous electrical activity	• CFAE ablation prolonged AF cycle length and resulted in similar rates of • AF termination (37% vs. 28%; P = 0.42)	AF, AFL and AT freedom without anti-arrhythmic drugs after 1-year follow-up significantly lower after selective CFAE ablation (28% vs.50%)
Atienza et al., 2014 RADAR-AF	• PAF = 115, AF induced in 95 pts • PsAF = 117, AF induced in 22pts	• PAF = CPVI or high frequency sources ablation (HFSA) • PSAF = CPVI or CPVI+ HFSA	• AF termination     ◦ PAF • CPVI = 38% • HFSA = 58%     ◦ PsAF • CPVI = 26% • CPVI + HFSA = 46%	• AF/AT freedom after 1 year-follow-up after a single procedure     ◦ PAF • 79% after CPVI • 81% after HFSA • PsAF     ◦ 72% after CPVI • 76% after CPVI + HFSA
Faustino et al., 2015	PAF: 150	• 75 PVI alone • 75 PVI + stepwise ablation (CFAEs + linear ablation)	• AF termination and non-inducibility achieved in 100% of the stepwise approach	• AF freedom after a first procedure at 1-year follow up significantly higher in the stepwise group:     ◦ 73,3% in the stepwise group     ◦ 53.3% after PVI (p < 0.01) • Similar results after a second procedure
Seitz et al., 2017	33 PAF 119 PsAF	• 105 = ablation only regions displaying electrogram dispersion during AF • 47 = PVI and stepwise approach	• Ablation only at dispersion areas terminated AF in 95% of the pts. PVI/stepwise approach terminated AF in 60% of the pts	• AF freedom after a mean of 1.5 procedures per patient procedures after 18 month-follow-up:     ◦ 85% = ablation only at regions displaying electrogram dispersion • 59% = PVI/Stepwise approach (P < 0.001)
ROTOR ABLATION AND FIRM ABLATION
Cuculich et al., 2010	• PAF: 11 • PsAF ≤12 months: 19 • PsAF >12 months:6	Driver domains identified by ECGi	• Multiple wavelets: most common pattern (92% of the patients) • Rotor activity detected in only 15% of the cases and only in patients with PsAF • AF complexity increased with the AF duration	N/A
Haissaguerre et al., 2014	• PsAF in SR = 26 • PsAF AF ≤12 months = 57 • PsAF > 12 months = 20	Driver domains identified by ECGi	80% AF termination after 28 ± minutes of RF ablation. AF complexity increased with AF duration	85% AF freedom at 12 months in group, no difference compared to the control group
Lim et al., 2017	• PsAF in SR = 32 • PsAF AF ≤12 months = 45 • PsAF > 12 months = 28	Driver domains identified by ECGi	• 70% AF termination, • Increased AF complexity and reduced success rate with the increase of AF duration	NA
Knecht et al., 2017	• PsAF in SR = 32 • PsAF AF ≤12 months = 45	Driver domains identified by ECGi in 8 different centers	64% AF termination after 46 ± 28min RF ablation	• AF freedom after 1-year follow-up was 77% • Of the patients with no AF recurrence, 49% experienced at least one episode of atrial tachycardia (AT) which required either continued AAD therapy, cardioversion, or repeat ablation
Narayan et al., 2012b	• PAF = 31 • PsAF = 76	FIRM guided: 36 Conventional ablation: 71	FIRM guided AF termination in 56% of the cases vs. 9% with conventional ablation	82% in the FIRM guided ablation vs. 45% AF freedom after 9 months
Pappone et al., 2018	PsAF: 81	• Group I: ablation of repetitive-regular activities followed by modified CPVI (mapping group; n = 41) • Group II: modified CPVI (control group; n = 40)	61% (25/41) AF termination in the mapping- guided ablation vs. 30% (12/40) with conventional strategy (P < 0.007)	• AF freedom after 1-year follow-up     ◦ 73.2% AF-free recurrence in the mapping group     ◦ 50% in the control group (P = 0.03)
Honarbakhsh et al., 2017	20 PsAF	• Driver domains identified by basket catheters • Drivers identified using global activation propagation and not phase mapping	• 30 potential drivers: 19 showing rotational activity and 11 focal • 26 drivers were ablated with a predefined response 84% of the cases (AF terminated with 12 and CL showed prolongation ≥30 ms with 10)	N/A
Cochet et al., 2018	PsAF = 41	Driver domains identified using ECGi during AF	• Left atrial (LA)LGE imaging significantly associated with the number of re-entrant regions (R = 0.52; P = 0.001) • Clustering of re-entrant activity at LGE borders • Areas with high re-entrant activity showed higher local LGE density as compared with the remaining atrial areas • Failure to achieve AF termination during ablation was associated with higher LA LGE burden, higher number of re-entrant regions and longer AF duration	AF freedom after 11 +/1 2 month-follow-up 25/34 (74%) pts.
LINEAR ABLATION
Jais et al., 2004	PAF = 100	PVI + MI line vs. PVI + CTI line	PVI was achieved in all the pts, MI block was achieved in 92% of the pts	87% AF freedom without anti arrhythmic drugs after MI ablation after 1-year follow-up vs. 69 in the PVI group
Fassini et al., 2005	• PAF = 126 • PsAF = 61	Randomization: 92 PVI vs. 95 PVI + MI line	MI block was achieved in 72% of the pts	AF freedom at 1-year follow-up: PsAF: 74% after MI line vs. 36%, p < 0.01 PAF: 76% after MI line vs. 62%, p < 0.05
Hocini et al., 2005	• PAF = 90	• PVI + roof line • PVI • Ablation of CTI and ostial PV fragmented signals and non PV triggers in all cases	Roof line blocked in 96% of the cases Perimitral flutter inducible in 22% of the cases	87% Af freedom after roof line after 15month-follow-up vs. 69% in the PVI group
Gaita et al., 2008	• PAF = 125 • PsAF and long lasting PsAF = 79	• 67 PVI alone (41 PAF + 26 PsAF) • 137 PVI plus left linear lesions (84 PAF + 53PsAF/Long-standing AF)	• PVI was acutely achieved in all pts. • MI block in 31% of the cases • Roof block in 92% of the cases • CTI block in all patients	• AF freedom after a single procedure at 12-month follow-up,     ◦ PVI alone = 46% for PAF     ◦ PVI alone = 27% for PsAF     ◦ PVI + lines = 57% for PAF     ◦ PVI + lines = 45% for PsAF • AF freedom after a single procedure at 3-year follow-up,     ◦ PVI alone: 29% for PAF     ◦ PVI alone: 19% for PsAF     ◦ PVI + lines: 53% for PAF     ◦ PVI + lines: 41% for PsAF • After a second procedure (in about 50% of the cases), long term AF freedom without AAD:     ◦ PVI: 62% for PAF     ◦ PVI: 39% for PsAF     ◦ PVI + lines: 85% for PAF     ◦ PVI + lines: 75% for PsAF
Mun et al., 2012	• PAF = 156	• 52 = CPVI, • 52 = CPVI+ roof line • 52 = CPVI+ posterior box	• CPVI = 100%, • CPVI +Roof line block = 80.8% • CPVI + posterior box = 59.6%	• AF freedom after 15.6 ± 5 months of follow-up,     ◦ 88.5% = CPVI     ◦ 78.8% = CPVI + roof line     ◦ 80.8% = CPVI + posterior (P = 0.44)
Kim et al., 2015	• PAF = 100	• 50 CPVI • 50 CPVI + posterior box lesion and anterior linear ablation	• CPVI + CTI block = 100% • Anterior Line block = 68% • Posterior box isolatio n = 60%	• AF freedom after 16.3 ± 4-month follow-up without AAD:     ◦ CPVI = 88%     ◦ CPVI + posterior box + anterior line = 84%
Kettering et al., 2017	PsAF = 250	• CPVI + roof line • CPVI alone • Additional MI line (6 pts), and right atrial ablation (11 pts)	• Roof blocked in all cases	• AF freedom after 1-year follow-up     ◦ 81% after roof line vs.     ◦ 74% after PVI (p = NS) • AF freedom after 3-year follow-up     ◦ 72% after roof line 63% after PVI, P = 0.04
SUBSTRATE MODIFICATION (FIBROTIC AREAS AND LOW VOLTAGE AREAS)
Jadidi et al., 2016	PsAF = 151	• Group 1: 85: PVI + ablation at low-voltage areas (LVA < 0.5 mV in AF) with fractionated activity or rotational activity or discrete rapid local activity • Group 2: 66: PVI (control group)	• AF termination targeting LVAs with specific electrogram patterns = 73% • AF termination sites colocalized within LVA in 80% and at border zones in 20%	• Single- procedural AF-free survival after 13-month follow-up     ◦ 69% = group 1     ◦ 47% = group 2 (P < 0.001)
Yamaguchi et al., 2016	PsAF = 117	• Group I: 101 = targeting low-voltage areas (<0.5 mV in SR)     ◦ Group Ia:39 = PVI + ablation of LVA     ◦ Group Ib:62 = PVI only (LVA not identified) • Group II: 16 = LVA non ablated group, only PVI	• Complete low voltage areas elimination in 92% of the cases • Additional linear lesions in 82% of the cases in group Ia	• AF freedom after a single procedure after 18 ±7 months     ◦ 72% = No LVA identified     ◦ 79% LVA ablation     ◦ 38% No LVA ablation
BIFA trial Schreiber et al., 2017	• PAF = 34 • PsAF = 49 • Long lasting PsAF = 9	• 92 PVI + box isolation of fibrotic area (BIFA) (<0.5 mV bipolar signals in sinus rhythm) • 49 PVI (no fibrotic area identified during mapping)	• Different stages of Fibrotic atrial cardiomyopathy (FACM)     ◦ 0 = no detectable voltage <1.5 mV     ◦ I = very limited severe fibrosis     ◦ II = confluence scar fibrotic areas (<0.5 mV)     ◦ III = pronounced ≥ 2 scar fibrotic areas (<0.5 mV) • IV = diffuse fibrosis (“strawberry”)	• AF freedom after 16 ± 8 months     ◦ Single procedure = 69%     ◦ Multiple procedures = 83% • The extent of fibrosis significantly associated to AF recurrence
STABLE SR Yang et al., 2017	PsAF = 229 pts	• STABLE-SR group: 114 = CPVI + CTI + ablation-homogenization of areas with low-voltage (LVZ 0.1–0.4 mV in SR) and complex electrograms • Stepwise group:115 = CPVI + linear lesions + CFAEs	• AF termination in STABLER-SR group = 12.3% • AF termination in stepwise group = 32.5%	AF-free survival after 18-month follow-up STABLE-SR group: 74% Stepwise group: 71.5% (P = 0.325)

AF, atrial fibrillation; AFL, atrial flutter; AT, atrial tachycardia; CTI, cavo-tricuspid isthmus; EAM, electro-anatomical mapping; LVEF, left ventricular ejection fraction; CPVI, circumferential pulmonary veins isolation; MI, mitral isthmus; PAF, paroxysmal AF; PsAF, persistent AF; PVI, pulmonary veins isolation.