Study population
A total of 325 PsAF patients who underwent a first-time catheter ablation (CA) in our institution between September 2008 and July 2015 were retrospectively included. In this population, PVI plus linear ablation or EGM-guided ablation was performed in 230 and 82 patients, respectively. Following propensity-matched score analysis, 104 patients (LINE-group: 52, EGM-group: 52) were included in the analysis. PsAF was defined as AF lasting more than 7 days with or without anti-arrhythmic drugs, and long-standing persistent AF was defined as continuous AF for more than 12 months.13 AF duration was defined as the duration from the date when the AF was detected on 12-lead electrocardiogram (ECG) to either the date of AF termination by medical/electrical cardioversion, or the date of the initial CA procedure (if AF persisted despite medical/electrical cardioversion).
Clinical investigations were conducted in accordance with the principles expressed in the Declaration of Helsinki. All data were compliant with the International Conference on Harmonization guidelines. The study was approved by the ethics committee of The Jikei University School of Medicine for Biomedical Research. All methods were carried out in accordance with relevant guideline and regulations. All patients provided their written informed consent.
Catheter ablation (CA)
Pre-procedure preparation and techniques for PsAF ablation have been described previously.14,15 In brief, all patients received oral anticoagulation at least 4 weeks prior to the ablation procedure. Anti-arrhythmic drugs were discontinued for at least five half-lives prior to ablation. After exclusion of left atrial (LA) thrombus using trans-esophageal echocardiography, CA was performed under mild deep sedation. Continuous and bolus heparin administered with a target activated clotting time of 300–400 seconds.
The initial ablation step involved segmental antral PVI (in AF or SR) with the guidance of a large circular mapping catheter (Lasso 20–30 mm; Biosense-Webster Inc, Diamond Bar, CA, USA). Ablation was performed using a non-contact force sensing open-irrigated 3.5 mm-tip ablation catheter (Cool Path™ Duo, FlexAbility™; St jude Medical or ThermoCool/SF; Biosense Webster) with a power limit of 25-35W. The procedural endpoint of PVI was bidirectional electrical conduction block between the LA and PVs.14 Following PVI, linear ablation or EGM-guided ablation was performed.
In LINE-group, following roof line ablation (connecting the superior PVs), MI line ablation was performed with the endpoint of a bidirectional electrical conduction block across the lines.16,17 MI line ablation was performed from the mitral annulus to the lower pole of the left inferior PV along the shortest line located (3–4 o’clock in the left-anterior oblique view). Epicardial ablation within the coronary sinus (CS) was subsequently added in cases with incomplete block from endocardial ablation. Ablation setting during linear ablation was as follows: a power output of 30–40 W on the roof and endocardial MI and 20-25W on the epicardium within the CS.
In the EGM-group, ablation was performed at all sites displaying any of the following EGM features: 1) continuous electrical activity, 2) rapid activity with cycle length (CL) shorter than the mean LA appendage AF CL, 3) complex and fractionated electrograms, and 4) a gradient of activation (a temporal gradient of at least 70 ms between the distal and proximal bipoles on the map electrode, potentially representing a local circuit) with the endpoint of AF termination.8 The power output during EGM-guided ablation was 30W except for the posterior wall adjacent to the esophagus (20W with ablation termination upon abolition of the local specific electrograms). Electrical cardioversion was performed at the end of the procedure where elimination of targeting signals in both right and left atrium failed to terminate AF.
In all cases, the presence/absence of dormant conduction was tested by administration of isoproterenol (4 ug) and adenosine triphosphate (10–20 mg) in each PV after a minimum waiting period of 30 minutes after PVI. Dormant conduction was eliminated by additional radiofrequency (RF) applications. In cases with evidence of non-PV foci, the ablation strategy involved targeting non-PV foci. Superior vena cava (SVC) isolation was performed if arrhythmogenicity was detected in the SVC. Sustained AT occurring during the procedure was also mapped and ablated. Carvotricuspid isthmus linear ablation was routinely performed in all patients regardless of the presence or absence of documented typical atrial flutter. 3D-electroanatomical mapping (EAM) systems (CARTO3, Biosense-Webster Inc. or Navx, St Jude Medical, Inc, Minneapolis, MN, USA) were used during CA.
In the case of re-do procedures, the ablation strategy involved re-isolation of pulmonary veins (where indicated), and/or additional EGM-guide ablation, and/or linear ablation (roof and MI lines where necessary) with operator’s discretion. Non-PV foci were targeted during the re-do procedure in the same way as the index procedure (following administration of isoproterenol [4 ug] and adenosine triphosphate [10–20 mg]). In case with AT recurrence, the arrhythmia was targeted with AT non-inducibility as the endpoint (no AT inducible with burst pacing up to 200ms).
Acute outcomes
Acute procedure related complications (cardiac tamponade, air embolism and major bleeding) were documented. Very early recurrences were defined as recurrences occurring within three days of the procedure.
Follow-up
Patients were followed-up with 12-lead ECG and 24-hour Holter ECG at 1, 3, 6 and 12 months and subsequently every 6–12 months. Amongst symptomatic patients in whom 24-hour monitors failed to document arrhythmia, a 5-day event recorder or portable ECG recorder (HeartScan, Omron Healthcare, Kyoto, Japan) was used. The primary end point was a recurrence of atrial arrhythmias (AAs), which included AF or AT. AA recurrence was defined as the presence of AF/AT lasting > 30 seconds after the blanking period of 3 months.
Statistical analyses
Due to differences in baseline characteristics between patients in the linear ablation versus EGM-guided ablation groups, propensity-score matching was used to identify a subsets of patients with similar baseline characteristics. Patients were matched in a 1:1 ratio based propensity scores. Propensity scores were calculated for each patient using multivariable logistic regression with following 14 covariates: age, gender, body mass index, AF duration, long-standing AF, asymptomatic AF, the number of failed AADs, structure heart disease, brain natriuretic peptide (BNP), estimated glomerular filtration rate, hypertension, diabetes mellitus, congestive heart failure, CHADS2 score, LA diameter (LAD) and left ventricular ejection fraction (LVEF), using a caliper width equal to 0.2 of the standard deviation of the logit of the propensity score. Quantitative data were expressed as the mean ± standard deviation. Comparisons between groups were performed using an unpaired Student’s t-test or Wilcoxon’s rank-sum test (based on the distribution of the values). Comparisons of means from the same individual were performed using a paired Student’s t-test. Categorical data were compared by χ2 test. Kaplan-Meier curves were used to analyze freedom from AAs, and groups were compared using the log-rank test. The multivariable analysis was described by Cox regression for the assessment of the predictors of AAs recurrence after the initial CA procedure. All tests were 2-tailed, and P values of < 0.05 were considered to indicate statistical significance. All of the statistical analyses were performed using the MedCalc software package, version 11.2 (MedCalc Software, Mariakerke, Belgium).