MATERIALS AND METHODS.
Study Population. Between February 2019 and January 2020, we enrolled 70 consecutive patients undergoing PVI for paroxysmal (P) AF (n=40, 57.14%) or PsAF (n=30, 42.87%). All patients were strongly symptomatic for palpitations, fatigue, dyspnea, or chest pain, and refractory to antiarrhythmic drugs (AAD). Tab. 1 reports their baseline characteristics at the time of ablation. All patients provided written informed consent after being adequately informed of the risks and benefits. Before PVI, all patients underwent evaluation of the LA and echocardiographic measurement of the volume of the four chambers by means of the Simpson method (cut-off normal value 28 ml/m2). Exclusion criteria were: extracardiac causes of atrial fibrillation (hyperthyroidism, rheumatic diseases, electrolyte imbalance, etc), age under 18 years or over 80 years, severe valvular heart disease, presence of contraindication for oral anticoagulation, and recent percutaneous coronary intervention or cardiac surgery. After PVI, we performed HD mapping in all patients during sinus rhythm: in 34 patients, we used the CARTO® mapping System (CARTO®3 V6, Biosense Webster, Inc., Irvine, CA, USA) and the Lasso® Nav Circular Catheter or the PentaRay® Nav Multipolar Catheter (Biosense-Webster, Inc., Irvine, CA, USA); in 36 patients,we used the Ensite-Precision™ 3d system (Abbott, Minneapolis, MN) and the Inquiry™ AFocus II™ Circular Catheter or Advisor™ HD-Grid Mapping Catheter (Abbott, Minneapolis, MN).
Procedural Setup: Ablation Settings. PVI was carried out through contact force-guided ablation by means of a 3.5-mm open irrigated-tip catheter: SmartTouch (Biosense Webster’s ThermoCool® SmartTouch®, Biosense Webster, Inc., Irvine, CA, USA) or TactiCath (Abbott, Minneapolis, MN). Surface electrocardiographic leads (aVF, V1 and V6) and bipolar intracardiac electrograms filtered at 30 to 500 Hz were recorded on a Prucka-Cardiolab EP v6.9.0 Recording System (GE Healthcare,Chicago, Illinois). RF was applied point-by-point around each PV under conscious sedation, after setting ablation index values of 330 for posterior segments and 450 for anterior segments in patients in whom the SmartTouch catheter was used, and lesion index values of 5 for posterior segments, 5.5 for lateral and 6 for anterior segments in patients in whom the TactiCath catheter was used. A minimum inter-lesion distance of 6 mm was the endpoint in all patients, and entrance and exit block of PVs was demonstrated by applying standard pacing maneuvers and other common criteria described in several previous studies(14,15,16,17,18) .
Voltage Mapping. After PVI, the patients underwent HD mapping of the lesions around PVs and of the entire LA. All HD maps were constructed during sinus rhythm, either spontaneous or restored by electrical cardioversion. The LA anatomy was subdivided into 6 non-PV regions: anterior wall (AW), lateral wall (LW), inferior wall (IW), septal wall (SW), posterior wall (PW), and LA roof. The boundaries of each area were defined as shown in Fig.1. Any LVs of the LA were classified according to their location. In 34 patients, HD maps were acquired by means of the CMC LassoNav (17) or the MC Pentarey (17) and the Coloring/Confidense mapping algorithm of the 3d-S CARTO, which enables automated map acquisition. We performed a qualitatively analysis of each HD map acquired, based on the standard voltage range reported in the literature (0.05-0.5 mV), to assess non-PV anatomical areas of the LA. For this purpose, we searched for numerous small islands of LV of blue/green/red color, which we considered potential patchy fibrosis, scattered within larger areas of LV>0.5 mV of purple color (healthy tissue) or within areas of LV ≤0.05 mV of blue/green/red color, considered dense fibrosis (DF), or of no electrical activity (only red color: scar tissue). Lesions compatible with DF or scar tissue around PVs was one of the criteria on which PVI was based. All HD maps were based on the acquisition of as many voltage points as possible, and the Tissue Proximity Indicator filter of 3d-S CARTO was used to exclude map points deemed not to be in contact with the shell. Fig. 1 A, C and E show HD maps acquired by means of 3d-S CARTO. In 36 patients, HD maps were acquired by means of the CMC AFocus (18) or a 16-electrode HD configuration with 3 mm spacing by means of the standard Advisor OC HD-Grid (18). For both types of catheter, the best duplicate algorithm of 3d-S Ensite Precision was used; this creates voltage maps by using the electrogram with the highest amplitude in the same position when multiple points are projected, while the worst voltage signals are automatically discarded, each time the catheter passes a point. We evaluated tissue contact by using the Proximity Indicator of the 3d-S Ensite Precision and exploiting the flexibility of the OC, which folds when it comes into contact with the wall. The voltage range used to characterize the substrate with the CMC AFocus was 0.05-0.5 mV. The same range was adopted when the CMC LassoNav and MC Pentarey were used. Qualitative analysis was performed in the same way as for the maps acquired with 3d-S CARTO. Only in the case of the OC did we try to identify the optimal voltage range for the definition of non-PV substrates. To do so, in each patient with LV in the maps constructed by means of the OC (11/18 patients), we compared the bipolar maps in the “along” and “across” configuration of the Ensite Precision with the omnipolar maps in the HD-wave configuration; in this operation, we used two contiguous voltage ranges: 0.05-0.5 mV and 0.5-1 mV. Indeed, the 3D-S Ensite-Precision allows us to change the voltage range even after completing and saving the maps and the patient has left the electrophysiology laboratory, and subsequently to compare the new maps. We used a total of 33 HD-wave and bipolar maps for the intra-patient comparison in each range considered. Anatomical areas of gray color were considered to be scar tissue and those of purple color to be normal tissue. On the basis of the results of the comparison of the 2 voltage ranges, we chose the range more able to identify anatomical areas that were characterized by a set of green/red/yellow/blue/gray/purple colors, which we considered compatible with patchy fibrosis. Subsequently, we considered the voltage value of 1 point of purple color and 1 point of gray or red color, close to the set of different colors, and at least 5 points of purple color and 5 points of gray or red color inside the set of different colors, in order to extrapolate mean, minimum and maximum values able to identify the new range to be used for further evaluations. Scar tissue, as indicated by the gray color around the PV lesion, was one criterion of PVI. All HD maps were based on the acquisition of as many voltage points as possible; we evaluated tissue contact by using the Proximity Indicator of the Ensite Precision and exploiting the flexibility of the OC, which folds when it comes into contact with the wall. Finally, in all patients with non-PV LV identified by means of both 3d-S, and with qualitative characteristics of HD maps compatible with potential patchy fibrosis, we also tried to quantify the extent of marked (M) LV areas as a percentage of the surface area of the 6 different LA anatomical regions; these were calculated in square centimeters from the measurements yielded by the two 3d-S. Fig. 1 B, D and F show the HD maps acquired by means of Ensite Precision. Omnipolar signals were occasionally compared with the bipolar signals acquired through the distal dipole of the ablation catheter positioned in contact with the electrodes of the HD-Grid detecting electrical activity. However, these comparisons were not used for evaluations in this study. Fig. 2 shows an example of direct comparison.
Post-ablation management and follow-up. The patients were followed up for a period of about 12 months. The protocol included the prescription of AAD: for a 3-month blanking period in patients with PAF and without interruption in patients with PsAF. Patients underwent clinical follow-up examinations 3, 6, 9 and 12 months after the procedure. AAD was resumed in patients with PAF in the event of recurrence. A 24-h Holter recording was performed at the scheduled controls. Anticoagulant therapy was continued indefinitely on the basis of the CHADSvasc score (≥2 in men and ≥3 in women).
Statistical Analysis. Continuous variables are expressed as mean±SD, and categorical variables as percentages. The Student t test and Pearson’s chi-square test were used to compare continuous and dichotomous variables, respectively. We constructed Kaplan-Meier curves to illustrate 1-year freedom from AF recurrence, using a log-rank test. Two-tailed tests were considered statistically significant at the level of 0.05. All analyses were performed by means of STATA 13.1 (STATA Corp., Texas, US).