This study was a single-centre, nonrandomized, open-label prospective clinical trial conducted at the Tianjin Chest Hospital. Patients with paroxysmal AF who received first-time CB ablation at the Tianjin Chest Hospital between October 2016 and January 2018 were enrolled in the trial. A total of 164 consecutive patients were included in the study. One method was a conventional dosing protocol. With this method, a 180-second freeze cycle was followed by a 180-second bonus freeze after acute PV isolation in the Cryo-AFConventional group. The second method had a shorter protocol that was based on the TT-PVI or achievement of -40°C within 60 seconds. Written informed consent was obtained from all patients. The inclusion criteria were age of 18 to 75 years, at least 2 paroxysmal AF episodes documented by electrocardiography, and no response to at least 1 antiarrhythmic drug. The exclusion criteria were acute coronary syndrome, persistent AF, left atrial size >50 mm, intracardiac thrombi, uncontrolled heart failure, and a history of a previous AF ablation procedure. Patients with a left common trunk or right middle PV were also excluded from the analysis. Three experienced operators performed the procedures. The same individual operators carried out both ablation strategies. The Institutional Review Board of Tianjin Chest Hospital approved the study protocol. The clinical baseline characteristics of the study patients are shown in Table 1.
Conscious sedation was established before the CB ablation procedure was performed. Vital parameters (oxygen saturation, blood pressure, pulse) were continuously monitored. During the ablation procedure, it was recommended that active clotting times be maintained between 300 and 350 seconds by intravenous administration of heparin. We used biplane fluoroscopy with 30° right and 45° left anterior oblique views. The electrophysiological study and cryoablation procedure were performed. A diagnostic catheter was delivered via the right internal jugular vein and positioned within the coronary sinus. An exchange wire was placed in the left superior PV after a single transseptal puncture access was made with an SL-1 sheath (St. Jude Medical, Inc.) using the modified Brockenbrough method (BRK-1, St. Jude Medical, Inc.). The PV anatomy and left atrial was visualized by using PV angiography. The SL-1 sheath was then replaced with a steerable sheath (FlexCath Advance™, Medtronic, Inc.). A 20-mm circular mapping catheter (Achieve™, Medtronic, Inc.) was used to guide the CB2 inside the left atrium (LA) and to try real-time recordings from the focused PV in all patients. Once a PV was catheterized, the CB was inflated and advanced to the vein ostium, and PV occlusion was documented by injection of contrast medium. Our standard set of lesions included the left superior pulmonary vein (LSPV), which was dealt with first, followed by the left inferior PV (LIPV), right inferior PV (RIPV), and right superior PV (RSPV). The Achieve catheter was placed and used during cryoablation; the TT-PVI was recorded “online” when the PV potentials have been dissociated from left atrial activity or completely disappeared. While ablating near the RSPV or RIPV, the phrenic nerve (PN) was stimulated with a bipolar catheter placed in the superior vena cava, and diaphragmatic stimulation was realized by pacing the ipsilateral phrenic nerve with a 1500-ms cycle and a 10-mA cycle. The operator periodically noticed the diaphragmatic contraction by using fluoroscopy and placed a hand on the abdomen of the patient to evaluate the strength of contraction. Cryoablation was terminated immediately if loss or reduction of the pacing capture was detected. The balloon was repositioned at the PV antrum if the PN function recovered and ablation was then reattempted. Radiofrequency (RF) ablation was used to complete PV isolation if PN function failed to recover within 10–15 minutes.
In our study, we compared two cryotherapy application protocols. Cryoablation of 180 seconds was applied in the Cryo-AFConventional group until a bidirectional block of the vein was observed. Following successful PVI, an additional 180-second freeze cycle was applied to each PV. In the Cryo-AFDosing group, the freeze duration was modified relying the observed TT-PVI or balloon temperature. If a spontaneous TT-PVI was observed, cryoenergy applications lasted for the TT-PVI plus 60-90 seconds. If the TT-PVI was <60 seconds, a TT-PVI plus 60-second freeze cycle was applied. If the TT-PVI was between 60 and 90 seconds, a TT-PVI plus 90 seconds freeze cycle was applied. We abandoned the cryoenergy applications that did not achieve TT-PVI within 90 s. The CB was placed in an alternate position to achieve a suitable TT-PVI. Additionally, if the TT-PVI was unavailable, cryoenergy of 120–180 s was applied until the vein was blocked according to the time from the beginning of ablation to the balloon temperature achievement of -40°C. In other words, if the temperature reached -40°C within 60 seconds, a 120-second freeze cycle was applied, and if the temperature reached -40°C within 60-90 seconds, a 180-second freeze cycle was carried out. A 120-second bonus operation was administered immediately in both cases, (Fig 1). If the balloon temperature fell beneath -55°C, the cryoapplication was terminated, and the balloon was placed in a different position at the PV antra to avoid ultra-cold temperatures. The endpoint of cryoablation for PVs was isolation. This was demonstrated by pacing the stimulation of the LA as well as the corresponding PV. The nadir cryotemperature and total cryotherapy time per vein during every cryoablation were recorded, as was the total procedure time. The main adverse events related to cryoablation, specifically, pericardial effusion or tamponade, transient ischaemic attack (TIA) or stroke, PN palsy, atrial-oesophageal fistulas, and symptomatic PV stenosis, were also recorded. Isolation of all PVs was reassessed by documentation of entrance- and exit-block after a 20-minute waiting period and in almost all cases following the administration of intravenous adenosine triphosphate (ATP). If PV reconnection was recorded, cryoenergy application of the reconnected PV was repeated.
Three parameters of cryokinetics were introduced: TT-PVI, defined as the time from the beginning of the application to the moment the vein is blocked; time to –40°C, defined as the balloon freezing time from the beginning of the application to the moment of achievement of –40°C; and achievement -40°C within 60 seconds, which was defined as the balloon freezing time; that is, from the beginning of the application to the achievement of –40°C within 60 seconds.
Postprocedural management and follow-up
Patients were discharged from the hospital within 3 days of the procedure. Oral anticoagulation treatment was initiated on the evening of ablation and was continued for at least 2 months. Antiarrhythmic drug (AAD) treatment was employed for 6 weeks and discontinued if the patient was free of AF recurrence. The patients were scheduled for follow-up visits at 1 and 3 months and then every 3 months after discharge from the hospital. The study considered a three-month blank period, and 12-lead electrocardiography and 24-hour Holter recordings were acquired at each follow-up visit. Any symptoms after ablation were deemed eligible for Holter monitoring. Furthermore, telephone calls were also executed throughout the follow-up. If atrial tachycardia (AT), AF, or atrial flutter (AFL) lasted more than 30 seconds, cryoablation was said to have failed, and the failure date was recorded as the date of recurrence. Otherwise, the treatment was regarded as successful.
Variables that composed a normal distribution were reported as the mean ± standard deviation and variables were compared with a Student's t-test. The classification data were compared with the test or Fisher exact test. Kaplan-Meier method was used to predict the recurrence-free survival of AF, and the survival curve was compared with the log-rank test. The reported P values were calculated using a two-tailed test, and statistical significance was defined as P< 0.05. All statistical analyses were performed using IBM SPSS statistical software (Version 19.0, SPSS).