Impact of pulmonary vein anatomy and ostial dimensions on long-term outcome after single-shot device–guided cryoablation for paroxysmal atrial fibrillation

This observational single-centre study included 353 consecutive patients undergoing CB-guided catheter ablation for symptomatic and drug refractory PAF between 2012 and 2018. Patients with a left ventricular dysfunction, a relevant mitral valve disease and a previous AF ablation were excluded. Patients were divided into two groups: regular versus variant pulmonary vein anatomy. We compared clinical characteristics and effects of PV anatomy on freedom from arrhythmia recurrence. The diagnosis of PAF was made using the definition from the ESC guidelines for the diagnosis and the management of AF [1]. Arrhythmia recurrence was defined as documented episode of any atrial tachycardia (AT)/AF > 30 s. AF-recurrence within the first 12 months excluding the blanking period of 90 days is defined as “early AF-recurrence.”

All patients underwent preprocedural transoesophageal echocardiography to rule out left atrial thrombus formation. Antiarrhythmic agents (AADs) except for amiodarone were discontinued at least 48 h before ablation. Anticoagulation with phenprocoumon was continued aiming for an International Normalized Ratio (INR) between 2.0 and 3.0. Direct oral anticoagulants (DOAC) were stopped one half-life before ablation. Pericardial effusion was ruled out immediately after ablation and the next day thereafter. Anticoagulation was continued within 4 h after the procedure with phenprocoumon or DOAC when there was no evidence for pericardial effusion. AADs were prescribed to the operators’ discretion for a period of 3 months following ablation.

All patients underwent MRI with (1.5 or 3 Tesla) prior to the ablation procedure. Cine imaging was performed in an end-expiration breath-hold using a standard multislice balanced steady-state free precession (bSSFP) technique (effective TR 2.7 ms, TE 1.3 ms, 1.4 × 1.4 mm² in-plane, slice thickness 10 mm, 50 phases). Contrast was injected with a dose of 0.1–0.2 mmol/kg at a rate of 1–2 mL/s, followed by saline flash. CSA was determined according to the established method described by Kato et al. In detail, PV diameters were measured in superoinferior and anteroposterior directions. To determine the long axis of the PV, axial and coronal tomograms at the junction of the PV and LA were displayed, and then oblique coronal and oblique axial images were identified parallel to each PV. The PV ostium was defined as the point of inflection between the LA wall and the PV wall [7]. Along with conventional MRI scans, we additionally reconstructed a 3D model of each PV, which facilitated the distinction between ostium and antrum. The size of each PV was given in coronary (D1) and transversal (D2) diameter. The cross-sectional area (CSA) was calculated using the following equation, p × (1/2 × D1 × D2) allowing for an approximate determination of the PV ostium dimension (Fig. 1).

The procedure was performed under conscious sedation with propofol and sufentanil. Intravenous heparin was administered to maintain an activated clotting time (ACT) of 300 s throughout the procedure.

The 28-mm AFA cryoballoon (Arctic Front Advance, Medtronic) was applied in all procedures. Following transseptal puncture, the balloon device was advanced into the LA via a steerable sheath (15-F FlexCath advance Medtronic). A multipolar mapping catheter (Achieve Advance Mapping Catheter, Medtronic) was used for PV mapping.

Diaphragmatic excursion during ablation of the right-sided veins was confirmed via continuous stimulation of the phrenic nerve and compound motor action potential (CMAP) visualization. Complete PV-occlusion prior to each freezing cycle was confirmed by PV-angiography with contrast media injection with the balloon inflated and placed at the PV-ostia. If an antral LCPV occlusion could not be obtained, a sequential ablation approach was adapted. At first, the first superior branch of the LCPV was targeted, followed by ablation of the first inferior branch. To verify complete occlusion of the targeted LCPV branch, contrast medium was injected. To achieve complete occlusion of RMPVs, the ablation technique described above was applied. In addition, “hockey stick,” “loop,” and “pull-down” techniques were performed, if necessary. Ablation was performed adherent to a 2*180s freeze per vein protocol. Persistent PVI (entrance and exit block) was confirmed after a waiting period of 20 min. Bonus freezes were not applied during standard protocol ablation but could have been used at the discretion of the operator. If isolation was not achieved, touch-up ablation with a focal cryo-energy catheter (Freezor MAX; Medtronic) was performed.

After discharge, follow-up visits were scheduled at 3, 6, and 12 months after the procedure, including 7-day-Holter-ECGs and interviews. Thereafter, 24-h-Holter ECGs were performed every 6 months during the whole observation period of 48 months. Additional unscheduled visits were performed in case of complaints. The total observation duration was 48 months. Most patients were followed up in our outpatient clinic. The other patients kindly provided their follow-up reports on our request.

All calculations were performed using the statistical package for the social sciences (IBM SPSS Statistics 27.0). The chi-squared test was used for categorical variables and Student’s t test for comparison of continuous variables. Data are presented as mean ± standard deviation or percentage value (%) unless stated otherwise. A two-tailed p-value < 0.05 was considered statistically significant. Multivariate analysis was conducted using multiple logistic regression. Data processing and analysis was performed using Excel 2010 (Microsoft Corp., Redmond, WA, USA). Event-free survival was calculated by Kaplan–Meier analysis as time from initial PVI to first documented AF/AT episode > 30 s. AF-recurrence within the blanking period of 90 days was excluded from data analyses. The log-rank test was used to assess differences in event-free survival time between two groups: normal versus variant PV anatomy.

The study population consisted of 353 consecutive patients (58 ± 11 years old, 56% males) who underwent an index CBA for symptomatic PAF. Baseline parameter is summarized in Table 1. No major, relevant differences were observed between the groups.

Acute PVI was achieved in all patients (n = 353, 100%). Procedural data of patients with a normal PV anatomy were compared to those patients with variant PV characteristics (Table 1). Although, procedural and fluoroscopy times were slightly longer in the variant PV-anatomy cohort of patients, this difference did not reach statistical relevance. Nadir temperatures and freezing times were similar between both groups (Table 2).

Two hundred twenty-three patients (63%) presented with a regular PV anatomy (2 right- and 2 left-sided PVs). A variant PV anatomy was present in 130 patients (37%) and distributed as follows: 27% (n = 95) left common ostium (LCPV), 5% (n = 16) right middle PV (RMPV), 5% (n = 19) right common ostium (RCPV). Further details are summarized in Table 3.

One patient (< 1%) developed a pericardial effusion after the procedure, and 3 patients (1%) had vascular groin complications (pseudoaneurysm of the femoral vein) not requiring intervention. No further postprocedural complications were observed.

In our previous study comparing two single-shot devices, patients with a variant PV anatomy presented with a significantly higher 12-month AF-recurrence rate (69%) compared to patients with a regular PV anatomy (44%) (p < 0.001) [8]. In our present study, we analysed patients’ 48-month long-term arrhythmia outcome. In line with the previously published study [8], variant PV characteristics were significantly more often observed in the AF-cohort compared to the No-AF group of patients (Table 3; Fig. 2). In detail, significantly more LCPVs, RCPVs and RMPVs were found in the AF-cohort of patients (p < 0.001) (Table 3; Fig. 2). The presence of variant PV characteristics, a right variant PV anatomy and a LCPV were revealed as independent predictors for AF-recurrence (Table 5).

Smaller CBA studies comparing AF-free survival rates depending on the presence of a LCPV reported on similar results [9, 10]. But compared to prior publications, our present study is the first to present 48 month long-term outcome data after single-shot guided CBA for PAF in a large cohort of patients depending on PV anatomy. Çöteli et al. compared AF-freedom after CBA and RFA depending on the presence of a LCPV in patients with PAF and PERS AF [11]. Mid-term AF/AT-recurrence-free survival between CBA and RFA did not differ significantly (p = 0.235). Similar results were presented by Khoueiry et al. comparing 15-month outcome data after CBA and RFA among patients with PAF and PERS AF depending on variant PV anatomy characteristics [12]. These results may be caused by the analysis of PAF and PERS AF as in our previous study, significant differences were observed between PAF and PERS AF. Especially in PAF, variant PV characteristics had a significant impact on AF-free survival whereas PV characteristics seem to play a minor role in PERS AF most likely due to advanced stages of atrial fibrosis and scar formation [8]. Moreover, different classifications and definitions for the left common ostium used in prior studies may in part explain discrepant results, too [11‐13].

The incidence of a RMPV among AF-patients is being reported to be 20% [12]. In our study, 13% of all patients with AF-recurrence had a RMPV (Table 3). A meta-analysis of Cheruiyot et al., including 12 CBA and RFA studies, demonstrated a significant association between the presence of a RMPV and AF-recurrence (OR = 1.85, 95% CI 1.26–2.72, p = 0.002) [14]. The authors suggested that technical difficulties in reaching a small PV may be the reason for AF-recurrence in these patients. Additionally, they proposed that small PVs can be easily overseen during ablation [14].

These results match our findings, as patients with right-variant PVs presented with the poorest outcome (Fig. 2). The data given above suggests that a more complex understanding of PV characteristics is strongly required to improve patients’ outcome.

The crucial moment in achieving acute PVI is not just the complete vein occlusion but also a wide antral ablation. It is well-recognized that antral positioning is more efficient in terms of long-term results [15]. It could be explained by involving more arrhythmogenic aerials of PV-LA connection sometimes also including the posterior wall of the LA. A wide antral ablation became more feasible after introducing the 2nd-generation cryoballoon. It allows for a shorter procedure duration and enables proper positioning in challenging PV anatomy [16, 17]. Although complete occlusion was routinely confirmed angiographically for each PV, we revealed a significant correlation between enlarged right-sided PVs as well as LSPVs and 48-month AF-recurrence rates (Table 4). These results act in concert with our previous study, analysing patients’ 12-month outcome data [8]. Another study by Güler et al. revealed the size of the RSPV as independent predictor for AF-recurrence [18]. This supports the hypothesis that PV anatomy seems to be an important issue [19]. Dilated PV orifices may lead to structural and electrical remodeling processes of the PVs that trigger AF recurrence. However, Bose et al. showed that PV-dimensions do not have a statistically significant impact on AF freedom [20]. These differences may be caused by procedural differences.

Further studies are warranted, e.g., comparing the impact of different ablation strategies (CBA vs. RFCA) on the outcome following catheter ablation for PAF in patients with variant PV characteristics.