The Influence of Pulmonary Veins’ Anatomic Features and Catheter Coaxiality on Cryoballoon Ablation Results for Paroxysmal Atrial Fibrillation

A total of 172 consecutive patients with sympathetic paroxysmal atrial fibrillation who received cryoballoon (CB) ablation from 2020 to 2021 were retrospectively analyzed in this study. Catheter coaxiality and anatomic features of pulmonary veins (PVs) on computed tomography images were explored by several parameters and their influence on the cryoablation results was then analyzed. The rate of incomplete CB occlusion was significantly higher for inferior than superior PVs. A multivariate analysis revealed that a short distance (<6.3 mm) from PV ostium to first branch (D-PVB) and a small angle (<32.5°) of first branch were independent predict factors for an incomplete CB occlusion in right inferior PVs (RIPVs). A combination of D-PVB and angle of first branch could elevate the predictor value for an incomplete balloon occlusion with a sensitivity of 0.85 and specificity of 1.0 for RIPVs. For PVs with a perfect balloon occlusion, the best catheter coaxiality was observed in right superior PV while the worst catheter coaxiality was observed in RIPV. A more aggressive catheter manipulation with a "7" or "reverse-U" shape of long sheath could obtain a better catheter coaxiality compared with conventional manipulation strategy for RIPVs. In Conclusion, a short D-PVB and a small angle of first branch were independent predict factors for an incomplete CB occlusion in RIPVs. A more aggressive catheter manipulation strategy was recommended to achieve a complete balloon occlusion and a better catheter coaxiality for RIPVs. A total of 172 consecutive patients with sympathetic paroxysmal atrial fibrillation who received cryoballoon (CB) ablation from 2020 to 2021 were retrospectively analyzed in this study. Catheter coaxiality and anatomic features of pulmonary veins (PVs) on computed tomography images were explored by several parameters and their influence on the cryoablation results was then analyzed. The rate of incomplete CB occlusion was significantly higher for inferior than superior PVs. A multivariate analysis revealed that a short distance (<6.3 mm) from PV ostium to first branch (D-PVB) and a small angle (<32.5°) of first branch were independent predict factors for an incomplete CB occlusion in right inferior PVs (RIPVs). A combination of D-PVB and angle of first branch could elevate the predictor value for an incomplete balloon occlusion with a sensitivity of 0.85 and specificity of 1.0 for RIPVs. For PVs with a perfect balloon occlusion, the best catheter coaxiality was observed in right superior PV while the worst catheter coaxiality was observed in RIPV. A more aggressive catheter manipulation with a "7" or "reverse-U" shape of long sheath could obtain a better catheter coaxiality compared with conventional manipulation strategy for RIPVs. In Conclusion, a short D-PVB and a small angle of first branch were independent predict factors for an incomplete CB occlusion in RIPVs. A more aggressive catheter manipulation strategy was recommended to achieve a complete balloon occlusion and a better catheter coaxiality for RIPVs. Pulmonary vein (PV) isolation (PVI) is the guideline-recommended cornerstone for the ablation of symptomatic paroxysmal and persistent atrial fibrillation (AF).1Haïssaguerre M Jaïs P Shah DC Takahashi A Hocini M Quiniou G Garrigue S Le Mouroux A Le Métayer P Clémenty J Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins.N Engl J Med. 1998; 339: 659-666Crossref PubMed Scopus (6593) Google Scholar, 2Nault I Miyazaki S Forclaz A Wright M Jadidi A Jaïs P Hocini M Haïssaguerre M Drugs vs. ablation for the treatment of atrial fibrillation: the evidence supporting catheter ablation.Eur Heart J. 2010; 31: 1046-1054Crossref PubMed Scopus (93) Google Scholar, 3Calkins H Kuck KH Cappato R Brugada J Camm AJ Chen SA Crijns HJ Damiano RJ Davies DW DiMarco J Edgerton J Ellenbogen K Ezekowitz MD Haines DE Haissaguerre M Hindricks G Iesaka Y Jackman W Jalife J Jais P Kalman J Keane D Kim YH Kirchhof P Klein G Kottkamp H Kumagai K Lindsay BD Mansour M Marchlinski FE McCarthy PM Mont JL Morady F Nademanee K Nakagawa H Natale A Nattel S Packer DL Pappone C Prystowsky E Raviele A Reddy V Ruskin JN Shemin RJ Tsao HM Wilber D Heart Rhythm Society Task Force on Catheter and Surgical Ablation of Atrial Fibrillation2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design: a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation. Developed in partnership with the European Heart Rhythm Association (EHRA), a registered branch of the European Society of Cardiology (ESC) and the European Cardiac Arrhythmia Society (ECAS); and in collaboration with the American College of Cardiology (ACC), American Heart Association (AHA), the Asia Pacific Heart Rhythm Society (APHRS), and the Society of Thoracic Surgeons (STS). Endorsed by the governing bodies of the American College of Cardiology Foundation, the American Heart Association, the European Cardiac Arrhythmia Society, the European Heart Rhythm Association, the Society of Thoracic Surgeons, the Asia Pacific Heart Rhythm Society, and the Heart Rhythm Society.Heart Rhythm. 2012; 9 (632–696.e21)Abstract Full Text Full Text PDF Scopus (1454) Google Scholar A similar safety and effectiveness for PVI by cryoballoon (CB) ablation had been proved by previous studies compared with the conventional radiofrequency catheter ablation (RFCA) technique.4Packer DL Kowal RC Wheelan KR Irwin JM Champagne J Guerra PG Dubuc M Reddy V Nelson L Holcomb RG Lehmann JW Ruskin JN STOP AF Cryoablation InvestigatorsCryoballoon ablation of pulmonary veins for paroxysmal atrial fibrillation: first results of the North American ArcticFront (STOPAF) pivotal trial.J Am Coll Cardiol. 2013; 61: 1713-1723Crossref PubMed Scopus (666) Google Scholar,5Kuck KH Brugada J Fürnkranz A Metzner A Ouyang F Chun KR Elvan A Arentz T Bestehorn K Pocock SJ Albenque JP Tondo C FIRE AND ICE InvestigatorsCryoballoon or radiofrequency ablation for paroxysmal atrial fibrillation.N Engl J Med. 2016; 374: 2235-2245Crossref PubMed Scopus (1228) Google Scholar Several parameters including balloon-to-vein occlusion, balloon nadir temperature (NT), and total freezing time had been proved to be closely related to tissue injury and longterm procedure efficacy. Several studies have also proved that a longer time-to-isolation (TTI) during cryoablation is a predictor of vein reconnection during follow-up, and a target of TTI within 60 seconds (TTI <60) is recommended.6Su W Aryana A Passman R Singh G Hokanson R Kowalski M Andrade J Wang P Cryoballoon Best Practices II: Practical guide to procedural monitoring and dosing during atrial fibrillation ablation from the perspective of experienced users.Heart Rhythm. 2018; 15: 1348-1355Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar, 7Ciconte G Velagić V Mugnai G Saitoh Y Irfan G Hunuk B Ströker E Conte G Sieira J Di Giovanni G Baltogiannis G Brugada P de Asmundis C Chierchia GB Electrophysiological findings following pulmonary vein isolation using radiofrequency catheter guided by contact-force and second-generation cryoballoon: lessons from repeat ablation procedures.Europace. 2016; 18: 71-77Crossref PubMed Scopus (65) Google Scholar, 8Aryana A Mugnai G Singh SM Pujara DK de Asmundis C Singh SK Bowers MR Brugada P d'Avila A O'Neill PG Chierchia GB Procedural and biophysical indicators of durable pulmonary vein isolation during cryoballoon ablation of atrial fibrillation.Heart Rhythm. 2016; 13: 424-432Abstract Full Text Full Text PDF PubMed Scopus (116) Google Scholar Further study demonstrated that the time to reach −40°C balloon temperature is an independent multivariate predictor of vein reconnection.9Ciconte G Mugnai G Sieira J Velagić V Saitoh Y Irfan G Hunuk B Ströker E Conte G Di Giovanni G Baltogiannis G Wauters K Brugada P de Asmundis C Chierchia GB On the quest for the best freeze: predictors of late pulmonary vein reconnections after second-generation cryoballoon ablation.Circ Arrhythm Electrophysiol. 2015; 8: 1359-1365Crossref PubMed Scopus (101) Google Scholar Furthermore, it was recommended to stop an ablation application after 60 seconds of freezing if no vein isolation is achieved or the CB has not reached −35°C according to the results of Cryoballoon vs. Irrigated Radiofrequency Catheter Ablation: Double Short vs. Standard Exposure Duration (CIRCA-DOSE) trial.10Andrade JG Champagne J Dubuc M Deyell MW Verma A Macle L Leong-Sit P Novak P Badra-Verdu M Sapp J Mangat I Khoo C Steinberg C Bennett MT Tang ASL Khairy P CIRCA-DOSE Study InvestigatorsCryoballoon or radiofrequency ablation for atrial fibrillation assessed by continuous monitoring: a Randomized Clinical Trial.Circulation. 2019; 140: 1779-1788Crossref PubMed Scopus (314) Google Scholar Although varied parameters that influence ablation results had been discussed in detail in previous studies, the real factor that influenced these important parameters was the approach of catheter manipulation, including the coaxiality of the steerable long sheath (LS) with the cryoballoon, the coaxiality of CB with PV and the selection of PV branch for the Achieve catheter. However, the coaxiality during the procedure was mainly determined by personal experience and lacked an objective judgment method. What is more, anatomic features of PVs could also influence the procedural difficulty and NT.11Takarada K Ströker E Abugattas JP de Regibus V Coutiño HE Lusoc I Capulzini L Sieira J Mugnai G Salghetti F Choudhury R Iacopino S de Asmundis C Brugada P Chierchia GB Impact of an additional right pulmonary vein on second-generation cryoballoon ablation for atrial fibrillation: a propensity matched score study.J Interv Card Electrophysiol. 2019; 54: 1-8Crossref PubMed Scopus (5) Google Scholar, 12Huang SW Jin Q Zhang N Ling TY Pan WQ Lin CJ Luo QZ Han YX Wu LQ Impact of pulmonary vein anatomy on long-term outcome of cryoballoon ablation for atrial fibrillation.Curr Med Sci. 2018; 38: 259-267Crossref PubMed Scopus (8) Google Scholar, 13Ströker E Takarada K de Asmundis C Abugattas JP Mugnai G Velagić V de Regibus V Coutiño HE Choudhury R Iacopino S De Greef Y Tanaka K Brugada P Chierchia GB Second-generation cryoballoon ablation in the setting of left common pulmonary veins: procedural findings and clinical outcome.Heart Rhythm. 2017; 14: 1311-1318Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar, 14Matsumoto Y Muraoka Y Funama Y Mito S Masuda T Sato T Akita T Awai K Analysis of the anatomical features of pulmonary veins on pre-procedural cardiac CT images resulting in incomplete cryoballoon ablation for atrial fibrillation.J Cardiovasc Comput Tomogr. 2019; 13: 118-127Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar Therefore, in this study, several parameters were utilized to evaluate the coaxiality of the catheter and anatomic features of PVs quantitatively and their influence on the efficacy of cryoablation. The study retrospectively enrolled 172 consecutive patients with sympathetic paroxysmal AF who were refractory to at least 1 antiarrhythmic drug from 2020 to 2021. Transesophageal echocardiography and contrast-enhanced computed tomography (CT) for PV were performed in all patients before the ablation procedure. Patients with structural heart disease or common trunk PV were excluded from the study. All patients had stopped antiarrhythmic drugs for 5 or more half-lives and then received CB ablation therapy at our hospital. The study was approved by the ethics committee of Zhongshan Hospital, Fudan University. Standard electrodes were placed in the coronary sinus and the right ventricular apex for pacing and recording. Both bipolar and unipolar electrograms were recorded by a Prucka system (GE Healthcare, Milwaukee, Wisconsin) (filtered at 30 to 500 Hz and 0.05 to 500 Hz, respectively). Single puncture transseptal left atrium (LA) access was performed under fluoroscopic guidance and a low and anterior transseptal location was considered for all patients. CB ablation was performed under mild conscious sedation with midazolam. A 15-mm or 20-mm-diameter inner luminal catheter (Achieve; Medtronic, Minneapolis, Minnesota) was placed in each targeted PV to record PV signals before, during, and after ablation. Through a steerable sheath placed in the LA (FlexCath; Medtronic), the 28-mm CB (Arctic Front Advance; Medtronic) was advanced over the Achieve catheter, inflated, and then directed to each PV ostium. Optimal vessel occlusion was assumed when contrast injection into the PV showed complete contrast retention without any backflow to the atrium. During ablation, if PV potentials were visible during energy delivery, TTI was recorded when PV potentials completely disappeared or were dissociated from LA activity. For TTI <60 seconds, a first 180-second application and a second 120-second application were delivered. If no isolation was achieved within 60 seconds, the balloon was repositioned, and a new cryo lesion was delivered. When recording of PV potential was not possible during cryo application, 2 cryo energy applications of 180 and 120 seconds were delivered when an isolation of PV was confirmed after the first cryo application. When the balloon NTs exceeded −55°C, the ablation was terminated. To avoid phrenic nerve injury, phrenic nerve pacing was performed during CB applications in right PVs. To analyze the technical difficulty in isolating each PV by a CB, the number needed to disconnect (NND) the PV was defined as the total number of freezes required to achieve an acute PVI. For PVs that failed to achieve a complete CB occlusion, a segmental CB ablation strategy was considered as an alternative selection. If the cryoablation failed to isolate the PVs, then a touch-up ablation with radiofrequency energy was considered. CT images of PVs for each patient were analyzed by an experienced physician blinded to the ablation procedure outcome. Anatomic parameters for LA and PV included the following: (1) long and short axis length of PV ostia; (2) PV ostial area; (3) distance from PV ostium to first branch (D-PVB); (4) ovality index of the PV ostia (OVI, calculated using the formula: 2 × (long-axis diameter − short axis diameter)/(long-axis diameter + short axis diameter)15Knecht S Kühne M Altmann D Ammann P Schaer B Osswald S Sticherling C Anatomical predictors for acute and mid-term success of cryoballoon ablation of atrial fibrillation using the 28 mm balloon.J Cardiovasc Electrophysiol. 2013; 24: 132-138Crossref PubMed Scopus (67) Google Scholar,16Schmidt M Dorwarth U Straube F Daccarett M Rieber J Wankerl M Krieg J Leber AW Ebersberger U Huber A Rummeny E Hoffmann E Cryoballoon in AF ablation: impact of PV ovality on AF recurrence.Int J Cardiol. 2013; 167: 114-120Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar; (5) PV angle: PV angle measured in coronal and transverse planes (Figure 1). In addition to the previously mentioned anatomic characteristics, a quantitative analysis of catheter coaxiality on x-ray images was also performed which included the following parameters (Figure 1): (1) angle of steerable LS (angle LS); (2) angle between the LS and the long axis of CB (angle LS-CB); (3) angle between the long axis of CB and the long axis of PV main trunk (angle CB-PV); (4) angle between the PV main trunk and the branch selected for inner luminal catheter (angle PV); (5) branch selected for inner luminal catheter (main trunk; superior branch; medial branch; inferior branch). All patients received electrocardiogram monitoring after the procedure until discharge from the hospital and were followed up through visits at the cardiology outpatient department thereafter. Oral anticoagulation was prescribed for at least 3 months postprocedurally and according to the CHA2DS2-VASc score thereafter. Antiarrhythmic drugs were resumed or newly prescribed at the discretion of the physician. Clinic electrocardiograms and 24-hour Holter monitoring were performed 1, 3, 6, and 12 months after the procedure. Additional visits were conducted if patients were symptomatic. All antiarrhythmics were discontinued at the 3-month visit. Recurrent atrial arrhythmia was defined as an episode of sustained AF or atrial tachycardial of ≥30 seconds duration. We defined early and late recurrence as the recurrence of an atrial arrhythmia before and after 90 days from the index procedure, respectively. Results were expressed as mean ± SD. Statistical differences were evaluated by t test or analysis of variance test for normally distributed data or by Wilcoxon test for data following a skewed distribution. Categorical variables are expressed as absolute and relative frequencies and were compared using the chi-square test. A multivariate analysis was performed by logistic regression analysis (backward hierarchical elimination method) to identify the predicted value of the parameters (clinical characteristics, catheter coaxiality, and anatomic parameters) on the ablation results. The optimal cut-off point was chosen as the combination with the highest sensitivity and specificity using a receiver operating characteristic curve. A 95% confidence interval was presented with the area under the curve (AUC). All analysis was run on SPSS (Armonk, New York) and a p value <0.05 was considered statistically significant. The baseline characteristics of patients are listed in Table 1. The outcome of CB ablation for 686 PVs in 172 patients was retrospectively evaluated. Acute PV isolation was achieved by a single CB ablation application for 71.5% (123 of 172) left superior PV (LSPV), 73.8% (127 of 172) left inferior PV (LIPV), 91.3% (157 of 172) right superior PV (RSPV), and 70% (119 of 170) right inferior PV (RIPV), respectively. In total, 20.3% (35 of 172) LSPV, 12.8% (22 of 172) LIPV, 7.6% (13 of 172) RSPV, and 22.4% (38 of 170) RIPV was isolated by a second CB ablation application. A complete PV occlusion could not be achieved in 0.5% (1 of 172) LSPV, 2.3% (4 of 172) LIPV, 0.5% (1 of 172) RSPV, and 5.8% (10 of 170) RIPV, respectively. The rate of incomplete CB occlusion was significantly higher for inferior to superior PVs (p = 0.007). For these patients, a segmental CB ablation strategy was used and all these PVs but one (LSPV) were successfully isolated by CB ablation. The remaining one LSPV required a touch-up ablation. The mean NND significantly differed in the 4 PVs and the NND was smallest for RSPVs (p <0.001). The NT differed in 4 PVs. A lowest NT was observed in RSPVs (−51.2 ± 5.5°C) whereas a highest NT was observed in LIPVs (−41.2 ± 5.5°C) (p <0.001).Table 1Clinical characteristics of the study populationPatient (N=172)Male gender62.8%Age (years)60.9±10.2Height, cm167.3±8.3Body weight, kg70.9±11.9Body mass index, kg/m225.3±3.3Comorbidity Hypertension55.8%(96/172) Diabetes mellitus18.6%(32/172) Coronary artery disease5.8%(10/172)History of stroke3.5%(6/172)UCG LVEF(%)66.6±4.2 Left atrial diameter(mm)40.9±3.9 Open table in a new tab In total, 8.7% (15 of 172) of patients had early recurrence within 3 months postablation. The 12-month AF-free survival of antiarrhythmics was 82% (141 of 172), and 2.9% (5 of 172) of patients underwent a repeat ablation procedure. Procedure-related complications occurred in 4 patients, including cardiac tamponade requiring pericardiocentesis in 1 (caused by pacing electrode in right ventricular apex) and transient right phrenic nerve injury that remained on the next day of the procedure in 3 patients (2 during RSPV CB application and 1 during RIPV CB application). The catheter coaxiality with a successful CB application for each PV was quantitatively analyzed retrospectively. Angle LS, angle LS-CB, and angle CB-PV differed in 4 PVs which have been listed in Table 2. Angle LS was biggest for RSPV (140.7 ± 13.7°) and smallest for LIPV (93.6 ± 13.6°) when a successful CB application was performed (p <0.001). The angle LS-CB was smallest for RIPV (147.6 ± 18.2°) whereas the other 3 PVs showed a similar result (p <0.001). The angle CB-PV was smallest for RIPV (165.0 ± 18.7°) and biggest for RSPV (176.3 ± 6.4°) (p <0.001). There was no significant difference in angle PV in 4 PVs (p = 0.48).Table 2Parameters of catheter coaxiality for 4 PVsLSPVLIPVRSPVRIPVP valueAngle of steerable long sheath135.4±16.793.6±18.6140.7±13.7115.3±25.1<0.001Angle between the long sheath and the axis of cryoballoon165.4±27.6162.8±25.6163.6±15.9147.6±18.2<0.001Angle between the axis of cryoballoon and the axis of PV main trunk168.1±10.8172.4±9.3176.3±6.4165.0±18.7<0.001Angle between the PV main trunk and the branch selected for inner lumen catheter170.6±17.1172.3±12.9175.7±11.6177.6±85.60.48Branch selected for inner lumen catheter (proportion of inferior branch)8/172(4.7%)32/172(18.6%)3/172(1.7%)28/170(16.5%)<0.001LIPV = LEFT inferior pulmonary vein; LIPV = left inferior pulmonary vein; LSPV = left superior pulmonary vein; RIPV = right inferior pulmonary vein. Open table in a new tab LIPV = LEFT inferior pulmonary vein; LIPV = left inferior pulmonary vein; LSPV = left superior pulmonary vein; RIPV = right inferior pulmonary vein. The proportion of selection for inferior branch was higher in inferior PV compared with superior PV (SPV: 3.2% vs IPV: 17.5%, p <0.001). For PVs that failed in their first CB ablation attempt, an adjustment of catheter coaxiality by LS manipulation and different branch selection was considered. 51% (25 of 49) PVs were successfully isolated by simply adjustment of LS manipulation whereas 49% (24 of 49) PVs were finally isolated with a different branch selection for LSPV. The proportion of adjustment of LS manipulation and different branch selection was 52% of 48%, 50% of 50%, and 10.2% of 89.8% for LIPVs, RSPVs, and RIPVs, respectively. Two catheter manipulation strategies for RIPVs were utilized in this study (Figure 2). A complete CB occlusion could be achieved in 100 RIPVs with a conventional strategy (LS>90°). A total of 60 RIPVs achieved a complete CB occlusion with more aggression LS manipulation with an LS ≤90° ("7" shape or reverse-U shape of LS) was utilized in the 60 RIPVs to achieve a complete CB occlusion. The rest 10 RIPVs were finally isolated with a segmental ablation strategy. Compared with the conventional strategy (LS >90°), a more aggressive LS manipulation with an LS ≤90° could obtain better catheter coaxiality (Table 3).Table 3The influence of branch selection and long-sheath manipulation on catheter coaxiality for RIPVsRIPVBranch selectionSuperiorTrunk/MediumInferiorP valueN1311829PV Coronal angle(degree)97.7±12.489.3±14.884.3±14.50.045Long sheath manipulationAngle LS(≤90°)Angle LS(>90°)P valueN60100PV Coronal angle(degree)89.5±13.189.5±15.40.994Angle LS-CB161.1±11.4143.3±17.8<0.001Angle CB-PV171.7±11.6163.2±18.80.008Angle CB-PV = angle between the axis of cryoballoon and the axis of PV main trunk; Angle LS = angle of steerable long sheath; Angle LS-CB = angle between the long sheath and the axis of cryoballoon; PV = pulmonary vein. Open table in a new tab Angle CB-PV = angle between the axis of cryoballoon and the axis of PV main trunk; Angle LS = angle of steerable long sheath; Angle LS-CB = angle between the long sheath and the axis of cryoballoon; PV = pulmonary vein. The details of anatomic parameters of CT images are listed in Table 4. There was a significant difference in long-axis length, short axis length, PV ostia area, OVI, and PV angle in 4 PVs. The long-axis length was longest in RSPV (21.6 ± 3.6 mm) and shortest in LIPV (17.4 ± 2.6 mm) (p <0.001). The short axis length of LIPV (11.3 ± 2.7 mm) was shorter than those of the other 3 PVs (p <0.001). The PV ostia area was biggest in RSPV (294.8 ± 96.3 mm²) and smallest in LIPV (149.1 ± 45.3 mm²) (p <0.001). The OVI was biggest in LIPV (0.44 ± 0.24) (p <0.001). The PV angle in the coronal plane was largest in LSPV (127.2 ± 14.9°) and smallest in LIPV (81.2 ± 13.0°) (p <0.001). The PV angle in the transverse plane was largest in RSPV (111.5 ± 10.4°) and smallest in RIPV (67.9 ± 11.1°) (p <0.001). The proportion of D-FVB≤10 mm was much smaller in left PVs compared with that in right PVs (LSPV 0.6% [1 of 172]; LIPV 25.6% [44 of 172]; RSPV 46.5% [80 of 172]; RIPV 72.1 [124 of 172], p <0.001).Table 4Anatomical parameters of PVs in cardiac CT imagesLSPVLIPVRSPVRIPVP valueLong axis length(mm)20.0±4.517.4±2.621.6±3.619.2±3.0<0.001Short axis length(mm)16.7±12.811.3±2.717.6±3.316.3±8.3<0.001PV ostial area(mm2)243.9±76.6149.1±45.3294.8±96.3231.4±77.6<0.001Distance from PV ostium to first branch(proportion of D-PVB<10mm)1/17244/17280/172124/172<0.001Ovality index of the PV ostia0.29±0.220.44±0.240.21±0.130.20±0.15<0.001PV angle in coronal plane(degree)127.2±14.981.2±13.0119.8±8.988.9±15.0<0.001PV angle in transverse plane(degree)98.0±11.271.3±14.2111.5±10.467.9±11.1<0.001LIPV = LEFT inferior pulmonary vein; LIPV = left inferior pulmonary vein; LSPV = left superior pulmonary vein; RIPV = right inferior pulmonary vein. Open table in a new tab LIPV = LEFT inferior pulmonary vein; LIPV = left inferior pulmonary vein; LSPV = left superior pulmonary vein; RIPV = right inferior pulmonary vein. For the RIPVs, a multivariate analysis revealed that the value of D-PVB and long-axis length were the independent predictors for an NND ≥2 (Table 5). Anatomic characteristics for PVs that cannot achieve a complete occlusion and receive a segmental CB ablation strategy were also explored in this study. A binary logistic regression analysis was used for the multivariate analysis and the results for RIPVs are listed in Table 6. The multivariate analysis for RIPVs revealed that D-PVB and the angle of the first branch were independent predictors for an incomplete occlusion. The optimal cutoff of the D-PVB was 6.3 mm (AUC 0.929; sensitivity: 0.82; specificity: 0.9). The optimal cutoff of the angle of the first branch was 32.5° (AUC 0.775; sensitivity: 0.7; specificity: 0.7). A combination of these 2 factors could elevate the predictor value for an incomplete occlusion with an AUC of 0.96 (sensitivity: 0.8; specificity: 1.0) (Figure 3).Table 5Results of univariate and multivariate logistic regression analyses of the effect of the anatomical features of interest on a higher NND(>2 for IPV and >1 for LPV)Univariate analysis P valueMultivariate analysis P valueLSPVLIPVRSPVRIPVLSPVLIPVRSPVRIPVLong axis length(mm)0.1520.0280.2980.0330.2910.0510.5560.042Short axis length(mm)0.1810.4240.1640.221////PV ostial area(mm2)0.8940.2110.1670.121////Angle of first branch(degree)///0.566///0.487Ovality index of the PV ostia0.8560.7190.4190.4980.1960.9230.4850.904PV angle in coronal plane(degree)0.1780.7990.3690.1330.1840.6400.3140.794PV angle in transverse plane(degree)0.9030.4080.220.2950.4850.6530.2920.298D-PVB(mm)/0.8840.0880.05/0.9280.0680.026D-PVB = distance from PV ostium to first branch; PV = inferior pulmonary vein; LIPV = left inferior pulmonary vein; LIPV = LEFT inferior pulmonary vein; LSPV = left superior pulmonary vein; RIPV = right inferior pulmonary vein; SPV = superior pulmonary vein. Open table in a new tab Table 6Results of univariate and multivariate logistic regression analyses of the effect of the anatomical features of interest on incomplete CB occlusion in the RIPVsIncomplete occlusion(10)Complete occlusion(160)Univariate analysis P valueMultivariate analysisROC curve (For risk factor)P valueORAUCSensitivitySpecificityLong axis length(mm)20.0±2.419.1±3.10.3920.2211.3550.612//Short axis length(mm)15.6±2.615.7±3.00.937//0.515//PV ostial area(mm2)235±60.1231.1±78.80.878//0.533//Angle of first branch(degree)31.2±21.743.0±18.10.0080.0380.8780.7750.700.70Ovality index of the PV ostia0.25±0.160.20±0.150.3510.2920.0010.595//PV angle in coronal plane(degree)93.8±10.988.9±15.00.3680.2840.9380.608//PV angle in transverse plane(degree)67.2±19.867.9±10.20.8320.1520.9280.601//D-PVB(mm)4.5±1.69.4±3.8<0.0010.0270.0570.9290.820.9AUC = area under the curve; D-PVB = distance from PV ostium to first branch; PV = pulmonary vein; ROC = receiver operating characteristic. Open table in a new tab D-PVB = distance from PV ostium to first branch; PV = inferior pulmonary vein; LIPV = left inferior pulmonary vein; LIPV = LEFT inferior pulmonary vein; LSPV = left superior pulmonary vein; RIPV = right inferior pulmonary vein; SPV = superior pulmonary vein. AUC = area under the curve; D-PVB = distance from PV ostium to first branch; PV = pulmonary vein; ROC = receiver operating characteristic. There was no difference in parameters for PV anatomic features and catheter coaxiality between the recurrence group and sinus group. In this study, we evaluated the effect of PV anatomic characteristics and catheter coaxiality on acute and long-term procedure success of catheter ablation using the second-generation CB. The main findings of this study were as follows: (1) there were obvious differences in anatomic characteristics in 4 PVs; (2) a short D-PVB and a small angle of the first branch were independent predictors for incomplete balloon occlusion for RIPVs; (3) for PVs with perfect balloon occlusion, the best catheter coaxiality was observed in RSPV whereas the worst catheter coaxiality was observed in RIPV. A more aggressive catheter manipulation strategy with a "7" or "reverse-U" shape of LS was recommended to achieve complete balloon occlusion and better catheter coaxiality for RIPVs. The anatomic characteristics of 4 PVs were evaluated in this study. In addition to the PV angle, obvious differences in ostia shape, D-PVB, and OVI had also been observed in 4 PVs which was not reported in previous studies. Antonio had first reported a higher ratio between maximum and minimum diameters in left PVs, which could cause difficulty in PV isolation.17Sorgente A Chierchia GB de Asmundis C Sarkozy A Namdar M Capulzini L Yazaki Y Müller-Burri SA Bayrak F Brugada P Pulmonary vein ostium shape and orientation as possible predictors of occlusion in patients with drug-refractory paroxysmal atrial fibrillation undergoing cryoballoon ablation.Europace. 2011; 13: 205-212Crossref PubMed Scopus (72) Google Scholar Further studies have proved the influence of PV ostia shape on balloon occlusion with a modified ovality index.18Kajiyama T Miyazaki S Matsuda J Watanabe T Niida T Takagi T Nakamura H Taniguchi H Hachiya H Iesaka Y Anatomic Parameters Predicting Procedural Difficulty and Balloon temperature Predicting Successful Applications in Individual pulmonary veins during 28-mm Second-Generation Cryoballoon ablation.JACC Clin Electrophysiol. 2017; 3: 580-588Crossref PubMed Scopus (20) Google Scholar In our study, a higher OVI was mainly observed in LIPV but not in the other 3 PVs which was partially different from the previous result. Although a relatively high OVI was observed in the 3 LIPVs which failed to achieve a complete occlusion, the multivariate analysis did not show a predictive value of OVI for an incomplete occlusion in LIPVs. This negative result was supposed to be caused by a relatively small sample size of LIPVs with incomplete occlusion. Another factor that influenced the balloon occlusion was D-PVB.15Knecht S Kühne M Altmann D Ammann P Schaer B Osswald S Sticherling C Anatomical predictors for acute and mid-term success of cryoballoon ablation of atrial fibrillation using the 28 mm balloon.J Cardiovasc Electrophysiol. 2013; 24: 132-138Crossref PubMed Scopus (67) Google Scholar,18Kajiyama T Miyazaki S Matsuda J Watanabe T Niida T Takagi T Nakamura H Taniguchi H Hachiya H Iesaka Y Anatomic Parameters Predicting Procedural Difficulty and Balloon temperature Predicting Successful Applications in Individual pulmonary veins during 28-mm Second-Generation Cryoballoon ablation.JACC Clin Electrophysiol. 2017; 3: 580-588Crossref PubMed Scopus (20) Google Scholar In 4 PVs, RIPVs had the shortest D-PVB compared with the other 3 PVs. All the RIPVs that failed to achieve a complete balloon occlusion in this study had a short D-PVB. Because the length of the nose of the CB catheter was 11 mm, optimal alignment could not be obtained and the freezing surface was predisposed to floating from the PV ostia in cases with a short D-PVB.18Kajiyama T Miyazaki S Matsuda J Watanabe T Niida T Takagi T Nakamura H Taniguchi H Hachiya H Iesaka Y Anatomic Parameters Predicting Procedural Difficulty and Balloon temperature Predicting Successful Applications in Individual pulmonary veins during 28-mm Second-Generation Cryoballoon ablation.JACC Clin Electrophysiol. 2017; 3: 580-588Crossref PubMed Scopus (20) Google Scholar In contrast, a short D-PVB could lead to an irregular shape of pulmonary ostium. A fixed shape of the freezing surface of CB may not fit perfectly for these pulmonary ostiums. A further evaluation of the angle of the first branch was also performed as complete balloon occlusion could also be obtained in some cases with short D-PVB. It had first been proved in our study that the angle of the first branch was also an independent factor for an incomplete occlusion in RIPVs. A combination of D-PVB and the angle of the first branch could elevate the predictor value for an incomplete balloon occlusion with a sensitivity of 0.85 and specificity of 1.0. It was supposed that a relatively small angle of first branch would form a sharper ridge which would influence the CB occlusion. Pulsed-field ablation is a new ablation technique that became widely used in recent years in the world. It also required good contact of catheter with atrial tissue. However, the variety of catheter morphology (basket, circle, or flower shape) could facilitate the approach to reaching good contact with atrial tissue. In this study, 2 PV anatomic features bad been described which will influence the difficulty for CB occlusion. However, this result was mainly because of the special morphology of the balloon shape but not the manipulation approach. As the pulsed-field ablation catheter presented with a different morphology and ablation mechanism, whether PV anatomic features would influence its ablation efficacy is still controversial and requires further studies. Catheter coaxiality and the choice of the pulmonary branch for Achieve catheter were the main subjective factors that influenced the CB occlusion results. To decrease the influence of transseptal location on the catheter coaxial with PVs, a low and anterior transseptal location was considered for all patients in this study which could facilitate the approach to reach a good coaxial with PVs according to previous studies. For most LPVs, the operators could obtain a good catheter coaxiality with a selection of PV trunk or superior branch for Achieve catheter as most LPVs had an upward direction on the coronal plane. For some other LPVs with a horizontal or downward direction, a media or inferior branch could be a better choice for the Achieve catheter to achieve complete occlusion. In contrast, most IPVs had a downward direction on the coronal plane. Therefore, we need a more aggressive strategy for LS manipulation to form a smaller LS angle and select a PV trunk or inferior branch for the Achieve catheter. In this study, inferior PVs succeeding with a superior or media branch had a much larger angle on coronal plane compared with those succeeding with an inferior branch. According to our study, RIPVs had the poorest catheter coaxiality and the rate of incomplete CB occlusion was also highest for RIPVs. It is well known that the RIPV is the most challenging target PV in the 4 PVs. The ostia of the RIPV is located not only close, but also posterior to the interatrial septum, and the inserted catheter is easily bent too sharp and impairs the pushability. In recent years, a "7-shape" curve or "reverse-U" technique of LS manipulation is more and more frequently used in the CB occlusion of RIPVs and could achieve complete occlusion in most RIPVs with a downward direction. It had also been proved in our study that although a complete CB occlusion could be achieved in more than 50% of RIPVs with a conventional catheter manipulation (LS >90°), a certain part of RIPVs still need a more aggressive manipulation (LS ≤90°) with a "7" or "reverse-U" shape of LS to obtain a complete CB occlusion. In contrast, a more aggressive manipulation of LS could obtain better catheter coaxiality and better contact in the bottom part of RIPV compared with conventional strategy (Figure 3). For other PVs, when we failed in the first attempt of CB occlusion, a slight adjustment of LS (rotation of LS or adjustment of LS angle) or an alteration of branch selection could help to achieve perfect occlusion in the following CB attempts. However, there seems no difference in catheter coaxiality between failed attempts and successful attempts. It was supposed that: (1) only coaxiality in a certain plane was evaluated in this study. The coaxiality on other different axis were not reflected in this study; (2) rotation of LS for adjustment of contact with different PVs' segmental could not be illustrated in a single coronal plane. For most EP centers, both RFCA and CB ablation could be considered for AF ablation. It has also been proved that the efficacy and safety of paroxysmal AF were similar between these 2 ablation methods. However, for some patients with special PV anatomic features, operators need more time to reach complete PV occlusion and isolation. It may lead to longer procedure time and increased radiation exposure. Therefore, a CT scan for PVs before the ablation procedure could help us to distinguish the patients who might be more difficult for a CB ablation strategy. An RFCA strategy instead of a CB ablation strategy might be considered for PVs with specific anatomic features which had been proved in this study and other previous studies. This study has some limitations. First, this study was a single-center and retrospective analysis study. A prospective and randomized study was needed to verify the predictive value of a short D-PVB and the angle of the first branch for an incomplete CB occlusion. Second, the catheter coaxiality was evaluated only from a certain plane in this study. A more detailed analysis of catheter coaxiality from a different axis is lacking in this study. Third, 3-dimensional mapping and intracardiac echo were not used in this study. Therefore, the real location of transseptal and its relation to RIPV could not be shown precisely. The voltage mapping results were also not illustrated before and after ablation in this study. The authors have no competing interests to declare. The data are available from the corresponding author on reasonable request.