This study elucidated several key anatomical features of PVs that might affect acute success, AF recurrence and complications in the treatment of patients with AF using cryoballoon ablation. CT analysis was helpful to identify benefits and limitations of cryoballoon ablation in terms of anatomy.
Anatomical factors of acute success and AF recurrence
Left superior pulmonary vein
Several articles reported the incidences of reconduction of PV isolation using cryoballoon for LSPV because the superior part of the LSPV specifically tended to reconnect.23 24 24 25 The LSPV generally exhibited an upright takeoff and a large trunk. However, catheter pushability might be impaired because of the longer distance from the interatrial septum. It is difficult to obtain sufficient pushability for oval and sharp ridges, which might be associated with the difficulty in PV isolation using the cryoballoon. In particular, the roof of the LSPV might be hard to cover with the balloon hemisphere even if the balloon and sheath have the correct force and direction.
Left inferior pulmonary vein
Regarding the incidence of reconduction of PV isolation after cryoballoon ablation for LIPV, the inferior part of the LIPV tended to reconnect.23–25 In addition to the LSPV, the distance from the septal is a problem. The inferior LIPV is a difficult target for achieving complete isolation with current cryoballoon technology because a bending sheath is necessary to hold the coaxial method.
Right superior pulmonary vein
Similar to LSPV, the superior part of RSPV tended to reconnect.23–25 This study showed that a shallower RSPV angle against the atrial septum was a predictor of acute success, and a larger RSPV was a predictor of AF recurrence. It may be difficult for the balloon hemisphere to touch the upper part of the RSPV in patients with a shallower RSPV angle.
Right inferior pulmonary vein
The bottom of the RIPV is the most difficult part to isolate, which is influenced by the distance between the atrial septum and RIPV.23–25 This study showed that a shorter PV distance is associated with lower acute success. In addition to LIPV, the inferior part of the RIPV tended to reconnect.23–25
In this study, a lower RIPV position from the non-coronary cusp and RIPV, which led to a sharp angle from the atrial septum, was associated with lower acute success. Lower RIPV and shorter distance of bifurcation were predictors of AF recurrence.
Advancing the cryoballoon catheter towards the ostium of the RIPV in anatomies with a lower RIPV position from the non-coronary cusp and RIPV, which has a sharp angle from the atrial septum, was regarded as difficult because physicians must create acute angulation with the stiff catheter. Furthermore, in cases with a shorter distance from the RIPV ostium to the RIPV first bifurcations, physicians may encounter difficulties in the stability and pushability of cryoballoon.
Complications related to cryoballoon ablation
Phrenic nerve injury
The prevalence of right phrenic nerve injury has been reported to be 11.2% due to various factors during cryoballoon ablation.3 The definition of phrenic nerve injury varies according to each paper. One definition of phrenic nerve injury is any perceived reduction in the strength of the diaphragmatic contractions or a significant reduction (>30%) in the maximal diaphragmatic amplitude of compound motor action potential from baseline.15 The most common definition is that paralysis of the hemidiaphragm noted by both manual palpation and fluoroscopy during intraprocedural high-output pacing. The definition of transient phrenic nerve injury or persistent phrenic nerve injury is also variable. Another definition is that transient phrenic nerve injury completely resolved before the end of the procedure, while persistent phrenic nerve injury remained after the procedure.16 Matsumoto et al initially demonstrated the feasibility of using 64-slice multidetector CT for the detection and anatomic outline of the phrenic nerves and their relation to the cardiac anatomic structures.26 They showed that the distance from the RSPV to the phrenic nerve or area of the RSPV and the RSPV angle can be a predictor of phrenic nerve injury. Gentle sealing of the RSPV is technically important to prevent such complications during the procedure, and preprocedural risk stratification seems to help further reduce this complication.
Oesophageal damage
Oesophageal thermal lesions tend to be associated with a shorter distance from the oesophagus to the posterior left atrium.27 Oesophageal thermal lesions were defined as erythema, erosions (partial loss of the epithelial or mucosal surface) or ulcerations (full-thickness loss of the epithelial or mucosal surface) based on their macroscopic appearance.28 Usually, the damage can be limited to oesophageal lesions, which frequently heal within a few weeks. The rate of atrial oesophageal fistula with first-generation cryoballoon and second-generation cryoballoon is reported to be approximately 0.01% (1:10 000), whereas the incidence of atrial oesophageal fistula with radiofrequency ablation varies between 0.1% (1:1000) and 0.25% (1:400).29
The distances from the oesophagus to the left atrium and from the left atrium to the descending aorta were predictors of oesophageal damage. Preprocedural examination of the distance from the oesophagus to the left atrium or the left atrium to the descending aorta is important.
PV stenosis
PV stenosis was classified into three groups according to the PV dimension reduction rate: mild stenosis (25%–50%), moderate stenosis (50%–75%) and severe stenosis (>75%).30 A previous study reported a 1.1%–3.1% incidence of severe PV stenosis (>75%).3 21 The mechanism of cellular damage due to freezing by cryoenergy has been shown to be a complex process with three primary factors: direct cellular damage, vascular failure and immunological effects.31 In this study, the size of the PV was found to be a predictor of PV stenosis. For larger PVs, radiofrequency ablation should be chosen to avoid PV stenosis.
Bronchial damage
There have been multiple reports of haemoptysis following cryoballoon ablation.32–34 Haemoptysis is considered a non-negligible complication. The mechanism of haemoptysis is considered to involve bronchi injury or PV stenosis. Clinically important haemoptysis was observed in 1.7%–5.6% of cases after cryoballoon ablation.22 34 35 A clinical study of the the Sustained Treatment of Paroxysmal Fibrillation (STOP-AF) trial which is a randomised study comparing cryoballoon ablation and drug therapy found an incidence of persistent cough to be as high as 17% following ablation using the first-generation cryoballoon.3 Verma et al reported that real-time bronchoscopy was performed during cryoballoon ablation. They described that ice formation was visualised in the left main bronchus during cryoballoon ablation of the LSPV in 70% (7/10) of patients.32 From this systematic analysis, the left main bronchus-LSPV distance was a predictor of bronchial damage. A shorter distance from the left main bronchus-LSPV might increase the risk of bronchial damage.
Challenges to overcome anatomical difficulty
In figure 7, we summarised ideas and techniques for overcoming anatomical difficulties in relation to cryoballoon. There are three aspects of difficulties: PV length, PV angle and PV ostium area. We need to solve these problems using procedure-related technique or improvement of device itself. To cope with the problem of PV angle especially RIPV, the anterior side puncture may be better for the access to RIPV (figure 7A–D).29 With a puncture at anterior side of atrial septum, we may be able to have enough distance to bend the sheath and cryoballoon from atrial septum to RIPV. However, when we do a septal puncture at anterior side, LSPV may be hard to be isolated. For patients with large inferior PV, ‘pull-down’ technique is useful (figure 7E,F).29 36 With the cryoballoon in contact with the superior circumference of the target PV angiographically, freezing of the cryoballoon by N2O flow is started. Next, the sheath and frozen cryoballoon in contact with the superior PV circumference are pulled down to close the gap of inferior PV circumference. Thus, full ablation of the target PV circumference can be achieved.37 ‘Hockey stick’ technique is useful for achieving contact of cryoballoon at the inferior PV circumference in patients with an early branching inferior PV. The Achieve catheter (Medtronic) is placed in an early branching inferior PV. The sheath is advanced over the catheter. Passing through the sheath bended, the cryoballoon can achieve contact with the ostium of inferior PV circumference (figure 7G).37 For patients with no early branch of LSPV, proximal sealing technique is useful (figure 7H,I). First, instead of initiating ablation after initial venogram, the cryoballoon is gently pulled back to reveal the PV ostium by noting contrast leak. Then, the cryoballoon is reapplied to the PV ostium with the minimal amount of pressure to achieve occlusion before ablation.29 This technique can lead to misinterpretation of the PV ostium. Care should be taken to not miss the slight contrast leak to avoid freezing of PV circumference at a relative inside. In case of tiny PV or as a bailout strategy in case of difficult anatomies, the smaller 23 mm cryoballoon in diameter is reported to be useful to achieve PV isolation.38
Technical challenges for patients with difficult anatomies. (A) The three-dimensional (3D) image of transseptal puncture at posterior side. (B) The horizontal image of transseptal puncture at posterior side. (C) The 3D image of transseptal puncture at anterior side. (D) The horizontal image of transseptal puncture at anterior side. (E) (F) ‘Pullback’ technique: cryoballoon is attached to superior part of pulmonary vein (PV) and started to freeze. Then an operator pulls back cryoballoon to inferior part of PV. (G) ‘Hockey stick’ technique: sheath is advanced with maximal bend, allowing the balloon to be pushed into the PV ostium. (H) (I) Proximal seal technique: first, instead of initiating ablation after initial venogram, the cryoballoon is gently pulled back to reveal the real PV ostium by noting contrast leak. Then, the cryoballoon is reapplied to the PV ostium with the minimal amount of pressure to achieve occlusion before ablation.
Safety measures should be considered to avoid complications shown in table 4. To prevent phrenic nerve palsy during ablation, monitoring diaphragmatic compound motor action potentials (CMAP) is helpful. There are several methods for phrenic nerve monitoring strategies such as fluoroscopy, palpation, electromyography, auditory cardiotocography and intracardiac echocardiography (ICE).39 Fluoroscopy and ICE are useful to directly see diaphragmatic motion. Using electromyography, operators can detect reduction of the amplitude of CMAP during procedure. In previous study, 30% reduction in the amplitude of CMAP was reported as the most predictive cut-off value for hemidiaphragmatic paralysis.40 As for oesophageal injury, monitoring oesophageal temperature may be helpful. Cryoballoon nadir ablation temperate above –55°C is appropriate.29 Based on the comparison between the lowest oesophageal temperature and the endoscopic finding, Metzner et al recommend that a cut-off value of oesophageal temperature is 10℃ (sensitivity 100%, specificity 93%), and Fürnkranz et al suggest that a cut-off value is 12℃ (sensitivity 100%, specificity 92%) to induce oesophageal injury.28 41 Monitoring oesophageal temperature using a probe may be helpful to avoid oesophageal injury during cryoballoon ablation. As to PV stenosis, ablation of PV circumference at a relative inside might be a predictor.42 Careful examination of the venogram should be done to not miss the slight contrast leak. For patients requiring reduction of fluoroscopy time or contrast, ICE and trans-oesophageal echocardiography are reported to be useful to check leak of blood or saline from PV to atrium.43 44 There is a report that transcatheter pressure inside PV can be monitored during balloon advancement. Verification of PV occlusive pressure during cryoballoon ablation is one of the indicators to confirm proper PV occlusion.45 We summarised procedural techniques and safety measures which should be considered when physicians encounter difficult anatomies of PV-LA (figure 8).
A flow chart for treating patients with AF using cryoballoon. How to cope with anatomical challenges while ensuring safety. ICE, intracardiac echocardiography; LSPV, left superior pulmonary vein; PV, pulmonary vein; TEE, trans-oesophageal echocardiography.
Other modalities
CT is a powerful tool to identify PV anatomy, location of phrenic nerve and oesophagus. However, radiation exposure could be a concern. There was a case report of fluoroscopy-free cryoablation with trans-oesophageal echocardiography.44 Three-dimensional mapping system, ICE and trans-oesophageal echocardiography may assist reducing fluoroscopic time.
Limitations
First, all studies were single-centre studies, and most of the predictors discussed in each study varied. Multicentre studies should be conducted to further quantify the thresholds of each predictor. An investigation using a unified and easier measurement definition should be used to further investigate the proper treatment of patients with AF using cryoballoon. Second, all the studies were observational with retrospective analysis of the CT anatomy. Third, it was not clear if the CT was available/integrated into the X-ray system as a full three-dimensional reconstruction in each study. Forth, it was not clear if patients were selected for cryoballoon ablation with/without CT examination before. Fifth, there is a major risk for operators’ or institutional bias. We could not identify from the articles if published data showed their initial experience with cryoballoon ablation and might include physician’s learning curves.