Color Atlas and Synopsis of Electrophysiology, 1st Ed.


Justin Ng, MBBS, Chirag Barbhaiya, MD, Gregory Michaud, MD


The patient is a 58-year-old man with a long-standing history of paroxysmal atrial fibrillation and flutter. On sotalol he developed atrial flutter and underwent a right-sided cavotricuspid isthmus flutter ablation. He was switched to dofetilide, but continued to have breakthrough episodes of symptomatic atrial fibrillation (AF). A decision was made to proceed with pulmonary vein isolation.

A preprocedural MRI was performed confirming suitable anatomy for pulmonary vein isolation with cryoballoon ablation. Isolation of the left pulmonary veins resulted in termination of AF. Pacing of the phrenic nerve was performed from the SVC during ablation of the right-sided veins. Two minutes into the first cryoapplication to the right superior pulmonary vein (RSPV), phrenic nerve capture diminished, indicating injury to the phrenic nerve. Despite immediate termination of the freeze, phrenic nerve capture was lost completely, and by case end the phrenic nerve had not recovered.

The patient continued to have persistent elevation of the right hemidiaphragm until about 1 year postablation (Figure 37-1), after which he became asymptomatic.


FIGURE 37-1A AND 37-1B PA (A) and lateral (B) chest radiograph demonstrating elevated right hemidiaphragm due to phrenic nerve injury following cryoablation.


This case highlights the risk of phrenic nerve palsy associated with cryoballoon ablation and the importance of early recognition of injury to the phrenic nerve. The course of the phrenic nerve typically traverses anterior to the right-sided pulmonary veins and may be injured during cryoapplication, particularly in the RSPV. A pacing catheter is usually inserted in a superior part of the superior vena cava to pace the phrenic nerve continuously during ablation. The simplest method of determining phrenic nerve capture is direct palpation of the abdomen to confirm contraction of the right hemidiaphragm. Phrenic injury during cryoapplication is often first recognized by reduced strength of diaphragmatic capture. Many other methods to determine phrenic capture have been developed, including direct measurement of diaphragmatic potentials via surface electrodes, and other means to detect the contraction, such as visualization with intracardiac ultrasound, auditory surveillance with Doppler ultrasound, and others. The earlier phrenic nerve injury is detected, the faster the recovery of diaphragmatic function, which often occurs by the end of the procedure.

Despite taking all these precautions, phrenic nerve paralysis will still occur, and often the patient is very symptomatic, with a recovery period of up to a year or more.


The mainstay of an ablative approach to paroxysmal AF is pulmonary vein isolation using a single-tip radiofrequency catheter. In an attempt to eliminate the need for point-by-point ablation, balloon-based ablation systems have been developed to produce circumferential lesions.

The most commonly used system is the Medtronic Arctic Front over-the-wire cryoballoon catheter. The catheter is introduced into the left atrium through a 12-Fr steerable sheath. The shaft of the cryoballoon catheter has a central lumen that can accommodate a wire or allow the passage of a spiral catheter for real time mapping and is used for injection of saline or contrast (Figure 37-2).


FIGURE 37-2 Illustration of the Medtronic Arctic Front cryoballoon catheter within a steerable sheath, with the Achieve spiral mapping catheter within the central lumen of the catheter. (Reproduced with permission of Medtronic, Inc.)

The inner balloon of the cryoballoon catheter is cooled to a temperature of −112°F (−80°C) with nitrous oxide.1 The cold outer skin of the balloon adheres to the underlying tissue (much like a tongue on a frozen metal pole), and a large thermal gradient removes heat causing irreversible cellular injury below 23°F (0°C). Cryothermal energy produces progressive necrosis but does not result in significant alteration of tissue structure at thaw.2 The cryothermal lesion formation can be divided in three sequential stages: the freeze/thaw phase, the hemorrhagic inflammatory phase, and the replacement fibrosis phase stage.2 Theoretically, the absence of endothelial disruption with cryoablation is thought to result in less thrombogenicity.2


• Cryoablation is reserved for patients with drug-refractory symptomatic paroxysmal AF for which pulmonary vein isolation is the mainstay of therapy. It is not ideal for the patient with persistent or chronic AF where additional lesion sets are generally required, since additional ablation catheters are often necessary.

• We strongly recommend the use of imaging prior to the procedure with either a CT pulmonary venogram or an MRI to assess the suitability of the pulmonary venous anatomy for the balloon and to assist with sizing of the cryoballoon.


• Shorter time to proficiency than point-by-point radiofrequency catheter ablation.

• Less dependent on operator dexterity.

• Potentially shorter procedural and fluoroscopy times in nonrandomized trials.3


• Not cost-effective if additional ablation is required to treat non-PV sources of arrhythmia, as is commonly encountered in patients with persistent AF, or if PV isolation cannot be achieved a high percentage of the time with cryoablation.

• Certain venous anatomy less compatible with cryoballoon ablation such as a large common left pulmonary vein trunk (Figure 37-3).


FIGURE 37-3 CT venogram of the left atrium showing a large common left pulmonary vein trunk, which is usually not suitable for cryoablation.

• Higher incidence of phrenic nerve paralysis.4


• Access: Given that most patients do not interrupt anticoagulation for the PVI procedure, safe vascular access is essential. We recommend micropuncture kits (21 gauge needle and 4 French dilator) for initial venous access prior to exchanging for larger sheaths. A minimum of two venous sheaths are required; one is exchanged for the steerable 12 Fr sheath after transseptal puncture and another as a conduit for a catheter to pace the phrenic nerve, which can be as small as 4 Fr. In our lab, we typically place a third venous sheath for the placement of a coronary sinus catheter and a fourth for placement of an intracardiac echocardiogram (ICE) probe (Figures 37-4 and 37-5).


FIGURE 37-4 LAO radiograph of standard set up: coronary sinus catheter, ablation catheter in SVC for phrenic nerve pacing, cryoballoon at antrum of left upper pulmonary vein, ICE catheter imaging from the right atrium at the level of the fossa.


FIGURE 37-5 RAO view of the set-up in Figure 37-4.

• Transeptal puncture: At our institution, the transeptal puncture is initially performed with a fixed curve sheath, such as the 8.5-Fr SL-1, with the 12-Fr steerable cryoballoon sheath exchanged over an 0.035” relatively stiff J-tip guide wire.

• Anticoagulation: Prior to transeptal access, a bolus of 80 to 120 units/kg of unfractionated heparin is administered, depending on the patient’s INR, followed by boluses every 20 to 30 minutes to maintain the ACT >350s.

• The only commercially available cryoballoon in the United States is the Medtronic Arctic Front CryoAblation Catheter. It comes in 23 mm and 28 mm balloon sizes. We rarely choose a 23-mm balloon, unless the largest PV size is 15 mm or less. The central lumen accommodates a spiral catheter (Achieve) for mapping and confirming isolation, which we use in place of a guide wire.

• Documentation of pulmonary vein electrical activity is performed with the mapping catheter prior to any ablation.

• Positioning the cryoballoon:

 1. The guidewire or mapping catheter is advanced into the target vein, which we visualize using ICE (Figure 37-6A).

 2. The cryoballoon is inflated in the body of the atrium as visualized on ICE or fluoroscopy (Figure 37-6B).

 3. The inflated cryoballoon is advanced into the antrum of the vein using ICE and fluoroscopy (Figure 37-6C).

 4. Cryoapplication begins only after occlusion of the vein is confirmed.

 5. Firm pressure should be applied during the first 60 to 90 seconds until freezing occurs and the balloon adheres.

 6. Two to three applications of 4 minutes duration is recommended, although shorter periods are being investigated using the newest generation of the cryoballoon, the Arctic Front Advance, which has more uniform cooling patterns on the outer surface and may require less application time and perhaps fewer applications.



FIGURE 37-6 Steps in positioning the cryoballoon: (A) mapping catheter advanced into the target vein; (B) cryoballoon is inflated in the body of the atrium; (C) inflated cryoballoon is advanced into the antrum of the target vein. (Reproduced with permission of Medtronic, Inc.)

• Assessing adequacy of venous occlusion: Complete occlusion of the pulmonary vein is necessary for successful isolation. Any leakage of blood around the balloon will limit the fall in temperature required for effective ablation.

 1. The traditional method for confirming total occlusion of the vein is the injection of contrast though the balloon’s tip lumen under fluoroscopy, while observing accumulation of contrast in the PV without flow back the left atrium.

 2. At our institution, ICE with color flow Doppler is used as an alternative to assess for leaks (Figures 37-7 and 37-8).


FIGURE 37-7 ICE catheter image of the cryoballoon in the left inferior pulmonary vein with a large leak demonstrated by color flow Doppler.


FIGURE 37-8 Adjustment of the cryoballoon in the left inferior pulmonary vein results in occlusion of the vein and closure of the leak.

• A surrogate for PV occlusion is the rate of drop in temperature measured in the balloon and the ultimate temperature achieved. Studies have shown that cryoballoon temperature achieved predicts acute pulmonary vein isolation; however, no cutoff value is practical because of the wide spread in temperatures associated with occlusion5 (Figure 37-9).


FIGURE 37-9 The Medtronic Cryoconsole Interface demonstrating an appropriate fall in balloon temperature with appropriate venous occlusion. (Reproduced with permission of Medtronic, Inc.)

• Another surrogate is the time it takes to achieve PV isolation as observed on the circular mapping catheter. Most occluded PVs will be electrically isolated by 30 to 60 seconds after the application has begun (Figure 37-10).


FIGURE 37-10 Isolation of pulmonary vein during cryoapplication. (Reproduced with permission of Medtronic, Inc.)

• Confirming isolation: The circular mapping catheter is used to confirm pulmonary vein isolation. Typically, the inferior surface of the right inferior vein is difficult to isolate and may require reangulation of the balloon, rewiring other branches of the same PV to provide a different angle of approach and other techniques.


• Techniques to achieve venous occlusion:

 1. Positioning the guidewire in different venous branches may aid in changing the balloon orientation in the antrum to achieve venous occlusion.

 2. The “pull down” technique can be useful when a gap is present in the inferior border of the vein. Freezing is commenced despite the presence of the gap. At 60 to 90 seconds into the freeze, the balloon and the sheath are both gently pulled down in order to close the gap in the inferior portion of the vein. With the new generation cryoballoon, this technique is rarely necessary, since small gaps will often seal during the cryoapplication.


• Avoiding phrenic nerve paralysis: During freezing of the right pulmonary veins, the phrenic nerve may be damaged, especially when ablating the right superior PV. A number of techniques can be used to minimize the risk of this complication.

 1. Pacing the phrenic nerve during ablation on the right: A catheter is placed in the SVC in a position to capture the phrenic nerve and freezing is performed during pacing of the right phrenic nerve. Loss of capture should prompt immediate termination of the freeze. It is important to capture the phrenic nerve proximal to where the potential injury will occur, and in the case of general anesthesia, also to remind the anesthetist to avoid paralytic agents.

 2. Use of the larger 28 mm balloon: Use of the larger 28 mm balloon results in a more antral lesion, which theoretically will reduce the risk of phrenic nerve palsy (PNP).1


• In the largest prospective study, 346 patients in 3 centers with drug refractory paroxysmal AF (n = 293) or persistent AF (n = 53) underwent cryoablation. At 12 months follow-up, 74% of the PAF group and 42% of the persistent group remained in sinus rhythm.6

• In a recent meta-analysis of cryoballoon ablation studies reporting a 3-month blanking period (time frame during which transient arrhythmias were not considered recurrences), at 1-year follow-up, 72.8% were free from recurrent AF.4

• The STOP-AF trial, randomized patients with PAF in a 2:1 fashion to either PV isolation with cryoballoon or antiarrhythmic drug (AAD). Balloon-only isolation of PVs was achieved in 90.8%. The success rate at 12-month follow-up was 69.9%, that is, patients free of symptomatic AF off AAD (60.1% with a single procedure).7

• Nonrandomized controlled trials have showed similar short-term efficacy compared with RF ablation along with slightly shorter procedural and fluoroscopic times.3 The Freeze AF trial is a randomized controlled trial currently underway to compare cryoballoon catheter ablation with open-irrigated RF ablation.

• Procedural times: In the STOP AF trial the mean procedural duration was 371 minutes (range 200-650) with 62.8 (8-229) minutes fluoroscopy time.7 In the subanalysis of operator experience presented at the 2011 Boston AF symposium, experience with the cryoballoon reduced procedure time by 15% and fluoroscopy time by 24% compared to first-time users.8


• Phrenic nerve palsy (PNP): The most common complication of cryoballoon ablation is PNP with an incidence of 6.38% in a recent meta-analysis. In the STOP AF study, PNP was reported in 29 out of 259 procedures (11.2%). Of these, only 4 patients (13.8%) had persistent PNP at 12 months and 1 had symptoms.7

• Pulmonary vein stenosis: STOP AF demonstrated 3.1% risk of PV stenosis in its study population defined as a >75% narrowing.7

• Atrial-esophageal fistula: There have been case reports of this catastrophic complication, but a true incidence is unknown. The incidence of Atrial-esophageal fistula using cryoablation appears less commonly then with RF ablation.

• Comparable with RF ablation, the incidence of thromboembolic complications including periprocedural stroke, TIA, or MI was 0.57%, and pericardial effusion or tamponade occurred in 1.46% of cases.4

• The incidence of secondary left atrial tachycardia following cryoablation is low.


The cryoballoon provides a comparable alternative to point-by-point RF ablation in patients with drug refractory paroxysmal atrial fibrillation where complete isolation of the pulmonary veins is the mainstay of therapy. Imaging is useful to select the appropriate patient for this therapy, and knowledge of the potential complications and the techniques used to minimize these are essential for a safe and successful procedure.


1. Kühne M, Sticherling C. Cryoballoon ablation for pulmonary vein isolation of atrial fibrillation: a better way to complete the circle? Innovations (Phila). 2011;2:264-270.

2. Lustgarten DL, Keane D, Ruskin J. Cryothermal ablation: mechanism of tissue injury and current experience in the treatment of tacharrhythmias. Prog Cardiovasc Dis. 1999;41(6):481-498.

3. Kojodjojo P, O’Neill MD, Lim PB, et al. Pulmonary venous isolation by antral ablation with a large cryoballoon for treatment of paroxysmal and persistent atrial fibrillation: medium-term outcomes and non-randomised comparison with pulmonary venous isolation by radiofrequency ablation. Heart. 2010:96,(17):1379-1384.

4. Andrade JG, Khairy P, Guerra PG, et al. Efficacy and safety of cryoballoon ablation for atrial fibrillation—a systematic review of published studies. Heart Rhythm. 2011;8(9):1828.

5. Fürnkranz A, Koster I, Chun KR, et al. Cryoballoon temperature predicts acute pulmonary vein isolation. Heart Rhythm. 2011;8(6):821-9.

6. Neumann T, Vogt J, Schumacher B, et al. Circumferential pulmonary vein isolation with the cryoballoon technique results from a prospective 3-center study. J Am Coll Cardiol. 2008;52(4): 273-278.

7. Packer D, Irwin JM, Champagne J, et al. Cryoballoon ablation of pulmonary veins for paroxysmal atrial fibrillation: first results of the North American Arctic Front STOP- AF pivotal trial. J Am Coll Cardiol. 2010;55:E3015-3016.

8. T Bunch. Cryoballoon ablation for atrial fibrillation. Is it the right choice for my practice? Innovations (Phila). 2011;2:272-273.

9. Van Belle Y, Janse P, Theuns D, Szili-Torok T, Jordaens L. One year follow-up after cryoballoon isolation of the pulmonary veins in patients with paroxysmal atrial fibrillation. Europace. 2008;10(11):1271-1276.