Phrenic nerve injury is a well-established complication of all types of atrial fibrillation (AF) ablation and is most common with balloon-based approaches, writes Hugh Calkins (Baltimore, USA) for Cardiac Rhythm News. However, he notes, “with careful monitoring for phrenic nerve injury during ablation the incidence of this complication has decreased dramatically to 0.3% or less.” In this commentary, Calkins details the strategies developed over the last years to prevent this complication.
Over the past two decades catheter ablation of atrial fibrillation (AF) has emerged as a commonly performed, effective, and generally safe treatment option for patients with AF. Despite the considerable progress that has been made, it is important to recognise that AF catheter ablation remains an imperfect procedure. Unlike catheter ablation of Wolff Parkinson White syndrome, which is associated with a >97% rate of cure and a negligible risk of complications, the efficacy of AF catheter ablation in optimal candidates lies somewhere in the 60% to 80% range with a 1% to 3% incidence of major complications.
The recently published multicentre Fire and Ice trial provides up to date information concerning the outcomes of AF ablation.1 This study randomised over 700 patients to AF ablation using either radiofrequency energy or the cryoballoon. The study revealed that the cryoballoon is non-inferior to radiofrequency energy with respect to efficacy and overall safety. More specifically, the primary efficacy endpoint (any atrial arrhythmias recurrence, use of antiarrhythmic drugs, or repeat ablation at one year) was not different between the cryoballoon and radiofrequency energy groups; neither was the primary safety endpoint. Based on the results of this and other studies, the cryoballoon has become a common alternative to radiofrequency energy for AF ablation. Fire and Ice also showed that phrenic nerve injury was the most frequent adverse event reported in the cryoballoon group (2.7%). Permanent phrenic nerve injury, lasting 12 months or longer, occurred in 0.3% of patients.
Phrenic nerve injury is an important complication of all types of AF ablation procedures and results from direct thermal injury. The right phrenic nerve is most commonly affected as it descends in close proximity to sites of ablation in the superior vena cava and both right superior and inferior pulmonary veins. Phrenic nerve injury is observed with all technologies for AF ablation including radiofrequency, cryoablation, ultrasound, and laser ablation. Phrenic nerve paralysis can be asymptomatic or can cause dyspnoea, tachypnoea, cough, hiccups, and thoracic pain. The diagnosis is suggested when newly elevated hemi-diaphragm with atelectasis of the ipsilateral lung base is observed on post-procedure chest radiograph. When suspected, diaphragm excursion should be evaluated using fluoroscopy to confirm the diagnosis.
The most common scenario in which phrenic nerve injury occurs is with cryoballoon ablation and the incidence of transient phrenic nerve injury is 3.5–11.2%.1–5 There are various stages of phrenic nerve injury ranging from detectable decrease in compound motor action potential (CMAP) before a reduction in diaphragmatic excursion is perceived to persistent paralysis. With cryoballoon ablation, most phrenic nerve injuries are transient and resolve within minutes. In patients with persistent nerve injury, most recover nerve function within weeks and almost all by 12 months. In a large meta-analysis of 22 studies enrolling 1,308 patients undergoing cryoballoon ablation, 4.7% had persistent phrenic nerve paralysis after the ablation procedure but only 0.37% had paralysis lasting longer than one year.6 As noted above, permanent phrenic nerve injury resulting from cryoballoon ablation had an incidence of 0.3% in the recently completed Fire and Ice trial. Studies have shown a higher risk of phrenic nerve injury associated with the smaller 23mm balloon as compared with the larger 28mm balloon with more proximal energy application. There is no active treatment known to facilitate phrenic nerve healing but in symptomatic patients with permanent nerve injury diaphragmatic plication may improve dyspnoea and functional status.
The second most common scenario of phrenic nerve injury is during electrical isolation of the superior vena cava using point-by-point radiofrequency ablation. Very rarely, ablation at the roof of the left atrial appendage can result in left phrenic nerve damage.
A number of strategies have been employed to prevent phrenic nerve injury. These include ensuring antral pulmonary vein ablation, high-output pacing to establish whether the phrenic nerve can be captured from the proposed ablation site before ablation, phrenic nerve mapping with anatomic tagging of its course using electroanatomic mapping system, and monitoring of diaphragmatic excursion with abdominal palpation, fluoroscopy or intracardiac ultrasound while pacing the phrenic nerve from the superior vena cava or subclavian vein during ablation.7 It is now standard practice to pace the phrenic nerve from the superior vena cava or subclavian vein during cryoballoon or laser balloon ablation—while palpating the abdomen and/or fluoroscopic imaging to be sure that diaphragmatic capture is present. If weakening or loss of diaphragmatic capture is observed, energy application should be stopped immediately. Several other strategies have been developed to monitor phrenic nerve function during cryoballoon AF ablation. One of these is diaphragmatic electromyography for direct monitoring of diaphragmatic compound motor action potentials during ablation. This technique has been reported to further reduce incidence of palsy.8–9 CMAPs are recorded using body surface electrodes, oesophageal electrodes or a diagnostic catheter positioned in the hepatic vein. A decrease in the amplitude of the myopotential by 30% has been reported in some studies to be more sensitive than abdominal palpation for predicting the subsequent reduction in diaphragmatic excursion and nerve injury.10 Energy delivery should be interrupted immediately at the first sign of phrenic nerve injury. In my experience, the CMAP approach is difficult to interpret and I have not found it terrible helpful. I have found it best to rely on pacing of the phrenic nerve from the superior vena cava while monitoring diaphragmatic function with fluoroscopy or palpation.
In summary, phrenic nerve injury is a well-established complication of all types of AF ablation. Phrenic nerve injury is most common with balloon-based approaches including the cryoballoon. With increased awareness of this complication and careful monitoring for phrenic nerve injury during ablation the incidence of this complication has decreased dramatically to 0.3% or less. I have been fortunate to have no patients who experienced permanent phrenic nerve paralysis following cryoballoon ablation. Despite this, I will remain vigilant in hopes of limiting the risk of this complication. At the end of the day, phrenic nerve injury is in the rear view mirror—but not completely out of sight.
- Calkins H et al. HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for personnel, policy, procedures and follow-up. A report of the Heart Rhythm Society (HRS) Task Force on catheter and surgical ablation of atrial fibrillation. HeartRhythm 2007;4(6):816–61
- Packer DL 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 2013;61(16):1713–23
- Guhl EN et al. Efficacy of cryoballoon pulmonary vein isolation in patients with persistent atrial fibrillation. J Cardiovasc Electrophysiol 2016;27(4):423–7
- Metzner A et al. The incidence of phrenic nerve injury during pulmonary vein isolation using the second-generation 28mm cryoballoon. J Cardiovasc Electrophysiol 2014;25(5):466–70
- Guiot A et al. Collateral nervous damages after cryoballoon pulmonary vein isolation. J Cardiovasc Electrophysiol 2012;23(4):346‒51
- Andrade JG et al. Efficacy and safety of cryoballoon ablation for atrial fibrillation: a systematic review of published studies. HeartRhythm 2011;8(9):1444–51
- Yong Ji S et al. Phrenic nerve injury: an underrecognized and potentially preventable complication of pulmonary vein isolation using a wide-area circumferential ablation approach. J Cardiovasc Electrophysiol, 2013;24(10):1086–91
- Franceschi F et al. Phrenic nerve monitoring with diaphragmatic electromyography during cryoballoon ablation for atrial fibrillation: the first human application. HeartRhythm 2011;8(7):1068‒71
- Miyazaki S et al. Prospective evaluation of bilateral diaphragmatic electromyograms during cryoballoon ablation of atrial fibrillation. J Cardiovasc Electrophysiol 2015;26(6): 622‒8
- Mondesert B et al. Clinical experience with a novel electromyographic approach to preventing phrenic nerve injury during cryoballoon ablation in atrial fibrillation. Circ Arrhythm Electrophysiol 2014;7(4):605-11
Hugh Calkins is director of the Cardiac Arrhythmia Service at Johns Hopkins Hospital, Baltimore, USA. He is consultant to Medtronic and reports he has received honoraria for lectures sponsored by Medtronic.