Long-term course of phrenic nerve injury after cryoballoon ablation of atrial fibrillation

While phrenic nerve palsy (PNP) due to cryoballoon pulmonary vein isolation (PVI) of atrial fibrillation (AF) was transient in most cases, no studies have reported the results of the

long-term follow-up of PNP. This study aimed to summarize details and the results of long-term follow-up of PNP after cryoballoon ablation. A total of 511 consecutive AF patients who

underwent cryoballoon ablation was included. During right-side PVI, the diaphragmatic compound motor action potential (CMAP) was reduced in 46 (9.0%) patients and PNP occurred in 29 (5.7%)

patients (during right-superior PVI in 20 patients and right-inferior PVI in 9 patients). PNP occurred despite the absence of CMAP reduction in 0.6%. The PV anatomy, freezing parameters and

the operator’s proficiency were not predictors of PNP. While PNP during RSPVI persisted more than 4 years in 3 (0.6%) patients, all PNP occurred during RIPVI recovered until one year after

the ablation. However, there was no significant difference in the recovery duration from PNP between PNP during RSPVI and RIPVI. PNP occurred during cryoballoon ablation in 5.7%. While most

patients recovered from PNP within one year after the ablation, PNP during RSPVI persisted more than 4 years in 0.6% of patients.

Cryoballoons have proven to be effective for pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF). Several recent randomized trials have shown the noninferiority of

cryoballoon ablation to radiofrequency ablation with respect to the treatment efficacy in patients with drug-refractory paroxysmal AF1, 2.

Phrenic nerve palsy (PNP) is the most frequently observed complication during cryoballoon ablation. Since the cryoballoon is not variable, it is difficult to freeze PV away from the position

of the phrenic nerve. Thus, the incidence of PNP was reported higher in comparison to that during radiofrequency catheter ablation1,2,3,4,5. Several methods for the early detection of PNP

have been reported6. Although, PNP is usually transient with complete resumption of right diaphragmatic contraction before the end of ablations, PNP persisted in some patients. However, the

long-term course of cryothermal PNP have not well been determined. The purpose of this study was to investigate the long-term consequence of PNP after cryoballoon ablation.

A total of 511 consecutive patients who underwent cryoballoon ablation for AF were included in the present study. Paroxysmal AF was defined as AF that spontaneously terminated within seven

days. Antiarrhythmic drugs were discontinued for at least five half-lives prior to ablation. A 3D image of the PV was reconstructed by preprocedural enhanced computed tomography. The size

and length of the PV trunk (between the ostium and the first branch) were measured by an electro-anatomical mapping system7.

Clinical investigations were conducted in accordance with the principles expressed in the Declaration of Helsinki. All data were compliant with the International Conference on Harmonization

guidelines. All experimental protocols were approved by The Ethical Committee of the Jikei University School of Medicine. All methods were carried out in accordance with relevant guideline

and regulations. The informed consent was obtained from all participants.

Details of cryoballoon ablation for AF and early detection of phrenic nerve injury were reported as previously described8,9,10. A single transseptal puncture was performed using a

radiofrequency needle (Baylis Medical, Montreal, QC, Canada) and an 8.5-Fr long sheath (SL0; Abbott, Chicago, IL). The transseptal sheath was exchanged over a guidewire for a 15-Fr steerable

sheath (Flexcath Advance; Medtronic, Minneapolis, MN). Another SL0 sheath was inserted to the left atrium via the same puncture site and a circumferential 20-pole catheter (Lasso 2515 NAV

eco variable catheter; Biosense Webster, Diamond Bar, CA) was inserted to map all PVs before and after the cryoballoon to confirm electrical isolation. PVI was performed with a single

balloon technique using a second-generation (Arctic Front Advance; Medtronic) or 4th-generation cryoballoon (Arctic Front Advance Pro; Medtronic). A 28-mm cryoballoon catheter was used in

all of the patients. A spiral mapping catheter (Achieve; Medtronic) was used to advance the cryoballoon and map the PV potentials. Complete sealing at the antral aspect of the PV was

confirmed by the injection of contrast medium. The proximal-seal technique was used, if possible. This was followed by a freeze cycle of 180 s. In 100 patients, a 120-s bonus-freeze was

applied after the successful application of a 180-s initial freeze. If electrical isolation was not achieved by cryoballoon, additional touch-up ablation was performed with a conventional

radiofrequency or cryothermal (Freezer Max; Medtronic) catheter.

To avoid phrenic nerve injury, the diaphragmatic compound motor action potentials (CMAPs) were monitored during right phrenic nerve pacing, as previously described6, 11, 12. A standard

decapolar catheter or a circumferential 20-pole catheter was placed in the superior vena cava (SVC) cranial to the RSPV in order to pace the PN, in recent cases, the circular catheter was

generally positioned in the subclavian vein in order to achieve better stability and a more reliable PN capture in comparison to the SVC. For the early detection of PNP, the pacing threshold

was measured, and the pacing output was set slightly above the pacing threshold. If a 30% reduction of CMAP or a loss of capture was observed, the freeze was immediately aborted using a

double-stop technique13 and observed for recovery. Additional cryo-applications were not performed even if PNI recovered during the procedure. CMAP monitoring between left side PVI was not

performed.

Details of patient follow-up were reported as previously described8,9,10. In patients with paroxysmal AF, no antiarrhythmic drugs were prescribed after the procedure. The patients underwent

continuous, in-hospital ECG monitoring for 2–4 days after the procedure. The patients underwent careful observation (two weeks after discharge, then every month thereafter) at the cardiology

clinic. The outcome of AF ablation was evaluated based on the patient’s symptoms, ECG at periodical follow-up examinations, and periodic 24-h ambulatory monitoring (at 1, 3, 6, 9, 12 months

and yearly after the procedure). The recurrence of AF was defined as AF lasting for more than 30 s after a blanking period of 90 days.

The degree of PNP was divided into three grades. A > 30% reduction in CMAP without weakening of diaphragmatic motility was considered as impending PNP. Definition of transient and persistent

PNP was previously described14. Specifically, transient PNP was defined as a progressive weakening of diaphragmatic motility, as assessed by manual palpation on the abdomen, confirmed by

fluoroscopy or the occurrence of a hemidiaphragm paralysis detected by both manual palpation and fluoroscopy during the procedure, and completely resolving before the end of the procedure.

Persistent PNP was defined as an elevated hemidiaphragm noted on post-procedural radiography, which persisted after the procedure. The diaphragmatic function on a chest X-ray was confirmed

by a radiologist based on the shape of an elevated hemidiaphragm in both postero-anterior and in lateral fluoroscopy projections during a sniff maneuver. The position and shape of the

diaphragm were determined by correlating measurements to skeletal structures and the radius of the curvature, respectively. Once the diagnosis of PNP was established, the patient was closely

monitored in the clinic with tests repeated every 3 months. Complete recovery of the phrenic nerve function was diagnosed in the case of normalization of the diaphragm position in X-ray

images both at rest and during a sniff test by comparison with the pre-procedural chest images.

Categorical variables were analyzed using a chi-squared test, unless the expected values in any cells were