Phrenic Nerve Damage After Atrial Fibrillation Ablation Using Second Generation

Objective: Cryoballoon ablation is a safe alternative to radiofrequency ablation in the treatment of atrial fibrillation. However, phrenic nerve damage is a bothersome complication of the procedure. In this study, we aimed to establish the incidence of phrenic nerve damage during cryoballon ablation and define the characteristics of affect-


INtroDUCtIoN
Atrial fibrillation (AF) is the most common chronic arrhythmia all around the world and is an important cause of cardiovascular morbidity and mortality.Isolation of pulmonary vein ostiums by cryoballoon (CB) ablation technique is a safe and effective treatment strategy in patients with both paroxysmal and persistent AF who have ongoing symptoms despite antiarrhyhtmic drugs.Developments in technology and increased operator experience improved the outcomes of AF ablation [1].Phrenic nerve damage (PND) is not a rare complication of CB ablation in patients with AF.PND incidence is reported as 3-11% despite precautions including pacing the phrenic nerve during ablation from electronic database.Patients in whom PND developed during or after the ablation procedure were included in the analysis.Transthoracic and transesophageal echocardiography was performed before the procedure in all patients.Cardiac computed tomography was also performed to assess pulmonary vein anatomy. Figure 1 a)Right phrenic nerve injury related right hemidiaphragma paralysis is seen in a male patient.PND persisted one year after the procedure.b)Left hemidiaphragma paralysis secondary to left PNI related with left atrial appendage isolation by cryoballoon ablation.PND resolved during the first year after ablation.PND was established by the reduced motility of hemidiaphragm detected by palpation during high output pacing of phrenic nerve or noted by radiologically with fluoroscopic views during ablation procedure or chest x-ray after the procedure (Figure -1).and evaluation of diaphragmatic contraction by palpation.PND usually develops on the course of right superior pulmonary vein (RSPV) ablation due to the close anatomical relationship with phrenic nerve but it is reported that it can also occur during the ablation of right inferior pulmonary vein and during left sided ablations [2,3].Preclinical studies demonstrated that the main underlying pathological mechanism of PND is Wallerian degeneration.Therefore, PND is a reversible complication in general [3].Age and the cryoballoon diameter were shown to be associated with the development of PND [4].
In the light of these data, in this study, we aimed to present our single center experience in terms of PND development and characteristics after second generation CB ablation for AF.

Study Population
In this retrospective analysis, all patients with the diagnosis of AF who underwent CB based ablation between January 2013 and June 2018 were scanned

Cryoballoon Ablation Procedure
Ablation was performed under deep sedation using boluses of midazolam and fentanyl in all patients.Oxygen saturation and electrocardiogram (ECG) were monitored non-invasively throughout the procedure.Right femoral vein and left femoral vein / artery punctures were performed with Seldinger technique.A 6 Fr steerable decapolar catheter was placed into the coronary sinus.Single transseptal puncture was performed under fluoroscopic guidance using a modified Brockenbrough technique

Monitoring Phrenic Nerve Function
The 6 Fr decapolar catheter was placed in the superior vena cava (SVC) to pace the right phrenic nerve with a 2000-msec cycle and a 10-mA output during ablation of the right-sided PVs to prevent PNP.Capture was detected by both observations under fluoroscopy and manual palpation of the abdomen.
In the case of phrenic nerve injury (PNP), cryoenergy application was aborted immediately and the balloon was deflated to avoid further damage to the nerve.Diaphragmatic contractions were followedup for 30 minutes.No additional cryoenergy application was performed to the vein.
In patients with left atrial appendage (LAA) isolation, the left phrenic nerve, because of its neighboring to the LAA, was monitored in all patients.The left phrenic nerve was constantly paced from the LAA using circular mapping catheter throughout the freezing cycle.Also direct palpation of the left hemi-diaphragmatic excursion was performed during phrenic nerve stimulation.In the absence of the capture for left phrenic nerve by circular mapping catheter before freezing, we preferred to use monitoring with fluoroscopy during spontaneous breathing.
In patients with an arrhytmogenic SVC, SVC isolation using CB was also attempted.In such cases, Achieve catheter was placed in the SVC ostium and after inflation of the CB at the SVC-right atrium border, a prolapsus movement was done with the Achieve catheter and right phrenic nerve was paced from Achieve catheter.

Definition of Phrenic Nerve Damage
PND was classified into 3 groups according to the time until recovery in the diaphragmatic contractile functions.Phrenic nerve injury was defined as any degree of decrease in diaphragmatic movement which was resolved prior to the end of the procedure.Phrenic nerve palsy was defined as loss of diaphragmatic movement evaluated by exhalation and inhalation under fluoroscopy or X-ray which revealed elevated diaphragm lasting less than 3 months and.Phrenic nerve paralysis was defined as palsy lasting > 3 months [5].

DISCUSSIoN
Pulmonary vein isolation is a safe and an effective treatment option for drug resistant AF.PND is a well defined complication of CB ablation as a result of close anatomic relationship between pulmonary veins and phrenic nerve [6].Phrenic nerves originate from 3rd and 5th cervical spinal nerve roots and innervates diaphragm.It is the only nerve that brings motor stimulus to diaphragm.Right phrenic nerve lies over vena cava superior and it is located so closely to the RSPV.The neighborhood of RSPV and right phrenic nerve is the main cause of PND in patients underwent CB ablation [7].
The incidence of PND is reported approximately 6% (1.7%-24.4%) in the literature [8].Most of patients recover from PND and only less than 0.4% of patients suffer from PN palsy / paralysis and related symptoms 1 year after the procedure [9].In our cohort, PND incidence was consistent with literature and slightly lower from mean reported incidence rates.Increased operator experience high patient volume may play role in the lower PND incidence in our center.
There are some predictors of PND occurrence during CB ablation.Patients with persistent AF are more prone to PND development.Horizontal and coronal diameter of RSPV ostium and balloon position relative to the cardiac shadow are also predictors of PND development [6].However, there are still some maneuvers to prevent PND during CB ablation.A single 28 mm balloon use, proximal seal technique and using compound motor action potential decreases the PND development [10][11][12][13].
PND is usually transient in patients who underwent CB ablation.Most of the patients recover from PND during the procedure which were defined as PN injury.PND resolves in the 78% of patients during the following 11 months [14].Similar to previous reports, in most of our patients, PN injury developed which was resolved prior to the end of the procedure.This was mostly due to the termination of the CB ablation when any decrease in diaphragmatic movement observed.Only in a minority of the patients PN palsy or paralysis developed which mostly resolved during the follow-up.In a post-approval study of patients enrolled in the STOP-AF trial, fewer than 1% of patients had PN paralysis after 12 months [15].In our study, PN paralysis persisted only in 2 patients 1 year after the procedure.Although most of reported PND cases are related with RSPV ablation; SVC isolation and LAA isolation is also associated with PND.Right phrenic nerve is adjacent to anterolateral wall of SVC and RSPV ostium.Left phrenic nerve lies over the LAA.So operators should be cautious during the isolation of SVC and LAA; and phrenic nerve functions should be monitored by pacing in the course of procedure [16].

LIMItAtIoNS
Although our study group was consisted of a large number of patient cohort, it was a retrospective analysis of a single center which might preclude the assessment of real-world incidence of PND.Moreover, our data reflected the incidence PND from high volume and experienced center.Finally, the effect of several preventive measures on PND development was not assessed in our analysis.

CoNCLUSIoN
CB-based AF ablation is a safe option for drug resistant atrial fibrillation; however, PND is still a major concern especially during RSPV isolation.PND usually resolves during the procedure and most of patients with PN palsy / paralysis recover during the first year after the procedure.Further studies evaluating the effect of different maneuvers on the development of PND is needed to better assess the risk of CB-based AF ablation on PND development.

CoNFLICt oF INtErESt
We have not any conflict of interest in this study.

Figure - 1 a
Figure -1 a)Right phrenic nerve injury related right hemidiaphragma paralysis is seen in a male patient.PND persisted one year after the procedure.b)Left hemidiaphragma paralysis secondary to left PNI related with left atrial appendage isolation by cryoballoon ablation.PND resolved during the first year after ablation.

(
BRK-1 transseptal needle, St. Jude Medical, St. Paul, MN, USA) and an 8.5 Fr transseptal sheath (Fast-Cath transseptal guiding introducer, St. Jude Medical, St. Paul, MN, USA) was placed into the left atrium (LA).Unfractionated heparin was administered immediately following transseptal puncture at doses adjusted to achieve and maintain an ACT of at least 300 sec.The transseptal sheath was exchanged over a guidewire (0.032 in., 180 cm Super Stiff, St. Jude Medical, St. Paul, MN, USA) for a 12 Fr steerable

Table 1 .
Baseline characteristics of patients with PND Flexcath Advance, Medtronic, Minneapolis, MN, USA).A 15 or 20 mm circular mapping catheter (Achieve, Medtronic, Minneapolis, MN, USA) was used in all patients to guide the CB within the LA and to attempt real-time recordings from the targeted pulmonary vein (PV).The balloon was inflated in the LA and then directed toward the PV ostia.

Table 2 .
Characteristics of patients with phrenic nerve damage This time was 100 (50-230) seconds in patients with PN paralysis while it was 197 (20-290) seconds in PN injury group.Atrial fibrillation recurrence developed in only one patient in the PN injury group and in 4 patients in the PN palsy / paralysis group.