# High incidence of phrenic nerve injury in patients undergoing pulsed field ablation for atrial fibrillation

Louis Chéhirlian, Linda Koutbi, Julien Mancini, Jérôme Hourdain, Robin Richard-Vitton, Marie Wilkin, Jean-Claude Deharo, Baptiste Maille, Frédéric Franceschi

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Louis Chéhirlian, Linda Koutbi, Julien Mancini, Jérôme Hourdain, Robin Richard-Vitton, et al.. High incidence of phrenic nerve injury in patients undergoing pulsed field ablation for atrial fibrillation. Heart Rhythm, 2025, 22 (12), pp.e1206-e1213. 10.1016/j.hrthm.2025.08.010. inserm-05441921

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# High incidence of phrenic nerve injury in patients undergoing pulsed field ablation for atrial fibrillation

Louis Chéhirlian, MD,¹,² Linda Koutbi, MD,¹,² Julien Mancini, MD, PhD,²,³ Jérôme Hourdain, MD,¹,² Robin Richard-Vitton, MD,¹,² Marie Wilkin, MD,¹,² Jean-Claude Deharo, MD,¹,²,⁴ Baptiste Maille, MD, PhD,¹,²,⁴ Frédéric Franceschi, MD, PhD¹,²,⁴

## ABSTRACT

**BACKGROUND** Pulsed field ablation (PFA) is thought to reduce the risk of phrenic nerve injury (PNI) during atrial fibrillation (AF) ablation because of its myocardial selectivity. However, several reports suggest PNI still occurs.

**OBJECTIVE** This study aimed to evaluate the incidence and characteristics of PNI during PFA using sequential compound motor action potential (CMAP) monitoring and assess diaphragmatic function at discharge.

**METHODS** This prospective study included 64 consecutive patients undergoing PFA for AF. Right phrenic nerve function was monitored using CMAP during ablation. A baseline amplitude was measured before right pulmonary vein ablation, and subsequently monitored sequentially throughout the procedure. In case of intra-procedural PNI, all patients underwent a chest X-ray, and the last 25 also had a fluoroscopic loop the following day.

**RESULTS** PNI occurred in 26 patients (40.6%). Incomplete recovery was observed in 12 (18.8%) at the end of the procedure. Chest X-rays were normal in all cases. Among the last 25 patients, 12 experienced intra-procedural PNI and underwent fluoroscopic assessment at discharge, of whom 6 patients (50%) had persistent incomplete PNI. The overall incidence of PNI at discharge was 24% (6/25). Follow-up fluoroscopy confirmed recovery in 4 of 5 patients reassessed, while 1 showed persistent dysfunction at 3 months.

**CONCLUSION** PNI is a frequent complication of PFA. Incomplete paralysis is commonly observed at the end of the procedure. Fluoroscopy enables diagnosis of incomplete PNI at discharge, which remains a frequent finding. One patient showed persistent dysfunction at 3 months.

**KEYWORDS** Atrial fibrillation; Pulsed field ablation; Phrenic nerve injury; Compound motor action potential; Catheter ablation
(Heart Rhythm 2025;22:e1206-e1213) © 2025 Heart Rhythm Society. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Right phrenic nerve injury (PNI) is a known complication of catheter ablation for atrial fibrillation (AF) using thermal energies.¹ Recently, pulsed field ablation (PFA) has emerged² and given the theoretical tissue specificity of the lesions, it was expected that PNI would disappear.³ However, several publications have reported PNI cases, including persistent cases at hospital discharge.²,⁴,⁵ Reported incidences remain low in the absence of specific diaphragmatic monitoring during procedures.

Compound motor action potential (CMAP) monitoring is a widely adopted approach to preventing PNI during cryoballoon procedures, with the advantage of obtaining an objective, quantifiable assessment of right phrenic nerve function.¹,⁶ Even though PFA applications are extremely short, their repetition is necessary to create lesions. Thus, sequential CMAP monitoring could be performed between PFA applications.⁷

The aim of this observational study is firstly to determine the incidence of PNI during PFA procedures by perform

<footnote>From the ¹Department of Cardiology, CHU Timone, Marseille, France, ²Aix-Marseille University, Marseille, France, ³Biostatistics Department, Aix-Marseille University, INSERM, IRD, ISSPAM, APHM, SESSTIM, Timone Hospital, Marseille, France, and ⁴Center for CardioVascular and Nutrition Research (C2VN), INSERM, INRA, Marseille, France.</footnote>
systematic sequential CMAP monitoring and secondly to assess the incidence of PNI at hospital discharge, the day after the procedure.

# Methods

## Study design

This research adhered to the principles outlined in the Declaration of Helsinki as revised in 2013. This was a prospective, single-center observational study. Consecutive patients admitted for a first-time AF ablation procedure were enrolled, provided they were over 18 years of age. Patients with a history of cardiac or thoracic surgery, known neuromuscular disorders, or any diaphragmatic pathology were excluded. AF ablation was performed using the FARAPULSE™ ablation system (Boston Scientific). Written informed consent was obtained from all participants. The study protocol was approved by the institutional ethics committee.

## Periprocedural management and PFA procedures with FARAPULSE

All patients underwent transesophageal and transthoracic echocardiography prior to the procedure. Deep sedation was achieved using propofol and midazolam in spontaneous ventilation, with local anesthesia. No skeletal muscle relaxants were used, to preserve diaphragmatic function. A triple right femoral vein puncture was performed. The first was for the PFA catheter, the second for the coronary sinus catheter, subsequently repositioned in the superior vena cava (SVC) during the procedure to pace the right phrenic nerve (steerable quadripolar deflectable catheter Xtrem™; Microport) and the third for the 12-electrode catheter, placed in the inferior vena cava (IVC) to record diaphragmatic CMAP (Woven™, Cournand fixed-curve, 6F, Boston Scientific; 1 cm interelectrode spacing). A single transseptal puncture was performed to introduce an 8F transseptal sheath into the left atrium (SLO™; Abbott). Thereafter, patients received a weight-adjusted dose of intravenous heparin 130 IU/kg with a target activated clotting time of >300 seconds. The FARADRIVE™ sheath (Boston Scientific) was then advanced in the left atrium. The FARAWAVE (diameter 31 or 35 mm, depending on the operator's choice) was manipulated using

a J 0.035 Rosen curved guide-wire (Cook Medical). At first, left pulmonary vein (PV) isolation was performed. Next, the right PVs were isolated (the superior and then the inferior). PFA was initiated with 2 consecutive applications using the basket configuration, and 2 applications after a slight catheter rotation. The catheter was then repositioned in the flower configuration, with 2 applications, followed by

another 2 after slight rotation. A minimum of 8 applications were delivered to each PV. If deemed necessary by the operator, additional flower-shaped applications were administered at more anterior or posterior positions. Ablation of the posterior wall, the left atrial roof, or the SVC was performed at the operator's discretion. For SVC ablation, the FARAWAVE catheter was positioned at the SVC-right atrial junction using a basket configuration. A standardized set of 6 PFA applications was delivered—2 in basket configuration, followed by 4 in flower configuration with slight rotations—unless early electrical isolation was achieved.

## Right phrenic nerve monitoring

Prior to ablation of the right PVs, the quadripolar catheter was repositioned from the coronary sinus to the SVC. Right phrenic nerve pacing was performed using bipolar stimulation (proximal to distal electrodes, 12V×2.9ms) at 60 bpm. The 12-electrode diagnostic catheter was placed in the IVC to record diaphragmatic CMAPs between electrodes 2 and 9 (Figure 1). Signals were amplified and filtered (5–150 Hz), and CMAP amplitudes were measured peak-to-peak on the electrophysiology workstation.

The detection catheter was manipulated to obtain the maximal CMAP amplitude and maintained in that position for the entire procedure. A single CMAP baseline measurement was recorded prior to the first PFA application on the right PVs. CMAP monitoring was systematically performed after every 2 PFA applications from a given catheter position, and prior to any repositioning of the FARAWAVE catheter.

<figure><img src="image_3.png" /><figcaption>**Figure 1**
CMAP recording catheter. Anteroposterior fluoroscopic view showing the CMAP recording catheter (12-pole Woven, Boston Scientific) positioned in the inferior vena cava. Bipolar recordings were obtained between electrodes 2 (negative) and 9 (positive), corresponding to an interelectrode spacing of 8 cm. CMAP = compound motor action potential.</figcaption></figure>

## Abbreviations

AF: atrial fibrillation

CMAP: compound motor action potential

PFA: pulsed field ablation

PNI: phrenic nerve injury

RIPV: right inferior pulmonary vein

RSPV: right superior pulmonary vein

SVC: superior vena cava
No recordings were made after individual applications. Subsequently, before each new positioning of the FARAWAVE catheter, a stimulation sequence consisting of at least 10 consecutive phrenic nerve stimulations was performed to reassess CMAP amplitude.

In cases of PNI, a minimum observation period of 20 minutes was maintained between the time of paralysis detection and the final CMAP reassessment, without interruption of the ablation sequence. To rule out loss of capture due to pacing catheter displacement, its position was assessed fluoroscopically and adjusted within the SVC if necessary. The duration of complete diaphragmatic paralysis was measured as the time interval between the first occurrence of a complete CMAP disappearance and the reappearance of a discernible CMAP signal following the pacing artifact. Phrenic nerve stimulation was performed repeatedly throughout the procedure, allowing for temporal monitoring of CMAP recovery.

CMAP monitoring was performed in an observational manner only and did not influence the ablation strategy. All planned applications were delivered according to the standard protocol, regardless of CMAP amplitude evolution or the occurrence of phrenic nerve dysfunction.

In cases of confirmed PNI, the presence of diaphragmatic contraction during right PV ablation was noted. During the final phrenic nerve stimulation sequence, diaphragmatic response was evaluated via abdominal palpation and fluoroscopic visualization.

After the procedure, CMAP amplitudes were reviewed on the electrophysiology system (CardioLab™, GE Healthcare) by an experienced electrophysiologist. Any suspected shifts in catheter position prompting a decrease in CMAP amplitude led to fluoroscopic repositioning. The total number of repositioning was recorded. If right PNI occurred, a chest X-ray and fluoroscopy loop were obtained the following day.

## Diaphragmatic CMAP measurement

CMAP amplitude was measured peak-to-peak and expressed in millivolts.⁸ The baseline amplitude was calculated as the average of 5 consecutive beats. A complete diaphragmatic paralysis was defined as the complete absence of a CMAP following the pacing artifact, combined with the absence of diaphragmatic movement on fluoroscopy during spontaneous respiration.

Partial reductions in CMAP amplitude were not classified as PNI, which was strictly defined as complete CMAP loss during the procedure to ensure consistent event definition.

At the end of the procedure, CMAP amplitude was considered abnormally reduced if <85% of baseline, and the reduction was expressed as a percentage.

## Chest X-ray

Chest radiographs were acquired in the standing position during deep inspiration. An abnormal result was defined as a right hemidiaphragm positioned more than 2 cm higher than the left.⁹

## Fluoroscopic assessment

Patients were in the supine position to minimize the risk of false-negative.⁹ The excursion amplitude of each hemidiaphragm was measured. One hemidiaphragm had to demonstrate an excursion greater than 4 cm. The test was considered abnormal when the excursion amplitude on one side was more than 15% lower than that of the contralateral side.

An incomplete unilateral diaphragmatic paralysis was defined as a fluoroscopic reduction in diaphragmatic excursion of more than 15% compared to the contralateral side.

A complete recovery during follow-up was defined as no reduction or a reduction of less than 15% in diaphragmatic excursion compared to the contralateral side.

## Follow-up

If the fluoroscopic loop performed the day after the procedure was abnormal, a repeat assessment was conducted at the end of the follow-up period. The presence of symptoms related to diaphragmatic dysfunction was not evaluated in this study.

## Study end points

The primary objective of this study was to characterize the evolution of diaphragmatic CMAP during PFA procedures, specifically the incidence of PNI and subsequent CMAP recovery in affected patients. The secondary objective was to evaluate diaphragmatic function the day after the procedure, prior to hospital discharge.

## Statistical analysis

Data were tested for normality using the Shapiro-Wilk test. Continuous variables are presented as means ± standard deviations if they are normally distributed or as medians with interquartile ranges if they are non-parametric. Categorical variables are summarized using descriptive statistics. The Mann-Whitney U test was applied to compare quantitative variables. For categorical data, Pearson's χ² test was used when the sample size was sufficient; otherwise, Fisher's exact test was employed. A P-value of <.05 was considered statistically significant. All authors had full access to the data and accept full responsibility for its integrity.

## Results

### Patients and procedures

Overall, 64 patients were included. Patient and procedural characteristics are summarized in Tables 1 and 2.

### CMAP evolution patterns during the procedure

Three distinct patterns of diaphragmatic CMAP evolution were observed during the procedure (Figure 2). The first pattern consisted of a stable CMAP amplitude, indicating the absence of PNI. In other cases, PNI occurred, resulting in a transient phase of complete signal loss lasting from a few seconds to several minutes (mean duration: 344.0 ± 298.0 seconds). This was consistently followed by a rapid
<table><caption>**Table 1** Baseline characteristics of the study population</caption><thead><tr><th>Variable</th><th>Value</th></tr></thead><tbody><tr><td>Age (ys)</td><td>66.1 ± 10.9</td></tr><tr><td>Male sex, n (%)</td><td>50 (78.1%)</td></tr><tr><td>Weight (kg)</td><td>85.2 ± 15.5</td></tr><tr><td>Height (cm)</td><td>174.9 ± 8.0</td></tr><tr><td>Body mass index (kg/m²)</td><td>27.8 ± 4.7</td></tr><tr><td>Sleep apnea, n (%)</td><td>14 (21.9%)</td></tr><tr><td>Diabetes mellitus, n (%)</td><td>8 (12.5%)</td></tr><tr><td>NYHA functional class, n (%)</td><td></td></tr><tr><td>Class I</td><td>16 (25.0%)</td></tr><tr><td>Class II</td><td>41 (64.1%)</td></tr><tr><td>Class III</td><td>7 (10.9%)</td></tr><tr><td>Left ventricular ejection fraction (%)</td><td>53.9 ± 10.9</td></tr><tr><td>Left atrial volume index (mL/m²)</td><td>47.2 ± 20.0</td></tr><tr><td>AF type, n (%)</td><td></td></tr><tr><td>Paroxysmal</td><td>25 (39.1%)</td></tr><tr><td>Persistent</td><td>39 (60.9%)</td></tr><tr><td>Time since AF diagnosis (months)</td><td>37.2 ± 49.6</td></tr><tr><td>CHADS-VA score, mean ± SD</td><td>2.3 ± 1.4</td></tr><tr><td>CHADSVA score distribution, n (%)</td><td></td></tr><tr><td>0</td><td>7 (10.9%)</td></tr><tr><td>1</td><td>11 (17.2%)</td></tr><tr><td>2</td><td>63 (43.8%)</td></tr><tr><td>3</td><td>15 (23.4%)</td></tr><tr><td>4</td><td>9 (14.1%)</td></tr><tr><td>5</td><td>2 (3.1%)</td></tr><tr><td>6</td><td>1 (1.6%)</td></tr><tr><td>EHRA symptom scale, n (%)</td><td></td></tr><tr><td>I</td><td>2 (3.1%)</td></tr><tr><td>II</td><td>28 (43.8%)</td></tr><tr><td>III</td><td>20 (31.3%)</td></tr><tr><td>IV</td><td>14 (21.9%)</td></tr></tbody></table>

Data are expressed as mean ± standard deviation.

AF = atrial fibrillation; EHRA = European Heart Rhythm Association; NYHA = New York Heart Association.

recovery phase (1–2 minutes), during which CMAP amplitude returned either to its baseline value (second pattern) or to a lower value (third pattern). Following this rapid recovery phase, CMAP amplitude reached a plateau.

## PNI and CMAP recovery

Diaphragmatic paralysis occurred in 26 of 64 patients (40.6%), during applications targeting the right superior PV (RSPV) in 21 of 26 patients (80.8%), the right inferior PV (RIPV) in 3 of 26 patients (11.6%), both veins in 2 of 26 patients (7.7%) and the SVC in 2 of 26 patients (7.7%) Paralysis occurred after the first 2 applications in basket configuration at the initial engagement of the target vein in 11 of 26 patients (42%), and during a subsequent application in 15 of 26 patients (58%). A basket-shaped configuration was associated with paralysis in 53.8% of cases, while a flower-shaped configuration was involved in 46.2%. Additional flower-shaped applications were performed in 50 of 64 patients, with a PNI prevalence (42%) comparable to the overall cohort (40.6%).

Among the 26 affected patients, 17 (65.4%) experienced an abrupt onset of paralysis, whereas the remaining patients showed a gradual CMAP amplitude decrease over successive

<table><caption>**Table 2** Procedural characteristics</caption><thead><tr><th>Variable</th><th>Value</th></tr></thead><tbody><tr><td>Operating time (min)</td><td>63.4 ± 16.6</td></tr><tr><td>Fluoroscopy time (min)</td><td>15.0 ± 4.6</td></tr><tr><td>Catheter size, n (%)</td><td></td></tr><tr><td>31 mm</td><td>39 (60.9%)</td></tr><tr><td>35 mm</td><td>21 (32.8%)</td></tr><tr><td>Additional ablation site, n (%)</td><td></td></tr><tr><td>Left atrial roof</td><td>18 (28.1%)</td></tr><tr><td>Posterior wall</td><td>40 (62.5%)</td></tr><tr><td>Superior vena cava (SVC)</td><td>9 (14.1%)</td></tr><tr><td>Cavo-tricuspid isthmus</td><td>6 (9.4%)</td></tr><tr><td>Number of CMAP catheter repositioning</td><td>1.6 ± 1.6</td></tr><tr><td>Applications number (mean ± SD)</td><td></td></tr><tr><td>Right superior pulmonary vein (RSPV)</td><td>9.5 ± 2.8</td></tr><tr><td>Right inferior pulmonary vein (RIPV)</td><td>9.5 ± 2.8</td></tr><tr><td>SVC (n = 9)</td><td>6.0 ± 1.7</td></tr></tbody></table>

Data are expressed as mean ± SD.

CMAP = compound motor action potential; SD = standard deviation.

catheter applications, indicating a progressive onset of phrenic nerve dysfunction.

Complete CMAP recovery (ie, CMAP amplitude ≥85% of the baseline value) was observed in 14 of 64 patients (21.9%). In the remaining 12 patients (18.8%), recovery was incomplete, with a mean CMAP amplitude reduction of 36.0 ± 16.6% from baseline. The minimum CMAP amplitude observed at the end of the procedure in patients with incomplete recovery was 31.8% of the baseline value, corresponding to a 68.2% reduction. The only factor significantly associated with incomplete CMAP recovery at the end of the procedure was the duration of complete diaphragmatic paralysis, which was longer in patients without full recovery (212.0 ± 179.0 s vs 498.4 ± 340.4 s, *P* = .027).

There was a trend toward an increased risk of diaphragmatic paralysis in patients with lower body weight (84.0 ± 2.0 kg vs 96.9 ± 4.2 kg, *P* = .083).

## Pacing catheter repositioning

This information was collected in the last 23 patients, among whom PNI occurred in 10. The stimulation catheter had to be repositioned in 17 patients, on average 1.6 times. It was systematically repositioned when diaphragmatic paralysis occurred, after diagnosis, to differentiate paralysis from loss of capture due to catheter displacement.

## Diaphragmatic contraction during PFA

Right diaphragmatic contractions were observed in all right PV applications, even in cases of complete right phrenic nerve paralysis. There was no difference in the intensity of perceived diaphragmatic contraction whether or not the phrenic nerve was paralyzed.

## Diaphragmatic contraction during phrenic nerve pacing at the end of the procedure

When phrenic nerve stimulation was performed at the end of the procedure, a right diaphragmatic contraction was always
<figure><img src="image_4.png" /><figcaption>**Figure 2**</figcaption></figure>

Representative patterns of diaphragmatic CMAP evolution during pulsed field ablation procedures. Three distinct CMAP response profiles were identified: A: Stable CMAP amplitude throughout the procedure, indicating preserved phrenic nerve function. B: PNI followed by complete recovery to baseline levels after a transient phase of paralysis. C: PNI followed by partial recovery to a subnormal plateau, indicating incomplete recovery. CMAP = compound motor action potential; PNI = phrenic nerve injury.

perceived on palpation and fluoroscopy, even when the CMAP was altered compared with baseline.

## Diaphragmatic function assessment at discharge

A chest X-ray was systematically performed the day after the procedure in all patients who developed diaphragmatic paralysis, and no radiographic abnormalities were identified. In the last 25 patients, a fluoroscopic loop was added to the chest X-ray. Among these, 12 developed right PNI during the procedure. All underwent a fluoroscopic loop the following day, which revealed alterations in diaphragmatic kinetics in 6 cases (50%): 4 on the right side and 2 on the left (Table 3). These were incomplete diaphragmatic paralysis, with diaphragmatic amplitude impairments ranging from 19% to 53% (median: 28.4 ± 15.4%). The left-sided paralysis were identified opportunistically, as radiological

<table><caption>**Table 3** Fluoroscopic follow-up and outcomes in patients with abnormal diaphragmatic motion after phrenic nerve palsy (PNP)</caption><thead><tr><th>PNP side</th><th>Discharge (%)</th><th>Follow-up</th><th>Timing</th><th>Value (%)</th></tr></thead><tbody><tr><td>Right</td><td>-19%</td><td>Not performed</td><td>-</td><td>-</td></tr><tr><td>Right</td><td>-47%</td><td>Yes</td><td>2 months</td><td>-8%</td></tr><tr><td>Right</td><td>-20%</td><td>Yes</td><td>6 months</td><td>-5%</td></tr><tr><td>Right</td><td>-35%</td><td>Yes</td><td>3 months</td><td>-35%</td></tr><tr><td>Left</td><td>-20%</td><td>Yes</td><td>2 months</td><td>-5%</td></tr><tr><td>Left</td><td>-53%</td><td>Yes</td><td>1 months</td><td>0%</td></tr></tbody></table>

This table summarizes the side of (PNP), the relative decrease in diaphragmatic excursion on fluoroscopy at discharge, the timing of follow-up imaging, and the recovery outcomes. Among the 6 patients with abnormal diaphragmatic motion, fluoroscopic follow-up was performed in 5 between 1 and 6 months, and showed complete recovery in 4 patients (green). One patient (red) exhibited no recovery at 3 months. Follow-up imaging was not performed in 1 case. Follow-up corresponds to the first post-discharge visit; earlier recovery may have occurred.
examinations were conducted in response to right-sided diaphragmatic paralysis. Among patients with a right PNI during the procedure, a dedicated analysis was performed comparing those with abnormal vs normal fluoroscopic findings on the right hemidiaphragm at discharge. The only difference observed was the degree of CMAP amplitude reduction from baseline at the end of the procedure, which was greater in patients with abnormal fluoroscopic findings (mean reduction: $28 \pm 19\%$ vs $15 \pm 14\%$, respectively), showing a trend toward statistical significance (P = .052).

## Diaphragmatic function assessment follow-up

Among the 6 patients, fluoroscopic loop follow-up was successfully conducted in 5 patients. Of these, 4 demonstrated recoveries of normal diaphragmatic function, whereas 1 showed no recovery at the 3-month follow-up (Table 3).

## Discussion

PNI appears to be a frequent event during PFA for AF and often persists in an incomplete form at the end of the procedure, as evidenced by CMAP amplitude reduction. Post-procedural fluoroscopy frequently reveals persistent diaphragmatic dysfunction. In one patient, fluoroscopic abnormality were still present at 3-month follow-up. These observations challenge the notion that PFA eliminates the risk of phrenic nerve damage and highlight the limitations of current standard assessment tools.¹⁰

Although PNI is a well-known complication of thermal ablation, especially cryoballoon procedures, its occurrence during PFA has been considered rare due to the technology's tissue selectivity. However, multicenter studies and registries have reported cases of PNI after PFA, including instances of persistent injury at discharge.²,⁴,⁵ Our study suggests that the incidence of incomplete injury is likely higher than previously estimated, largely due to the absence of systematic monitoring in routine clinical practice.

Fifteen years ago, our team developed the concept of diaphragmatic CMAP monitoring during cryoballoon ablation procedures,¹¹,¹² which has since become a widely accepted and routinely applied technique for the prevention of phrenic nerve injury.¹,¹³,¹⁴ Its use in this study enabled detection of PNI during PFA. A complete diaphragmatic paralysis occurred in 26 of 64 patients (40.6%) during the procedure. Among them, 12 patients (18.8%) showed incomplete CMAP recovery at the end of the procedure.

Chest radiography is routinely used to diagnose PNI after AF ablation, though it has imperfect sensitivity even for complete forms. Although complete PNI has been described with both cryoballoon and PFA, our findings suggest that incomplete PNI represents the most common form of paralysis observed in PFA. In this setting, chest X-ray appears insufficient, and fluoroscopy is needed for accurate detection.⁹ We also identified 2 cases of incomplete left-sided PNI. Whether this represents a rare or underrecognized complication of PFA remains unclear, and further

studies are needed to determine the value of systematic left phrenic nerve monitoring and the risk of persistent dysfunction.

The incidence of incomplete diaphragmatic paralysis at hospital discharge was 24% in our study (6/25), which represents a notably high rate.

In several recent studies on PFA, diaphragmatic monitoring was performed using phrenic nerve stimulation, and in some cases, chest radiography was also conducted post-procedure.¹⁵,¹⁶ These studies consistently reported a zero incidence of PNI at the end of the procedure and at hospital discharge. This discrepancy is most likely explained by the inadequate monitoring techniques. Several factors likely explain the underestimation of PNI incidence. First, diaphragmatic contraction often persists during PFA applications, even in cases of complete phrenic nerve paralysis (Figure 3). Second, during phrenic nerve stimulation at the end of the procedure, diaphragmatic movement appears normal on abdominal palpation in cases of incomplete paralysis. Third, in cases of incomplete PNI, chest radiography is typically normal and fails to reveal partial functional deficits. These limitations highlight the critical value of CMAP monitoring.

The mechanisms underlying diaphragmatic paralysis remain uncertain. A transient electrical effect, such as membrane hyperpolarization,¹⁷ may explain cases with intra-procedural recovery. However, post-procedural or persistent dysfunction is unlikely to result from this mechanism alone. Other potential causes include direct phrenic nerve ablation by pulsed field energy,¹⁸ mechanical trauma, or thermal injury.

SVC ablation was performed in a minority of patients (9/64). Among these 9 patients, PNI occurred in 4 cases. Two of them exhibited incomplete CMAP recovery at the end of the procedure, with amplitude reductions of 39% and 24%, respectively, but fluoroscopic follow-up was not performed. As such, it is not possible to confirm whether these cases were associated with persistent fluoroscopic diaphragmatic paralysis, and the contribution of SVC ablation to the overall PNI incidence may therefore be underestimated or uncertain.

In 2 patients with right-sided PNI during the procedure, next-day fluoroscopy revealed left-sided PNI. As left phrenic function was not monitored intra-procedurally, bilateral PNI during the procedure cannot be excluded, although delayed onset of left-sided PNI is also a possible explanation.

The long-term impact of PNI remains unclear, but Multinational Assessment of Novel non-thermal Endocardial iSolation using pulsed field energy for the Treatment of atrial fibrillation (MANIFEST) 1-year data⁵ confirm the risk of permanent paralysis. Our findings suggest a dose-effect relationship, with increased nerve injury as PFA applications accumulate.⁷ CMAP monitoring may help guide the procedure, particularly when prolonged paralysis or incomplete recovery is observed. Limiting additional applications in such cases could reduce risk, a hypothesis that warrants further study. These results support the value of systematic CMAP monitoring and post-procedural dynamic imaging.
<figure><img src="image_5.png" /><figcaption>**Figure 3**</figcaption></figure>

Schematic representation of phrenic nerve conduction and diaphragmatic response under different conditions. A: Normal conduction: proximal phrenic nerve pacing (red star) results in effective signal propagation and diaphragmatic contraction. B: Conduction block: although pacing is performed at the same proximal site, a lesion (black bar) prevents signal transmission distally, resulting in absence of diaphragmatic contraction. C: PFA with conduction block: Despite a proximal conduction block at the site of a prior PFA application, local electric fields generated during subsequent PFA deliveries may still stimulate the phrenic nerve distal to the block (yellow arrows). This results in direct diaphragmatic activation and contraction, even in the presence of a conduction block. This illustrates how diaphragmatic movement may persist despite phrenic nerve paralysis, because of distal nerve fiber activation within the pulsed field area—at a current density that may be below or above the threshold for durable injury, but still sufficient to elicit stimulation. PFA = pulsed field ablation.

One may question the clinical relevance of diagnosing partial diaphragmatic paralysis, particularly since symptoms are rarely prominent. As the symptoms are non-specific, typically presenting as exertional or positional dyspnea, clinical diagnosis can be challenging. However, there is substantial evidence in the literature demonstrating that partial diaphragmatic dysfunction leads to significant and quantifiable respiratory impairment.<sup>19-22</sup>

We believe that any iatrogenic complication should be reported. No patient expects to be discharged from hospital with a new diaphragmatic deficit without being informed. It is the physician's responsibility to identify such complications and to make every effort to prevent them.

## Limitations

This was a single-center study with a limited sample size. Left phrenic nerve monitoring was not performed, and post-procedural fluoroscopy was added only in the latter part of the study. As such, the prevalence of left-sided dysfunction may be underestimated. Additionally, follow-up data beyond 3 months are limited.

## Conclusion

PNI during PFA is more common than previously recognized when objective monitoring is employed. Incomplete PNI may persist at the end of the procedure (detected by CMAP), the following day, and even at 3 months (detected by fluoroscopy), yet remain undetectable by standard radiography.

These findings support routine use of dedicated diaphragmatic monitoring and post-procedural dynamic imaging in ablation workflows. Large-scale prospective studies are needed to better assess the incidence, risk factors, and long-term clinical impact of PNI in this context.

**Funding Sources:** This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

**Disclosures:** Prof Frédéric Franceschi is a consultant and holds stock in the company Circle-Safe; the other authors have no conflicts of interest to declare.

**Address reprint requests and correspondence:** Prof Frédéric Franceschi, Timone Hospital, 264 Rue Saint-Pierre, 13005 Marseille, France. E-mail address: frederic.franceschi@ap-hm.fr

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