Diaphragmatic Evaluation by Fluoroscopy to Identify Phrenic Nerve Dysfunction Related to Electroporation

Official title

Diaphragmatic Evaluation by Fluoroscopy to Identify Phrenic Nerve Dysfunction Related to Electroporation Prospective Multicentre Study on the Evaluation of the Incidence of Diaphragmatic Paralysis After Pulsed Field Ablation Procedures to Treat Atrial Fibrillation

Overview

Pulsed Field Ablation (PFA) represents a recent advance in the treatment of atrial fibrillation (AF), with a safety profile potentially superior to traditional thermal techniques, such as radiofrequency or cryoablation. Its mechanism of action allows tissue selectivity which in theory limits damage to extracardiac structures. However, several cases of right diaphragmatic paralysis have been reported in the literature after PFA, particularly during applications on the right pulmonary veins, near the right phrenic nerve. The available data are from studies without specific diaphragmatic monitoring. The diagnosis of diaphragmatic paralysis is most often based on chest X-ray, a static examination of limited sensitivity, especially for the detection of incomplete paralysis. To date, no prospective multicentre study has evaluated the incidence of diaphragmatic paralysis after PFA with systematic dynamic imaging, such as fluoroscopy, considered the gold standard for the diagnosis of unilateral paralysis.

Detailed description

The current study, DEFINE-PFA, aims to include 250 patients spread over 9 centres (France, New-Zealand and Canada). Each patient will benefit from dynamic fluoroscopy before and after the procedure. A new fluoroscopy will be performed at 3 months in patients with a significant reduction (\>15%) in postoperative diaphragmatic amplitude.

The primary endpoint is based on the appearance of post-procedure inter-hemi diaphragmatic asymmetry, rather than a simple decrease in craniocaudal amplitude compared to the reference fluoroscopy. Indeed, the absolute diaphragmatic amplitude is highly dependent on the examination conditions, in particular the degree of cooperation of the patient and the intensity of forced inspiration, making inter-examination comparisons unreliable. Conversely, the simultaneous comparison of the two hemidiaphragms during the same inspiratory cycle makes it possible to attenuate these biases by using the contralateral hemidiaphragm as a stable internal reference. Pre-procedure fluoroscopy is nevertheless systematically performed in order to check the absence of basic asymmetry.

The threshold of 15% inter-hemi diaphragmatic asymmetry was empirically retained, in the absence of a cut-off validated in the literature for dynamic fluoroscopy. In diaphragmatic ultrasound, asymmetry is generally considered significant for differences in amplitude \> 20% between the two hemi domes, but these measurements are performed successively, which makes them sensitive to variations between respiratory cycles. Conversely, fluoroscopy allows simultaneous observation of the two hemidiaphragms during the same respiratory cycle, offering a more reliable comparison. This threshold aims to detect significant asymmetry while minimizing false positives related to physiological variability.

Interventions

• Procedure Dynamic fluoroscopy
  Fluoroscopic loop recording or continuous digital scopy of the thoracic window, over at least one complete breathing cycle at maximum amplitude.

Primary outcome measures

• Diaphragmatic paralysis [Time frame: Day1: Before the Pulsed Field Ablation and after the Pulsed Field Ablation (at hospital discharge between 2 and 30 hours after ablation, according to a rigorously standardized protocol in all participating centres)]

Secondary outcome measures (3)

• Rate of complete or partial recovery of diaphragmatic function at 3 months. [Time frame: At 3 months]
• Evaluation of symptoms associated with diaphragmatic paralysis [Time frame: Day 1, at 3 months]
• Evaluation of the efficiency of the procedure [Time frame: Day1]

Eligibility criteria

Inclusion criteria

• Men and women aged 18 years or older at the time of signing the consent (age≥ 18).
• Diagnosis of paroxysmal or persistent atrial fibrillation, documented in any type of means: ECG, Holter, invasive monitoring (memories of an implantable device) or not (connected objects).
• Indication for ablation decided as part of routine care, according to the recommendations of learned societies.
• First, ablation procedure (including pulmonary vein isolation) planned with the use of a commercially available Pulsed Field Ablation catheter.
• Possibility of performing a fluoroscopic diaphragmatic evaluation before and after the operation (before discharge from the hospital).
• Free, informed and signed consent by the patient before any data collection

Exclusion criteria

• Known history of diaphragmatic paralysis (right or bilateral) or pre-existing clinical suspicion.
• History of atrial fibrillation ablation.
• History of neuromuscular disease.
• History of major thoracic surgery or chronic pulmonary pathology that may impair diaphragmatic kinetics.
• Evidence of diaphragmatic paralysis on the pre-procedure fluoroscopy loop, defined as:

• Cranio-caudal excursion amplitude ≤35 mm on both hemidiaphragms, Or
• An asymmetry in contraction amplitude ≥15% between the two sides.
• Inability to perform a post-procedure follow-up fluoroscopy (logistical limitation, patient refusal, contraindication to irradiation).
• Pregnancy or breastfeeding in progress.
• Concurrent participation in another interventional study that may interfere with the objectives of this research.
• Major impairment in cognitive function or inability to understand the objectives of the study or sign a valid consent.
• Individuals deprived of liberty by judicial or administrative decision.
• Adults subject to a legal protection measure (guardianship, curatorship, or judicial protection/safeguard of justice).
• Individuals unable to provide informed consent.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Diagnostic

Study locations

France · 7 centers

• CHRU de Tours - Hôpital Trousseau — Chambray-lès-Tours
• CHU de Lyon - Hôpital Croix-Rousse — Lyon
• Centre Hospitalier de Pau - Hôpital François Mitterrand — Pau
• CHU de Bordeaux - Hôpital Haut-Lévêque — Pessac
• Centre Cardiologique du Nord — Saint-Denis
• Institut Cardiovasculaire de Strasbourg - Clinique Rhéna — Strasbourg
• Clinique Pasteur — Toulouse

Canada · 1 center

• Montreal Heart Institute — Montreal

New Zealand · 1 center

• Auckland City Hospital — Auckland

Identifiers

NCT: NCT07462910 · 2025-07

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗