Inflammatory and Endothelial Function Response, and Arrhythmia Recurrence Following Catheter Ablation for Atrial Fibrillation

Not Applicable

Withdrawn

• Conditions: Paroxysmal Atrial Fibrillation; Persistent Atrial Fibrillation
• Interventions: Device: Radiofrequency ablation; Device: Cryoballoon ablation

• Registration Number: NCT04269785
• Lead Sponsor: Karan Saraf

Brief Summary

Current international guidelines recommend a three-month blanking period after pulmonary vein isolation (PVI) for atrial fibrillation (AF). Early recurrence of atrial tachyarrhythmia (ERAT; comprising of AF, left atrial tachycardia and atrial flutter) is common, occurring in up to 65% of patients, but in the first month is generally thought not to predict long-term AF recurrence, and re-intervention is not recommended. Suggested causes for ERAT include inflammation and arrhythmogenic structural changes caused by ablation lesions. Early, purely inflammatory ERAT would not lead to late AF recurrence as pulmonary vein reconnection is established as the main factor associated with long-term recurrence in paroxysmal AF. Previous studies have shown ERAT in the second to third month (rather than first month) to be a stronger predictor of late AF recurrence, due to presumed reduction in the contribution of the acute inflammatory response after this. Biochemical data have shown that the post-ablation inflammatory phase is usually limited to the first month after both radiofrequency (RF) and cryoballoon (CB) ablation, though inflammatory markers have been shown to be less elevated following CB PVI. Histologically, lesions formed by the two modalities differ significantly. RF lesions are characterised by irregular boundaries and significant disruption to the endothelium, exposing the sub-endothelial layer and resulting in significant and sustained platelet activation, changes which can last for many months. CB lesions on the other hand, are observed as well demarcated and homogenous within one week, with reduced thrombogenicity, which may lead to reduced inflammation. ERAT following CB ablation cannot be accurately predicted by inflammatory response and it is postulated that endothelial function may play a role in the development of ERAT in such patients. Some studies have shown reduced recurrence rate and re-hospitalisation amongst the CB population, including the FIRE and ICE trial, potentially resulting in a better patient experience with CB and the possibility of a shorter blanking period. Post-ablation inflammatory response is more predictive of ERAT following RF than CB PVI, and the latter is considered to be associated with less inflammation. There is however, a paucity of data evaluating endothelial function post-AF ablation and its correlation with ERAT or late recurrences of arrhythmia. Given that earlier re-intervention in patients with ERAT in the third month of the blanking period can result in greater outcomes with respect to late recurrence of AF, if it can be demonstrated that endothelial function testing in the first few months post-CB PVI can be predictive of later ERAT, then shortening the blanking period following CB PVI and performing repeat ablation to control troublesome later ERAT may reduce overall patient morbidity and re-hospitalisation.

The purpose of this novel pilot study is to examine the relationship between the post-ablation inflammatory response, endothelial function and timing and frequency of ERAT for patients undergoing RF and CB PVI for paroxysmal or short-lived persistent (less than 6 months' duration) AF. If the initial data provides hypothesis generating information, the aim would be to perform the study on a larger basis with higher statistical power to determine whether early post-ablation endothelial function testing can predict recurrences and identify those suitable for earlier re-intervention.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-01-23
• Study First Submitted QC: 2020-02-11
• Study First Posted: 2020-02-17
• Study Start: 2023-01-30
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-29
• Last Update Posted: 2023-11-01
• Primary Completion: 2024-01-30
• Study Completion: 2024-06-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Radiofrequency ablation	Radiofrequency ablation	These patients will receive ablation by radiofrequency catheter, guided by of 3-dimensional electro-anatomic mapping technology
Cryoballoon ablation	Cryoballoon ablation	These patients will receive ablation by cryoballoon catheter, guided by X-ray fluoroscopy

Primary Outcome Measures

Name	Time	Method
Incidence of recurrence of atrial arrhythmia in the 3 months following ablation	3 months	Whether patients have experienced a recurrence of atrial arrhythmia (AF, left atrial flutter or left atrial tachycardia) in the 3 months following their ablation

Secondary Outcome Measures

Name	Time	Method
Rate and degree of rise of inflammatory markers in the 3 months following ablation	3 months	Inflammatory blood markers such as CRP
Degree of endothelial dysfunction in the 3 months following ablation (EndoPAT testing)	3 months	Endothelial function measured using the EndoPAT technology