Substrate Ablation and Remodelling in Non-paroxysmal Atrial Fibrillation (AF) (SMAAN-PAF)

Substrate Modification With Ablation and Antiarrhythmic Drugs in Non-Paroxysmal Atrial Fibrillation

The investigators hypothesise that modification of the Atrial Fibrillation (AF) substrate by radiofrequency ablation would improve single procedure success rates for Radio Frequency Ablation (RFA) for Non-paroxysmal AF when compared to that achieved with short-term peri-procedural anti-arrhythmic drug therapy alone.

Study Overview

• Status: Unknown
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Procedure: Pulmonary vein isolation (PVI); Drug: Pharmacological Substrate modification; Procedure: Pulmonary vein isolation + linear lesions

• Study Type: Interventional
• Enrollment (Anticipated): 130
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Liverpool, United Kingdom, L14 3PE
    • Liverpool Heart and Chest Hospital
  • London, United Kingdom
    • Royal Brompton and Harefield Hospitals NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ongoing symptoms (European Heart Rhythm Association Class 2 or above) in spite of treatment with rate control medication

• Non-paroxysmal atrial fibrillation, as pre-classified as

  • Persistent AF: AF requiring Electrical/ Chemical cardioversion or that lasting >7 days. These patients may be in AF or in sinus Rhythm at the time of their initial assessment and/ or at the time of their ablation.
  • Continuous Persistent AF: These patients are persistently in AF with or without antiarrhythmic drug therapy, as confirmed on a 24 hour Holter. They may have undergone previous cardioversion(s).

  • Sustained Paroxysmal AF with underlying substrate: Patients with Individual AF episode(s) lasting >12 hours but less than 7 days plus one or more of the following:

    • Age >65 years 21
    • Individual AF episode(s) lasting >24 hours
    • Significant left atrial dilatation of >45 mm on Echo (Parasternal Long Axis view)
    • Obesity (Body Mass Index >30), and/ or history suggestive of sleep apnoea
    • Diabetes Mellitus requiring hypoglycaemic drugs and/or Insulin

Exclusion Criteria:

• Inability or unwillingness to receive oral anticoagulation with warfarin
• Previous Ablation procedure for AF
• Unwillingness or inability to complete the required follow up arrangements
• Presence of long standing persistent AF with continuous AF longer than 12 months. This includes patients in whom sinus rhythm may have been maintained following electrical cardioversion for a period of less than 1 week at a stretch.
• Documented typical atrial flutter
• Prior prosthetic mitral valve replacement or severe structural cardiac abnormality
• Contraindications and/ or prior intolerance to both Amiodarone and Flecainide.
• Reversible cause for atrial fibrillation
• Known hypertrophic or infiltrative cardiomyopathy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Pulmonary vein isolation; Patients will undergo pulmonary venous isolation plus pharmacological substrate modification	Procedure: Pulmonary vein isolation (PVI); Using a 4mm irrigated tip radiofrequency ablation catheter a series of lesions >2 mm outside pulmonary vein (PV) ostia will be made to encircle and electrically isolate the pulmonary veins in two ipsilateral pairs (wide area circumferential ablation, WACA). A 20-pole PV mapping catheter will be used to confirm electrical isolation. If the patient is in atrial fibrillation at this stage, sinus rhythm would be restored with electrical cardioversion and PVI would be confirmed in sinus rhythm; Drug: Pharmacological Substrate modification; at least 6 weeks therapy with oral amiodarone prior to the ablation procedure and 6 weeks post.
Experimental: Pulmonary vein isolation + Linear Lesions; Patients will undergo pulmonary venous isolation plus both pharmacological and interventional substrate modification	Drug: Pharmacological Substrate modification; at least 6 weeks therapy with oral amiodarone prior to the ablation procedure and 6 weeks post.; Procedure: Pulmonary vein isolation + linear lesions; Using a 4mm irrigated tip radiofrequency ablation catheter a series of lesions >2 mm outside PV ostia will be made to encircle and electrically isolate the pulmonary veins in two ipsilateral pairs (wide area circumferential ablation, WACA)34. A 20-pole PV mapping catheter will be used to confirm electrical isolation. Once PVI has been achieved, patients will go onto to receive additional linear ablation lesions. These will include a left atrial roof line, mitral isthmus line, (including ablation inside the coronary sinus if necessary), and ablation on the cavotricuspid isthmus. If the patient is in atrial fibrillation at this stage, the acute end-point would be signal obliteration at the ablated area. Once sinus rhythm is restored with electrical cardioversion, PVI would be confirmed in sinus rhythm and conduction block across the LA roof line, Mitral line and CTI will then be verified with appropriate pacing manoeuvres.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Freedom from atrial fibrillation/ atrial tachycardia at 6 months following a single procedure.	Defined as >30 sec of AF/ atrial tachycardia identified on ECG or ambulatory ECG monitoring following a 3 month blanking period.	12 months

Collaborators and Investigators

• Sponsor: Liverpool Heart and Chest Hospital NHS Foundation Trust
• Investigators: Principal Investigator: Dhiraj Gupta, MD DM MRCP, Liverpool Heart and Chest Hospital

Publications and helpful links

General Publications

• Wynn GJ, DAS M, Bonnett LJ, Hall MCS, Snowdon RL, Waktare JEP, Modi S, Todd DM, Gupta D. A novel marker to predict early recurrence after atrial fibrillation ablation: the ablation effectiveness quotient. J Cardiovasc Electrophysiol. 2015 Apr;26(4):397-403. doi: 10.1111/jce.12618. Epub 2015 Feb 25.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Anticipated): November 1, 2014
• Study Completion (Anticipated): November 1, 2014

Study Registration Dates

• First Submitted: September 30, 2011
• First Submitted That Met QC Criteria: October 3, 2011
• First Posted (Estimate): October 4, 2011

Study Record Updates

• Last Update Posted (Estimate): August 22, 2013
• Last Update Submitted That Met QC Criteria: August 21, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: LHCH901