AF Substrate Mapping and Guided Ablation

Substrate-Targeted Catheter Ablation to Treat Persistent Atrial Fibrillation

In this study, the investigators aim to identify and characterize, by means of an EnSite Velocity Research Software, the electrophysiological characteristics of substrates that sustain AF in patients with persistent AF and to test whether ablation of such patient-specific substrates might improve the acute and long-term success of conventional catheter ablation therapy.

Study Overview

• Status: Completed
• Conditions: Persistent Atrial Fibrillation
• Intervention / Treatment: Device: mCPVA; Device: Substrate+mCPVA

Detailed Description

This study is a prospective, single center, randomized, single-blind, controlled, 2-arm parallel group trial in Milan, Italy.

The total duration of the study is expected to be 24 months with ~12 months of enrollment.

Approximately 80 subjects suffering from persistent AF will be randomized in a 1:1 fashion to the following investigation arms:

• Modified circumferential pulmonary vein ablation alone (mCPVA);

• Substrate-targeted ablation guided by AF substrate mapping, followed by completion of modified circumferential pulmonary vein ablation (Substrate+ mCPVA)

  • Ablate the areas that have fast and regular electrical activities, starting from the fastest cycle length (defined by Mean CL in the range of 120-250 milliseconds, and SD CL in the range of 1-30 milliseconds
  • Ablate the areas that have consistent rotational or focal propagation pattern (defined by conduction velocity vectors)
  • Ablate the areas that comprises the slow conduction zone of possible arrhythmia circuits
  • If AF terminates during RF ablation, stimulation protocol will be used to examine if AF is re-inducible. If AF sustains or is re-inducible and physician decides to remap, mapping will be performed again for substrate-targeted ablation. If AF is not re-inducible, mCPVA will be completed

Subjects will be followed up at 3, 6, 12 months.

The primary objective of the study is to assess acute and long-term outcome of patient-tailored substrate-targeted ablation (Substrate) plus modified circumferential pulmonary vein ablation (Substrate+mCPVA) versus modified circumferential pulmonary vein ablation alone (mCPVA). The secondary objective of the study is to map and characterize electrophysiological substrates during AF, including regular and fast activities, complex fractionated electrograms, wave front propagation directions, and fibrosis.

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • MI
    • San Donato Milanese, MI, Italy, 20097
      • I.R.C.C.S. Policlinico San Donato

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 - 85 years of age
• Persistent AF scheduled to undergo catheter ablation with approved standard indication by ESC/EHRA guidelines
• First or second time ablation for persistent AF
• Ability to provide written informed consent for study participation and be willing and able to comply with the study evaluations and follow up schedule

Exclusion Criteria:

• Had two or more previous AF ablation procedures
• Secondary AF
• Hyperthyroidism
• Left ventricular ejection fraction <30%
• NYHA functional class IV
• Left atrial area > 35 cm2
• Uncorrected severe valvular heart disease
• Contraindication to anticoagulation
• Presence of left atrial thrombus
• Recent (<6 Months) myocardial Infarction or unstable angina or coronary artery by-pass
• Thoracic surgery for congenital, valvular or aortic disease
• History of cerebrovascular accidents
• Pregnancy
• Significant comorbidities such as cancer, severe renal insufficiency requiring hemodialysis, severe obstructive lung disease, cirrhosis, with a life expectancy less than 2 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: mCPVA; Subjects in the mCPVA arm will undergo intervention called "modified circumferential pulmonary vein ablation", which is considered to be the standard ablation treatment for AF.	Device: mCPVA; The intervention in the active comparator arm includes using the commercially available EnSite Velocity mapping and ablation system for modified circumferential pulmonary vein ablation.
Experimental: Substrate+mCPVA; Subjects in the Substrate+mCPVA arm will undergo intervention of substrate mapping and substrate-targeted ablation guided by the investigational device, followed by completion of modified circumferential pulmonary vein ablation.	Device: Substrate+mCPVA; The intervention in the experimental arm includes using a research software (investigational device) to map AF substrate and guide ablation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long-term Clinical Success Rate	Freedom from symptomatic AF off antiarrhythmic drug therapy assessed from the end of the 3 months blanking period to 12 months following the ablation procedure, documented by implantable loop recorder (ILR) monitoring or trans-telephonic (TT) ECG monitoring.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Ablation Procedure Outcome	Acute AF termination or significant AF cycle length slowing during RF application in ablation procedure	During Ablation

Collaborators and Investigators

• Sponsor: Abbott Medical Devices
• Investigators: Principal Investigator: Carlo Pappone, MD, PhD, I.R.C.C.S. Policlinico San Donato

Publications and helpful links

General Publications

• Pappone C, Ciconte G, Vicedomini G, Mangual JO, Li W, Conti M, Giannelli L, Lipartiti F, McSpadden L, Ryu K, Guazzi M, Menicanti L, Santinelli V. Clinical Outcome of Electrophysiologically Guided Ablation for Nonparoxysmal Atrial Fibrillation Using a Novel Real-Time 3-Dimensional Mapping Technique: Results From a Prospective Randomized Trial. Circ Arrhythm Electrophysiol. 2018 Mar;11(3):e005904. doi: 10.1161/CIRCEP.117.005904.

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): February 1, 2017
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: July 27, 2015
• First Submitted That Met QC Criteria: October 6, 2015
• First Posted (Estimate): October 8, 2015

Study Record Updates

• Last Update Posted (Actual): July 5, 2019
• Last Update Submitted That Met QC Criteria: April 16, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: atrial fibrillation; ablation; mapping; substrate
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: SJM-CIP-10054