Substrate-Targeted Catheter Ablation to Treat Persistent Atrial Fibrillation
Phase: NA
Conditions: Persistent Atrial Fibrillation
Sponsor: Abbott Medical Devices

 
Clinical Investigational Plan Synopsis 
Study Name: Substrate-targeted Catheter Ablation to 
Treat Atrial Fibrillation Ver. 1.0 11MAR2015 
Clinical Investigational Plan Synopsis 
 
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Title: 
Substrate-Targeted Catheter Ablation to Treat Persistent Atrial Fibrillation 
Acronym: 
AF Substrate Mapping and Guided Ablation 
Purpose: 
Evaluate the feasibility of substrate-targeted catheter ablation to treat 
Persistent AF   
Objectives: 
Primary Objective 
 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) 
 
Secondary Objective 
 Map and characterize electrophysiological substrates during AF, 
including regular and fast activities, complex fractionated 
electrograms, wave front propagation directions, and fibrosis 
Endpoints: 
Primary Endpoint 
Twelve-month clinical success rate defined as  
 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. 
 
Secondary Endpoint 
- 
Collect maps that identify substrates that could serve as mechanisms 
of AF maintenance, such as: 
o Areas with fast but regular activities  
o Areas with consistent wave front propagation pattern  
o Areas with low P-P voltage  
o Areas with complex fractionated electrograms  
- 
Acute AF termination or significant AF cycle length slowing during 
RF application in ablation procedure 
- 
Inducibility of AF by programmed stimuli at the end of the ablation 
procedure before and after administration of Isoproterenol 
- 
Freedom from symptomatic atrial tachycardia and atrial flutter off 
antiarrhythmic drug therapy assessed from the end of the 3 months 
blanking period to 12 months following the ablation procedure, 
documented by ILR monitoring or TT ECG monitoring 
- 
Freedom from asymptomatic AF, atrial tachycardia, and atrial flutter 
off antiarrhythmic drug therapy assessed from the end of the 3 months 
blanking period to 12 months following the ablation procedure, 
documented by ILR monitoring or TT ECG monitoring 
- 
Need for a new ablation procedure 
- 
Need to prescribe antiarrhythmic drugs after the blanking period 
AF burden measured by ILR at follow-up visits 

 
Clinical Investigational Plan Synopsis 
Study Name: Substrate-targeted Catheter Ablation to 
Treat Atrial Fibrillation Ver. 1.0 11MAR2015 
Clinical Investigational Plan Synopsis 
 
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Design: 
Prospective, single center, randomized, single-blind, controlled, 2-arm 
parallel group trial in Milan, Italy (Pr. Pappone, Targeted Research Center) 
 
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 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. 
Devices used: 
- 
EnSiteTM VelocityTM mapping system (CE marked) 
- 
InquiryTM AFocusIITM diagnostic catheter (CE marked) 
- 
EnSite Velocity Research Platform consisting of: 
o EnSite Velocity Research Display Workstation (CE marked) 
o EnSite Velocity Research Switch (OEM CE marked) 
o EnSite Velocity Research software (not CE marked) 
- 
Any commercially available Radiofrequency (RF) ablation system   
- 
Any commercially available irrigated tip RF ablation catheter 
(minimum 4 electrodes)  
- 
Any CE-marked EP diagnostic catheter (minimum 4 electrodes) 
Study Population 
Patients with persistent AF scheduled to undergo first or second time catheter 
ablation with approved standard indication by ESC/EHRA Guidelines 
Inclusion/Exclusion 
Criteria  
Inclusion Criteria 
1. Age between 18 and 85 years  
2. Persistent AF 
3. Ability to provide informed consent for study participation and be willing 
and able to comply with study evaluations and follow-up schedule 

 
Clinical Investigational Plan Synopsis 
Study Name: Substrate-targeted Catheter Ablation to 
Treat Atrial Fibrillation Ver. 1.0 11MAR2015 
Clinical Investigational Plan Synopsis 
 
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Exclusion Criteria 
1. Two or more previous AF ablations  
2. Secondary AF  
3. Hyperthyroidism  
4. Left ventricular ejection fraction <30%  
5. NYHA functional class IV  
6. Left atrial area > 35 cm2 
7. Uncorrected severe valvular heart disease  
8. Contraindication to anticoagulation  
9. Presence of left atrial thrombus  
10. Recent (<6 Months) myocardial Infarction or unstable angina or 
coronary artery by-pass  
11. Thoracic surgery for congenital, valvular or aortic disease  
12. History of cerebrovascular accidents  
13. Pregnancy  
14. Significant comorbidities such as cancer, severe renal insufficiency 
requiring hemodialysis, severe obstructive lung disease, cirrhosis, with a 
life expectancy less than 2 years 
Data Collection 
- 
Pre-procedure: Data collection per standard clinical practice for 
patients undergoing AF ablation 
- 
During-procedure: EnSite Velocity Study Backup DVDs, including 
3D geometry of LA, contact maps collected by AFocus II catheter, 
electrograms, RF lesion locations, marker locations, electrode 
locations, user annotations, events of acute AF termination or  
significant CL slowing 
Post-procedure: AF recurrence documented by ILR or TT ECG monitoring 
 
 

 
Clinical Investigational Plan Synopsis 
Study Name: Substrate-targeted Catheter Ablation to 
Treat Atrial Fibrillation Ver. 1.0 11MAR2015 
Clinical Investigational Plan Synopsis 
 
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1. 
Study Flow Chart 
 
 

 
Clinical Investigational Plan Synopsis 
Study Name: Substrate-targeted Catheter Ablation to 
Treat Atrial Fibrillation Ver. 1.0 11MAR2015 
Clinical Investigational Plan Synopsis 
 
Page 5 of 5 
 
 
 
2. 
Statistical analysis 
In subjects with persistent AF, it is possible to demonstrate a one-year clinical difference among 
the two therapies with a significance level of 0.5 and a power of 0.80 using a Log-rank test in 38 
subjects per group, estimated success of 50% and 80% in the control arm and mapping arm, 
respectively. The expected difference is based on extensive experience of the operators. 
Considering 5% drop-out rates, thus a total of 80 subjects will be included and assigned to either 
treatment group according to a randomization schedule stratified by the previous ablation 
procedures (none and one previous ablation procedure). Categorical and continuous variables are 
expressed as absolute and relative frequencies or as mean±SD or median (interquartile range 
[IQR]) as appropriate. Comparisons of continuous variables were done with a Student t-test or 
the Mann-Whitney U test as appropriate and binomial variables with chi-square or Fisher test. 
Long-term outcome was assessed, after a single ablation procedure, by Kaplan-Meier method and 
compared using the log rank test. A 2-tailed probability value of ≤ 0.05 was deemed significant. 
Statistical analyses were conducted using SPSS (SPSS v22, USA).