Microfidelity (MIFI) Ablation Technology Versus Standard Ablation Catheter for Atrioventricular Nodal Ablation A Comparative Pilot Study of Time to Success
Phase: NA
Conditions: Atrial Fibrillation
Sponsor: University of Florida

NCT03114124 1/25/2021 
 
 
 
 
 
 
Microfidelity (MIFI) Ablation Technology versus Standard  Ablation Catheter for 
Atrioventricular Nodal Ablation   
A Comparative Pilot Study of Time to Success 
 
 
 
 
 
 
Principal Investigator: John N. Catanzaro, MD  
Co-investigators: Robert Kim MD 
 
 
 
 
 
 
 
 
 

NCT03114124 1/25/2021 
 
 
 
 
 
 
Introduction 
In some elderly patients with atrial fibrillation (AF), especially in combination with heart failure, 
a rate control strategy may be preferred. When pharmacological therapy is ineffective or not 
tolerated, it is reasonable to perform atrioventricular (AV) node ablation with ventricular pacing 
as a class IIA indication per current guidelines [1]. 
 
Usually, the procedure is simple and straightforward and complete heart block can be achieved 
without any difficulty. However, this “simple” procedure can sometimes prove to be a most 
difficult case. The most common reason for failure to achieve complete heart block is the 
inability to localize the compact AV node using the His signal with standard intracardiac 
electrograms. As these patients come to the laboratory in AF, the His signal may be obscured by 
AF waves. In some patients with a deeper intramyocardial location of the His bundle and 
compact AV node it becomes necessary to produce deeper ablation lesions using an irrigated 
catheter to achieve block.  
 
In patients with AF, the target of ablation for the “ablate and pace” approach is the compact AV 
node, located at the apex of the triangle of Koch. Ideally, ablation is performed at the most 
proximal penetrating part of the His bundle in order to maintain a proximal automatic junctional 
rhythm and avoid pacemaker dependence.  

NCT03114124 1/25/2021 
 
 
 
Para Hisian pacing is most commonly used to reveal the presence of a septal accessory pathway. 
[2-3]  
The His bundle is a deep insulated structure and it is difficult to capture it at usual energy 
outputs. Using a high- output pacing (usually 20 mA at 2 msec) it is possible to directly capture 
the deeply situated His bundle, which is confirmed by a narrower QRS complex on the paced 
electrograms. Thus, high-output pacing can be utilized to map the His bundle area in difficult 
situations. 
 
By applying this electrophysiologic principle of differential tissue capture to help identify the 
location of the compact AV node, which is in close proximity to the His bundle.  Ventricular 
pacing was performed initially at high output to capture both the basal right ventricular 
myocardium and the His bundle and the output was gradually lowered to lose His bundle 
capture. The QRS duration is relatively narrow with high output pacing and increases when the 
pacing output is lowered, representing ventricular myocardial capture alone. Finally, loss of 
ventricular capture is seen with further reduction of pacing output. This maneuver has been 
shown to aid in determining the proximity of the ablation catheter to compact AV node as was 
validated by successful ablation at this site.  Parahisian pacing in conjunction with av nodal 
ablation has recently been described in the literature [4-5]. 
 
A novel catheter with three mini electrodes within the ablation tip (IntellaTip MiFi, Boston 
Scientific, Boston, MA) may enhance the available data for such a signal dependent technique. 
In this catheter, bipolar signals can be recorded between the three 0.8-mm-wide electrodes that 

NCT03114124 1/25/2021 
 
 
are arranged radially 1.3 mm from the end of the catheter alongside the standard distal and 
proximal bipolar recordings. Animal studies have already demonstrated that the mini electrodes 
in this novel catheter are more accurate in identifying conducting gaps in linear ablations than 
conventional electrode recordings [6]. 
Study Aims:  
The aim of our study is to investigate the comparative efficacy of high fidelity multi 
electrode ablation catheters vs the standard bipolar configuration in success of AV nodal 
ablation. Both catheters are FDA approved and are being used as indicated on its label.  For the 
purpose of this study, the standard bipolar catheter will be 8mm non-irrigated, and from the 
following list: Boston Scientific Blazer, Biosense Thermocool Non-Nav, and the St. Jude 
Sapphire. All of these catheters are currently used in ablation cases at the study site. This study 
will provide insights on the use of new technology where application may increase efficacy, 
promote patient and physician safety and decrease costs.  
 
Primary and secondary objectives 
Primary endpoints 
1. Acute success of ablation identified by a junctional rhythm or complete heart block 
2. Time from application of radiofrequency energy to acute success 
  
Secondary endpoints include 
1. Procedure time 
2. Radiation time 

NCT03114124 1/25/2021 
 
 
3. Frequency of ablation application 
4. Duration of ablation application 
 
Research Plan 
Inclusion Criterion 
1. Patients with a diagnosis of persistent or permanent atrial fibrillation 
documented on electrocardiography 
2. Patients must meet ACC/HRS guidelines for atrioventricular nodal 
ablation procedure 
3. Patients have already been scheduled for their standard of care ablation 
4. Patients must be available for at least 1 month post procedure 
5. Patients must be greater than or equal to 18 years old. 
 
Exclusion Criterion 
 
1. Patients who do not meet ACC/HRS indications for av nodal ablation 
2.  Women who are pregnant 
 
 
Research Design 
The study will be performed at the University of Florida Health Science Center at UF Health, 
Jacksonville-Division of Cardiology. Patients will be recruited in the Cardiology Clinics of 
our institution and will be screened by Cardiology Research Staff, who will verify all 

NCT03114124 1/25/2021 
 
 
candidates meet inclusion and exclusion criteria. 
Patients found eligible, n=30 for this study will already have a diagnosis of atrial fibrillation 
and be indicated for an ablation per standard of care.After providing written informed consent, 
subjects will be randomized by random computer programming to receive an ablation with 
MIFI technology or standard ablation catheter for their procedure.  Data will be collected 
prospectively (perioperatively and at follow up visit). 
During the ablation each patient will have a 3D electroanatomical map of the his bundle 
region created in addition to pacing along the region of interest.  The target will be where the 
HIS electrogram amplitude is greatest and where the QRS complex from pacing is narrowest.  
Data will be collected until the primary endpoint of success is achieved.   
 
Subjects will return to UF Shands -Jacksonville on day 30(+/- 14 days) to assess underlying 
conduction.  If conduction has returned they will be offered an additional av nodal ablation 
per standard of care.  If they undergo additional ablation this data will be included  
 
Statistics 
Sample Size Justification 
This is a pilot study in which the primary aim is to estimate the time until successful end point in each of 
the two study arms.  Thirty patients will be randomized ( 15 in each study arm).  Variable block sizes will 
be used to improve the blinding of the clinical team.  This information will then be used to design a fully-
powered randomized study to compare these two arms.  Patients will be randomly assigned to study arms.  
The project biostatistician and team will generate a set of envelopes which contain the random 
assignments for each patient.  Once a patient has consented to participate, the next envelope will be 
opened for that patient and the catheter assignment will be revealed.  This will maintain the blinding of 

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the clinical team.   
Statistical Analyses 
The baseline demographic and clinical characteristics of the patients included in this study will be 
summarized by study arms.  Frequencies and percentages will be summarized for categorical variables 
and means, standard deviations, medians, minima, and maxima will be summarized for numeric variables.  
For ordinal variables, the medians, minima, and maxima will be summarized.  Based on the descriptive 
summaries and graphical summaries (e.g. box-and-whiskers plots), if there are individual baseline 
characteristics that differ between the study arms, these characteristics will be included a regression 
analysis to reduce the estimated variance of the difference between the study arms. 
The primary analysis is the estimation of Kaplan-Meier median times to successful endpoints for each of 
the two study arms.  Time zero is when the ablation procedure begins and the successful outcomes are 
either complete heart block or junctional rhythm.  Patients in whom a successful endpoint is not reached 
will be censored at the time the procedure is stopped.  A log-rank test will also be performed to compare 
these groups.  If there are baseline characteristics that differ between the study arms based on the 
summaries described above, a Cox proportional hazards model will be fit that includes these baseline 
characteristics to adjust for these baseline differences in the study arms.   
 
Additional Information 
 
Subjects will be identified with a number and data collection sheets which will be stored 
in limited access areas, locked filing cabinets, and or in computers with security passwords. Data 
will be kept for 6 years after study completion to comply with UF and HIPAA regulations. 
Subjects will receive a hand out with names and phone numbers of the physicians and 
coordinators involved with the study.   
 
Possible Discomforts and Risks 

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The most common risks associated with the procedure are per standard of care and include but 
are not limited to cardiac perforation, tamponade, vascular injury and pain. Possible serious 
adverse events may include cardiac tamponade, preforation and or death 
Adverse Event 
An adverse event is any unintended or undesirable experience that occurs during the course of 
the clinical investigation whether or not it is considered to be therapy related.  This includes any 
newly occurring event or previous condition that has increased in severity or frequency since the 
initiation of study treatment.  Adverse events will be followed until resolution while the patient 
remains on-study.  Once the patient is removed from study, events thought to be related to the 
study therapy will be followed until resolution. 
 
Serious Adverse Event 
Serious Adverse Events (SAE): An adverse event occurring while on study and considered 
related (reasonable possibility that the study treatment caused the adverse experience) to the 
study treatment that results in any of the following outcomes: 
 Death 
 A life-threatening adverse experience. 
 A persistent or significant disability, incapacity, or is a congenital anomaly, or birth 
defect. 
 Requires inpatient hospitalization, or prolongation of existing hospitalization. 
The definition of serious adverse event also includes ‘important medical event’.  Medical and 
scientific judgment should be exercised in deciding whether expedited reporting is appropriate in 
other situations, such as important medical events that may not be immediately life-threatening 

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or result in death or hospitalization but may jeopardize the patient and/or may require medical or 
surgical intervention to prevent one of the other outcomes listed in the definition above.  These 
should also usually be considered serious.  Example of such event is an intensive treatment in an 
emergency room. 
Serious adverse events will be reported per Boston Scientific and UF  policy & procedure. 
 
Any clinical events described above will be recorded and if required reported. 
 
The investigator is responsible for informing the IRB and/or the Regulatory Authority of the 
SAE as per local requirements. 
 
Conflicts of Interest 
Dr. Catanzaro does not have any conflicts of interest 
 
Product 
The PI is not requesting catheters be included.  The catheter or product will be purchased 
separately as it is done with standard of care. 
 
References 
1. January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr, Conti JB, 15 
et. al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial 
fibrillation: executive summary: a report of the American College of 

NCT03114124 1/25/2021 
 
 
Cardiology/American Heart Association Task Force on practice guidelines and the Heart 
Rhythm Society. Circulation. 2014;130 :2071-04. 
2. Hoffmayer KS, Scheinman M. Current role of atrioventricular junction (AVJ) ablation. 
Pacing Clin Electrophysiol. 2013;36:257 - 65. 
3. Hirao K, Otomo K, Wang X, Beckman KJ, McClelland JH, Widman L, Gonzalez MD,et. 
al . Para- Hisian pacing. A new method for differentiating retrograde conduction over an 
accessory AV pathway from conduction over the AV node. Circulation. 1996;94:10. 
4. Ip JE, Cheung JW, Liu CF, Thomas G, Markowitz SM, Lerman BB. Ablating the Imperceptible: 
A Novel Application of Para-Hisian Pacing. Pacing Clin Electrophysiol. 2016 May 26. 
doi: 10.1111/pace.12898 
5. Kanjwal K1, Grubb BP. Utility of High-Output His Pacing during Difficult AV Node 
Ablation. An Underutilized Strategy. Pacing Clin Electrophysiol. 2016 Jun;39(6):616-9. 
doi: 10.1111/pace.12829 
6. Price A, Leshen Z, Hansen J, Singh I, Arora P, Koblish J, et al. Novel ablation catheter 
technology that improves mapping resolution and monitoring of lesion maturation. J 
Innovations Card Rhythm Manage 2012; 2:1–11.