Dynamic Data-Driven Management of Atrial Fibrillation Using Implantable Cardiac Monitors: The MONITOR-AF Study
Conditions: Atrial Fibrillation
Sponsor: Kansas City Heart Rhythm Research Foundation

 
 
 
Dynamic Data-Driven Management of Atrial Fibrillation Using 
Implantable Cardiac Monitors: The MONITOR-AF Study 
 
 
 
 
 
NCT06352060 
 
 
 
 
 
 
 
 
 
 
Version 1.5 
Last Updated 2.9.2024 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Protocol Template, Version 2.0 
 
 
Dynamic Data-Driven Management of Atrial Fibrillation Using Implantable Cardiac Monitors: The 
MONITOR-AF Study 
 
 
Primary Investigator:  
Dhanunjaya Lakkireddy MD, MBA1 
 
Co-Investigators: 
Jalaj Garg MD2, Poojita Shivamurthy MD3, Mina Chung MD4, Luigi DiBiase MD5, Andrea Natale MD6 
 
 
 
 
 
SPONSOR PROTOCOL NO.: KCHRRF_MONITOR AF_0030 
 
 
 
 
 
 
 
Supported by: 
Kansas City Heart Rhythm Research Foundation 
 
 
 
 
 
 
 
 
 
 
 
 
 
Version 1.5 
Last Updated 2.9.2024

Protocol Template, Version 2.0 
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AUTHOR AFFILIATIONS 
1Kansas City Hearth Rhythm Institute, Overland Park, KS 
2Loma Linda University Health, Loma Linda, CA 
3University of Pennsylvania, Philadelphia, PA 
4Cleveland Clinic, Cleveland, OH 
5Montefiore Medical Center, Bronx, NY 
6Texas Cardiac Arrhythmia Institute, Austin, TX 
 
 
 
 

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ABBREVIATIONS 
AAD – antiarrhythmic drug 
AE – adverse events 
AF – atrial fibrillation 
CA – catheter ablation 
ECG – electrocardiogram  
ICM – implantable cardiac monitor 
IRB – Institutional Review Board 
KCHRRF – Kansas City Heart Rhythm Research Foundation 
MCOT – mobile cardiac outpatient telemetry 
OAC – oral anticoagulation 
SAE – serious adverse events 
 
 

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1 
STUDY OBJECTIVES 
1.1 
Primary Objective 
• 
Evaluate the differences in outcomes between implantable cardiac monitors (ICM) and routine 
management in patients with atrial fibrillation (AF). 
• 
Freedom from AF and continued anti-arrhythmic drug (AAD) and oral anticoagulation (OAC) use 
following ICM implantation.  
1.2 
Secondary Objectives 
• 
To evaluate differences in catheter ablation (CA) and AAD for rhythm control and AF-related 
complications in those with and without ICM.  
2 
BACKGROUND AND RATIONALE  
2.1 
Background on Condition, Disease, or Other Primary Study Focus 
AF is the most frequent cardiac arrhythmia, with a global prevalence that is only expected to increase. A 
significant number of patients – up to 38% – may be asymptomatic, making management more difficult. 
[1] Regardless of symptoms, AF is associated with significant morbidities, including but not limited to 
heart failure, stroke, dementia, and death.  
 
The management of AF is complex, with clinical decisions related to rate and rhythm control strategies 
with AADs and CA and stroke prevention. Like other chronic diseases, frequent routine assessments help 
select, assess, and change management strategies. Implantable cardiac monitors (ICMs) are another 
option that store electrocardiogram (ECG) tracings for years at a time, enabling continuous monitoring, 
assessment of AF burden, and therapy efficacy. Previous studies have demonstrated a threefold 
increase in AF detection, including asymptomatic AF in cryptogenic stroke, syncope, and after CA. using 
ICMs.[2-4] Their use in AF management has gained popularity for this reason.  
2.2 
Study Rationale 
Even with its increasing popularity and use, the impact of ICMs on AF management is still being 
determined and can even be conflicting. Furthermore, the use of ICM is dependent on physician 
preference. We hypothesize that dynamic monitoring with ICMs is superior to conventional methods 
and should be used for all patients with AF. Thus, we aim to measure the outcomes of using ICM versus 
more traditional approaches in patients with AF.  
 
3 
STUDY DESIGN 
We propose a multi-center, retrospective study to evaluate the use of ICM versus traditional, non-ICM 
methods such as ECGs, Holter, and mobile cardiac outpatient telemetry (MCOT) units, referred to as 
non-ICM from here on out, from 2018 to 2021. The primary outcome will be the evaluation of AF 
freedom at 12 months with continued AAD and OAC use. Secondary outcomes are described above. This 
study will be approved by the Institutional Review Board (IRB), and patient consent will not be required 
due to the nature of the study.   

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4 
SELECTION AND ENROLLMENT OF PARTICIPANTS  
4.1 
Study Enrollment Procedures 
4.1.1 
Screening 
Patients will be identified for screening via diagnosis codes for AF on chart review. This can be easily 
identified by querying current electronic medical record systems. If needed, patients with ICMs can be 
identified by lists maintained at each study center of those who undergo ICM insertion.  
4.1.2 
Consent and Enrollment 
Patients who meet inclusion and exclusion criteria after screening will be directly enrolled in the study. 
No randomization will occur, but patients will be separated into an ICM and non-ICM arm. We will enroll 
approximately 2500 patients [n=1250 (ICM) and n=1250 (non-ICM)] from 2018-2021. No consent will be 
required due to the nature of the study. 
4.2 
Inclusion Criteria  
• 
Patients > 18 years of age 
• 
Present for management of AF 
• 
ICM is inserted at the discretion of the treating physician 
4.3 
Exclusion Criteria  
• 
Patients < 18 years of age 
• 
Presence of a permanent pacemaker, implantable cardiac defibrillator, or cardiac 
resynchronization therapy 
• 
Unable to tolerate ICM or traditional monitoring with ECG, Holter, or MCOT monitoring 
• 
Unable to tolerate AAD, OAC, and CA as part of AF standard of care 
• 
ICM inserted for cryptogenic stroke or syncope 
• 
Was not followed > 12 months 
• 
CA performed for AF before ICM implant 
4.4 
Adherence 
The Investigator may make no changes or amendments to this protocol after the protocol has been 
agreed to and signed by all parties unless such change(s) or amendment(s) have been thoroughly 
discussed and agreed upon by the Investigator, the IRB, or the sponsor. Any change or amendment 
decided upon will be recorded in writing, the Investigator and the Sponsor will sign the written 
agreement, and the signed agreement will be appended to this protocol. 
 
5 
STUDY INTERVENTIONS  
5.1 
Interventions, Administration, and Duration  
No intervention or administration will be performed due to the observational nature of each phase. 
Charts of patients enrolled in the study will be reviewed for an initial monitoring method, any changes in 

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management, including AAD, OAC, CA, as per physicians' preference, arrhythmia recurrence, need for 
redo CA, and AF-related complication, for 12 months after enrollment. Lastly, the primary outcomes of 
AF freedom and continued AAD and OAC use will be noted at the end of the study duration.  
5.2 
Handling of Study Interventions  
Screening, enrollment, and data collection will be performed by the Electrophysiology team and Kansas 
City Heart Rhythm Research Foundation (KCHRRF) members or respective institutions. Once data is 
collected, it will be analyzed by KCHRRF staff.  
 
6 
STUDY PROCEDURES 
6.1 
Description of Evaluation 
Table 1. Variables for data collection will include but are not limited to the following. 
  
Variables 
Description and Definition 
Age 
## Years  
Gender 
0 = Male, 1 = Female 
BMI 
## kg/m2 
Race 
0 = Caucasian, 1 = African American, 2 = Hispanic, 
3 = Asian, 4 = Other 
Hypertension 
0 = No, 1 = Yes 
Hyperlipidemia 
0 = No, 1 = Yes 
Diabetes Mellitus 
0 = No, 1 = Yes 
Coronary Artery Disease 
0 = No, 1 = Yes 
CVA/TIA 
0 = No, 1 = Yes 
Peripheral Artery Disease 
0 = No, 1 = Yes 
Obstructive Sleep Apnea 
0 = No, 1 = Yes 
Compensated HF (EF > 35%) 
0 = No, 1 = Yes 
History of Smoking 
0 = No, 1 = Yes 
Thyroid Dysfunction 
0 = None, 1 = Hypothyroidism, 2 = 
Hyperthyroidism 
Chronic Obstructive Pulmonary Disease 
0 = No, 1 = Yes 
Gastrointestinal Disorders 
0 = No, 1 = Yes 
CHADS2VASC2 Score 
## 
Antiarrhythmic Drug 
 
History of Cardioversion 
0 = No, 1 = Yes 
Baseline AAD Use 
0 = No, 1 = Yes 
Duration of Arrhythmia 
## Mos. 
Left Atrial Size 
## cm. 
Left Ventricular Ejection Fraction 
## % 
Access to EP 
0 = No, 1 = Yes 
Compliance to OAC 
0 = No, 1 = Yes 
Attempted AAD  
0 = No, 1 = Yes 
Need for Catheter Ablation 
0 = No, 1 = Yes 
Time to Catheter Ablation 
## Days 
Number of Monitors used Post-CA 
## 

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Type of Monitors Used 
0 = MCOT, 1 = 48-Hr Holter 
Need for Redo Ablation 
0 = No, 1 = Yes 
Time to Redo Ablation 
## Days 
CV-Related Hospital Duration 
## Days 
Length of Stay 
## Days 
AF-Related Hospitalization 
0 = No, 1 = Yes 
HF-Related Hospitalization 
0 = No, 1 = Yes 
Bleeding Complication 
0 = No, 1 = Yes 
Stroke and TIA 
0 = No, 1 = Yes 
Freedom of AF at 12 Mos. 
0 = No, 1 = Yes 
Continued OAC Use 
0 = No, 1 = Yes 
Continued AAD Use 
0 = No, 1 = Yes 
 
Abbreviations: BMI – body mass index, CVA = cerebrovascular accident, TIA – transient ischemic 
attack, AAD = antiarrhythmic drug, CV – cardiovascular, CA = catheter ablation, AF – atrial fibrillation, 
HF – heart failure, OAC – oral anticoagulation, MCOT – mobile cardiac outpatient telemetry 
6.2 
Randomization 
No randomization will occur due to the nature of the study.  
6.3 
Follow-up Visits 
Follow-up will occur up to 12 months after enrollment into the study. Follow-up visits and management 
changes will occur at the treating physician's discretion.  
 
7 
SAFETY ASSESSMENTS  
There are no safety concerns for this study. Adverse AF, AAD, OAC, and ICM insertion events will be 
noted as outcomes.  
 
8 
INTERVENTION DISCONTINUATION  
The study will only be discontinued if instructed by the IRB, primary investigator, or other oversight 
organization. 
 
9 
STATISTICAL CONSIDERATIONS  
9.1 
General Design Issues  
The null hypothesis is that there is no difference in outcomes between patients who underwent ICM 
insertion versus more traditional monitoring methods. Patients who start with traditional monitoring 
can cross into the ICM group at any time throughout the study. Primary and secondary endpoints are 
described below. 

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9.2 
Sample Size and Randomization 
We will aim for 2500 enrolled participants to result in a 99% power for statistical significance, assuming 
no difference in AAD, OAC, or CA use rates between those with ICM and non-ICM monitoring methods. 
We cannot control the exact number of subjects but will attempt a 1:1 allocation into the ICM and non-
ICM arms to result in 1250 patients each.  
 
9.3 
Outcomes  
Primary 
Secondary 
• 
Access to care 
• 
Time of AAD initiation 
• 
Time of OAC initiation 
• 
Time to CA 
• 
Any changes or discontinuation of AAD post-
ablation 
• 
Any changes or discontinuation of OAC post-
ablation 
• 
Arrhythmia recurrence 
• 
Redo Ablation 
• 
Systemic thromboembolic events 
• 
All AF and cardiovascular related 
hospitalization 
• 
Heart failure exacerbations 
• 
Bleeding complications 
• 
Cardiovascular mortality 
 
 
9.4 
Data Analyses 
Statistical analysis will be performed on both continuous and categorical variables. As appropriate, 
continuous variables will be reported as mean ± standard deviation and compared with two-tailed T-
tests and Mann-Whitney testing. Categorical variables will be reported as frequency and percentages 
and compared with Chi-square testing as appropriate. Cox proportional regression models will be used 
for hazard ratios and confidence intervals. A p-value < 0.05 will be used to determine statistical 
significance. Kaplan-Meier graphs will be calculated when appropriate. We will use SPSS [IBM, Armonk, 
New York] for all statistical analysis.  
10 DATA COLLECTION AND QUALITY ASSURANCE 
10.1 Data Collection 
Data will be collected at each site(s) and recorded in paper or electronic forms. 
10.2 Data Management  
Physical and identifying data will be housed in a locked space at each site. De-identified data will be 
entered into a secure database at the KCHRRF system, from which they can be analyzed.  
 

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11 PARTICIPANT RIGHTS AND CONFIDENTIALITY  
11.1 Institutional Review Board Review 
This protocol and any subsequent modifications will be reviewed and approved by the IRB or ethics 
committee responsible for oversight of the study. Study activities should not begin until the document 
has been approved by the IRB of the investigator’s institution or by a central IRB. Patient consent will 
not be required due to the nature of the study.  
11.2 Participant Confidentiality  
All reports and communications relating to patients in the study will identify each patient only by an 
investigative site number, the patient’s initials, or the patient’s study number. The investigator will 
maintain a patient identification log containing identifying information for each patient enrolled in the 
study.  This document should contain sufficient information and detail to permit the identification of 
study patients in case follow-up is required.  This information should be treated with strict adherence to 
professional standards of confidentiality and be kept by the investigator under adequate security and 
restricted access along with other study records. 
11.3 Study Discontinuation  
The IRB or principal investigator may discontinue the study at any time as part of their duties to ensure 
that research participants are protected.  
 
12 ETHICAL CONSIDERATIONS 
The study will undergo IRB approval and thus meet all institutional ethical guidelines. All other ethical 
considerations shall be per the Declaration of Helsinki.  
 
13 PUBLICATION OF RESEARCH FINDINGS 
Publication of the results of this trial will be governed by the policies and procedures developed.   
14 
REFERENCES 
1. 
Israel, C.W., et al., Long-term risk of recurrent atrial fibrillation as documented by an implantable 
monitoring device. Journal of the American College of Cardiology, 2004. 43(1): p. 47-52. 
2. 
Reiffel, J.A., et al., Rhythm monitoring strategies in patients at high risk for atrial fibrillation and 
stroke: A comparative analysis from the REVEAL AF study. Am Heart J, 2020. 219: p. 128-136. 
3. 
Svendsen, J.H., et al., Implantable loop recorder detection of atrial fibrillation to prevent stroke 
(The LOOP Study): a randomised controlled trial. The Lancet, 2021. 398(10310): p. 1507-1516. 
4. 
Reiffel, J.A., et al., Incidence of Previously Undiagnosed Atrial Fibrillation Using Insertable 
Cardiac Monitors in a High-Risk Population: The REVEAL AF Study. JAMA Cardiology, 2017. 2(10): 
p. 1120-1127.