Comparison of Holter With Leadless Patch Ambulatory Electrocardiographic Monitoring in Children
Phase: NA
Conditions: Arrhythmias, Cardiac, Heart Block
Sponsor: Columbia University

NCT03309956 
 
 
 
 
 
 
 
 
 
Protocol: AAAR5436 
Principal Investigator: Liberman, Leonardo 
Title: Comparison of Holter with Leadless Patch Ambulatory Electrocardiographic Monitoring in Children 
Version Date (Last IRB Approved): 9/26/2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Study Purpose and Rationale:  
The utility of ambulatory electrocardiography has been reported using a variety of devices, including the 
short-term (24- to 48-hour) Holter monitor and the longer term event monitor (7-30 days). Each 
monitoring modality has its strengths and limitations. The Holter monitor can detect asymptomatic 
arrhythmias by continuously recording, however the multiple leads are cumbersome and it is not ideal 
for capturing infrequent arrhythmias because of the short wear time. The Holter monitor’s ability to 
detect an arrhythmia, or diagnostic yield, was 10% in a retrospective study of 1319 children. The event 
monitor is preferred for infrequent arrhythmias, however it requires cognitive capacity to press a trigger 
button, and patient compliance may be difficult in the pediatric population. The adhesive patch monitor 
(Zio Patch; iRhythm Technologies, San Francisco, California) is a single-lead, intermediate-duration, 
water-resistant adhesive patch monitoring device that can continuously record for up to 14 days. The 
Zio patch has demonstrated great utility in the adult population as it detected more arrhythmias in the 
first 24 hours as compared with the Holter monitor when worn simultaneously. In a retrospective study 
of 3,209 pediatric patients across the United States who used the Zio patch, the diagnostic yield was 
12%.While both the Holter and the Zio patch are continuously recording and are able to detect 
asymptomatic arrhythmias, to date there has been no direct comparisons of the diagnostic yield (ability 
to detect an arrhythmia) of the Holter monitor versus the Zio patch in the pediatric population. 
Study Design:  
Pediatric patients less than or equal to 21 years at Children’s Hospital of New York (CHONY) who are 
referred for ambulatory ECG monitoring will be consented and enrolled prospectively to have the Holter 
monitor and the Zio patch placed simultaneously in the pediatric cardiology clinic. Patients will be 
instructed to wear both devices for 48 hours. Demographic data will be collected, including date of birth, 
age, gender, weight, height, chest circumference, body surface area, indication for ambulatory ECG 
monitoring, prior congenital heart disease, prior cardiac surgery, and prior Holter or Zio patch use. A one 
page patient satisfaction survey will be given to the patient and parent/guardian after completion of the 
study to compare the comfort, interference with daily activities, adverse events (such as skin irritation 
or if either device fell off), and preference for each device. Holter monitors will be returned to the clinic 
along with the patient satisfaction survey, and the Zio patch will be mailed back to manufacturer 
headquarters and the report will be returned to us. Primary Objective: This prospective study aims to 
compare the diagnostic yield of the Holter monitor versus the Zio patch in children by having patients 
wear both devices simultaneously for 48 hours. We will compare the incidence of specific abnormal 
heart rhythms using each device, specifically supraventricular tachycardia 4 beats (SVT), ventricular 
tachycardia 4 beats (VT), advanced second degree or complete heart block, atrial flutter or fibrillation 
(AF), pause > 3 seconds, premature ventricular contractions (PVCs) > 5%, premature atrial contraction 
(PACs) > 5%, and presence of preexcitation suggestive of Wolff-Parkinson-White syndrome 
(WPW).Secondary objective: We will compare the minimum, maximum, and average heart rates, as well 
as the percent analyzable data for each device over the 48 hours.Tertiary objective: To determine if age, 
weight, gender, presence of congenital heart disease, or prior cardiac surgery had an effect on 
diagnostic yield of Holter monitor versus the Zio patch.Quaternary objective: To compare the patient 
and/or parental satisfaction for the Holter monitor versus the Zio patch using a one page survey at the 
end of the 48 hour study. 
 

Statistical Procedures:  
Descriptive statistics will be used for patient demographics and survey results. To compare presence or 
absence of any of the clinically significant arrhythmias (SVT > 4 beats, VT > 4 beats, advanced second 
degree or complete AV block, atrial fibrillation or flutter, pause > 2 seconds, PVCs > 5%) over 48 hours, 
McNemar’s test will be used. Further subgroup analysis of each of the arrhythmia types can be done 
between the 2 devices using McNemar’s test again. Logistic regression will be used to determine if age, 
weight, gender, presence of congenital heart disease, or prior cardiac surgery has an effect on diagnostic 
yield of Holter monitor versus the Zio patch. Using a power of 80% and allowing for 25% variability, the 
number of patients needed for the study was determined to be 255 using McNemar’s test. We 
anticipate enrolling about 260 patients in this study. 
Study Procedures: 
Informed consent will be obtained in a private room in the pediatric cardiology clinic. If the patient 
agrees to participate in the research, the Holter monitor and the Zio patch will be placed on the patient 
in that private room. The Holter monitor will be returned to the clinic and the Zio patch will be returned 
in the mail, per protocol from the manufacturers. The results of both ambulatory ECG monitors will 
become part of the patient's confidential medical record. 
After the data is collected, it will be de-identified and stored in a password protected electronic 
database on an encrypted endpoint (desktop and labtop computer). The patient satisfaction survey will 
be a hardcopy that will be stored in a binder locked inside the filing cabinet of the study coordinator. 
Only research investigators will have access to the electronic database or the binder of patient 
satisfaction surveys. 
Study Devices: 
Device name: Holter  
Device description: Traditional ambulatory electrocardiographic monitor  
Device Model/Version #: H3+ Digital Holter Recorder  
Already approved by FDA and used as gold standard 
 
Device name: Zio Patch  
Device description: Leadless ambulatory patch electrocardiographic monitor  
Device Model/Version #: Zio XT  
FDA approved in adults, off-label use in children. This is a Nonsignificant Risk device (21 CFR 812.2(b)); 
no more than Minimal Risk (45 CFR 46.404/21 CFR 50.51; i.e., 'Section 404'). 
 
Research Question(s)/Hypothesis(es):  
Primary objective: This prospective study aims to compare the diagnostic yield (ability to detect an 
arrhythmia) of the Holter monitor versus the Zio patch in children by having patients wear both devices 
simultaneously for 48 hours. We will compare the incidence of specific abnormal heart rhythms in 
children using each device, specifically supraventricular tachycardia 4 beats (SVT), ventricular 
tachycardia 4 beats (VT), advanced second degree or complete heart block, atrial flutter or fibrillation 
(AF), pause > 3 seconds, premature ventricular contractions (PVCs) > 5%, premature atrial contractions 
(PACs) > 5%, and presence of preexcitation suggestive of Wolf Parkinson White syndrome (WPW). 

Secondary objective: We will compare the minimum, maximum, and average heart rates, as well as the 
percent analyzable data for each device over the 48 hours. Tertiary objective: To determine if age, 
weight, gender, presence of congenital heart disease, or prior cardiac surgery had an effect on 
diagnostic yield of Holter monitor versus the Zio patch.Quaternary objective: To compare the patient 
and/or parental satisfaction for the Holter monitor versus the Zio patch using a one page survey at the 
end of the 48 hour study. Hypotheses:1. There will be no difference in the diagnostic yield or the heart 
rate parameters (maximum, minimum, or average heart rate, percent analyzable data) of the Zio patch 
compared to the Holter monitor during the 48 hours of monitoring2. Age, weight, gender, presence of 
congenital heart disease, or prior cardiac surgery will not affect diagnostic yield of the Holter versus the 
Zio patch.3. Patients will prefer the Zio patch over the Holter monitor based on the patient satisfaction 
survey. 
Scientific Abstract:  
Ambulatory electrocardiographic (ECG) monitoring is common diagnostic tool used to detect 
arrhythmias in the outpatient setting. The traditional Holter monitor is the gold standard ambulatory 
ECG monitoring device that is commonly used in children. However, it has multiple leads and can be 
cumbersome. The Zio patch is a new singlelead patch ECG monitor that has been FDA approved for use 
in adults and has been used off-label in children for several years. While both the Holter and the Zio 
patch are continuously recording and are able to detect asymptomatic arrhythmias, to date there has 
been no direct comparisons of the diagnostic yield (ability to detect an arrhythmia) of the Holter 
monitor versus the Zio patch in the pediatric population. This prospective study aims to compare the 
diagnostic yield, heart rate parameters, and patient satisfaction of the Holter versus the Zio patch in 
pediatrics. Patients less than or equal to 21 years of age referred for ambulatory ECG monitoring at the 
pediatric cardiology clinic at Children’s Hospital of New York (CHONY) will be recruited to participate in 
the study. ECG technicians will obtain informed consent and place the Holter monitor and Zio patch 
simultaneously on the patient. After 48 hours of monitoring, the patient will mail the Zio patch to the 
manufacturer and the return the Holter monitor to the clinic. The patient satisfaction survey will be 
submitted to the researchers in clinic upon completion of the study. Descriptive statistics will be used 
for patient demographics and survey results. To compare presence or absence of any of the clinically 
significant arrhythmias (supraventricular tachycardia (SVT) > 4 beats, ventricular tachycardia (VT) > 4 
beats, advanced second degree or complete atrioventricular block, atrial fibrillation or flutter, pause > 2 
seconds, premature ventricular contractions (PVCs) > 5%) over 48 hours, McNemar’s test will be used. 
Further subgroup analysis of each of the arrhythmia types will be done using McNemar’s test again. 
Logistic regression will be used to determine if age, weight, gender, presence of congenital heart 
disease, or prior cardiac surgery has an effect on diagnostic yield of Holter monitor versus the Zio patch. 
Lay Abstract:  
Ambulatory electrocardiographic (ECG) monitoring is common diagnostic tool used to detect 
arrhythmias in the outpatient setting. The traditional Holter monitor is the gold standard ambulatory 
ECG monitoring device that is commonly used in children. However, it has multiple leads and can be 
cumbersome. The Zio patch is a new singl lead patch ECG monitor that has been FDA approved for use 
in adults and has been used off-label in children for several years. While both the Holter and the Zio 
patch are continuously recording and are able to detect asymptomatic arrhythmias, to date there has 
been no direct comparisons of the diagnostic yield (ability to detect an arrhythmia) of the Holter 

monitor versus the Zio patch in the pediatric population. This prospective study aims to compare the 
diagnostic yield, heart rate parameters, and patient satisfaction of the Holter versus the Zio patch in 
pediatrics. Patients less than or equal to 21 years of age referred for ambulatory ECG monitoring at the 
pediatric cardiology clinic at Children’s Hospital of New York (CHONY) will simultaneously wear both the 
Holter and the Zio for 48 hours. Data parameters will be compared using descriptive statistics, 
McNemar’s test, and logistic regression. 
Subject Population Justification:  
Any patient from birth through 21 years of age who is referred for ambulatory ECG monitoring at 
CHONY will be recruited for participation in this study. In a large retrospective study using the Zio patch, 
neonates (under 1 month of age) have used the Zio patch off label, therefore this study will 
prospectively study the device in all ages from birth through 21 years. We will obtain informed consent 
in English or in Spanish. Target enrollment is 260 participants.