A Comparative Study of the Findings of Dynamic Electrocardiography (Holter System) Using the an Innovative 3-lead Wireless Water Resistant Device and a Conventional Device
Phase: NA
Conditions: Cardiac Arrhythmia
Sponsor: Hospital Israelita Albert Einstein

 
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A COMPARATIVE STUDY BETWEEN THE DYNAMIC ECG 
(HOLTER SYSTEM) FINDINGS OBTAINED BY QUORETECH'S 
QUOREONE SYSTEM WITH THOSE OBTAINED BY CARDIOS' 
CARDIOLIGHT RECORDER. 
 
 
 
 
 
Authors 
 
Dr. Bruno Pereira Valdigem (Cardiologist) 
Dr. Dalmo Antonio Ribeiro Moreira (Cardiologist) 
 
 
 
 
 
São Paulo 
2020 

        
 
 
 
 
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Summary 
Summary ..................................................................................................................................................2 
SUMMARY OF CHANGES ..........................................................................................................................4 
1. 
Study Design .....................................................................................................................................5 
1.1. 
Summary ..................................................................................................................................5 
1.2. 
Introduction .............................................................................................................................6 
1.3. 
Hypothesis ................................................................................................................................8 
1.4. 
Objectives .................................................................................................................................8 
1.4.1. 
Primary Objective: ............................................................................................................8 
1.4.2 
Secondary Objective .........................................................................................................9 
2. 
Materials and methods ................................................................................................................. 10 
2.1. 
Sample ................................................................................................................................... 10 
2.2. 
Inclusion Criteria ................................................................................................................... 10 
2.3. 
Exclusion Criteria ................................................................................................................... 10 
2.4. 
Holter Device ......................................................................................................................... 10 
2.5. 
Data Collection ...................................................................................................................... 11 
3. 
Methodology ................................................................................................................................. 12 
4. 
Statistical analysis.......................................................................................................................... 13 
4.1. 
Descriptive Analysis ............................................................................................................... 13 
4.2. 
Primary Endpoint................................................................................................................... 13 
4.3. 
Secondary Endpoints ............................................................................................................. 13 
4.4. 
Sample size calculation ......................................................................................................... 15 
5. 
Ethical Aspects............................................................................................................................... 15 
5.1. 
About Informed Consent Form (ICF) ..................................................................................... 15 
6. 
Study personnel and Organiztions Involved ................................................................................. 16 
6.1. 
Study personnel .................................................................................................................... 16 
6.2. 
Organizations ........................................................................................................................ 17 

        
 
 
 
 
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7. 
Schedule ........................................................................................................................................ 18 
8. 
Budget ........................................................................................................................................... 19 
9. 
Statement of Conflicts of Interest and Funding ............................................................................ 20 
10. 
Bibliography .............................................................................................................................. 21 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

        
 
 
 
 
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SUMMARY OF CHANGES 
 
Protocol 
Amendment 
Version 
No.: 
Date 
Amendment 
No. 
Protocol 
Section 
Summary of Changes 
(to/from) 
1.0 
26-Oct-2020 
 
 
N/A – First version 
2.0 
21-Jan-2021 
1 
2.5 Data 
Collection 
Inclusion of the 
application of a 
questionnaire about the 
convenience of use and 
functions of QuoreOne. 
3.0 
10-Sep-2021 
2 
1.4.1 
Primary 
Objective 
Modification of the 
primary endpoint with a 
focus on detection of 
arrhythmias 
3.0 
10-Sep-2021 
2 
1.4.2 
Secondary 
Objective 
Addition of a secondary 
objective  
3.0 
10-Sep-2021 
2 
3. 
Methodology 
Modification about same 
physicians evaluating 
both exams  
3.0 
10-Sep-2021 
2 
4.2 Primary 
Endpoint 
Modification of the 
primary endpoint with a 
focus on arrhythmia 
detection 
3.0 
10-Sep-2021 
2 
4.3 
Secondary 
Endpoints 
Addition of secondary 
endpoints 
3.0 
10-Sep-2021 
2 
4.4 
Exploratory 
Endpoints 
Deletion of exploratory 
endpoints 
3.0 
10-Sep-2021 
2 
4.5 Sample 
calculation 
Update of the sample 
calculation 
4.0 
25-Feb-2022 
3 
4.2 Primary 
Endpoint 
Modification of the 
primary endpoint´s 
statistical analysis 
method  
4.0 
25-Feb-2022 
3 
4.3 
Secondary 
Endpoints 
Modification of the 
secondary endpoints’ 
statistical analysis 
method  
 
 

        
 
 
 
 
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1. Study Design 
 
1.1. Summary 
 
There has been an important advance in the technology for capturing 
electrocardiographic signals by the Holder system in recent years. Among these 
advances, the following stand out: a) the miniaturization of devices; b) the possibility 
of capturing electrical signals by electrodes applied to the thorax without the need for 
cable intermediation with the recorder; c) the direct positioning of the recorder on the 
thoracic surface, allowing greater movement of the patient without the inconvenience 
of artifact records or interference in the signal line; d) possibility of transmitting 
electrocardiographic signals almost in real time over the computer network (internet), 
speeding up medical intervention in cases of high-risk arrhythmias or suspected clinical 
condition (syncope) being caused by such arrhythmias. No less important, it should be 
highlighted the speed of the preparation of the reports by the analysis software itself, 
which interprets the records and issues an initial report, with little or no interference 
from a technician or physician to edit the records. This is possible when neural 
networks, machine learning, and artificial intelligence are used to analyze those 
signals. The system in question is based on the capture of electrocardiographic 
recordings by Quoretech's QuoreOne recorder.  
In order to reliably detect, electrocardiographic recordings obtained by 
QuoreOne should be compared with others already routinely used in clinical practice.  

        
 
 
 
 
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The objective of this study will be to analyze the data obtained by QuoreOne 
and compare it with those obtained by Cardiolight recorder analyzed by Cardios' 
software.   
 
1.2. Introduction 
The 24-hour ambulatory electrocardiogram, performed by the Holder system, is 
a procedure whose objective is to find the correlation between symptoms and possible 
changes in the electrocardiogram in order to establish a cause-effect relationship 1-5. 
In practice, a digital recorder is connected to a cable with electrodes at its ends, which 
are then applied to the thoracic surface. The objective is for the electrical signal emitted 
by the heart to be captured and recorded in at least three channels that correspond to 
the electrocardiographic leads 6. Once captured, the signals recorded on a digital card 
are transferred to a computer that, by means of specific software, performs the analysis 
and issues a result that includes the maximum, minimum and mean heart rates, in 
addition to the total number of atrial and ventricular ectopic heart beats, total 
tachycardias and ST segment alterations and T waves. The interpretation of the 
electrocardiographic recordings is then carried out by a specialized technical analyst 
who confirms the data or corrects the information that is in disagreement. The following 
result is confirmed by a physician6. 
Current systems are limited to this type of analysis, but they suffer from some 
limitations. These are of a technical nature related to signal capture, the dependence 
on electrode cables, which often limit the mobility of patients and is associated with 
greater risks of interference in the recording channels (50/60 Hz electrical network, 

        
 
 
 
 
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touching of clothing on the electrodes; electrode displacements, etc.)1. Depending on 
the intensity and duration of these alterations, there may be a need to repeat the 
examination.  
With the advancement of technology, new signal capture systems have been 
developed. The possibility of applying the recorder directly to the thoracic surface 
eliminated the need for electrode cables. This fact not only improved the quality of the 
signs, but also allowed greater patient mobility, making the test better tolerated. The 
possibility of sending the recorded signals over the internet speeds up their 
interpretation. In addition, an analysis software previously trained by neural networks 
allows the editing of records more quickly by issuing a pre-report, facilitating the routine 
of the physician who will have less work to prepare the final report. With this approach, 
it is expected that the more exams the system analyzes, the better its performance 
should be, probably reaching almost the point of minimal medical interference in the 
final result.  
In the study, which is now proposed to be carried out at the Cardiac Arrhythmias 
Outpatient Clinic of the Dante Pazzanese Institute of Cardiology (IDPC), Holter 
recordings will be performed in about 180 consecutive patients with the two systems 
simultaneously, the QuoreOne from Quoretech (system under test) and the Cardiolight 
from Cardios (conventional 24-hour Holter-system), a system that has been on the 
market for more than 30 years and is widely used in the country today. This approach 
will allow for the comparison of QuoreOne's results with those of Cardiolight. 

        
 
 
 
 
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1.3. Hypothesis 
 
The initial hypothesis in this study is that the electrocardiographic recordings 
obtained by the two systems are comparable, thus validating the information obtained 
by QuoreOne. Therefore, the study will test the hypothesis of comparability of the 
QuoreOne system in relation to the conventional Holter system.  
 
Figure 1 – Holter, Quoreone (Quoretech) and Cardiolight (Cardios) recorders that will 
be used in this study. 
 
1.4. Objectives 
1.4.1. Primary Objective: 
To assess whether the detection of arrhythmias by QuoreOne is comparable to 
Cardiolight. Detection of the following arrhythmias will be compared: atrial fibrillation or 
atrial flutter, supraventricular tachycardia, ventricular tachycardia, polymorphic 
ventricular tachycardia or ventricular fibrillation; atrioventricular block and pauses. 

        
 
 
 
 
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1.4.2 Secondary Objective 
Compare the 24-hour electrocardiographic recordings detected by both 
systems. The following will be included in the analysis: a) maximum, minimum and 
mean heart rates; b) total atrial and ventricular ectopic heart beats; c) episodes of 
supraventricular tachycardia, ventricular tachycardia, and pauses. In addition to these 
variables, the duration of the examination and the convenience of using both systems 
should also be compared.  
 
 
 
 
 
 
 
 
 
 
 
 
 

        
 
 
 
 
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2. Materials and methods 
2.1. Sample 
It will consist of data from Holter recordings to be performed on patients from 
the Electrophysiology and Cardiac Arrhythmias outpatient clinic of the Medical Section 
of Electrophysiology of IDPC. The sample size calculation foresees the inclusion of a 
minimum of 182 patients with complete data from both exams.  
 
2.2. Inclusion Criteria 
• Patients aged ≥ 18 years, with indication for continuous 24-hour 
electrocardiographic monitoring by 24-hour Holter at the IDPC outpatient clinic, 
and who agree to participate in the study by signing the free and informed 
consent form (ICF).  
 
2.3. Exclusion Criteria 
• Patients who do not sign the informed consent form will be excluded.  
 
2.4. Holter Device 
The Holter-type cardiac monitor is a portable ambulatory electrocardiography 
device. It aims to monitor the electrical activity of the heart over a prolonged period, 
usually twenty-four hours. 

        
 
 
 
 
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For this study, the Cardiolight recorder from the company Cardios, the 
predominant equipment in the medical practice of the IDPC, and the QuoreOne 
recorder, from Quoretech, will be used, which will be submitted to comparison. 
 
2.5. Data Collection 
All exams will be performed at IDPC, the exams performed with the Cardiolight 
equipment will be stored both in the original file (.xcm) and in the final version of the 
report (.pdf). The exams performed with the QuoreOne equipment will be saved directly 
on the online report platform and in the final version of the report (.pdf). These files will 
be exported to an external hard drive and sent for tabbing. If there has been a report 
of symptoms by the patient, this data will be included in both files to establish the 
relationship between the complaint and any alteration in the electrocardiogram. The 
parameters will be analyzed with anonymized data from the participants.  
After the Holter devices are removed, the participant will be asked to answer a 
questionnaire about the convenience of use and functions of the QuoreOne device. 

        
 
 
 
 
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3. Methodology 
The exams performed by the conventional system (Cardiolight, Cardios) and by 
the QuoreOne system will be analyzed and the reports released by physicians from 
the Electrophysiology Section of the IDPC. These tests will be implemented at the 
same time in the same patient and for the same duration. The physicians evaluating 
the results of one method will be the same as the physicians evaluating the results 
obtained by the other method, but these will be blinded to the patients' data, making it 
impossible to identify that the tests being evaluated are from the same patient.   
 
 
 
 
 
 
 
 
 
 
 
 

        
 
 
 
 
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4. Statistical analysis 
4.1. Descriptive Analysis  
Data will be collected regarding demographic variables, underlying diseases, 
use of medications, and medical indication for Holter monitoring. Categorical variables 
will be presented with counts and percentages. Quantitative variables will be presented 
as means and standard deviations if normal distribution and as medians and 
interquartile ranges if non-Gaussian distribution. The Kolmogorov-Smirnov test will be 
used to evaluate the normality of the distributions of quantitative variables.  
 
4.2. Primary Endpoint 
To compare the detection of arrhythmias between the two methods mentioned with 
regard to the set of the following arrhythmias: a) atrial fibrillation or atrial flutter; b) 
supraventricular tachycardia (≥ 3 beats); c) ventricular tachycardia (≥ 3 beats); d) 
polymorphic ventricular tachycardia or ventricular fibrillation; e) atrioventricular block 
(2nd degree Mobitz AVB I and II, 2:1 AVB and total AVB); and f) pauses (≥ 2.5 seconds). 
The comparison between the two methods will be evaluated by the accuracy of 
QuoreOne compared to the conventional system, in addition to the other diagnostic 
statistics: sensitivity, specificity, positive and negative predictive values will also be 
presented always followed by 95% confidence intervals. 
 
4.3. Secondary Endpoints 
• Comparison of the detection of each type of arrhythmia between the two devices 

        
 
 
 
 
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• Comparison of the duration of the examination between the two devices;  
• Comparison of mean, minimum, and maximum heart rate captured between the 
two devices;  
• Comparison of the total atrial ectopic heart beats captured between the two 
devices;  
• Comparison of total ventricular ectopic heart beats captured between the two 
devices; 
• Comparison of total episodes of supraventricular tachycardia, ventricular 
tachycardia, and pauses between the two devices; 
• Evaluate the convenience of using the two registration systems. 
The individual categorical secondary endpoints (detection of each type of 
arrhythmia) will also be evaluated by diagnostic statistics (accuracy, sensitivity, 
specificity, positive and negative predictive values) with respective 95% confidence 
intervals.  
The continuous secondary endpoints (mean, minimum and maximum heart rate, 
total atrial and ventricular ectopic heart beats, total episodes of supraventricular 
tachycardia, ventricular tachycardia and pauses) will be described by Bland-Altman 
plots accompanied by Lin and Pearson correlation coefficients.   
Lists with the patient's reports will be made to evaluate the convenience of the 
systems. The Chi-square test or Fisher's exact test will be used to evaluate the 

        
 
 
 
 
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proportion of patients who report greater comfort (comfort of the device) with Quoreone 
versus Cardiolight. 
 
4.4. Sample size calculation  
The sample size calculation of the study was established assuming the hypothesis of 
comparability of the QuoreOne device in relation to the conventional device. 
Considering data from a previous study,7 a two-tailed alpha of 5% and a power of 80% 
for the primary endpoint, the study will need to include a minimum of 182 patients with 
valid and complete measures of the 24-hour records by both methods.  
 
5. Ethical Aspects 
5.1. About Informed Consent Form (ICF) 
When recordings are made, all patients must sign an informed consent form. 
 
 
 
 
 
 
 
 
 
 

        
 
 
 
 
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6. Study personnel and Organiztions Involved 
6.1. Study personnel 
Dr. Bruno Pereira Valdigem – Cardiologist of the Dante Pazzanese Institute of 
Cardiology (IDPC).  
Dr. Dalmo Antonio Ribeiro Moreira – Cardiologist of the Medical Section of 
Electrophysiology at the Dante Pazzanese Institute of Cardiology (IDPC). 
Dr Otávio Berwanger – Director of the Academic Research Organization of 
Hospital Israelita Albert Einstein 
Dr. Karla Espírito Santo – Cardiologist and Researcher at the Academic 
Research Organization of Hospital Israelita Albert Einstein 
Dr Remo Holanda de Mendonça Furtado – Cardiologist and Researcher at the 
Academic Research Organization of Hospital Israelita Albert Einstein  
Lucas Damiani – Statistitician at the Academic Research Organization of 
Hospital Israelita Albert Einstein 
Silvia Lamas – Biostatistician of the Academic Research Organization of 
Hospital Israelita Albert Einstein 
Ronaldo Soares – Manager of the Academic Research Organization of 
Hospital Israelita Albert Einstein 
Luciana Piano – Regulatory Affairs Manager of the Academic Research 
Organization of Hospital Israelita Albert Einstein 
 

        
 
 
 
 
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6.2. Organizations 
Instituto Dante Pazzanese de Cardiologia (IDPC). 
ARO of Hospital Israelita Albert Einstein – Responsible for support in protocol 
design, data analysis and operational and regulatory support. 
Quoretech S.A. – Innovation and technology company in health and cardiac 
monitoring. 
 
 

 
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7. Schedule 
Activities 
2021 
2022 
Feb 
Mar 
Apr 
May 
Jun 
Jul 
Aug 
Sep 
Oct 
Nov 
Dec 
Jan 
Feb 
Mar 
Apr-
Aug 
 Data collection* 
x 
x 
* 
* 
* 
* 
x 
x 
x 
x 
 
 
 
 
 
Data cleaning and preparation of 
reports 
 
 
 
 
 
 
 
 
 
 
x 
x 
x 
 
 
 Data analysis 
 
 
 
 
 
 
 
 
 
 
 
 
 
x 
 
 Results presentation 
 
 
 
 
 
 
 
 
 
 
 
 
 
- 
x 
*Recruitment paused due to the COVID-19 pandemic. 
 
 
 
 

 
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8. Budget 
The company Quoretech will bear the costs involved in conducting the study. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

        
 
 
 
 
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9. Statement of Conflicts of Interest and Funding 
This study proposal is funded by Quoretech S.A. – a company of innovation 
and technology in health and cardiac monitoring (homepage: www.quore.tech e-
Mail: contato@quore.tech). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

        
 
 
 
 
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10. 
Bibliography 
1. Crawford MH, Bernstein SJ, Deedwania PC, et al. ACC/AHA Guidelines for 
Ambulatory Electrocardiography. A report of the American College of 
Cardiology/American Heart Association Task Force on Practice Guidelines 
(Committee to Revise the Guidelines for Ambulatory Electrocardiography). 
Developed in collaboration with the North American Society for Pacing and 
Electrophysiology. J Am Coll Cardiol. 1999;34(3):912-948. 
 
2. Gale C P, Camm JA.  Assessment of palpitations. BMJ 2016; 352:h5649. 
 
3. Summerton N, Mann S, Rigby A, PetkarS,  Dhawan J. New-onset palpitations in 
general practice: assessing the discriminant value of items within the clinical 
history. Family practice 2001; 18:383-392 
 
4. RINGQVIST, I. et al. Diagnostic value of long-term ambulatory ECG in patients with 
syncope, dizziness or palpitations. Clinical Physiology 1989; 9:47-55. 
 
5. WEBER, Barbara E.; KAPOOR, Wishwa N. Evaluation and outcomes of patients 
with palpitations. Am J Med1996; 100:138-148. 
 
6. Lorga Filho A, Cintra FD, Lorga A et al. Recomendações da sociedade brasileira 
de arritmias cardíacas para serviços de Holter. Arquivos Brasileiros de Cardiologia 
2013; 10:101-105. 

        
 
 
 
 
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7. Barrett PM, Komatireddy R, Haaser S, Topol S, Sheard J, Encinas J, Fought AJ, 
Topol EJ. Comparison of 24-hour Holter monitoring with 14-day novel adhesive 
patch electrocardiographic monitoring. Am J Med. 2014 Jan;127(1):95.e11-7..