Validation of a Smartphone-based Recorder for Detection of Cardiac Arrhythmias
Phase: NA
Conditions: Cardiac Arrhythmia
Sponsor: Blackpool Teaching Hospitals NHS Foundation Trust

 
 
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Validation of a smartphone-based 
Recorder for Detection of Cardiac 
arrhythmias 
 
Principal 
Investigator: 
 
Sub-Investigators: 
 
Research Trust: 
Blackpool Teaching Hospitals NHS Foundation Trust 
  
Funder: 
Blackpool Teaching Hospitals NHS Foundation Trust 
Sponsor: 
Blackpool Teaching Hospitals NHS Foundation Trust 
  
 
 

 
 
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Table of Contents 
1 
STUDY SUMMARY .......................................................................................................................................... 3 
1.1 
FLOWCHART OF TREATMENT SCHEDULE ......................................................................................................... 7 
2 
INTRODUCTION .............................................................................................................................................. 8 
2.1 
BACKGROUND .................................................................................................................................................. 8 
 
THE REHEARSE-AF (ASSESSMENT OF REMOTE HEART RHYTHM SAMPLING USING THE 
ALIVECOR HEART MONITOR TO SCREEN FOR ATRIAL FIBRILLATION) STUDY IS A 
RANDOMIZED CONTROLLED TRIAL OF AF SCREENING USING AN ALIVECOR KARDIA 
MONITOR ATTACHED TO A WIFI-ENABLED IPOD TO OBTAIN ECGS (IECGS) IN AMBULATORY 
PATIENTS. PATIENTS ≥65 YEARS OF AGE WITH A CHADS-VASC SCORE ≥2 FREE FROM AF 
WERE RANDOMIZED TO THE IECG ARM (500 INDIVIDUAL) OR ROUTINE CARE “RC” (501 
INDIVIDUAL). IECG PARTICIPANTS ACQUIRED IECGS TWICE WEEKLY OVER 12 MONTHS 
(PLUS ADDITIONAL IECGS IF SYMPTOMATIC) ONTO A SECURE STUDY SERVER WITH OVER 
READ BY AN AUTOMATED AF DETECTION ALGORITHM AND BY A CARDIAC PHYSIOLOGIST 
AND/ OR CONSULTANT CARDIOLOGIST. TIME TO DIAGNOSIS OF AF WAS THE PRIMARY 
OUTCOME MEASURE. THE OVERALL COST OF THE DEVICES, ECG INTERPRETATION, AND 
PATIENT MANAGEMENT WERE CAPTURED AND USED TO GENERATE THE COST PER AF 
DIAGNOSIS IN IECG PATIENTS. CLINICAL EVENTS AND PATIENT ATTITUDES/EXPERIENCE 
WERE ALSO EVALUATED.  RESULTS SHOWED THAT 19 PATIENTS IN THE IECG GROUP WERE 
DIAGNOSED WITH AF OVER THE 12-MONTH STUDY PERIOD VERSUS 5 IN THE RC ARM 
(HAZARD RATIO, 3.9; 95% CONFIDENCE INTERVAL=1.4–10.4; P=0.007) AT A COST PER AF 
DIAGNOSIS OF $10 780 (￡8255). THERE WAS A SIMILAR NUMBER OF STROKE/TRANSIENT 
ISCHEMIC ATTACK/SYSTEMIC EMBOLIC EVENTS (6 VERSUS 10, IECG VERSUS RC; HAZARD 
RATIO=0.61; 95% CONFIDENCE INTERVAL=0.22–1.69; P=0.34). THE STUDY CONCLUDED THAT 
SCREENING WITH TWICE-WEEKLY SINGLE-LEAD IECG WITH REMOTE INTERPRETATION IN 
AMBULATORY PATIENTS ≥65 YEARS OF AGE AT INCREASED RISK OF STROKE IS 
SIGNIFICANTLY MORE LIKELY TO IDENTIFY INCIDENT AF THAN RC OVER A 12-MONTH 
PERIOD.8 ..................................................................................................................................................................... 9 
 
THE IPHONE HELPING EVALUATE ATRIAL FIBRILLATION RHYTHM THROUGH 
TECHNOLOGY (IHEART) 9 IS AN ONGOING TRIAL RECRUITING A TOTAL OF 300 PATIENTS 
WITH A HISTORY OF AF, WITH 150 PATIENTS RECEIVING AN IPHONE WITH THE MOBILE 
MONITORING DEVICE AND EDUCATIONAL TEXT MESSAGING) THE AILVECOR SYSTEM) AND 
THE REMAINING 150 PATIENTS CONTINUING WITH THEIR REGULAR MEDICAL CARE. EACH 
PATIENT WILL BE INCLUDED IN THE INTERVENTION PERIOD FOR 6 MONTHS. THE RATE OF 
RECURRENT AF AND TREATMENTS MEANT TO MANAGE AF AND OTHER HEART CONDITIONS 
WILL BE DETERMINED FOR BOTH GROUPS. PATIENTS IN BOTH GROUPS WILL COMPLETE A 
SERIES OF QUESTIONNAIRES AT THE START AND END OF THE 6-MONTHS STUDY PERIOD TO 
LOOK AT DIFFERENCES IN QUALITY OF LIFE AND KNOWLEDGE OF AF. ......................................... 10 
2.2 
STUDY OBJECTIVES ........................................................................................................................................ 11 
3 
STUDY DESIGN .............................................................................................................................................. 11 
3.1.1 
General ................................................................................................................................................ 11 
3.1.2 
Study procedure ................................................................................................................................... 11 
3.2 
PRIMARY STUDY ENDPOINTS ......................................................................................................................... 11 
3.3 
SECONDARY STUDY ENDPOINTS .................................................................................................................... 11 
3.4 
END OF STUDY ............................................................................................................................................... 12 

 
 
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4 
METHODS ....................................................................................................................................................... 12 
4.1 
PARTICIPANT SELECTION AND WITHDRAWAL ................................................................................................ 12 
4.1.1 
Inclusion Criteria ................................................................................................................................. 12 
4.1.2 
Exclusion Criteria ................................................................................................................................ 12 
4.2 
PARTICIPANT RECRUITMENT AND SCREENING ............................................................................................... 12 
4.3 
RANDOMISATION PROCESS ............................................................................................................................ 12 
4.4 
INFORMED CONSENT ...................................................................................................................................... 13 
4.5 
WITHDRAWAL OF PARTICIPANTS ................................................................................................................... 13 
5 
STUDY PROCEDURES .................................................................................................................................. 13 
6 
STATISTICAL PLAN ..................................................................................................................................... 14 
6.1 
SAMPLE SIZE DETERMINATION ...................................................................................................................... 14 
6.2 
STATISTICAL METHODS ................................................................................................................................. 14 
6.3 
INTERIM ANALYSES ....................................................................................................................................... 14 
7 
SAFETY AND ADVERSE EVENTS ............................................................................................................. 14 
7.1 
RECORDING OF ADVERSE EVENTS ................................................................................................................. 15 
8 
DATA HANDLING AND RECORD KEEPING .......................................................................................... 15 
8.1 
CONFIDENTIALITY .......................................................................................................................................... 15 
8.2 
CASE REPORT FORMS..................................................................................................................................... 15 
8.3 
RECORDS RETENTION .................................................................................................................................... 16 
9 
STUDY MONITORING, AUDITING, AND INSPECTING ....................................................................... 16 
10 
ETHICAL CONSIDERATIONS .................................................................................................................... 16 
10.1 PATIENT INFORMATION SHEETS ..................................................................................................................... 16 
11 
INDEMNITY .................................................................................................................................................... 16 
12 
SPONSORSHIP: .............................................................................................................................................. 17 
13 
PUBLICATION PLAN .................................................................................................................................... 17 
14 
REFERENCES ................................................................................................................................................. 18 
8- 
JULIAN P.J. HALCOX, KATHIE WAREHAM, ANTONIA CARDEW, ET AL. ASSESSMENT OF 
REMOTE HEART RHYTHM SAMPLING USING THE ALIVECOR HEART MONITOR TO SCREEN 
FOR ATRIAL FIBRILLATION: THE REHEARSE-AF STUDY. CIRCULATION. 2017;136:1784–1794. ... 18 

 
 
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1 
Study Summary 
Title 
Validation of a smartphone-based Recorder for Detection of Cardiac 
arrhythmia 
Short Title 
Validation of AliveCor system for Detection of Cardiac arrhythmia 
Version & Date 
Version4a-AC-27072018 
Principal 
Investigator 
Dr Khalid Abozguia 
Sub-Investigators 
Dr Gavin Galasko, Dr Hossamaldin Abuomara. 
Objectives 
We will evaluate the diagnostic yield of the new AliveCor device versus a 
12 lead ECG when used simultaneously to detect cardiac arrhythmia  
Methodology / 
Design 
Non-randomised open label diagnostic study 
We are planning to record 250 pre-defined abnormal ECGs (50 each of atrial 
fibrillation, atrial flutter, pre-excitation, ventricular tachycardia, , 
supraventricular tachycardia) and 150 control ECGs (100 sinus rhythm, 50 
sinus tachycardia) using both the AliveCor Smartphone device and a 12-lead 
ECG.  All 400 ECGs will then be read by 3 blinded reporters – a Consultant 
Electrophysiologist, a Consultant General Cardiologist and a General 
Practitioner.  The output of the AliveCor automatic detection algorithm will 
also be recorded as a fourth reporter.  The screening characteristics of all 4 
reporters using the AliveCor device vs the definitive 12 lead ECG will be 
analysed and compared. 
Patients can be recruited from different cardiology clinics; at the end of an 
exercise test to record sinus tachycardia, and in the catheter lab during 
electrophysiological studies/ ablation procedures to record arrhythmias. 
Every patient will be counselled about the project by a member of the 
cardiology / research team (doctor or qualified research nurse) and will be 
provided with a patient information sheet.  Patients will be given up to 2 
weeks to consider participation in the study.  If in agreement, written 
informed consent will be obtained.  
A 30-second ECG tracing will be obtained by simply holding the 
Smartphone and placing at least 1 finger from each hand on electrodes 
embedded into the back of the Smartphone case (figure 2). For sedated 
patients in the catheter lab, AliveCor electrodes will be placed and taped on 
patient chest wall, left parasternal third intercostal space.  The AliveCor 
ECG tracing will be recorded as close to simultaneously as the 12 lead ECG 

 
 
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recording as possible.  
Duration 
2 years 
Participating 
Centres 
Blackpool Victoria Hospital 
Primary End 
Point 
Screening characteristics and diagnostic accuracy of AliveCor ECG 
recordings to detect cardiac arrhythmias 
Number of 
participants 
400 
Main Inclusion 
/Exclusion 
Criteria 
Inclusion:  
 Male or female patients >18 years with 12 lead ECG finding of 
arrhythmia, manifest pre-excitation, pacing rhythm, sinus rhythm or 
sinus tachycardia. 
Exclusion Criteria: 
 Patients <18 years of age. 
 Patients unable to or unwilling to use the device. 
 

 
 
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Statistical 
Methodology and 
Analysis 
400 patients are planned to be recruited as follows: 
 
50 patients with supraventricular tachycardia (SVT) 
50 patients with atrial flutter (AFl) 
50 patients with atrial fibrillation (AF) 
50 patients with ventricular tachycardia (VT) 
50 patients with manifest pre-excitation 
50 patients with sinus tachycardia to constitute the tachycardia control group 
 
100 normal ECGs will also be collected from the first 100 patients who have 
regular sinus rhythm to constitute the sinus rhythm control group.   
 
ECGs will be recorded in duplicate, with one recording being made using 
the AliveCor device, and one recording being made using a normal 12-lead 
ECG.  Recordings will be undertaken as close to simultaneously as possible.  
The ECG diagnosis will be made by the lead Electrophysiologist on the 12-
lead ECG so produced and this will be taken as the correct ECG diagnosis. 
 
All ECGs (both 12-lead and AliveCor) will be reported by a Consultant 
Electrophysiologist, a General Cardiologist and a General Practitioner, 
blinded to the full study protocol and the patient allocation group.  The 
output of the AliveCor algorithm for automatic ECG diagnosis will also be 
recorded.  The readers will firstly read the AliveCor ECGs and at a later date 
read the 12-lead ECGs to prevent comparisons between the ECGs and to 
give accurate screening characteristics for AliveCor ECGs. 
 
The diagnostic accuracy and screening characteristics of ECGs generated by 
the AliveCor device will be reported for each arrhythmia individually and in 
combination both by each reporter.  To calculate screening characteristics, 
ECGs of sinus rhythm and sinus tachycardia will also be included in each 
analysis as normal controls.  95% confidence intervals will be calculated. 
 
The primary end-point will be the sensitivity and screening characteristics of 
detecting each arrhythmia individually and in combination by each reporter 
using the AliveCor device, calculating 95% confidence intervals.  
 
The binomial exact calculation would be used to calculate confidence 
intervals. 
 
With a sample size of 50 patients with one arrhythmia, a sensitivity of 80% 
would produce a 95% confidence interval of 68.9% to 91.1%.  With a 
sample size of 250 (all arrhythmias combined), a sensitivity of 70% would 
produce a 95% confidence interval of 64.5% to 75.1%, i.e. an absolute error 
of ± 5%. 
 
The main secondary end-point will be to compare the sensitivity of a 

 
 
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Consultant Electrophysiologist in detecting all arrhythmias using the 
AliveCor device vs the originally coded 12-lead ECG, to test whether the 
AliveCor device is non-inferior to the original 12-lead ECG diagnosis.  
Assuming a 95% one-sided confidence interval and a power of 80%, if there 
is a true difference in sensitivity in favour of the 12-lead ECG over an 
AliveCor ECG of 10%, and then a sample size of 301 would be needed to 
exclude a difference in favour of the 12-lead ECG of more than 16%.  
 
Further secondary end-points will be to compare a Consultant 
Electrophysiologist with a General Consultant Cardiologist with a General 
Practitioner and with the automated AliveCor ECG diagnosis using their 
automatic algorithm. 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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1.1 Flowchart of Treatment Schedule 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Recruitment 
Cardiology OPD, ETT room, Pacing 
Clinic and Cath lab 
Blackpool Victoria Hospital 
Informed written 
Consent 
12 lead ECG 
AliveCor recording 
Statistical Analysis and 
End of Study 
Demographic data collection: 
Age, gender, height, weight, Heart rate, Blood pressure, 
medication list, past medical history 
Blinded interpretation of all 12-lead ECGs and 
AliveCor recordings by 3 readers.  AliveCor 
automated ECG report recorded. 
Study ID allocation 

 
 
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2 
Introduction 
This is non-invasive diagnostic study. It is easily achievable and simple to conduct. If proven to 
be a positive study, this may potential be a cost-effective method to detect cardiac arrhythmia.  
2.1 
Background 
In the past few years, the use of smart phones and tablets with health-related applications has 
significantly proliferated. AliveCor ECG (figure 1) is an FDA-approved, CE-marked portable 
electrocardiogram (ECG) recorder that records a single channel (lead I) ECG rhythm strip using 
a compatible smart phone running a specific application.1,2 The recordings can be sent to a 
healthcare professional for interpretation. The healthcare professional accesses this information 
through the Provider Dashboard software.3 
AliveCor Heart Monitor is an easy-to-use, highly-accessible, and cost-effective device which 
could be used to detect both paroxysmal and persistent arrhythmias in people who are 
asymptomatic as well as people with intermittent palpitations to determine the cause of their 
symptoms. 
Figure 1 
 
 
 
Description 
 
The AliveCor Heart Monitor is a pocket‑sized rectangular device containing 2 electrodes. Itis 
either attached directly via an adhesive attachment plate to a mobile device or must be within 30 
cm of the mobile device during operation. The AliveCor Heart Monitor can be removed from the 
plate when not in use, with the plate remaining attached to the mobile device. The mobile device 
must be a standard internet‑enabled mobile phone or tablet, onto which the AliveECG app must 
be downloaded. The AliveCor Heart Monitor and AliveECG app are compatible with devices 
running Apple or Android operating systems.3 
How to use it? 
 
To record an ECG, the user places 2 or more fingers from the left hand onto 1 of the AliveCor 
Heart Monitor electrodes and 2 or more fingers from the right hand onto the other electrode. The 
user keeps contact with the electrodes for at least 30 seconds to ensure that a complete reading is 
taken, while keeping their arms still because arm movement may interfere with the ECG reading. 

 
 
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After the AliveCor Heart Monitor has taken a reading, it is sent wirelessly by a patented high 
frequency sound transmission to the mobile device, where it can be viewed using the AliveECG 
(Kardia) app. If or when the device has a suitable Wi‑Fi or mobile connection, the recording will 
automatically synchronise with the secure encrypted AliveCor cloud server. The user can also 
send the recording directly to a relevant healthcare professional, such as a GP, to be read using 
the Provider Dashboard, which is a web‑based application run from any standard PC.4,5. For this 
study, we will only use trust enabled devices such as iPod/iPad available in Cardiology 
department- Cardiac Investigation Unit (CIU).  
 
Cost: 
 
The AliveCor system consists of an AliveCor Heart Monitor and the Kardia app. The AliveCor 
Heart Monitor costs £62.49, excluding VAT, for a single unit. For orders of 50 units or more, the 
price reduces to £50 each, excluding VAT. The Kardia app is available as a free download from 
the Apple App Store or from Google Play, and the web‑based Provider Dashboard is free to use. 
The estimated cost of a standard 12‑lead ECG, in which a practice nurse applies the test and a 
GP reviews the results, to be £36.33 with the cost of an ambulatory ECG as £170 (NICE 2014).2 
 
Evidence from literature 
 
 To date, the device has been used in current practice to improve the detection of recurrent AF 
6 and to reliably monitor the QTc interval.7  
 Lowres et al. (2014)5 conducted a community-based, opportunistic screening programme of 
1000 people aged 65 years and over, using the AliveCor Heart Monitor to detect AF. The 
study was set in 10 pharmacies in Sydney, Australia. Following the analysis of 996 readings, 
excluding 4 people with pacemakers, the AliveECG app had 98.5% sensitivity (67/68; 95% 
CI 92.1%–100%) and 91.4% specificity (849/929; 95% CI 89.4–93.1%), using the 
cardiologists' diagnosis from the AliveCor Heart Monitor reading as the reference case. 
 The REHEARSE-AF (Assessment of Remote Heart Rhythm Sampling Using the AliveCor 
Heart Monitor to Screen for Atrial Fibrillation) study is a randomized controlled trial of AF 
screening using an AliveCor Kardia monitor attached to a WiFi-enabled iPod to obtain ECGs 
(iECGs) in ambulatory patients. Patients ≥65 years of age with a CHADS-VASc score ≥2 
free from AF were randomized to the iECG arm (500 individual) or routine care “RC” (501 
individual). iECG participants acquired iECGs twice weekly over 12 months (plus additional 
iECGs if symptomatic) onto a secure study server with over read by an automated AF 
detection algorithm and by a cardiac physiologist and/ or consultant cardiologist. Time to 
diagnosis of AF was the primary outcome measure. The overall cost of the devices, ECG 
interpretation, and patient management were captured and used to generate the cost per AF 
diagnosis in iECG patients. Clinical events and patient attitudes/experience were also 
evaluated.  Results showed that 19 patients in the iECG group were diagnosed with AF over 
the 12-month study period versus 5 in the RC arm (hazard ratio, 3.9; 95% confidence 
interval=1.4–10.4; P=0.007) at a cost per AF diagnosis of $10 780 (￡8255). There was a 
similar number of stroke/transient ischemic attack/systemic embolic events (6 versus 10, 
iECG versus RC; hazard ratio=0.61; 95% confidence interval=0.22–1.69; P=0.34). The study 
concluded that screening with twice-weekly single-lead iECG with remote interpretation in 

 
 
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ambulatory patients ≥65 years of age at increased risk of stroke is significantly more likely to 
identify incident AF than RC over a 12-month period.8 
 The iPhone Helping Evaluate Atrial Fibrillation Rhythm Through Technology (iHEART) 9 is 
an ongoing trial recruiting a total of 300 patients with a history of AF, with 150 patients 
receiving an iPhone with the mobile monitoring device and educational text messaging) the 
AilveCor system) and the remaining 150 patients continuing with their regular medical care. 
Each patient will be included in the intervention period for 6 months. The rate of recurrent 
AF and treatments meant to manage AF and other heart conditions will be determined for 
both groups. Patients in both groups will complete a series of questionnaires at the start and 
end of the 6-months study period to look at differences in quality of life and knowledge of 
AF. 
Expected benefit: 
The AliveCor Heart Monitor could be used in primary care as an alternative to other portable 
ECGs recorders to detect paroxysmal arrhythmias. There are several different portable ECGs 
available to the NHS. These devices, and the number of people in England who were monitored 
using these devices in 2013–14 following an outpatient appointment, are listed below (Health & 
Social Care Information Centre 2015) :10 
 
ECG loop recorder – 63 people 
 
24-hour ambulatory ECG – 80,264 people 
 
48-hour ambulatory ECG – 2863 people 
 
Holter extended ECG – 7186 people 
 
Cardiomemo ECG monitor – 4973 people. 
Given that the mean cost of ambulatory ECG monitoring is £170, the adoption of the AliveCor 
may produce savings to the NHS.  
 
Why we are conducting this study? 
There are no validated studies to evaluate its use in arrhythmias other than AF. 
 

 
 
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2.2 Study Objectives 
Primary objectives: To assess the sensitivity and screening characteristics of AliveCor 
recording to detect a wide range of cardiac arrhythmias (AF, atrial flutter, SVT, VT, paced 
rhythm and pre-excitation) by 4 different readers. 
Secondary Objectives:  
 To test whether the AliveCor device will be non-inferior to the 12 lead ECG with respect 
to diagnosis of the arrhythmia when read by a Consultant Electrophysiologist. 
 To compare the screening characteristics of the AliveCor’s automated diagnostic 
algorithm 
with 
its 
screening 
characteristics 
when 
read 
by 
a 
Consultant 
Electrophysiologist, a general Consultant Cardiologist and a General Practitioner. 
3 
Study Design 
3.1.1 General 
Open label non-randomised diagnostic study.  Readers will be blinded to the ECG diagnosis. 
Expected study duration: 2 years 
3.1.2 Study procedure 
Every patient will be counselled about the project by a member of the Cardiology / Cardiology 
research team (doctor or qualified research nurse) and will be provided with a patient 
information sheet. Patients will be given up to 2 weeks to consider participation in the study.  If 
in agreement, written informed consent will be obtained.  
 
A 30-second ECG tracing will be obtained by simply holding the Smartphone and placing at 
least 1 finger from each hand on electrodes embedded into the back of the Smartphone case 
(figure 2). For sedated patients in the cath lab, AliveCor electrodes will be placed and taped on patient 
chest wall, left parasternal third intercostal space.  A 12-lead ECG will also be recorded as near to 
simultaneously as possible. The 12-lead ECG will be reviewed by Principal Investigator (PI) to 
ensure that the ECG rhythm has not changed. 
3.2 Primary Study Endpoints 
Sensitivity and screening characteristics of AliveCor recording to detect cardiac arrhythmias. 
3.3 Secondary Study Endpoints 
To test whether AliveCor is non-inferior to the 12-lead ECG. 

 
 
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To compare the screening characteristics of the automated AliveCor algorithm to that of a 
Consultant Electrophysiologist, general Consultant Cardiologist and General Practitioner. 
3.4 End of study 
The study will end on the date the last patient completing the protocol. 
4 
Methods 
4.1 Participant Selection and Withdrawal 
Patients can be recruited from different cardiology clinics; at the end of an exercise test to record 
sinus tachycardia, and in the catheter lab during electrophysiological studies/ ablation procedures 
to record arrhythmias. Participants can withdraw from the study at any time and their standard 
care pathway will not be affected. If a participant decided to withdraw from the study at any 
point, we will continue to use any data collected up to withdrawal date. 
4.1.1 Inclusion Criteria 
1 
Male or female patients 
2 
Age > 18 
3 
12 lead ECG finding of sinus rhythm, arrhythmia and manifest pre-excitation  
4.1.2 Exclusion Criteria 
1 
Patients <18 years of age. 
2 
Patients unable to or unwilling to use the device. 
3 
Patients with cardiac pacemaker, ICDs, or other implanted electronic devices 
4.2 Participant Recruitment and Screening 
Patients with known positive ECG findings can be recruited from different cardiology clinics, 
following exercise testing, and in the catheter lab during electrophysiological study/ ablation. 
 
Every patient will be counselled about the project by a member of cardiology / research team 
(doctor or qualified research nurse) and will be provided by a patient information sheet. Patient 
will be given choice to take up to 2 weeks to consider participation in the study.  If in agreement, 
written informed consent will be obtained.  
4.3 Randomisation Process 
This is a diagnostic comparative study. No randomisation is required.  

 
 
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4.4 Informed Consent 
Every patient will be counselled about the project by a member of cardiology / research team 
(doctor or qualified research nurse) and will be provided with a patient information sheet. 
Patients will be given up to 2 weeks to consider participation in the study.  If in agreement, 
written informed consent will be obtained.  
A copy of the consent form is included as an appendix. 
4.5 Withdrawal of Participants 
Participants can withdraw from the study at any time. This study is a diagnostic study and does 
not involve follow up visit.  
5 
Study Procedures 
 List of patients details (name and DOB) with study number will be kept safely in a locked 
cupboard in research office, cardiac education centre, Blackpool Victoria Hospital. This can 
only be accessed by Principal Investigator and research team members.  
 Each patient will be given ID ‘for example AC-001’. For 12 lead ECG ‘AC-ECG-001’ and 
for AliveCor recording ‘AC-AliveCor-001’. 
 A 30-second ECG tracing will be obtained by simply holding the Smartphone and placing at 
least 1 finger from each hand on electrodes embedded into the back of the Smartphone case 
(figure 2). For sedated patients in the catheter lab, AliveCor electrodes will be placed and taped on 
patient chest wall, left parasternal third intercostal space.  The AliveCor ECG tracing will be 
recorded as close to simultaneously as the 12 lead ECG recording as possible.  
 All 12 lead ECGs will be anonymised and kept safely in locked cupboard in research office, 
cardiac education centre, Blackpool Victoria Hospital. This can only be accessed by 
Principal Investigator and research team members. 
 
 All data will be stored anonymously on the Trust Server in a folder called ‘AliveCor Study’. 
This will be password protected. Only PI will have access to this folder. 
 
 All AliveCor traces (anonymised) will be sent electronically via secure trust enabled device 
to the PI who will store these traces on folder ‘AliveCor Study’ as described above. 
Figure 2 
 
 
 

 
 
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6 
 Statistical Plan 
Statisticians within the Sponsor organisation wrote and designed the sample size calculation and 
statistical description method. 
6.1 Sample Size Determination 
With a sample size of 50 patients with one arrhythmia, a sensitivity of 80% would produce a 
95% confidence interval of 68.9% to 91.1%.  With a sample size of 250 (all arrhythmias 
combined), a sensitivity of 70% would produce a 95% confidence interval of 64.5% to 75.1%, 
i.e. an absolute error of ± 5%. 
 
The main secondary end-point will be to compare the sensitivity of a Consultant 
Electrophysiologist in detecting all arrhythmias using the AliveCor device vs the originally 
coded 12-lead ECG, to test whether the AliveCor device is non-inferior to the original 12-lead 
ECG diagnosis.  Assuming a 95% one-sided confidence interval and a power of 80%, if there is a 
true difference in sensitivity in favour of the 12-lead ECG over an AliveCor ECG of 10%, and 
then a sample size of 301 arrhythmias would be needed to exclude a difference in favour of the 
12-lead ECG of more than 16%.  
 
6.2 Statistical Methods 
The diagnostic sensitivity, screening characteristics and accuracy of the AliveCor device will be 
reported for each arrhythmia individually and for all arrhythmias combined, measuring 95% 
confidence intervals using the binomial exact method. 
Non-inferiority will be assessed for each arrhythmia individually, and all arrhythmias combined 
for a Consultant Electrophysiologist reading the AliveCor generated ECG vs a near-
simultaneously recorded 12-lead ECG. 
The Chi-squared test and Fisher’s exact test will be used to compare proportions.  The McNemar 
test will be used to compare paired dichotomous dependent variables.  
6.3 Interim Analyses 
No interim follow-up is planned as this is a diagnostic study. There is no therapeutic intervention 
in this study. However, the Principal Investigator will be closely monitoring this study and its 
progression. 
7 
Safety and Adverse Events 
A search of the Medicines and Healthcare Products Regulatory Agency website revealed no 
Manufacturer Field Safety Notices or Medical Device Alerts for this device. No reports of 
adverse events were identified from a search of the US Food and Drug Administration (FDA) 

 
 
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database: Manufacturer and User Device Facility Experience (MAUDE).10 No drug or 
intervention in this study.  All Adverse Events (AE) will be recorded according to the R&D 
Office Procedure and the Trust Policy on Incident Reporting. 
 
7.1 Recording of Adverse Events 
All Adverse Events (AE) Serious Adverse Events (SAE) will be recorded according to the R&D 
Office Procedure and the Trust Policy on Incident Reporting. 
All adverse events occurring during the study period will be recorded.  The clinical course of 
each event will be followed until resolution, stabilisation, or until it has been determined that the 
study treatment or participation is not the cause.  Serious adverse events that are still ongoing at 
the end of the study period will be followed up to determine the final outcome.  
8 
Data Handling and Record Keeping 
8.1 Confidentiality 
Information about study participants will be kept confidential and managed according to the 
requirements of the Data Protection Act and the UK Policy Framework for Health and Social 
Care Research  
The identifiable details (Hospital number and date of birth) will be collected from participants in 
this study. 
Principal Investigator will have access to this information 
Data will be anonymised if placed on a computer database. Patient will be given a study ID 
(AliveCor 001, AliveCor 002, etc.) as per order of recruitment. 
The Principal Investigator is the custodian of the data. 
8.2 Case Report Forms 
The study case report form (CRF) is the primary data collection instrument. 
 
All data requested on the CRF/DCF will be recorded. 
 
All missing data must be explained.  If a space on the CRF/DCF is left blank because the 
procedure was not done, or the question was not asked, we will write “N/D”. 
 
If the item is not applicable to the individual case, we will write “N/A”. 
 
All entries should be printed legibly in black ink. 
 
To correct any data entry error, will draw a single straight line through the incorrect entry 
and enter the correct data above it.  All such changes must be initialled and dated. 

 
 
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8.3 Records Retention 
Period of record retention will be 5 years 
Filing arrangements for the CRFs and consent forms will be kept in research office in Lancashire 
Cardiac Centre, Blackpool Victoria Hospital. Records will also be archived in line with R&D 
Standard Operating Procedures (SOP). 
9 
Study Monitoring, Auditing, and Inspecting 
The investigator will permit study-related monitoring, audits and inspections by the Ethics 
Committee, the Sponsor and the Research Governance Manager. 
Participation as an investigator in this study implies adherence to the principles and 
responsibilities of the UK Policy Framework for Health and Social Care Research, ICH/GCP and 
Directive 2000/20/EC. 
10 Ethical Considerations 
Informed consent will be obtained from each participant as detailed in the consent section. 
Data protection will be ensured throughout the study. The data will be anonymous and 
information governance guidelines will be religiously followed to ensure confidentiality. 
No added potential harm could be caused to any participant from the use of the AliveCor device. 
The study will not be funded by any company with an interest into their desired outcome. 
Investigators participating in the study must declare no conflict of interest. 
 
This study will be conducted according to the standards of International Conference on 
Harmonization, Good Clinical Practice Guideline, Health Research Authority regulations, any 
applicable government regulations, Trust and Research Office policies and procedures. 
This protocol and any amendments will be submitted to the Health Research Authority for 
review and approval of the study conduct.  
No research studies can commence until the principal investigator has received a letter 
Confirming Capability and Capacity from the Trust issued by the Research and Development 
Office and a letter of approval from the Health Research Authority and REC. 
10.1 Patient information Sheets 
All participants for this study will be provided with an information sheet describing the elements 
of this study and sufficient information for subjects to make an informed decision about their 
participation in this study.   
11 Indemnity 
NHS indemnity will apply. 

 
 
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12 Sponsorship: 
This study is a single-centre study as is sponsored by Blackpool Teaching Hospitals NHS 
Foundation Trust, the PI‘s employer.    
 
13 Publication Plan 
Principal Investigator will be responsible to publish these data in a peer-reviewed journal. 

 
 
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14 References 
1- Baquero 
GA, Banchs 
JE, Ahmed 
S, Naccarelli 
GV1, Luck 
JC 
Surface 12 lead electrocardiogram recordings using smart phone technology. 
JElectrocardiol. 2015 Jan-Feb;48(1):1-7 
 
2- AliveCor Heart Monitor and AliveECG app (Kardia Mobile) for detecting atrial 
fibrillation. MedTech Innovation Briefing (MIB 35) published August 2015. 
https://www.nice.org.uk/advice/mib35/chapter/technology-overview. 
[accessed 
22 
October 2017]. 
 
3- Haberman ZC, Jahn RT, Bose R et al. (2015) Wireless smartphone ECG enables large-
scale screening in diverse populations. Journal of Cardiovascular Electrophysiology 26: 
520–6 
 
4- Lau J, Lowres N, Neubeck L et al. (2013) iPhone ECG application for community 
screening to detect silent atrial fibrillation: a novel technology to prevent stroke. 
International Journal of Cardiology 165: 193–4 
 
5- Lowres N, Neubeck L, Salkeld G et al. (2014) Feasibility and cost-effectiveness of stroke 
prevention through community screening for atrial fibrillation using iPhone ECG in 
pharmacies. The SEARCH-AF study. Thrombosis and Haemostasis 111: 1167–76 
 
6- Kathleen T. Hickey EdD, FNP-BC, ANP-BC, FAHA, FAAN1, Jose Dizon, MD2, Ashton 
Frulla, BS3. Detection of Recurrent Atrial Fibrillation Utilizing Novel Technology. 
Journal of Atrial Fibrillation 
http://www.jafib.com/published.php?type=full&id=936 
 
7- Kimberly D Guise, Eugene H Chung.  Abstract 19756: QTC Intervals Can Be Monitored 
With the AliveCor Heart Monitor in Patients on Dofetilide for Atrial Fibrillation. 
Circulation. 2014;130:A19756 
http://circ.ahajournals.org/content/130/Suppl_2/A19756.short 
 
8- Julian P.J. Halcox, Kathie Wareham, Antonia Cardew, et al. Assessment of Remote Heart 
Rhythm Sampling Using the AliveCor Heart Monitor to Screen for Atrial Fibrillation: 
The REHEARSE-AF Study. Circulation. 2017;136:1784–1794. 
 
9- Hickey KT, Hauser NR, Valente LE,  et al. A single-center randomized, controlled trial 
investigating the efficacy of a mHealth ECG technology intervention to improve the 
detection of atrial fibrillation: the iHEART study protocol. BMC Cardiovasc Disord. 
2016 Jul 16;16:152. doi: 10.1186/s12872-016-0327-y.  
 
10- Health & Social Care Information Centre. Hospital Episode Statistics [accessed 22 
October 2017]