Performance of commercially available SmartWatch-based electrocardiography to identify atrial fibrillation during exercise testing: the WATCH-ECG study

Atrial fibrillation (AF) affects millions of patients worldwide and is a cause
of substantial morbidity and stroke. Asymptomatic AF is gaining worldwide
interest for its potentially serious clinical consequences.(1) Furthermore,
paroxysmal AF may evolve into persistent or permanent AF when left untreated.
Screening and early detection of this * in its paroxysmal stage somewhat
elusive * arrhythmia may lead to reductions in stroke, hospitalizations and
death due to early treatment initiation.

The Apple Watch (series 4) is among the first commercially available devices
capable of a single-lead electrocardiographic (ECG) registration using
electrodes embedded within components of the device (Figure 1). The ECG
application algorithm detects whether atrial fibrillation is present and
medical expertise should be consulted. Data from these recordings are encrypted
and users will be able to share a report with their doctors via PDF. De Novo
classification for this technology was recently obtained by the FDA, making it
the second consumer device to gain Class II clearance for ECG monitoring.(2)

Extensive research using deep neural networks has been conducted to test the
accuracy of heart rate detection using photoplethysmography (PPG) in older
models.(3) The model exhibited a C-statistic of 0.97 to detect AF against the
reference standard 12-lead ECG-diagnosed AF in a validation cohort of 51
patients undergoing cardioversion; sensitivity was 98.0% and specificity was
90.2%.The authors may be applauded for this effort to improve early detection
rhythm assessment, which will undoubtedly prove valuable in reducing AF-related
complications in the future. However, the performance of the new AF detection
algorithm using electrocardiographic data, especially in more challenging
real-world situations, is yet to be determined. Despite the fact that this is
promising technology, attention should be paid to its potential limited
accuracy in younger users and patients with concomitant heart disease.

Screening using the AliveCor Kardia monitor has proven to be significantly more
effective in identifying AF than routine care in patients > 65 years of age.(4)
However, AF detection may be less accurate at higher heart rates and during
distorted signals and artifacts caused by physical exertion. Therefore, younger
and more physically active users of this device * a large relatively healthy
population * may be at risk of receiving AF notifications during exercise and
other causes of tachycardia, potentially leading to unnecessary out-patient
visits or even wrongful diagnosis. Herein lies this new wearable technology*s
main pitfall and source of skepticism by some health care providers. We seek to
further determine whether this is concern is justified, or whether this
commercially available noninvasive screening tool has the potential to expand
the diagnostic arsenal for AF.

The objective of this study is to determine the performance, as defined by
sensitivity and specificity, of the commercially available Apple Watch-based
electrocardiographic registration to identify AF during tachycardia, validated
against the gold standard 12-lead electrocardiography.(5)

Type of study:
This is an acute prospective non-randomized single-arm monocenter study to
evaluate an additional diagnostic tool in adult patients that were already
scheduled for routine exercise testing. The study is set to start on April 1st
2019. All data will be collected in the Academic Medical Center in Amsterdam.
All participants will be asked for written informed consent prior to enrolment.

Sample size:
No data on test performance of this specific technology has previously been
reported and the difference in diagnostic accuracy between the device and the
reference standard is yet to be determined. In this explorative, observational
study, we estimated that 70 enrolled patients will provide enough information
to determine diagnostic accuracy.

Study methodology:

Study procedure
DuringBefore their planned visit to the cardiology outpatient clinic in which
the exercise test was planned, eligible subjects will be informed about the
study. Hence, the conduct of this study will not influence the indication for
exercise testing. During the visit, the subject information sheet (SIS)
containing information on purpose, background, participation and risks of the
study will be handed for further reading. After sufficient time to read and
process the information the subject will asked for written informed consent.
The in-hospital exercise test (either on treadmill or ergometer) during routine
care will mimic real world exercise. Tachycardia is defined as a heart rate
>100 bpm. In case this target frequency is not reached, the subject will be
excluded from analysis. Rhythm evaluation with the investigational device will
be performed in the recovery phase of the exercise test. This way, the patient
can use both hands as normal during the high intensity exercise phase, avoiding
the additional risk of falling due to instability. In case of participation,
the subject will receive the device on their left wrist (before the exercise
test) and place their right index finger on the crown of the watch (during
recovery phase), as indicated by the manufacturer. In case this not possible,
the right arm may be used instead.
An electrocardiographic registration of around 30 seconds will be made, after
which the device algorithm indicates the registered heart rhythm, being either
sinus rhythm or atrial fibrillation. This process may be repeated up to three
times in total during the recovery phase in case of failed rhythm detection. A
12-lead ECG as part of the routine resting will be obtained simultaneously to
ensure synchronous analysis of heart rhythm between the two methods of
diagnosis. No personal information will be stored on the Apple Watch and no
additional measurements of any kind will be obtained from it.
Patient safety during exercise testing will be warranted by adherence to local
safety protocol for exercise testing. A research fellow will be present to aid
in device positioning and to record its findings on the anonymized case report
form (CRF), along with baseline characteristics on age, gender, BMI and medical
history. Concurrent 12-lead ECG interpretation by an experienced physician will
serve as the gold standard in diagnosing AF. Subjects serve as their own
controls in the evaluation in difference in proportions between two
within-subject observations of the outcome.

The device under investigation is the Apple Watch series 4 (released September
2018 by Apple Inc., Cupertino, CA, USA), and obtained clearance by the Food and
Drug Administration (FDA) as a class II medical device. A number of these
devices will be purchased by the department of cardiology to conduct the study.
If over the course of this study, new models of the Apple Watch become approved
for use, the protocol allows the use of newer series that are market approved
with similar instructions by the regulatory authorities in the country of the
study center.

Follow-up
There will be no follow-up in this acute study.

Statistical analysis
Continuous variables within the baseline characteristics are expressed as
median and interquartile range (IQR) or mean and standard deviation when
normally distributed. Categorical variables are expressed as frequency with
corresponding percentages. Continuous values were compared using the
Mann-Whitney U test or unpaired t-test and categorical variables with Fisher*s
Exact test. The new diagnostic modality is compared to the existing reference
standard by the proportion of the true positive and true negative samples that
it identifies. All reported p-values were 2 tailed, and p-values <0.05 were
considered statistically significant. Statistical analyses were performed in
IBM SPSS Statistics 24 and R version 3.5.1.

Risks and benefits

The participant will not benefit directly from this study. However, in the
future accumulating knowledge on the effectiveness of screening for AF might be
beneficial in reducing AF-related morbidity and mortality on a population
level. There are no additional post-procedural limitations or visits required
for this study.

Subjects will not be exposed to additional risks when choosing to participate
as exercise testing was already indicated on their physician*s discretion, and
the additional burden that subjects will experience is predicted to be low.