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Computers in Biology and Medicine 116 (2020) 103540

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Computers in Biology and Medicine


journal homepage: http://www.elsevier.com/locate/compbiomed

Implementation and validation of real-time algorithms for atrial fibrillation


detection on a wearable ECG device
Italo Agustin Marsili a, Luca Biasiolli a, Michela Mas�e b, c, *, Alberto Adami a,
Alberto Oliver Andrighetti a, Flavia Ravelli c, Giandomenico Nollo b, d
a
Medicaltech Srl, Rovereto, Italy
b
IRCS-HTA, Healthcare Research and Innovation Program, Fondazione Bruno Kessler, Trento, Italy
c
Department of Physics, University of Trento, Trento, Italy
d
BIOtech Labs, Department of Industrial Engineering, University of Trento, Trento, Italy

A R T I C L E I N F O A B S T R A C T

Keywords: Background: Due to the growing epidemic of atrial fibrillation (AF), new strategies for AF screening, diagnosis,
Wearable devices and monitoring are required. Wearable devices with on-board AF detection algorithms may improve early
Mobile health diagnosis and therapy outcomes. In this work, we implemented optimized algorithms for AF detection on a
Smart health
wearable ECG monitoring device and assessed their performance.
Entropy
Embedded algorithms
Methods: The signal processing framework was composed of two main modules: 1) a QRS detector based on a
Cardiac arrhythmias finite state machine, and 2) an AF detector based on the Shannon entropy of the symbolic word series obtained
Cardiac rhythm monitoring from the instantaneous heart rate. The AF detector was optimized off-line by tuning its parameters to reduce the
computational burden while preserving detection accuracy. On-board performance was assessed in terms of
detection accuracy, memory usage, and computation time.
Results: The on-board implementation of the QRS detector produced an overall accuracy of 99% on the MIT-BIH
Arrhythmia Database, with memory usage ¼ 672 bytes, and computation time �90 μs. The on-board imple­
mentation of the optimized AF algorithm gave an overall accuracy of 98.1% (versus 98.3% of the original
version) on the MIT-BIH AF Database, with increased sensitivity (99.2% versus 98.5%) and decreased specificity
(97.3% versus 98.2%), memory usage ¼ 4648 bytes, and computation time � 75 μs (consistent with real-time
detection).
Conclusions: This study demonstrated the feasibility of real-time AF detection on a wearable ECG device. It
constitutes a promising step towards the development of novel ECG monitoring systems to tackle the growing AF
epidemic.

1. Introduction of AF events, which are often paroxysmal and asymptomatic. These


features make AF one of the most important public health issues and a
Atrial fibrillation (AF) is the most common arrhythmia in clinical significant cause of healthcare expenditure in western countries.
practice, affecting 1–2% of the general population [1]. The prevalence of New strategies for AF screening may improve stroke prevention and
AF increases with age, reaching 18% in the population older than 85 patient stratification for different treatment options, ultimately leading
years [2]. Due to population ageing, by 2030 AF is expected to affect to better patient outcomes [8]. Mobile health technologies may enable
14–17 million people in Europe and 12.1 million people in the US [3,4]. earlier AF detection and assessment through an extended physiological
AF is characterized by the absence of proper atrial activation and monitoring by mobile and wearable devices [9–14]. The use of smart­
contraction and by an irregular ventricular response [5,6], which are phones and smartwatches for AF detection has recently received atten­
associated with worsened hemodynamics and an increased risk of tion as a mean for low-cost mass-screening [9–13]. While trials are
ischemic stroke [7]. AF diagnosis can be hindered by the episodic nature ongoing to evaluate the accuracy of these devices [9,11], AF detection

* Corresponding author. IRCS-HTA, Healthcare Research and Innovation Program, Fondazione Bruno Kessler, Department of Physics, University of Trento, 38123,
Trento, Italy.
E-mail address: michela.mase@unitn.it (M. Mas�e).

https://doi.org/10.1016/j.compbiomed.2019.103540
Received 31 July 2019; Received in revised form 11 November 2019; Accepted 11 November 2019
Available online 12 November 2019
0010-4825/© 2019 Elsevier Ltd. All rights reserved.
I.A. Marsili et al. Computers in Biology and Medicine 116 (2020) 103540

from standard electrocardiographic (ECG) signals remains the gold physiological parameters in mobility, for hospital, ambulatory, and
standard for diagnosis. Therefore, new technologies for continuous domestic monitoring. The device was designed to work in different
recording of ECG signals during daily activity and for extended periods configurations, such as 12-lead ECG, Holter, and tele-Holter/event
of time are under development. In particular, tele-Holter or event recorder. In real-time monitoring configuration, the device recorded
recorder systems with on-board algorithms for AF detection may in­ and analysed 3 ECG channels, at 250 Hz sampling rate, 16 bits, and 1
crease the likelihood of detecting events by allowing longer recording μV/bit resolution. A high-pass digital filter (0.5 Hz) removed baseline
times in real-life scenarios. However, on-board AF detectors require not wandering from the raw ECG signal. Notch (50–60 Hz) and low-pass
only high performance, but also minimization of energy consumption, (35 Hz) filters removed line and muscular activity noise before dis­
which is mostly driven by data storage and computational complexity. playing the signal. Acquired signals could be transmitted via Wi-Fi to a
Previous studies have proposed to detect AF by analyzing ECG and P- telemedicine server workstation for data storage and further analysis.
wave morphology [15–17], the ventricular interval (RR) series [10, The device included an integrated CPU with a 32-bit ARM Cortex M3
18–27], or a combination of the two [28–30]. For mobile applications, processor (NXP LPC1788), a 512 kB internal FLASH memory bank and a
RR-based algorithms are generally preferred to morphology-based al­ 64 kB internal RAM memory bank, a low-power 24-bit analog front-end,
gorithms, due to the lower amount of incoming data and the lower noise a RedPine BT/WiFi module, a Telit 2G/3G cellular module, two RAM
sensitivity of QRS-complex detection with respect to P-wave analysis. memory external banks of 2 MB each, and a μSD slot (Fig. 1A). The
RR-based algorithms can detect AF by quantifying the complexity of RR firmware was loaded into the FLASH memory to execute low-level
series using different metrics, such as coefficient of variation and density functions for peripheral management and higher-level functions, such
histograms [18], heart rate variability parameters from Poincar� e plots as signal processing and analysis. After subtracting the memory required
[31], pattern similarity [20], sample entropy [10,25] or coefficient of by other operations, we estimated that the maximum amount of memory
sample entropy [22,24,25], Shannon entropy [19,21], or normalized available to the QRS and AF detection algorithms was <20 kB.
fuzzy entropy [27].
Despite the large number of studies on AF detection algorithms, the 2.2. Framework for AF detection
efforts to implement them on hardware devices are sparse [10,32]. In
this study we addressed the implementation of an algorithmic frame­ The framework for AF detection consisted of two main modules
work for real-time AF detection on a prototype ECG monitoring device. (Fig. 1B). The QRS detector (first module) was based on the algorithm
The framework included a finite-state machine QRS detector [33] and a proposed by Guti� errez-Rivas et al. [33], which analysed a single-lead
Shannon entropy-based AF detector [19], which had been previously ECG signal and detected the sequence of R-waves, yielding the heart
selected for their low computational burden and high accuracy [34]. We rate (hr) series as output. The AF detector (second module) was based on
aimed to: 1) optimize the off-line version of the AF detector to further the algorithm by Zhou et al. [19], which converted the hr series into a
reduce the computational burden; and 2) measure the real-time per­ symbolic word series, then calculated the Shannon entropy of the series,
formance of the on-board implementation in terms of detection accu­ and finally classified heart beats as ‘AF’ and ‘non-AF’. The two algo­
racy, memory usage, and computation time. rithms were selected for their intuitive implementation, real-time
capability, and low computational burden [34].
2. Methods
2.2.1. QRS detector
2.1. Hardware Algorithm. The QRS detector included a pre-processing step, which
reduced baseline wandering (discrete derivative with Nd sample inter­
The algorithms were designed to work on a prototype monitoring val) and high-frequency artefacts (moving average filtering of window
system developed by Medicaltech srl (Rovereto, Italy), which allowed length NQRS), and emphasized R-peaks (square operation). After that,
continuous acquisition and recording of ECG signals and other QRS detection was performed by an adaptive threshold, based on a

Fig. 1. Hardware and software components of the AF detection system. (A). Prototype board of the wearable device with main processing units highlighted and
labelled. (B). Block diagram of the algorithmic framework, composed of QRS detector (orange) and AF detector (cyan).

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I.A. Marsili et al. Computers in Biology and Medicine 116 (2020) 103540

finite-state machine with three states: RAM to be used as input of the on-board algorithm. Raw signals were not
pre-processed by the prototype filters, but only by the QRS module fil­
- State 1 (Peak Detector): the algorithm searched for the maximum ters. The results of the QRS detector were validated using ‘bxb’.
peak in a fixed search window of 260 ms (i.e., minimum RR þ QRS The amount of on-board resources used by the QRS detector was
complex duration); the detected maximum was classified as R-peak; assessed in terms of memory usage, number of operations, and compu­
the threshold th was updated as the mean amplitude of all the tation time for each of the three machine states. The memory usage
detected R-peaks. indicated the size of the static structure used by the QRS detector and
- State 2 (Wait): the algorithm waited for a time period equal to the was measured from the change of heap size using RealTerm software
minimum RR (200 ms) minus the time between the last detected R- (CRUN, version 2.0.0.70) via serial connection. The number of times
peak and the end of State 1. each operation (shift, compare, sum or subtraction, division or multi­
- State 3 (Threshold): the threshold th was set at the last updated value plication) appeared in the source code was summarized as minimum and
and was progressively reduced at each sample according to the maximum sets, depending on conditional statements being satisfied or
function: not.
PTh The range of computation times was estimated by probing the
th ½n� ¼ th ½n 1� � e fs (1) voltage of a motherboard pin that was activated at the beginning and
deactivated at the end of each state, and measuring the interval between
where PTh was a parameter and fs was the sampling frequency; this state activation and deactivation with a digital oscilloscope (Tektronix model
ended when the signal became higher than the threshold; the system MSO2024B).
returned to State 1 and a new R-peak was searched.
As indicated in ½33�; the parameters were adapted to the sampling 2.2.2. AF detector
frequency (fs ¼ 250 ​ Hz), and set to: NQRS ¼ 6; Nd ¼ 5; PTh ¼ 6:07: Algorithm. The AF detector proposed by Zhou et al. [19] consisted of
The output of the QRS detector was the R-peak time series (in sec­ four main processing steps: 1. conversion of the hr series into a symbolic
onds), which was then converted into the hr series (in bpm). Given its sequence (sy); 2. combination of the symbolic series into a word series
low computational burden, in the present work the algorithm was (wv); 3. quantitative characterization of the word distribution by
implemented without modifications with respect to the original version. Shannon Entropy; 4. thresholding of Shannon Entropy values for binary
Off-line testing. The QRS detection algorithm was implemented ‘off- classification of each beat.
line’ in MATLAB (version R2019a, MathWorks, Inc., Natick, Massa­ The conversion stage encoded the hr series into few symbols, sy,
chusetts, USA) to provide the reference baseline for detection perfor­ according to a predefined base of dimension b, formed by the sequence
mance, which was assessed in terms of accuracy, sensitivity, and positive of integers [0, …, b-1]. The conversion was performed by the mapping
predictive value (PPV). The algorithm was tested on the American Heart function:
Association Database (AHADB), the MIT-BIH Noise Stress Test Database 8
(NSTDB [35]), and the MIT-BIH Arrhythmia Database (MITDB [36]), as < b 1 if hr½n� � hrmax
required by the International Electrotechnical Commission (IEC sy½n� ¼ hr½n� (2)
: other cases
60601-2-47 [37]). The analysis started 5 min after the beginning of each d
ECG recording, following the guidelines of the American National
Standards (ANSI/AAMI EC38:1998 [38] and ANSI/AAMI EC57:1998 where ⌊ ⌋ was the floor operator, hrmax was a cut-off value, and d was a
[39]). quantization factor equal to hrmax/(b-1).
The AHADB is composed of 80 ECG recordings (½ hour each), Symbols were combined into words, wv, of m symbols, according to:
sampled at 250 Hz with 12-bit resolution over a 10 mV range [40]. After
wv½n� ¼ sy½n� þ ðsy½n 1�Þ � ðbÞ… þ ðsy½n m�Þ � ðbÞm 1
​ (3)
removal of the first 5 min of each recording, the total number of QRS
complexes annotated by the cardiologists (Ground Truth) was 181,564. Word values were in the range [0, wvmax], with maximum given by:
The MITDB is a class 1 core database [41], which has been exten­ X
m
sively used as a benchmark in the literature, including [33]. The MITDB wvmax ¼ ðb 1Þ � ðbÞi 1
(4)
contains 48 ECG recordings (½ hour each) obtained from 47 subjects, i¼1

sampled at 360 Hz (here re-sampled at 250 Hz) with 11-bit resolution The information stored in a sequence of N words, wv [n-Nþ1],… wv
over a 10 mV range. The total number of QRS complexes annotated by [n], was quantified by a coarse version of Shannon Entropy, H:
the cardiologists was 91,285.
The NSTDB [35] is a class 1 core database, which includes 12 ECG k Xk
H½n� ¼ pi � log2 ðpi Þ (5)
recordings (½ hour each, same characteristics of the MITDB) from 2 N � log2 ðNÞ i¼1
subjects and 3 noise recordings (baseline wander, muscle artefacts, and
electrode motion ‘em’ artefacts) [42]. The ECG recordings with different where 1 � k � N was the number of characteristic elements in the
signal-to-noise ratios (SNR from 24 to 6 dB) were obtained by adding sequence, and 0 � pi � 1 was the probability associated to the ith char­
the ‘em’ noise to 2 ‘clean’ ECG recordings from the MITDB. The total acteristic element. This was estimated as pi ¼ Ni/N, where Ni was the
number of QRS complexes annotated by the cardiologists was 21,462. number of repetitions of the element in the sequence. The calculation of
The results of the QRS detector were validated against Ground Truth H was repeated beat-to-beat, lowering the computational cost by a
annotations using the ‘bxb’ function of the WaveForm DataBase (WFDB) recursive implementation [19].
Software Package ([43], version 10.6.0 for Linux downloaded from Finally, H values were compared with an Optimal Threshold (OT),
Ref. [44]). and cardiac beats were classified as ‘AF’ if H � OT, and as ‘non-AF’
On-board testing. For the on-board implementation, the source code otherwise.
of the QRS detection algorithm was re-written in C using μVision (ARM, Optimization. The AF detector was optimized to minimize resource
version 5.23), integrated in the firmware, compiled with Armcc (version consumption for on-board implementation by testing different config­
5.06), and loaded into the internal FLASH memory of the prototype ECG urations of the encoding base (b), word length (m), and window length
device. The algorithm parameters were set as in the ‘off-line’ imple­ for H computation (N). In the original implementation by Zhou et al.
mentation for comparison. [19], indicated as ‘Zhou x64 3f’, the parameters were set to b ¼ 64,
MITDB recordings were re-sampled at 250 Hz, loaded into the μSD m ¼ 3, and N ¼ 127 (‘f’ ¼ full window size), which required a memory
memory card of the device, and then loaded one by one into the external buffer size of 256 kB, i.e. much larger than what was available on the

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I.A. Marsili et al. Computers in Biology and Medicine 116 (2020) 103540

device. In this study, we tested four modified versions of the AF detec­ validated against Ground Truth annotations that were re-indexed to the
tion algorithm: QRS complexes detected by the proposed method.
On-board testing. The source code of the AF detection algorithm was
- ‘Zhou x64 2f’, with parameters b ¼ 64, m ¼ 2, and N ¼ 127, corre­ re-written in C using μVision, integrated in the firmware, compiled with
sponding to a buffer size of 4 kB. Armcc, and loaded into the internal FLASH memory of the prototype
- ‘Zhou x64 2h’, with b ¼ 64, m ¼ 2, and N ¼ 63 (‘h’ stands for half ECG device. For the on-board implementation, we selected the set of
window), corresponding to a buffer size of 4 kB. parameters of the best performing algorithm among the modified
- ‘Zhou x32 2f’, with b ¼ 32, m ¼ 2, and N ¼ 127, corresponding to a versions.
buffer size of 1 kB. The test dataset included the same RR series from the AFDB that were
- ‘Zhou x32 2h’, with b ¼ 32, m ¼ 2, and N ¼ 63, corresponding to a used for off-line testing. All series were loaded into the device μSD
buffer size of 1 kB. memory card, and then one by one into the external RAM. Results were
validated against Ground Truth annotations. On-board resource con­
For ‘x64’ configurations hrmax was set to 315 bpm and d to 5, while sumption for encoding and complexity assessment in the AF detector
for ‘x32’ ones hrmax was set to 310 bpm and d to 10. It is worth noting were measured, as described for the QRS detector.
that the decrease of m from 3 to 2 led to a decrease in buffer size from
256 kB to 4 kB for ‘x64’ configurations and further to 1 kB for ‘x32’ ones. 3. Results
Off-line training. The AF detection algorithm proposed by Zhou
et al. [19] was implemented off-line in MATLAB using the original set of 3.1. QRS detection
parameters (‘Zhou x64 3f’) and the four modified versions. AF detection
performance was evaluated by Receiver Operating Characteristic (ROC) 3.1.1. Off-line testing
analysis on training data to find the OTs for each version. RR series from The performance of the off-line implementation of the QRS detector
the Long Term AF Database (LTAFDB) [45] were used as training on the AHADB, NSTDB, and MITDB are reported in Table 1. Excellent
dataset. LTAFDB is a class 3 core database, which includes 84 long-term sensitivity and PPV (>99%) were obtained on the AHADB and MITDB,
(24–25 h each) ECG recordings of subjects with paroxysmal or sustained whereas PPV and detection error worsened significantly on the NSTDB,
AF. Each record contains two simultaneously recorded ECG signals mostly due the extreme cases with SNR ¼ 0 and 6 dB (Table 2).
sampled at 128 Hz with 12-bit resolution over a 20 mV range. The However, at SNR ¼ 24, 18, and 12 dB, optimal performance was ach­
LTAFDB contains 8,995,973 cardiac beats in total, of which 58.2% are ieved, indicating robustness to noise at realistic SNR levels.
classified by experts as AF.
The AF detection algorithm performed a binary classification 3.1.2. On-board testing
(AF ¼ true or false). Sensitivity and specificity were calculated from the The performance of the on-board implementation of the QRS de­
number of true positives (TP), true negatives (TN), false positives (FP), tector was assessed on MITDB signals loaded into the μSD card of the
and false negatives (FN). To obtain the ROC curves, sensitivity and device. The results were practically identical to the off-line imple­
specificity of the binary classification were calculated while changing mentation (Table 1). The on-board memory usage of the QRS detector
the detection threshold from 0 to 1. ROC analysis used empirical prior was 672 bytes, with an indicative range of computation times between 2
probabilities derived from the class frequencies, and the OT for each and 10 μs for State 1, 10–70 μs for State 2, and 1–10 μs for State 3
version was found at the intersection between the ROC curves and a (Table 3 and Fig. 2). The number of operations for each state depended
straight line with slope S, calculated as: on the ECG signal satisfying certain conditions. The minimum and
maximum sets of operations are detailed in Table 3.
costðFPÞ N
S¼ � (6)
costðFNÞ P
3.2. AF detection
where P ¼ TP þ FN was the total number of positives (‘AF’ beats) and N
¼ TN þ FP the total number of negatives (‘non-AF’ beats), while cost(FP) 3.2.1. Off-line training
and cost(FN) were the misclassification costs of FP and FN, respectively. The off-line performance of different versions of the AF detector on
OTs were found assuming equal misclassification costs, i.e. cost the LTAFDB (training dataset) are shown as ROC curves in Fig. 3A. The
(FP) ¼ cost(FN) ¼ 0.5. Additional thresholds TA and TB were calculated highest score for the Area Under the Curve (AUC) was achieved by the
using misclassification costs that favoured either sensitivity or speci­ original ‘Zhou �64 3f’ algorithm (98.4%), while the best performance
ficity (i.e. changed the slope of the line intersecting the ROC curves). among the modified versions was achieved by ‘Zhou �64 2h’ with
Specifically, threshold TA, favouring sensitivity, was obtained by setting AUC ¼ 97.9%. Due to different encoding lengths and window sizes, H
cost(FP) ¼ 0.4 and cost(FN) ¼ 0.6; while threshold TB, favouring speci­ values computed by the modified versions tended to be lower, which
ficity, by setting cost(FP) ¼ 0.6 and cost(FN) ¼ 0.4. resulted in lower OTs with respect to the original algorithm.
Off-line testing. All the different versions of the AF detector were At OT ¼ 0.416, ‘Zhou �64 2 h’ yielded sensitivity ¼ 95.7% and
validated against Ground Truth annotations, evaluating sensitivity, specificity ¼ 93.0%, compared to sensitivity ¼ 96.6% and speci­
specificity, PPV, and overall accuracy at their respective OTs (obtained ficity ¼ 93.7% of ‘Zhou �64 3f’. Additional detection thresholds for
from the off-line training phase). RR series from the MIT-BIH Atrial ‘Zhou �64 2 h’ were calculated: setting TA ¼ 0.366 increased sensitivity
Fibrillation Database (AFDB [46]) were used as test dataset. The AFDB is to 97.0% (specificity ¼ 90.7%), while setting the threshold to TB ¼ 0.453
a class 3 core database that is used as benchmark in the literature, increased specificity to 94.3% (sensitivity ¼ 94.6%).
including [19]. It is made of 25 ECG recordings (~10 h each) of subjects
with AF (mostly paroxysmal), sampled at 250 Hz with 12-bit resolution 3.2.2. Off-line testing
over a range of 20 mV. Some records (00735, 03665, 04936 and 05091) The off-line performance of different versions of the AF detection
were excluded due to missing data or incorrect annotations, as in Zhou algorithm was measured on the AFDB (test dataset) and the resulting
et al. [19]. The resulting database included 1,039,748 cardiac beats in ROC curves are shown in Fig. 3B. The behaviour of the ROC curves for
total, of which 45.2% were classified by experts as AF. the test dataset was similar to that on the training data (Fig. 3A), albeit
Finally, the performance of the complete analysis framework, i.e. with superior overall performance. The highest AUC was achieved by
combined QRS and AF detectors, was assessed on ECG recordings from the original ‘Zhou �64 3f’ algorithm (99.7%), followed by ‘Zhou �64
the AFDB. The resulting AF classification for each RR interval was 2h’ (99.5%).
The OTs found on the training dataset were used for off-line testing

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I.A. Marsili et al. Computers in Biology and Medicine 116 (2020) 103540

Table 1
Performance of the QRS detection algorithm on the AHADB, NSTDB, and MITDB.
Database Implem Total QRS TP FN FP Sensitivity PPV Error

AHADB Off-line 181564 180426 1138 695 99.4% 99.6% 1.0%


NSTDB Off-line 21462 21186 276 3753 98.7% 85.0% 18.8%
MITDB Off-line 91285 90566 719 204 99.2% 99.8% 1.0%
MITDB On-board 91285 90567 718 211 99.2% 99.8% 1.0%

FN, false negatives; FP, false positives; Implem, implementation; PPV, positive predictive value; TP, true positives.

The results obtained using thresholds TA and TB on the AFDB are


Table 2
reported in Table 4. Using TA ¼ 0.366 increased sensitivity (99.6%), but
Performance of the QRS detector on the NSTDB, detailed at different noise
reduced specificity to a larger extent (95.9%). Differently, TB ¼ 0.453
levels.
produced a more balanced performance with lower sensitivity (98.6%)
SNR [dB] Total QRS TP FN FP Sensitivity PPV Error and higher specificity (97.9%) than OT ¼ 0.416.
24, 18, 12 3577 3577 0 1 100% 100% 0% The performance of the whole ECG analysis framework (QRS þ AF
6 3577 3562 15 164 99.6% 95.6% 5.0% detectors) on the AFDB is shown in Table 4. All results were slightly
0 3577 3521 56 1121 98.4% 75.9% 32.9%
lower than for the AF detector alone, which could be mostly attributed
6 3577 3372 205 2465 94.3% 57.8% 74.6%
to the different number of QRS complexes detected (1,054,238 RR in­
FN, false negatives; FP, false positives; PPV, positive predictive value; TP, true tervals found by our QRS detector versus 1,039,076 in the QRS anno­
positives. tations). It is worth noting that reference QRS annotations in the AFDB
were detected automatically and not manually corrected.

3.2.3. On-board testing


Table 3 The detection performance of the on-board implementation of ‘Zhou
Resource consumption for the on-board implementation of the detection �64 2 h’ on the AFDB was identical to that of the off-line version
algorithms. (Table 4). The on-board memory usage of the AF detector was 4648
Algorithm Memory Number of Operations Computation Bytes, with an indicative range of computation times between 1 and 5 μs
Usage Maximum Time for the encoding step and 60–70 μs for the complexity assessment step
[Bytes] Minimum Range [μs] (Table 3 and Fig. 2).
QRS detector 672
State 1 2 compare; 3 compare; 2–10 4. Discussion
2 sum/sub 7 sum/sub
State 2 2 compare; 2 compare; 10–70
1 div/mult 4 sum/sub; In this study, we optimized, implemented, and validated an algo­
4 div/mult rithmic framework for real-time AF detection on a prototype ECG
State 3 1 compare; 2 compare; 1–10 monitoring device. ECG recordings from gold-standard public databases
1 sum/sub 2 sum/sub;
were loaded directly into the device to assess detection accuracy,
1 div/mult
AF detector 4648 memory usage, and computation time of the on-board algorithms. We
Encoding 2 compare 1 int div; 1–5 demonstrated the feasibility of real-time AF detection on a wearable
2 compare; device by achieving excellent performance with limited memory usage
1 shift; and computation time.
1 sum
Complexity 4 compare; 4 compare; 60–70
Assessment 4 sum/sub; 6 sum/sub;
4.1. Algorithm optimization for hardware implementation
3 div/mult 3 div/mult

Div, division; int, integer; mult, multiplication; sub, subtraction. The ECG analysis framework was based on published algorithms for
QRS and AF detection, which were required to work in real-time within
on the AFDB. The thresholds are marked on the ROC curves in Fig. 3B to the limitations imposed by the hardware. The QRS detector was spe­
show that they were close to optimal also on the test dataset, which cifically designed by the authors for real-time applications with low
indicated their generalizability to unseen data. The performance metrics power consumption and performed like the Pan & Tompkins’ algorithm
for all the algorithms at their respective OTs are reported in Table 4. All [47], but with only half the computational cost [33]. Since the resource
the modified algorithms showed higher sensitivity than the original one. consumption of the QRS detector was well-within the limits of our
However, the ranking of algorithms in terms of accuracy remained un­ hardware, we implemented the original algorithm without further
altered with respect to the training phase, since the increase in sensi­ optimization, and tested it on ECG recordings from the AHADB and
tivity was balanced by a decrease in specificity. ‘Zhou �64 2h’ was MITDB, and on recordings with increasing levels of noise from the
confirmed the best performer among the modified algorithms, with ac­ NSTDB. QRS detection performance on the MITDB was only slightly
curacy of 98.1% compared to 98.3% in ‘Zhou �64 3f’, an increased lower than that reported by the original study [33], likely due to the fact
sensitivity (þ0.7%), but decreased specificity ( 0.9%) and PPV that we did not run QRS detection on the first 5 min of each ECG
( 1.0%). recording. Results on the NSTDB compared favorably with those ob­
Overall, ‘Zhou �64 2 h’ improved the number of cardiac beats tained by top-ranking algorithms from the Physionet Challenge 2014
correctly classified as AF with respect to ‘Zhou �64 3f’, i.e. increased TP [48]. In particular, on data with SNR ¼ 6 dB the performance was very
and reduced FN. This behaviour can be appreciated in the representative close to the top scores, while on data with SNR ¼ 0 dB both sensitivity
example shown in Fig. 4. However, in some cases the modified algorithm and PPV were the highest. For the on-board implementation, we ob­
increased FP, as exemplified in Fig. 5. These results can be explained by tained sensitivity and PPV larger than 99% on the MITDB, memory
the faster response of ‘Zhou �64 2 h’ to brief AF events and heart rate usage <1 kB and total computational time <0.1 ms per beat, which
changes, mostly due to the shorter word length, half-size window, and demonstrated the suitability of the QRS detection algorithm for robust
lower OT. and reliable real-time applications.

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I.A. Marsili et al. Computers in Biology and Medicine 116 (2020) 103540

Fig. 2. Computational burden of the AF detection framework. Typical computation times for each of the three machine states (1, 2, or 3) of the QRS detector, and for
the encoding (A) and complexity assessment (B) steps of the AF detector. The output voltage was measured directly from the device using an oscilloscope.

Fig. 3. Receiver Operating Characteristic (ROC) curve analysis on training (A) and test (B) datasets for different versions of the AF detection algorithm: original
‘Zhou �64 3f’ algorithm vs. modified ‘Zhou �64 2h’, ‘Zhou �64 2f’, ‘Zhou �32 2h’, and ‘Zhou �32 2f’ versions. Legends report the Area Under the Curve (AUC) and
the Optimal Threshold (OT) for each algorithm. The thresholds applied on the test dataset and reported in panel (B) were the OTs resulting from the off-line training
phase (A). Plots are magnified at different scales.

Table 4
Performance of the original and modified versions of the AF detection algorithm on the AFDB (test dataset).
Algorithm Threshold Implementation Total RR TP FN FP Sensitivity Specificity PPV Accuracy

Zhou �64 3f OT ¼ 0.630 Off-line 1038383 462655 7039 10463 98.5% 98.2% 97.8% 98.3%
Zhou �64 2h OT ¼ 0.416 Off-line 1039076 466227 3731 15600 99.2% 97.3% 96.8% 98.1%
Zhou �64 2f OT ¼ 0.308 Off-line 1038383 466213 3481 17911 99.3% 96.9% 96.3% 97.9%
Zhou �32 2h OT ¼ 0.178 Off-line 1039076 464976 4982 31453 98.9% 94.5% 93.7% 96.5%
Zhou �32 2f OT ¼ 0.104 Off-line 1038383 467080 2614 41470 99.4% 92.7% 91.9% 95.8%
Zhou �64 2h OT ¼ 0.416 On-board 1039076 466227 3731 15600 99.2% 97.3% 96.8% 98.1%
Zhou �64 2h OT ¼ 0.416 QRS þ AF off-line 1054238 469910 4123 19786 99.1% 96.6% 96.0% 97.7%
Zhou �64 2h TA ¼ 0.366 Off-line 1039076 467966 1992 23226 99.6% 95.9% 95.3% 97.6%
Zhou �64 2h TB ¼ 0.453 Off-line 1039076 463386 6572 11852 98.6% 97.9% 97.5% 98.2%

FN, false negatives; FP, false positives; PPV, positive predictive value; RR, ventricular intervals; TP, true positives.

The algorithm by Zhou et al. [19] was selected for its low compu­ entropy beat-to-beat computation [19]. The present work aimed at
tational burden compared to similarly performing algorithms [20,34]. further reducing the computational cost by optimizing the main pa­
The encoding of the hr series into a symbolic sequence allowed a concise rameters for symbolic sequence generation and Shannon Entropy
description of the series, whose complexity could be easily quantified in computation. Decreasing the word length from 3 to 2 symbols provided
terms of Shannon entropy [19]. The encoding step required a small set of major improvements (shrinking memory consumption by 64 times)
arithmetic operations without any convolution/filtering operation, and while not significantly affecting detection accuracy (only 0.2–0.4%
a recursive calculation algorithm reduced the burden of Shannon lower on the AFDB). On the other hand, changing the encoding base

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Fig. 4. Performance of different AF detectors on a segment of recording ‘04048’ from the AFDB. (A) Heart rate signal with Ground Truth annotation of AF events
(segments highlighted in green). (B) Shannon Entropy estimated by ‘Zhou �64 3f’ (original algorithm) with detected AF events in orange. (C) Shannon Entropy
estimated by ‘Zhou �64 2h’ (modified algorithm) with detected AF events in orange. ‘Zhou �64 2h’ improved the number of cardiac beats correctly classified as AF
(i.e. true positives) compared to ‘Zhou �64 3f’. Optimal thresholds for both algorithms were calculated on the training dataset (LTAFDB).

Fig. 5. Performance of different AF detectors on a segment of recording ‘05261’ from the AFDB. (A) Heart rate signal without AF events. (B) Shannon Entropy
estimated by ‘Zhou �64 3f’ (original algorithm) with detected AF events in orange. (C) Shannon Entropy estimated by ‘Zhou �64 2h’ (modified algorithm) with
detected AF events in orange. ‘Zhou �64 2h’ increased the number of cardiac beats misclassified as AF (i.e. false positives) compared to ‘Zhou �64 3f’. Optimal
thresholds for both algorithms were calculated on the training dataset (LTAFDB).

from 64 to 32 elements led to a further 4-fold memory reduction, but limits imposed by the hardware configuration and consistent with
caused a larger deterioration of the detection accuracy (1.8–2.5% real-time detection. It is worth noting that, compared to the original
decrease). Finally, different window lengths for Shannon entropy version, the modified algorithm demonstrated higher sensitivity
computation yielded very similar performance. ’Zhou �64 2h’ offered (þ0.7%) in detecting AF beats, due to a faster response to short AF ep­
the best compromise between detection accuracy and computational isodes. On the other hand, lower specificity ( 0.9%) was observed, most
burden, with on-board accuracy of 98.1%, memory usage <5 kB, and likely due to the lower detection threshold and the coarser description of
computation time �75 μs per beat. The performance was well within the hr dynamics in the two-dimensional (versus three-dimensional) word

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state space. The proposed algorithm compared favorably with the so that AF events are not missed. In such a scenario, the use of TA would
best-performing RR-based algorithms in the literature (Table 5), increase sensitivity to 99.6%, but at the cost of specificity being
demonstrating the highest sensitivity for all the considered detection decreased to 95.9%. As a future development, in order to reduce the
thresholds (OT, TA, TB). In terms of specificity, it displayed the third-best false alarms associated with lower specificity, one could devise a two-
performance after Petrenas et al. [20] ( 0.4%) and Huang et al. [49] step detection process, in which “potential AF” episodes detected by
( 0.2%), when adopting TB. However, we should bear in mind that the device are then automatically analysed on a telemedicine worksta­
minor differences in performance among algorithms may be due to tion. Remote AF detection could benefit from the use of
differences in the validation procedure on the AFDB (e.g. removal of computationally-expensive algorithms, e.g. artificial intelligence and
recordings, exclusion of the initial 5 min of each recording, etc). machine learning approaches [30,51,52], since energy and memory
Our results demonstrated the feasibility of implementing real-time consumption would no longer be a concern. As a second example, when
QRS and AF detection algorithms on a prototype device. Studies on working in Holter modality for diagnostic purposes, a better balance
hardware implementations are sparse [10,32], and direct comparison between sensitivity and specificity could be obtained by setting the
with other hardware systems may be difficult due to differences in the detection threshold to TB.
implementation, detection settings, and signals. Andersson et al. [32] Finally, it is worth noting that our prototype device may not be
designed and fabricated an ASIC (Application-Specific Integrated Cir­ suitable for mass-screening. However, the reduced computational cost
cuit) real-time AF detector performing ultra-low voltage operations for and memory usage of the optimized algorithms, combined with the
implantable loop recorders. The detector, based on the combination of progress in smartphone technology, would potentially support the
three RR metrics, had a sensitivity of 94.9% and specificity of 95.8% implementation of the AF detector on smartphones for screening ap­
(90.6% and 97.6% for the memory-saving version) on the AFDB plications. With this aim, further studies should assess detection accu­
(Table 5). Lee et al. [10] optimized three RR-based detection algorithms racy as a function of type, quality, and length of the signals provided by
for implementation on iPhone4S technology. The highest performance the wearable technology. For instance, in a recent study on AF detection
was obtained by the sample entropy detector, which achieved an ac­ by smartphone technology, only 66% of the traces acquired by the
curacy of 96.1% on the combined AFDB þ NSRDB datasets, and a “Kardia Band” were found to be analyzable [8].
computation time of ~25 ms for the analysis of a 64-beat segment.
4.3. Study limitations
4.2. Clinical use of the technology
The main limitation of this study was that the algorithms were not
The feasibility of performing on-board AF detection with high ac­ tested on ECG signals acquired directly from AF patients by the proto­
curacy, as demonstrated in this study, may have implications for the type device. Although validation on public databases allowed compar­
development of mobile health systems for AF monitoring [9]. Algo­ isons with other methods, future studies should use ECG signals acquired
rithms were implemented on a prototype wearable ECG monitoring by the device under real-world conditions. This would allow us to
device, characterized by a small size, limited cost, and the ability to investigate the actual level and type of noise and artefacts corrupting the
work in different modalities, e.g. tele-Holter and event-recorder. signals and their effect on AF detection, as well as to devise suitable
Wearability and small economic cost of the device might encourage its filtering strategies to maximize performance.
adoption for long-term monitoring of cardiac rhythm in large population
studies. In particular, since the device acquires standard ECG signals, it 5. Conclusion
could be used for AF diagnosis and burden assessment following ther­
apeutic interventions. This study demonstrated the feasibility of real-time AF detection on
Since working in different modalities may require some performance wearable devices. A low-complexity algorithmic framework was opti­
trade-offs, we identified two detection thresholds that favoured either mized and implemented on a prototype ECG monitoring device. The on-
sensitivity or specificity. As a first example, when working in event- board implementation achieved excellent real-time performance (98%
recorder modality, the highest possible sensitivity should be pursued, accuracy) with limited memory usage (less than 6 kB) and computation

Table 5
Performance of the optimized AF detector (‘Zhou �64 2h’) in comparison with previously proposed RR-based detectors.
AF Detectors Performed Analysis Database Sensitivity Specificity

Proposed detector (’Zhou �64 2h’) Shannon entropy of symbolic series AFDB1 99.2% (at OT) 97.3% (at OT)
99.6% (at TA) 95.9% (at TA)
98.6% (at TB) 97.9% (at TB)
Liu et al., 2018 [27], Normalized fuzzy entropy AFDB2 98.46% 89.85%
Andersson et al., 2015x [32], Turning point ratio þ Root mean square AFDB 94.9% 95.8%
of ΔRR þ Shannon entropy
Petrenas et al., 2014 [20], Ectopic beat filtering þ Bigeminal AFDB 97.1% 98.3%
suppression þ RR irregularity þ Signal fusion AFDB3 97.1% 98.1%
AFDB4 98.0% 98.2%
Lee et al., 2013x [10], Root mean square of ΔRR AFDB4 þ NSRDB 90.49% 94.17%
Shannon entropy 74.15% 96.81%
Sample entropy 97.26% 95.91
Lee et al., 2013 [23], Time varying coherence function þ Shannon entropy AFDB4 98.22% 97.68%
Huang et al., 2011 [49], ΔRR distribution difference curve AFDB 96.1% 98.1%
Lake and Moorman 2011 [22], Coefficient of sample entropy AFDB 91% 94%
Lian et al., 2011 [50], RR-ΔRR map AFDB 95.8% 96.4%
Dash et al., 2009 [21], Turning points ratio þ Root mean square AFDB4 94.4% 95.1%
of ΔRR þ Shannon entropy
Tateno and Glass 2001 [18], Kolmogorov-Smirnov test on ΔRR AFDB 94.4% 97.2%

AFDB , recordings no.00735, no.03665, no.04936, and no.05091 excluded; AFDB , recordings no.05091 and no.0.7859 manually corrected; AFDB3, recordings
1 2

no.00735 and no.03665 excluded; AFDB4, recordings no.04936 and no.05091 excluded; x, device implementation.

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