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The repeatability of estimated systolic time
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9 intervals in healthy subjects using
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seismocardiogram and electrocardiogram
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15 Vahid Zakeri1, Kouhyar Tavakolian2, 3, Andrew P. Blaber3, Erwin P. Bauer1, Parastoo
16 Dehkordi4, and Farzad Khosrow-khavar1
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Heart Force Medical Inc., Vancouver, Canada
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19 School of Electrical Engineering and Computer Science, University of North Dakota, Grand Forks,
USA
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Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, Canada
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The Electrical and Computer Engineering Department, University of British Columbia, Vancouver,
22 Canada
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24 E-mail: vahid.zakeri@heartforcemedical.com
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26 Submitted August 16, 2019; Revised January 07, 2020
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Abstract
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29 Objective: We investigated the repeatability of systolic time intervals (STIs) in healthy
30 subjects using a combination of seismocardiogram (SCG) and electrocardiogram (ECG). STIs
31 have been extensively used in the past to quantify heart performance, particularly the left
32 ventricle. In this study, STIs included pre-ejection period (PEP), left ventricular ejection time
33 (LVET), and their ratio. Approach: We conducted the repeatability test of STI estimation
34 through two experiments. The first involved three consecutive one-minute recordings separated
35 by one-minute intervals, and the second involved two one-minute recordings separated by 24
36 hours. Twenty healthy subjects participated in our study. We considered the coefficient of
37 variation (CV) to quantify the repeatability. As there was no agreed upon values for optimal
38 CV values, we compared our results with an alternative method using a combination of
39 impedance cardiography (ICG) and ECG. Similar to our method, the alternative method was
40 noninvasive and could be employed for personal heart monitoring. We also studied the
41 repeatability after STIs were corrected for heart rate using two approaches. The first approach
42 used a multiplicative factor per subject based on the heart rates in each recordings of that
43 subject. The second approach employed sex-specific regression models for all subjects
44 (Weissler's equations). Main results: We found that the repeatability of our method (SCG and
ECG) was in agreement with the alternative method (ICG and ECG) in both experiments.
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Moreover, the Weissler’s equations approach for heart rate increased the repeatability.
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Significance: It can be concluded that estimation of PEP, LVET and their ratio through SCG
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and ECG signals was repeatable in healthy subjects.
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Keywords: systolic time intervals, repeatability, seismocardiogram, electrocardiogram
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AUTHOR SUBMITTED MANUSCRIPT - PMEA-103248.R1 Page 2 of 26
Journal XX (XXXX) XXXXXX Zakeri et al

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21 Figure 1: Estimation of systolic time intervals (STIs) using seismocardiogram (SCG) and electrocardiogram (ECG). STIs
22 are pre-ejection period (PEP) and left ventricular ejection time (LVET). AO and AC are aortic valve opening and closure
23 characteristic points, respectively.
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25 ECG requires less electrodes and sensors, which provides
26 1. Introduction
more flexibility and less constraint.
27 Systolic time intervals (STIs) are critical timing parameters SCG provides information on mechanical aspects of heart,
28 with diagnostic and prognostic implications in the assessment in contrast to ECG that indicates the electrical activities of
29 of heart performance, particularly the left ventricle. STIs have heart. Therefore, considering both signals may provide a more
30 been suggested as a noninvasive technique in the evaluation complete assessment of cardiac functions.
31 of heart for suspected myocardial, coronary artery, and valve In mid-1990’s, Crow, et al. used SCG for estimation of
32 diseases [1]. Also, they have been proposed to assess the STIs, and compared their results with Echo as the gold
33 efficacy of procedures such as biventricular pacing [2]. One of standard. They concluded that both methods were equally
34 the earliest investigation on the estimation of STIs was accurate in the measurements of STIs [10]. Among the
35 conducted by Garrod in the late 19th century [3]. Since then, different STIs, we considered pre-ejection period (PEP), left
36 various methods have been proposed to estimate STIs such as ventricular ejection time (LVET), and their ratio (PEP/LVET)
37 concurrent electrocardiogram (ECG), phonocardiogram, and for the purpose of this study. PEP can be estimated from Q-
38 carotid pulse [4] [5], echocardiography (Echo) [6] [7], and wave on ECG to the aortic valve opening (AO) characteristic
39 impedance cardiography (ICG) [8]. A brief review of these point on SCG. LVET can be estimated from AO to the aortic
40 methods is presented by Tavakolian [9]. valve closure (AC) characteristic point on SCG (Figure 1). It
41 Seismocardiography has gained popularity as a convenient has been shown that PEP and LVET correlate with stroke
42 and inexpensive method. The seismocardiogram (SCG) signal volume and cardiac output [5]. The PEP/LVET ratio is
43 is commonly obtained by placing an accelerometer on the considered as the most useful STIs for assessment of left
44 sternum and captures the movement of the chest induced by ventricular performance [1]. It is possible that PEP and/or
45 heart vibrations. The inexpensive, small-size, and low-weight LVET do not indicate ventricular dysfunction, but their ratio
46 modern accelerometers, particularly micro-electromechanical can imply such a dysfunction [1]. The PEP/LVET is correlated
47 systems (MEMS), make acquiring SCG convenient. Such with the ejection fraction, and is a more robust parameter with
48 accelerometers are available in many portable and personal respect to the heart rate [1]. A ratio of less than 0.4
49 devices such as smartphones, which make SCG potentially (PEP/LVET < 0.4) can be considered as the range for healthy
accessible to all users of these devices. In STI estimation, subjects [9] [11].
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unlike Echo, SCG-ECG method is less expensive, does not The purpose of this study was to investigate the
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need a skilled operator, and can be used for self-monitoring. repeatability of STI estimation (test-retest reliability, [12]) in
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Moreover, in comparison to other methods of STI estimation healthy subjects using SCG and ECG. We compared our
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such as ICG-ECG or ECG-pulse-phonocardiogram, SCG- results with an alternative method using a combination of ICG
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25 Figure 2: A picture showing our experimental setup for data collection (ECG: electrocardiogram, SCG: seismocardiogram,
26 ICG: impedance cardiography). The ICG electrodes for upper abdomen are not observable in the above picture.
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29 and ECG. We selected this alternative, because similar to our SCG and ECG signals were recorded from these subjects in
30 method, it was noninvasive and could be employed for the supine position. SCG was obtained by placing a triaxial
31 personal heart monitoring. Also, ICG is commercially accelerometer (Silicon Designs Inc. Model 2476, USA) on the
32 available, and has been widely studied by the clinical sternum and collecting the acceleration signal in the
33 community [13] [14]. dorsoventral direction. ECG signal (lead I) was recorded
34 Despite various investigations on SCG, the repeatability of simultaneously by the iWorx Systems, Inc., IX-BIO8-SA,
STI estimation in combination with ECG has not been NH, USA. All the recordings were transferred to a personal
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thoroughly investigated. We found only one report in the computer using the iWorx data acquisition system (iWorx
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literature that considered the repeatability of STIs estimated Systems, Inc., IX-416, NH, USA) sampled at 1000 Hz with
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through SCG and ECG [10]. However, this report did not 16-bit resolution.
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include any results for LVET and PEP/LVET. We also did not To provide a comparison for our repeatability results, we
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find any studies analyzing the repeatability of PEP/LVET also recorded the ICG signal from the subjects, and estimated
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ratio using any estimation method. Therefore, our focus in this PEP, LVET, PEP/LVET, and determined their corresponding
41 study was to address these gaps. repeatability. ICG was obtained by placing two pairs of
42 electrodes on upper neck and upper abdomen, respectively
43 (BoMed Inc., USA). Figure 2 depicts our experimental setup
44 2. Methods for data collection. In this figure, the ICG electrodes for upper
45 abdomen are not observable.
46 2.1 Data collection Ethics approval was issued by the Office of Research
47 Ethics, Simon Fraser University (SFU), Burnaby, Canada. The
48 Twenty healthy subjects participated in this study (age:
data collection was conducted in the Aerospace Physiology
49 29±5 years, height: 172±6 cm, weight:70±12 kg, and sex: 12
Labratory at SFU.
males and 8 females). These subjects had no prior history of
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cardiovascular or respiratory diseases. They were also
51 2.2 Repeatability experiments
scanned with Echo for possible visible complications such as
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valvular regurgitations or congenital heart diseases. Two repeatability experiments were considered in our
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study, and 24-hour. In the consecutive repeatability
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3 experiment, our objective was to assess if the estimated STIs To assess the agreement between the repeatability of our
4 derived from SCG and ECG signals of healthy subjects method (SCG-ECG) and the alternative (ICG-ECG), we used
5 significantly change within a short period. Three consecutive the Bland-Altman analysis that is a well-established graphical
6 1-minute recordings with a one-minute interval in between, approach for comparison of two measurement techniques
7 were used for comparison. [21]. In this study, we considered 95% limits of agreement
In the 24-hour repeatability experiment, the objective was (LoA) in the Bland-Altman analysis.
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to investigate if the STIs of the healthy subjects significantly
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change when the recordings are conducted under the same 2.4 Correction for heart rate
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conditions over a period of at least 24 hours. To accomplish
11 It has been shown that the PEP and LVET inversely
this objective, for each subject, two 1-minute measurements
12 correlate with the heart rate [1]. To provide a more accurate
were conducted at least 24 hours apart. The recordings were
13 analysis for STI repeatability, a correction should be
roughly taken at the same time each day to reduce the diurnal
14 variation in the systolic intervals.
considered for PEP and LVET with respect to heart rate. We
15 In both experiments, the subjects were advised not to
pursued two different correction approaches that derived a
16 exercise, drink caffeinated beverages, alcohol, or smoke
linear relation between heart rate and STIs. We compared the
17 cigarettes four hours prior to data recordings.
repeatability of STIs before and after correction for each of
18 these approaches.
19 In the first approach, PEP and LVET were corrected with
2.3 Annotation, repeatability, and statistical analysis
20 respect to a predefined heart rate as suggested by [22],
HR
21 There is a consensus among experts that usually 10 cycles
PEP = PEP ×
HR
22 are sufficient for STI estimation [1] [15] [16]. To obtain STIs (2)
23 from SCG, an expert annotated the Q-wave on the ECG and
the AO and AC points on the SCG for at least 10 cycles per
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HR
LVET = LVET ×
SCG recording. In total, 735 and 2558 cycles of SCG were
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HR
(3)
annotated in the consecutive and 24-hour experiments,
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respectively.
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To estimate STIs from ICG, another expert annotated the
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Although different values of HR
Q-wave on the ECG, and the ICG characteristic points that where HR indicates the heart rate in beat-per-minute (BPM).
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correspond to the aortic valve opening and closure [17]. For change the values
30 each ICG recording, 10 cycles were annotated except for one of corrected STIs, they do not change the coefficient of
31 record in the consecutive experiment where, due to noise, only variation (CV). The proof is provided in the Appendix. Since,
32 5 cycles could be annotated. In total, 595 and 400 ICG cycles
of generality, we can set HR
we are interested in analyzing the repeatability, without loss
33 were annotated in the consecutive, and 24-hour experiments, per subject as the mean
34 respectively. of heart rate across all recordings of that subject.
35 For each method of STI estimation (SCG-ECG or ICG- The subscript C1 corresponds to the corrected STIs using
36 ECG), PEP, LVET, and their ratio were computed per cycle, this approach. The unit of PEP and LVET and their corrected
37 and the median value for each recording was considered for values are in milli-second (ms). It should be mentioned that in
38 the repeatability analysis. Repeatability indicates the degree to this approach, the ratio between PEP and LVET does not
39 which the same results are obtained in repeated identical change, because both PEP and LVET are corrected with a
40 experiments [18]. To satisfy the identical conditions, one
same factor (i.e. ),
41 expert applied a same measurement method (either SCG-ECG
PEP PEP
42 or ICG-ECG) in our repeated experiments. Repeatability can
Ratio = =
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LVET LVET
be expressed by the coefficient of variation (CV) as, (4)
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45 CV = σ/μ (1)
46 In another correction approach, the following equations
47 where μ is the mean and σ is the standard deviation of were used to correct STIs for heart rate (Weissler's equations)
48 estimated STIs across recordings of each subject. [5] [15],
49 CV is a descriptive statistic and measures the variability of
50 the data independently of the unit of measurements [19]. This PEP ! = 0.4HR + PEP (5)
51 statistic has also been employed in some prior studies
LVET = 1.7 HR + LVET for males
investigating the repeatability of STIs [10], [20]. The CV
!
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LVET = 1.6 HR + LVET for females
(6a)
!
53 value has an inverse relation with repeatability, with a lower (6b)
54 CV value represents higher repeatability.
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3 Table 1: The comparison between the repeatability of our method (SCG and ECG) and the alternative method (ICG and
4 ECG) in different experiments when no correction for heart rate was considered
5 Method CV Values in the Consecutive Experiment CV Values in the 24-hour Experiment
6 (AVE ± SD) (AVE ± SD)
7 PEP LVET Ratio PEP LVET Ratio
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9 SCG & ECG 1.7% ± 1.1% 1.2% ± 1.0% 2.4% ± 1.7% 3.2% ± 3.0% 3.3% ± 2.9% 5.2% ± 3.8%
10 ICG & ECG 2.8% ± 1.4% 1.4% ± 1.2% 2.1% ± 0.7% 4.5% ± 3.1% 3.6% ± 2.3% 3.5% ± 2.8%
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12 STIs: systolic time intervals, CV: coefficient of variation, AVE: average, SD: standard deviation, PEP: pre-ejection period,
13 LVET: left ventricular ejection time, Ratio: PEP/LVET, SCG: seismocardiogram, ECG: electrocardiogram, ICG:
14 impedance cardiography
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16 Table 2 The comparison between the repeatability of our method (SCG and ECG) and the alternative method (ICG and
17 ECG) in different experiments when STIs were corrected for heart rate using equations (2)-(4) (C1 approach)
20 PEPC1 LVETC1 RatioC1 PEPC1 LVETC1 RatioC1
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22 SCG & ECG 3.4% ± 2.5% 2.9% ± 2.5% 2.4% ± 1.6% 6.1% ± 3.3% 4.2% ± 3.2% 5.2% ± 4.2%
23 ICG & ECG 4.0% ± 2.2% 3.3% ± 2.2% 2.0% ± 0.8% 5.0% ± 3.1% 5.2% ± 4.0% 3.6% ± 3.2%
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SCG & ECG 1.3% ± 0.9% 0.7% ± 0.7% 1.8% ± 1.2% 2.1% ± 2.1% 2.0% ± 1.3% 3.8% ± 2.8%
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36 ICG & ECG 2.3% ± 1.5% 1.1% ± 0.8% 1.7% ± 0.5% 2.6% ± 1.9% 2.1% ± 1.6% 2.8% ± 2.4%
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where subscript C2 indicates the corrected STIs in equations

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In Table 1, no correction for heart rate was considered,
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As the above equations indicate, in this approach, PEP !
(5) and (6). whereas in Tables 2 and 3, STIs were corrected for heart rate
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does not dependent on sex, whereas LVET ! does.
using equations (2)-(4) and (5)-(6), respectively. For instance,
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the no-correction average CV values of PEP in the 24-hour
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experiment (Table 1) were 3.2% ± 3.0% (our method) and
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4.5% ± 3.1% (alternative). Using the C1 approach (Table 2)
47 3. Results increased these values to 6.1% ± 3.3% (our method) and 5.0%
48 ± 3.1% (alternative), whereas the C2 approach decreased them
49 Tables 1-3 provide a comparison between the repeatability
to 2.1% ± 2.1% (our method) and 2.6% ± 1.9% (alternative).
50 of our method (SCG and ECG) and the alternative method
The Bland-Altman plots in Figure 3 provide the analysis for
51 (ICG and ECG). These results are represented as the average
the repeatability of corrected STIs (C2 approach) in the
52 and standard deviation of CV values over 20 subjects in the
consecutive and 24-hour experiments. Dashed lines indicate
53 consecutive and 24-hour experiments.
the mean (blue) and top/bottom 95% LoA (red). The
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3 shadowed areas indicate the corresponding 95% confidence study. A general method to derive the equations for corrected
4 intervals for the mean and LoA. STIs is described by Wolf et al., [23].
5 Figures 4 and 5 compare the CV values for different By comparing the results of C1 and C2 approach, it can be
6 correction approaches per subject in the consecutive and 24- concluded that choosing an appropriate correction approach
7 hour experiments, respectively. As we can see in these figures, could increase the repeatability. In the best results (Table 3),
for most of the subjects, the C2 approach caused lower CV the CV values of PEPC2 and LVETC2 were smaller for our
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values compared to the C1 approach. In the consecutive method in comparison to the alternative; whereas, the CV
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experiment and among different subjects, the maximum CV values of RatioC2 in our method were slightly higher compared
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value of different STIs after C1 approach was 12.4 and was to the alternative. One possible explanation could be that in
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occurred for subject 6 (Figure 4, top plot), whereas the the alternative method, the variations of PEP and LVET were
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maximum CV value after C2 approach was 4.9 that was more correlated to each other, which reduced the variability of
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happened for subject 10 (Figure 4, bottom plot). For the 24- their ratio. However, in the overall assessment of the best
14 hour experiment, the maximums of CV values among results (C2 correction), the CV values of the alternative and
15 different subjects were 12.8 and 9 for C1 (subject 13, top plot our method were in agreement as depicted by Bland-Altman
16 of Figure 5) and C2 (subject 11, bottom plot of Figure 5) plots in Figure 3.
17 approaches, respectively. In all Bland-Altman plots (Figure 3), no more than one
18 Also, Tables 4 and 5 indicate the values of corrected STIs datapoint was outside of LoA (considering their confidence
19 and their corresponding heart rates per subject for C1 and C2 intervals), which indicated that for each plot, 95% of
20 approaches, respectively. For example, according to Table 4 datapoints were within 95% LoA. Therefore, in both
21 (Top), the LVET values of subject 6 in the consecutive consecutive and 24-hour experiments, the repeatability of our
22 experiment after the C1 approach (that caused the maximum estimated STIs (using SCG and ECG) was in agreement with
23 CV values among subjects according to Figure 4 – top plot), the repeatability of the alternative method (using ICG and
24 were 274 ms, 267 ms, and 332 ms for the respective hear rates ECG).
25 of 49 BPM, 48 BPM, and 61 BPM. The source of STI variations during the repeatability
26 experiments could be physiological, methodological (possible
27 errors due to using SCG-ECG method), or operational
28 4. Discussion (possible errors that could be caused by the person who
29 conducted the experiments). Identifying and differentiating
Among various comparisons shown in Tables 1-3, the
30 average difference between the CV values of our method and
between these sources of variation is very challenging and was
31 the alternative was less than 2%. Moreover, applying the C1
out of the scope of our study.
32 correction approach (Table 2) increased the average CV
However, independent of the source, the STI variations of
33 values of all STIs (reduced repeatability) in both the
each subject could be described by the CV values that are
34 alternative and our method. On the other hand, the C2
plotted in Figures 4 and 5 for both correction approaches and
35 correction approach (Table 3) could decrease the average CV
in the respective consecutive and 24-hour experiments.
36 values of all STIs (increased repeatability) in our method and
According to these figures, although the maximums of CV
37 values in the C1 approach were close to each other in the
the alternative. These observations are consistent with Figures
38 consecutive and 24-hour experiments, the CV values were
4 and 5 that indicate in our method, the CV values of C2 are
39 larger in the 24-hour experiment for most of the subjects. This
less than C1 for most of the subjects in the consecutive and
40 comparison was also true for C2 approach, in which the CV
24-hour experiments, respectively.
41 values of 24-hour experiment were higher than the
As we explained in the Methods section, the C1 approach
42 consecutive for most of the subjects. These observations were
did not change the ratio (equation (4)), and consequently its
expected because of longer time between the recordings in the
43 CV values were very close to the no-correction case (ideally,
24-hour experiment, which could cause higher variations in
44 the values should be the same, however because of numerical
the STIs.
45 errors, the CVs of RatioC1 in both experiments were slightly
In our best results (C2 approach in Figures 4 and 5), all the
46 different).
CV values in the consecutive experiment were less than 5%.
47 Our best results in both experiments were obtained using
For the 24-hour experiment, the CV values were less than
48 the C2 correction described by equations (5) and (6). These
10%, and more than half of the subjects had CV values of less
49 equations were based on regression models developed by
than 5%.
50 Weissler, et al. [5]. These regression models were derived
There is no unique and predefined value for CV that
51 from the relation of PEP and LVET to the heart rate and sex
indicates the acceptable repeatability of STI estimation using
52 among 211 healthy subjects. Such models can be used for
SCG and ECG signals. However, we indicated that our results
53 correction of STIs in other groups such as the subjects of our
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3 were in agreement with a relevant alternative method using We analyzed STIs repeatability in two experimental
4 ICG and ECG. settings, consecutive and 24-hour. Considering the practical
5 Moreover, for healthy subjects, the CV values were aspects, perhaps the situations similar to the consecutive
6 acceptable in that their corresponding Ratios remained within experiment occur more frequently. Here, among consecutive
7 the range of healthy individuals (i.e. PEP/LVET < 0.4, [9] measurements of SCG and ECG in one session, we expected
average CV values of 1.3%, 0.7%, and 1.8% for PEP ! ,

[24]). According to Tables 4 and 5, despite all variations to observe consistent and repeatable estimation of STIs. The
8
LVET !, and their ratio (Table 3) were acceptable for such an
among estimated STIs of different subjects, the ratio of
9
PEP/LVET in all the recordings never exceeded the reference
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range of healthy subjects. As was stated in the Introduction expectation in healthy subjects.
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section, the ratio of PEP/LVET is the most useful STIs, and to
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the best of our knowledge this study was the first one that
13 Conclusion
investigated its repeatability.
14 The repeatability analysis has been conducted for
15 estimating STIs using other methods such as Echo [11], and
In this study, we investigated the repeatability of STI
16 arterial pulse tracing, ECG, and phonocardiogram [20]. Since
estimation (PEP, LVET, and their ratio) in healthy subjects
17 Echo is the gold standard for STI estimation, its repeatability
using SCG and ECG. It can be concluded that such estimation
18 can be considered as a baseline for our results. Reant, et al.,
was repeatable. Moreover, the repeatability was increased
19 [11] performed a comprehensive study on STIs using Echo
after STIs were corrected for heart rate using sex-specific
20 regression models (Weissler's equations).
method. They reported the average repeatability for PEP and
21 In our research, we focused on healthy subjects and the
LVET respectively as 2% and 4% based on 10 measures on
22 repeatability of their STIs. In the future we will be expanding
134 heart failure patients and 43 healthy subjects. Our results
23 our study to include patients with cardiac diseases, and
(Tables 1-3) were almost in the same range of the reported
24 scrutinize if STI estimation using SCG and ECG is also
values by Reant, et al. Our best results (Table 3, after
repeatable.
25 correcting for heart rate using C2 approach) were slightly
26 better than the reported values, most possibly because we
27 investigated only healthy subjects, whereas the Acknowledgements
28 aforementioned study considered both healthy subjects and Vahid Zakeri and Parastoo Dehkordi are employed by
29 patients with heart failure, which could induce more Heart Force Medical Inc. (HFM), Vancouver, Canada.
30 variability to the estimated STIs. Also, while we obtained the Kouhyar Tavakolian is on the Board of Directors at HFM.
31 repeatability of PEP/LVET, no values were reported for the Farzad Khosrow-khavar and Erwin P. Bauer are respectively
32 Ratio in the Reant’s study. the CTO and CMO of HFM.
33 Considering the estimation method of SCG-ECG, the VZ contributed to the study design, statistical analysis, and
34 closest study to our work was conducted by Crow, et al., [10] results interpretation, and wrote the manuscript. KT
35 in which the repeatability of PEP was investigated. In their contributed to the study design, data acquisition, and critical
36 study, an average CV value of 5.4% was obtained after 10 revision of the paper. APB, EPB, and PD revised the paper
37 consecutive recordings over 39 subjects. Their result is critically for important intellectual content. FKK contributed
38 comparable to ours. We obtained higher repeatable results for to the study design, statistical analysis, and critical revision of
39 PEP (Tables 1-3), but among a smaller number of healthy the paper.
40 subjects. Moreover, we included the repeatability analysis of
41 LVET and PEP/LVET as well as carrying out the 24-hour References
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6 1975. seismocardiogram,” Sci. Rep., vol. 8, no. 1, p. 15455, Dec.
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S. Kaplan, “Measurement of right and left ventricular [26] P. Dehkordi et al., “Comparison of different methods for
8 systolic time intervals by echocardiography,” Circulation, estimating cardiac timings: a comprehensive multimodal
9 vol. 51, no. 2, pp. 304–309, 1975. echocardiography investigation,” Front. Physiol., vol. 10, p.
10 [8] V. Balasubramanian, O. Mathew, A. Behl, S. Tewari, and 1057, 2019.
11 R. Hoon, “Electrical impedance cardiogram in derivation of
systolic time intervals,” Br. Hear. J. , vol. 40, no. 3, p. 268,
12 1978.
13 [9] K. Tavakolian, “Systolic time intervals and new
Appendix
14
(CV) is not dependent on HR
measurement methods,” Cardiovasc. Eng. Technol., vol. 7, In this Appendix, we prove that the coefficient of variation
15 no. 2, pp. 118–125, 2016.
, when STIs are
[10] R. S. Crow, P. Hannan, D. Jacobs, L. Hedquist, and D. M.
16 corrected through equations (2) and (3) (C1 approach). We can
Salerno, “Relationship between seismocardiogram and
17 echocardiogram for events in the cardiac cycle,” Am. J. summarize equation (2) and (3) as,
HR
18 Noninvasive Cardiol., vol. 8, no. 1, pp. 39–46, 1994.
STI = STI ×
19
HR
[11] P. Reant et al., “Systolic time intervals as simple (A1)
20 echocardiographic parameters of left ventricular systolic
performance: correlation with ejection fraction and
21 longitudinal two-dimensional strain,” Eur. J.
numbers and α is a non-negative constant (real number), then,

22 Echocardiogr., vol. 11, no. 10, pp. 834–844, Dec. 2010. where STI can be PEP or LVET. If X is a vector of real
23 [12] W. M. K. Trochim, J. P. Donnelly, and K. Arora, The
σ5αX7 = α σ5X7
24 research methods: The Essential knowledge base. 2016.
[13] N. M. Albert, “Bioimpedance cardiography measurements (A2)
25 of cardiac output and other cardiovascular parameters,”
μ5αX7 = α μ5X7 5A37
26 Crit. Care Nurs. Clin. North Am., vol. 18, no. 2, pp. 195–
27 202, 2006.
where σ and μ indicate the standard deviation and the mean,

28 [14] G. Cotter, A. Schachner, L. Sasson, H. Dekel, and Y.
Moshkovitz, “Impedance cardiography revisited,” Physiol.
29 Meas., vol. 27, no. 9, pp. 817–827, Sep. 2006. respectively. The coefficient of variation (CV) can be written
30 [15] H. Boudoulas, “Systolic time intervals,” Eur. Heart J., vol. as,
31 11, no. suppl I, pp. 93–104, Dec. 1990.
σ5αX7 α σ5X7 σ5X7 5A4-a7
CV5αX7 = = =
32 [16] Q. Li and G. G. Belz, “Systolic time intervals in clinical
μ5αX7 α μ5X7 μ5X7

pharmacology,” Eur. J. Clin. Pharmacol., vol. 44, no. 5, pp.
33
= CV5X7
415–421, Jun. 1993.
34 [17] P. Carvalho, R. P. Paiva, J. Henriques, M. Antunes, I.
35
In the above equation, if we set X and α as follows,
Quintal, and J. Muehlsteff, “Robust characteristic points for
36 ICG-definition and comparative analysis,” in International
37 Conference on Bio-inspired Systems and Signal Processing
X = STI × HR 5A4-b7
(BIOSIGNALS), 2011, pp. 161–168.
1
38
α= E ⟹
[18] P. Laake, H. Benestad, and B. Olsen, Research methodology
HR
39 in the medical and biological sciences. 2007.
40 [19] H. Abdi, “Coefficient of variation,” Encycl. Res. Des., vol.
41 1, pp. 169–171, 2010.
[20] M. Kupari, “Reproducibility of the systolic time intervals:
42 effect of the temporal range of measurements,” Cardiovasc. Then, we have,
5A4-c7
43
1
Res., vol. 17, no. 6, pp. 339–343, Jun. 1983.
44 CV5STI 7 = CV G × 5STI × HR7H
HR
[21] J. Martin Bland and D. Altman, “Statistical methods for
45
= CV5STI × HR7
assessing agreement between two methods of clinical
measurement,” Lancet, vol. 327, no. 8476, pp. 307–310,
46
Feb. 1986.
47
corrected STIs (CV5STI 7) is not dependent upon
[22] H. M. Mertens, H. Mannebach, G. Trieb, and U. As equations (A4-a)-(A4-c) indicate, the repeatability of the
48 Gleichmann, “Influence of heart rate on systolic time
49 intervals: Effects of atrial pacing versus dynamic exercise,”
HR . The corrected repeatability is equivalent to
50 Clin. Cardiol., vol. 4, no. 1, pp. 22–27, Jan. 1981.
[23] G. K. Wolf, G. G. Belz, and M. Stauch, “Systolic time correcting the STIs with respect to the HR; i.e. for each record,
51
(STI × HR7.
intervals—correction for heart rate,” Basic Res. Cardiol., the estimated STIs are multiplied by the HR of that record
52 vol. 73, no. 1, pp. 85–96, Jan. 1978.
53 [24] H. Boudoulas et al., “Assessment of ventricular function by
54 combined noninvasive measures: factors accounting for
55
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58 8
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49 Figure 3: The Bland-Altman plots in the consecutive (left side) and 24-hour (right side) experiments, comparing the CV
50 values of our method (SCG and ECG) to the alternative method (ICG and ECG), when the STIs were corrected for heart
51 rate using C2 approach (equations (5) and (6)). Dashed lines indicate the mean (blue) and top/bottom 95% limits of
52 agreement (red). The shadowed areas indicate the corresponding 95% confidence intervals for the mean and limits of
53 agreement.
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58 9
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55 Figure 4: Comparison of the CV values of STIs per subject in the consecutive experiment between C1 (top) and C2
56 (bottom) approaches in our method (SCG & ECG).
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Figure 5: Comparison of the CV values of STIs per subject in the 24-hour experiment between C1 (top) and C2 (bottom)
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58 11
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3 Table 4: HR and STIs Per Subject in the Consecutive (Top) and 24-Hour (Bottom) Experiments After Correcting for
4 Heart Rate Using C1 Approach.
5
6 Subj. HR1 PEP1 LVET1 Ratio1 HR2 PEP2 LVET2 Ratio2 HR3 PEP3 LVET3 Ratio3
7 1 74 97 275 0.35 71 94 264 0.36 71 94 264 0.36
8 2 65 88 278 0.32 65 88 281 0.31 63 87 277 0.31
9 3 73 86 300 0.29 70 81 297 0.27 73 85 307 0.28
10 4 81 79 295 0.27 82 80 299 0.27 82 79 298 0.27
11
5 52 83 294 0.28 53 83 300 0.28 52 84 301 0.28
12
13 6 49 88 274 0.32 48 90 267 0.34 61 107 332 0.32
14 7 63 77 330 0.23 59 72 316 0.23 64 76 338 0.22
15 8 66 76 288 0.26 70 86 302 0.28 63 77 278 0.28
16 9 73 73 286 0.26 77 75 300 0.25 84 82 309 0.27
17
10 78 76 311 0.24 76 80 296 0.27 80 75 313 0.24
18
11 74 75 257 0.29 76 75 278 0.27 70 71 264 0.27
19
20 12 65 93 252 0.37 67 96 257 0.37 66 94 256 0.37
21 13 59 86 304 0.28 57 82 300 0.27 60 88 310 0.28
22 14 66 86 312 0.28 62 81 299 0.27 63 81 304 0.27
23 15 74 65 304 0.21 70 63 288 0.22 75 66 305 0.22
24
16 52 90 289 0.31 53 93 295 0.32 50 88 279 0.32
25
26 17 53 90 336 0.27 52 93 332 0.28 53 94 332 0.28
27 18 61 93 275 0.34 62 95 292 0.33 61 91 292 0.31
28 19 55 81 300 0.27 59 89 310 0.29 55 82 300 0.27
29 20 52 88 329 0.27 49 83 310 0.27 49 80 310 0.26
30
31
32 Subj. HR1 PEP1 LVET1 Ratio1 HR2 PEP2 LVET2 Ratio2
33 1 68 95 284 0.33 66 100 273 0.37
34 2 64 79 257 0.31 75 93 260 0.36
35
3 72 83 297 0.28 74 83 306 0.27
36
37 4 74 80 314 0.25 72 78 313 0.25
38 5 54 87 311 0.28 52 87 307 0.28
39 6 55 90 326 0.28 49 83 287 0.29
40 7 65 69 311 0.22 73 74 338 0.22
41 8 70 77 294 0.26 69 84 271 0.31
42
9 76 78 298 0.26 79 86 300 0.29
43
44 10 90 79 320 0.25 75 72 285 0.25
45 11 69 71 279 0.25 69 83 273 0.3
46 12 66 89 239 0.37 73 95 265 0.36
47 13 62 93 315 0.3 54 78 306 0.25
48 14 66 82 318 0.26 61 77 283 0.27
49
15 79 78 296 0.26 70 70 299 0.23
50
51 16 49 88 274 0.32 54 95 293 0.32
52 17 60 81 341 0.24 61 89 319 0.28
53 18 62 92 308 0.3 60 89 287 0.31
54 19 62 91 320 0.28 53 81 277 0.29
55
20 52 78 311 0.25 58 87 332 0.26
56
57 The unit of HR is beat per minute (BPM). The unit of PEP and LVET is milli-second. Ratio is unitless.
58 Subj. = subject; HR = heart rate; STIs = systolic time intervals. C1 Approach is described by equations (2)-(4)
59 HRi & STIi = The values of HR and STI for the recording i in12the consecutive (i = 1, 2, 3) and 24-hour (i = 1, 2) experiments
60

1
2
4 Heart Rate Using C2 Approach
5
7 1 74 124 390 0.32 71 124 389 0.32 71 124 389 0.32
8 2 65 113 386 0.29 65 113 390 0.29 63 115 389 0.3
9 3 73 114 414 0.28 70 112 416 0.27 73 113 420 0.27
10 4 81 113 424 0.27 82 112 428 0.26 82 112 424 0.26
11
5 52 106 386 0.27 53 103 389 0.26 52 105 388 0.27
12
13 6 49 115 381 0.3 48 117 378 0.31 61 117 388 0.3
14 7 63 101 427 0.24 59 100 427 0.23 64 100 427 0.23
15 8 66 102 403 0.25 70 109 404 0.27 63 106 402 0.26
16 9 73 107 421 0.25 77 107 426 0.25 84 110 421 0.26
17
10 78 108 436 0.25 76 112 423 0.26 80 105 432 0.24
18
11 74 104 376 0.28 76 103 397 0.26 70 102 395 0.26
19
20 12 65 120 366 0.33 67 121 369 0.33 66 122 368 0.33
21 13 59 109 398 0.27 57 108 395 0.27 60 111 396 0.28
22 14 66 109 412 0.26 62 108 413 0.26 63 107 413 0.26
23 15 74 94 415 0.23 70 94 410 0.23 75 94 411 0.23
24
16 52 111 374 0.3 53 112 376 0.3 50 112 374 0.3
25
26 17 53 112 418 0.27 52 114 417 0.27 53 115 416 0.28
27 18 61 118 382 0.31 62 118 393 0.3 61 115 392 0.29
28 19 55 104 399 0.26 59 109 400 0.27 55 106 399 0.27
29 20 52 105 403 0.26 49 104 398 0.26 49 103 401 0.26
30
31
33 1 68 120 394 0.3 66 129 389 0.33
34 2 64 111 386 0.29 75 115 368 0.31
35
3 72 113 413 0.27 74 112 420 0.27
36
37 4 74 109 427 0.26 72 109 433 0.25
38 5 54 107 393 0.27 52 110 405 0.27
39 6 55 107 397 0.27 49 109 393 0.28
40 7 65 98 433 0.23 73 99 436 0.23
41 8 70 106 408 0.26 69 112 388 0.29
42
9 76 110 426 0.26 79 115 422 0.27
43
44 10 90 108 437 0.25 75 109 432 0.25
45 11 69 99 396 0.25 69 111 390 0.28
46 12 66 120 363 0.33 73 120 375 0.32
47 13 62 112 394 0.28 54 106 416 0.25
48 14 66 105 418 0.25 61 105 397 0.26
49
15 79 106 406 0.26 70 103 428 0.24
50
51 16 49 112 375 0.3 54 111 369 0.3
52 17 60 106 440 0.24 61 112 414 0.27
53 18 62 115 406 0.28 60 115 392 0.29
54 19 62 110 402 0.27 53 109 389 0.28
55
20 52 103 415 0.25 58 105 411 0.26
56
58 Subj. = subject; HR = heart rate; STIs = systolic time intervals. C2 Approach is described by equations (5) and (6)
60
IOP Publishing Physiological Measurement

1 Journal XX (XXXX) XXXXXX https://doi.org/XXXX/XXXX
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The repeatability of estimated systolic time
8
9 intervals in healthy subjects using
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seismocardiogram and electrocardiogram
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15 Vahid Zakeri1, Kouhyar Tavakolian2, 3, Andrew P. Blaber3, Erwin P. Bauer1, Parastoo
16 Dehkordi4, and Farzad Khosrow-khavar1
17
18 1
Heart Force Medical Inc., Vancouver, Canada
2
19 School of Electrical Engineering and Computer Science, University of North Dakota, Grand Forks,
USA
20 3
Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, Canada
21 4
The Electrical and Computer Engineering Department, University of British Columbia, Vancouver,
22 Canada
23
24 E-mail: vahid.zakeri@heartforcemedical.com
25
26 Submitted August 16, 2019; Revised January 07, 2020
27
Abstract
28
29 Objective: We investigated the repeatability of systolic time intervals (STIs) in healthy
30 subjects using a combination of seismocardiogram (SCG) and electrocardiogram (ECG). STIs
31 have been extensively used in the past to quantify heart performance, particularly the left
32 ventricle. In this study, STIs included pre-ejection period (PEP), left ventricular ejection time
33 (LVET), and their ratio. Approach: We conducted the repeatability test of STI estimation
34 through two experiments. The first involved three consecutive one-minute recordings separated
35 by one-minute intervals, and the second involved two one-minute recordings separated by 24
36 hours. Twenty healthy subjects participated in our study. We considered the coefficient of
37 variation (CV) to quantify the repeatability. As there was no agreed upon values for optimal
38 CV values, we compared our results with an alternative method using a combination of
39 impedance cardiography (ICG) and ECG. Similar to our method, the alternative method was
40 noninvasive and could be employed for personal heart monitoring. We also studied the
41 repeatability after STIs were corrected for heart rate using two approaches. The first approach
42 used a multiplicative factor per subject based on the heart rates in each recordings of that
43 subject. The second approach employed sex-specific regression models for all subjects
44 (Weissler's equations). Main results: We found that the repeatability of our method (SCG and
ECG) was in agreement with the alternative method (ICG and ECG) in both experiments.
45
Moreover, the Weissler’s equations approach for heart rate increased the repeatability.
46
Significance: It can be concluded that estimation of PEP, LVET and their ratio through SCG
47
and ECG signals was repeatable in healthy subjects.
48
49
Keywords: systolic time intervals, repeatability, seismocardiogram, electrocardiogram
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21 Figure 1: Estimation of systolic time intervals (STIs) using seismocardiogram (SCG) and electrocardiogram (ECG). STIs
22 are pre-ejection period (PEP) and left ventricular ejection time (LVET). AO and AC are aortic valve opening and closure
23 characteristic points, respectively.
24
25 ECG requires less electrodes and sensors, which provides
26 1. Introduction
more flexibility and less constraint.
27 Systolic time intervals (STIs) are critical timing parameters SCG provides information on mechanical aspects of heart,
28 with diagnostic and prognostic implications in the assessment in contrast to ECG that indicates the electrical activities of
29 of heart performance, particularly the left ventricle. STIs have heart. Therefore, considering both signals may provide a more
30 been suggested as a noninvasive technique in the evaluation complete assessment of cardiac functions.
31 of heart for suspected myocardial, coronary artery, and valve In mid-1990’s, Crow, et al. used SCG for estimation of
32 diseases [1]. Also, they have been proposed to assess the STIs, and compared their results with Echo as the gold
33 efficacy of procedures such as biventricular pacing [2]. One of standard. They concluded that both methods were equally
34 the earliest investigation on the estimation of STIs was accurate in the measurements of STIs [10]. Among the
35 conducted by Garrod in the late 19th century [3]. Since then, different STIs, we considered pre-ejection period (PEP), left
36 various methods have been proposed to estimate STIs such as ventricular ejection time (LVET), and their ratio (PEP/LVET)
37 concurrent electrocardiogram (ECG), phonocardiogram, and for the purpose of this study. PEP can be estimated from Q-
38 carotid pulse [4] [5], echocardiography (Echo) [6] [7], and wave on ECG to the aortic valve opening (AO) characteristic
39 impedance cardiography (ICG) [8]. A brief review of these point on SCG. LVET can be estimated from AO to the aortic
40 methods is presented by Tavakolian [9]. valve closure (AC) characteristic point on SCG (Figure 1). It
41 Seismocardiography has gained popularity as a convenient has been shown that PEP and LVET correlate with stroke
42 and inexpensive method. The seismocardiogram (SCG) signal volume and cardiac output [5]. The PEP/LVET ratio is
43 is commonly obtained by placing an accelerometer on the considered as the most useful STIs for assessment of left
44 sternum and captures the movement of the chest induced by ventricular performance [1]. It is possible that PEP and/or
45 heart vibrations. The inexpensive, small-size, and low-weight LVET do not indicate ventricular dysfunction, but their ratio
46 modern accelerometers, particularly micro-electromechanical can imply such a dysfunction [1]. The PEP/LVET is correlated
47 systems (MEMS), make acquiring SCG convenient. Such with the ejection fraction, and is a more robust parameter with
48 accelerometers are available in many portable and personal respect to the heart rate [1]. A ratio of less than 0.4
49 devices such as smartphones, which make SCG potentially (PEP/LVET < 0.4) can be considered as the range for healthy
accessible to all users of these devices. In STI estimation, subjects [9] [11].
50
unlike Echo, SCG-ECG method is less expensive, does not The purpose of this study was to investigate the
51
need a skilled operator, and can be used for self-monitoring. repeatability of STI estimation (test-retest reliability, [12]) in
52
Moreover, in comparison to other methods of STI estimation healthy subjects using SCG and ECG. We compared our
53
such as ICG-ECG or ECG-pulse-phonocardiogram, SCG- results with an alternative method using a combination of ICG
54
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25 Figure 2: A picture showing our experimental setup for data collection (ECG: electrocardiogram, SCG: seismocardiogram,
26 ICG: impedance cardiography). The ICG electrodes for upper abdomen are not observable in the above picture.
27
28
29 and ECG. We selected this alternative, because similar to our SCG and ECG signals were recorded from these subjects in
30 method, it was noninvasive and could be employed for the supine position. SCG was obtained by placing a triaxial
31 personal heart monitoring. Also, ICG is commercially accelerometer (Silicon Designs Inc. Model 2476, USA) on the
32 available, and has been widely studied by the clinical sternum and collecting the acceleration signal in the
33 community [13] [14]. dorsoventral direction. ECG signal (lead I) was recorded
34 Despite various investigations on SCG, the repeatability of simultaneously by the iWorx Systems, Inc., IX-BIO8-SA,
STI estimation in combination with ECG has not been NH, USA. All the recordings were transferred to a personal
35
thoroughly investigated. We found only one report in the computer using the iWorx data acquisition system (iWorx
36
literature that considered the repeatability of STIs estimated Systems, Inc., IX-416, NH, USA) sampled at 1000 Hz with
37
through SCG and ECG [10]. However, this report did not 16-bit resolution.
38
include any results for LVET and PEP/LVET. We also did not To provide a comparison for our repeatability results, we
39
find any studies analyzing the repeatability of PEP/LVET also recorded the ICG signal from the subjects, and estimated
40
ratio using any estimation method. Therefore, our focus in this PEP, LVET, PEP/LVET, and determined their corresponding
41 study was to address these gaps. repeatability. ICG was obtained by placing two pairs of
42 electrodes on upper neck and upper abdomen, respectively
43 (BoMed Inc., USA). Figure 2 depicts our experimental setup
44 2. Methods for data collection. In this figure, the ICG electrodes for upper
45 abdomen are not observable.
46 2.1 Data collection Ethics approval was issued by the Office of Research
47 Ethics, Simon Fraser University (SFU), Burnaby, Canada. The
48 Twenty healthy subjects participated in this study (age:
data collection was conducted in the Aerospace Physiology
49 29±5 years, height: 172±6 cm, weight:70±12 kg, and sex: 12
Labratory at SFU.
males and 8 females). These subjects had no prior history of
50
cardiovascular or respiratory diseases. They were also
51 2.2 Repeatability experiments
scanned with Echo for possible visible complications such as
52
valvular regurgitations or congenital heart diseases. Two repeatability experiments were considered in our
53
study, and 24-hour. In the consecutive repeatability
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1
2
3 experiment, our objective was to assess if the estimated STIs value has an inverse relation with repeatability, with a lower
4 derived from SCG and ECG signals of healthy subjects CV value represents higher repeatability.
5 significantly change within a short period. Three consecutive To assess the agreement between the repeatability of our
6 1-minute recordings with a one-minute interval in between, method (SCG-ECG) and the alternative (ICG-ECG), we used
7 were used for comparison. the Bland-Altman analysis that is a well-established graphical
In the 24-hour repeatability experiment, the objective was approach for comparison of two measurement techniques
8
to investigate if the STIs of the healthy subjects significantly [21]. In this study, we considered 95% limits of agreement
9
change when the recordings are conducted under the same (LoA) in the Bland-Altman analysis.
10
conditions over a period of at least 24 hours. To accomplish
11 2.4 Correction for heart rate
this objective, for each subject, two 1-minute measurements
12
were conducted at least 24 hours apart. The recordings were
13 It has been shown that the PEP and LVET inversely
roughly taken at the same time each day to reduce the diurnal
14 variation in the systolic intervals.
correlate with the heart rate [1]. To provide a more accurate
15 In both experiments, the subjects were advised not to
analysis for STI repeatability, a correction should be
16 exercise, drink caffeinated beverages, alcohol, or smoke
considered for PEP and LVET with respect to heart rate. We
17 cigarettes four hours prior to data recordings.
pursued two different correction approaches that derived a
18 linear relation between heart rate and STIs. We compared the
19 repeatability of STIs before and after correction for each of
2.3 Annotation, repeatability, and statistical analysis
20 these approaches.
21 There is a consensus among experts that usually 10 cycles In the first approach, PEP and LVET were corrected with
22 are sufficient for STI estimation [1] [15] [16]. To obtain STIs respect to a predefined heart rate as suggested by [22],
HR
23 from SCG, an expert annotated the Q-wave on the ECG and
PEP = PEP ×
HR
the AO and AC points on the SCG for at least 10 cycles per (2)
24
SCG recording. In total, 735 and 2558 cycles of SCG were
25
annotated in the consecutive and 24-hour experiments,
26
HR
LVET = LVET ×
respectively.
27
HR
(3)
To estimate STIs from ICG, another expert annotated the
28
Q-wave on the ECG, and the ICG characteristic points that
29
correspond to the aortic valve opening and closure [17]. For
30
Although different values of HR
each ICG recording, 10 cycles were annotated except for one where HR indicates the heart rate in beat-per-minute (BPM).
31 record in the consecutive experiment where, due to noise, only change the values
32 5 cycles could be annotated. In total, 595 and 400 ICG cycles of corrected STIs, they do not change the coefficient of
33 were annotated in the consecutive, and 24-hour experiments, variation (CV). The proof is provided in the Appendix. Since,
34 respectively.
of generality, we can set HR
we are interested in analyzing the repeatability, without loss
35 For each method of STI estimation (SCG-ECG or ICG- per subject as the mean
36 ECG), PEP, LVET, and their ratio were computed per cycle, of heart rate across all recordings of that subject.
37 and the median value for each recording was considered for The subscript C1 corresponds to the corrected STIs using
38 the repeatability analysis. Repeatability indicates the degree to this approach. The unit of PEP and LVET and their corrected
39 which the same results are obtained in repeated identical values are in milli-second (ms). It should be mentioned that in
40 experiments [18]. To satisfy the identical conditions, one this approach, the ratio between PEP and LVET does not
41 expert applied a same measurement method (either SCG-ECG change, because both PEP and LVET are corrected with a
42 or ICG-ECG) in our repeated experiments. Repeatability can
same factor (i.e. ),
43 be expressed by the coefficient of variation (CV) as,
σ PEP PEP
44
CV = Ratio = =
μ
45
LVET LVET
(1) (4)
46
47
48 where μ is the mean and σ is the standard deviation of In another correction approach, the following equations
49 estimated STIs across recordings of each subject. were used to correct STIs for heart rate (Weissler's equations)
50 CV is a descriptive statistic and measures the variability of [5] [15],
the data independently of the unit of measurements [19]. This
51
52
statistic has also been employed in some prior studies PEP $ = 0.4HR + PEP (5)
investigating the repeatability of STIs [10], [20]. The CV
53
54 LVET $ = 1.7 HR + LVET for males (6a)
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58 4
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2
3 Table 1: The comparison between the repeatability of our method (SCG and ECG) and the alternative method (ICG and
4 ECG) in different experiments when no correction for heart rate was considered
7 PEP LVET Ratio PEP LVET Ratio
8
9 SCG & ECG 1.7% ± 1.1% 1.2% ± 1.0% 2.4% ± 1.7% 3.2% ± 3.0% 3.3% ± 2.9% 5.2% ± 3.8%
10 ICG & ECG 2.8% ± 1.4% 1.4% ± 1.2% 2.1% ± 0.7% 4.5% ± 3.1% 3.6% ± 2.3% 3.5% ± 2.8%
11
15
21
22 SCG & ECG 3.4% ± 2.5% 2.9% ± 2.5% 2.4% ± 1.6% 6.1% ± 3.3% 4.2% ± 3.2% 5.2% ± 4.2%
23 ICG & ECG 4.0% ± 2.2% 3.3% ± 2.2% 2.0% ± 0.8% 5.0% ± 3.1% 5.2% ± 4.0% 3.6% ± 3.2%
24
28
34
SCG & ECG 1.3% ± 0.9% 0.7% ± 0.7% 1.8% ± 1.2% 2.1% ± 2.1% 2.0% ± 1.3% 3.8% ± 2.8%
35
36 ICG & ECG 2.3% ± 1.5% 1.1% ± 0.8% 1.7% ± 0.5% 2.6% ± 1.9% 2.1% ± 1.6% 2.8% ± 2.4%
37
LVET = 1.6 HR + LVET for females

41
$ (6b) and standard deviation of CV values over 20 subjects in the
42
where subscript C2 indicates the corrected STIs in equations
consecutive and 24-hour experiments.
43
In Table 1, no correction for heart rate was considered,
44
As the above equations indicate, in this approach, PEP $
(5) and (6). whereas in Tables 2 and 3, STIs were corrected for heart rate
45
does not dependent on sex, whereas LVET $ does.
using equations (2)-(4) and (5)-(6), respectively. For instance,
46
the no-correction average CV values of PEP in the 24-hour
47 experiment (Table 1) were 3.2% ± 3.0% (our method) and
48 4.5% ± 3.1% (alternative). Using the C1 approach (Table 2)
49 3. Results increased these values to 6.1% ± 3.3% (our method) and 5.0%
50 ± 3.1% (alternative), whereas the C2 approach decreased them
51 Tables 1-3 provide a comparison between the repeatability
to 2.1% ± 2.1% (our method) and 2.6% ± 1.9% (alternative).
52 of our method (SCG and ECG) and the alternative method
The Bland-Altman plots in Figure 3 provide the analysis for
53 (ICG and ECG). These results are represented as the average
the repeatability of corrected STIs (C2 approach) in the
54 consecutive and 24-hour experiments. Dashed lines indicate
55
56
57
58 5
59
60

1
2
3 the mean (blue) and top/bottom 95% LoA (red). The study. A general method to derive the equations for corrected
4 shadowed areas indicate the corresponding 95% confidence STIs is described by Wolf et al., [23].
5 intervals for the mean and LoA. By comparing the results of C1 and C2 approach, it can be
6 Figures 4 and 5 compare the CV values for different concluded that choosing an appropriate correction approach
7 correction approaches per subject in the consecutive and 24- could increase the repeatability. In the best results (Table 3),
hour experiments, respectively. As we can see in these figures, the CV values of PEPC2 and LVETC2 were smaller for our
8
for most of the subjects, the C2 approach caused lower CV method in comparison to the alternative; whereas, the CV
9
values compared to the C1 approach. In the consecutive values of RatioC2 in our method were slightly higher compared
10
experiment and among different subjects, the maximum CV to the alternative. One possible explanation could be that in
11
value of different STIs after C1 approach was 12.4 and was the alternative method, the variations of PEP and LVET were
12
occurred for subject 6 (Figure 4, top plot), whereas the more correlated to each other, which reduced the variability of
13
maximum CV value after C2 approach was 4.9 that was their ratio. However, in the overall assessment of the best
14 happened for subject 10 (Figure 4, bottom plot). For the 24- results (C2 correction), the CV values of the alternative and
15 hour experiment, the maximums of CV values among our method were in agreement as depicted by Bland-Altman
16 different subjects were 12.8 and 9 for C1 (subject 13, top plot plots in Figure 3.
17 of Figure 5) and C2 (subject 11, bottom plot of Figure 5) In all Bland-Altman plots (Figure 3), no more than one
18 approaches, respectively. datapoint was outside of LoA (considering their confidence
19 Also, Tables 4 and 5 indicate the values of corrected STIs intervals), which indicated that for each plot, 95% of
20 and their corresponding heart rates per subject for C1 and C2 datapoints were within 95% LoA. Therefore, in both
21 approaches, respectively. For example, according to Table 4 consecutive and 24-hour experiments, the repeatability of our
22 (Top), the LVET values of subject 6 in the consecutive estimated STIs (using SCG and ECG) was in agreement with
23 experiment after the C1 approach (that caused the maximum the repeatability of the alternative method (using ICG and
24 CV values among subjects according to Figure 4 – top plot), ECG).
25 were 274 ms, 267 ms, and 332 ms for the respective hear rates The source of STI variations during the repeatability
26 of 49 BPM, 48 BPM, and 61 BPM. experiments could be physiological, methodological (possible
27 errors due to using SCG-ECG method), or operational
28 (possible errors that could be caused by the person who
29 4. Discussion conducted the experiments). Identifying and differentiating
30 Among various comparisons shown in Tables 1-3, the
between these sources of variation is very challenging and was
31 average difference between the CV values of our method and
out of the scope of our study.
32 the alternative was less than 2%. Moreover, applying the C1
However, independent of the source, the STI variations of
33 correction approach (Table 2) increased the average CV
each subject could be described by the CV values that are
34 values of all STIs (reduced repeatability) in both the
plotted in Figures 4 and 5 for both correction approaches and
35 alternative and our method. On the other hand, the C2
in the respective consecutive and 24-hour experiments.
36 correction approach (Table 3) could decrease the average CV
According to these figures, although the maximums of CV
37 values in the C1 approach were close to each other in the
values of all STIs (increased repeatability) in our method and
38 consecutive and 24-hour experiments, the CV values were
the alternative. These observations are consistent with Figures
39 larger in the 24-hour experiment for most of the subjects. This
4 and 5 that indicate in our method, the CV values of C2 are
40 comparison was also true for C2 approach, in which the CV
less than C1 for most of the subjects in the consecutive and
41 values of 24-hour experiment were higher than the
24-hour experiments, respectively.
42 consecutive for most of the subjects. These observations were
As we explained in the Methods section, the C1 approach
expected because of longer time between the recordings in the
43 did not change the ratio (equation (4)), and consequently its
24-hour experiment, which could cause higher variations in
44 CV values were very close to the no-correction case (ideally,
the STIs.
45 the values should be the same, however because of numerical
In our best results (C2 approach in Figures 4 and 5), all the
46 errors, the CVs of RatioC1 in both experiments were slightly
CV values in the consecutive experiment were less than 5%.
47 different).
For the 24-hour experiment, the CV values were less than
48 Our best results in both experiments were obtained using
10%, and more than half of the subjects had CV values of less
49 the C2 correction described by equations (5) and (6). These
than 5%.
50 equations were based on regression models developed by
There is no unique and predefined value for CV that
51 Weissler, et al. [5]. These regression models were derived
indicates the acceptable repeatability of STI estimation using
52 from the relation of PEP and LVET to the heart rate and sex
SCG and ECG signals. However, we indicated that our results
53 among 211 healthy subjects. Such models can be used for
54 correction of STIs in other groups such as the subjects of our
55
56
57
58 6
59
60

1
2
3 were in agreement with a relevant alternative method using We analyzed STIs repeatability in two experimental
4 ICG and ECG. settings, consecutive and 24-hour. Considering the practical
5 Moreover, for healthy subjects, the CV values were aspects, perhaps the situations similar to the consecutive
6 acceptable in that their corresponding Ratios remained within experiment occur more frequently. Here, among consecutive
7 the range of healthy individuals (i.e. PEP/LVET < 0.4, [9] measurements of SCG and ECG in one session, we expected
average CV values of 1.3%, 0.7%, and 1.8% for PEP $ ,

[24]). According to Tables 4 and 5, despite all variations to observe consistent and repeatable estimation of STIs. The
8
LVET $, and their ratio (Table 3) were acceptable for such an
among estimated STIs of different subjects, the ratio of
9
PEP/LVET in all the recordings never exceeded the reference
10
range of healthy subjects. As was stated in the Introduction expectation in healthy subjects.
11
section, the ratio of PEP/LVET is the most useful STIs, and to
12
the best of our knowledge this study was the first one that
13 Conclusion
investigated its repeatability.
14 The repeatability analysis has been conducted for
15 estimating STIs using other methods such as Echo [11], and
In this study, we investigated the repeatability of STI
16 arterial pulse tracing, ECG, and phonocardiogram [20]. Since
estimation (PEP, LVET, and their ratio) in healthy subjects
17 Echo is the gold standard for STI estimation, its repeatability
using SCG and ECG. It can be concluded that such estimation
18 can be considered as a baseline for our results. Reant, et al.,
was repeatable. Moreover, the repeatability was increased
19 [11] performed a comprehensive study on STIs using Echo
after STIs were corrected for heart rate using sex-specific
20 regression models (Weissler's equations).
method. They reported the average repeatability for PEP and
21 In our research, we focused on healthy subjects and the
LVET respectively as 2% and 4% based on 10 measures on
22 repeatability of their STIs. In the future we will be expanding
134 heart failure patients and 43 healthy subjects. Our results
23 our study to include patients with cardiac diseases, and
(Tables 1-3) were almost in the same range of the reported
24 scrutinize if STI estimation using SCG and ECG is also
values by Reant, et al. Our best results (Table 3, after
repeatable.
25 correcting for heart rate using C2 approach) were slightly
26 better than the reported values, most possibly because we
27 investigated only healthy subjects, whereas the Acknowledgements
28 aforementioned study considered both healthy subjects and Vahid Zakeri and Parastoo Dehkordi are employed by
29 patients with heart failure, which could induce more Heart Force Medical Inc. (HFM), Vancouver, Canada.
30 variability to the estimated STIs. Also, while we obtained the Kouhyar Tavakolian is on the Board of Directors at HFM.
31 repeatability of PEP/LVET, no values were reported for the Farzad Khosrow-khavar and Erwin P. Bauer are respectively
32 Ratio in the Reant’s study. the CTO and CMO of HFM.
33 Considering the estimation method of SCG-ECG, the VZ contributed to the study design, statistical analysis, and
34 closest study to our work was conducted by Crow, et al., [10] results interpretation, and wrote the manuscript. KT
35 in which the repeatability of PEP was investigated. In their contributed to the study design, data acquisition, and critical
36 study, an average CV value of 5.4% was obtained after 10 revision of the paper. APB, EPB, and PD revised the paper
37 consecutive recordings over 39 subjects. Their result is critically for important intellectual content. FKK contributed
38 comparable to ours. We obtained higher repeatable results for to the study design, statistical analysis, and critical revision of
39 PEP (Tables 1-3), but among a smaller number of healthy the paper.
40 subjects. Moreover, we included the repeatability analysis of
41 LVET and PEP/LVET as well as carrying out the 24-hour References
42 experiment.
The aim of our study was to analyze if SCG and ECG could [1] R. P. Lewis, S. E. Rittogers, W. F. Froester, and H.
43 Boudoulas, “A critical review of the systolic time intervals,”
obtain repeatable STI estimation for healthy subjects. Our
44 Circulation, vol. 56, no. 2, pp. 146–158, 1977.
basic assumption was that SCG and ECG could provide
45 [2] F. Marcus et al., “Accelerometer-derived time intervals
accurate estimations of STIs, which was highly dependent during various pacing modes in patients with biventricular
46 pacemakers: comparison with normals,” Pacing Clin.
upon the annotations (i.e. Q, AO, and AC points). The
47 Electrophysiol., vol. 30, no. 12, pp. 1476–1481, Dec. 2007.
accuracy and repeatability of STI estimation are related to
48 [3] A. H. Garrod, “On some points connected with the
each other, but are different problems. The accuracy
49 evaluation of STI estimation was beyond the scope of this
circulation of the blood, arrived at from a study of the
sphygmograph-trace,” Proc. R. Soc. London, vol. 23, no.
50 study, and was investigated by others, e.g. [10] [25]. Also, our 156–163, pp. 140–151, 1875.
51 group has recently conducted a study to assess the STIs [4] L. N. Katz and H. S. Feil, “Clinical observations on the
52 accuracy [26]. dynamics of ventricular systole: I. Auricular fibrillation,”
53 Arch. Intern. Med., vol. 32, no. 5, pp. 672–692, 1923.
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pp. 149–159, 1968. pp. 493–506, 1983.
4 [6] M. Stefadouros and A. Witham, “Systolic time intervals by [25] K. Sørensen, S. E. Schmidt, A. S. Jensen, P. Søgaard, and J.
5 echocardiography,” Circulation, vol. 51, no. 1, pp. 114–117, J. Struijk, “Definition of fiducial points in the normal
6 1975. seismocardiogram,” Sci. Rep., vol. 8, no. 1, p. 15455, Dec.
7 [7] S. Hirschfeld, R. Meyer, D. C. Schwartz, J. Korfhagen, and 2018.
S. Kaplan, “Measurement of right and left ventricular [26] P. Dehkordi et al., “Comparison of different methods for
8 systolic time intervals by echocardiography,” Circulation, estimating cardiac timings: a comprehensive multimodal
9 vol. 51, no. 2, pp. 304–309, 1975. echocardiography investigation,” Front. Physiol., vol. 10, p.
10 [8] V. Balasubramanian, O. Mathew, A. Behl, S. Tewari, and 1057, 2019.
11 R. Hoon, “Electrical impedance cardiogram in derivation of
systolic time intervals,” Br. Hear. J. , vol. 40, no. 3, p. 268,
12 1978.
13 [9] K. Tavakolian, “Systolic time intervals and new
Appendix
14
(CV) is not dependent on HR
measurement methods,” Cardiovasc. Eng. Technol., vol. 7, In this Appendix, we prove that the coefficient of variation
15 no. 2, pp. 118–125, 2016.
, when STIs are
[10] R. S. Crow, P. Hannan, D. Jacobs, L. Hedquist, and D. M.
16 corrected through equations (2) and (3) (C1 approach). We can
Salerno, “Relationship between seismocardiogram and
17 echocardiogram for events in the cardiac cycle,” Am. J. summarize equation (2) and (3) as,
HR
18 Noninvasive Cardiol., vol. 8, no. 1, pp. 39–46, 1994.
STI = STI ×
19
HR
[11] P. Reant et al., “Systolic time intervals as simple (A1)
20 echocardiographic parameters of left ventricular systolic
performance: correlation with ejection fraction and
21 longitudinal two-dimensional strain,” Eur. J.
numbers and α is a non-negative constant (real number), then,

22 Echocardiogr., vol. 11, no. 10, pp. 834–844, Dec. 2010. where STI can be PEP or LVET. If X is a vector of real
23 [12] W. M. K. Trochim, J. P. Donnelly, and K. Arora, The
σ6αX8 = α σ6X8
24 research methods: The Essential knowledge base. 2016.
[13] N. M. Albert, “Bioimpedance cardiography measurements (A2)
25 of cardiac output and other cardiovascular parameters,”
μ6αX8 = α μ6X8 6A38
26 Crit. Care Nurs. Clin. North Am., vol. 18, no. 2, pp. 195–
27 202, 2006.
where σ and μ indicate the standard deviation and the mean,

28 [14] G. Cotter, A. Schachner, L. Sasson, H. Dekel, and Y.
Moshkovitz, “Impedance cardiography revisited,” Physiol.
29 Meas., vol. 27, no. 9, pp. 817–827, Sep. 2006. respectively. The coefficient of variation (CV) can be written
30 [15] H. Boudoulas, “Systolic time intervals,” Eur. Heart J., vol. as,
31 11, no. suppl I, pp. 93–104, Dec. 1990.
σ6αX8 α σ6X8 σ6X8 6A4-a8
CV6αX8 = = =
32 [16] Q. Li and G. G. Belz, “Systolic time intervals in clinical
μ6αX8 α μ6X8 μ6X8

pharmacology,” Eur. J. Clin. Pharmacol., vol. 44, no. 5, pp.
33
= CV6X8
415–421, Jun. 1993.
34 [17] P. Carvalho, R. P. Paiva, J. Henriques, M. Antunes, I.
35
In the above equation, if we set X and α as follows,
Quintal, and J. Muehlsteff, “Robust characteristic points for
36 ICG-definition and comparative analysis,” in International
37 Conference on Bio-inspired Systems and Signal Processing
X = STI × HR 6A4-b8
(BIOSIGNALS), 2011, pp. 161–168.
1
38
α= E ⟹
[18] P. Laake, H. Benestad, and B. Olsen, Research methodology
HR
39 in the medical and biological sciences. 2007.
40 [19] H. Abdi, “Coefficient of variation,” Encycl. Res. Des., vol.
41 1, pp. 169–171, 2010.
[20] M. Kupari, “Reproducibility of the systolic time intervals:
42 effect of the temporal range of measurements,” Cardiovasc. Then, we have,
6A4-c8
43
1
Res., vol. 17, no. 6, pp. 339–343, Jun. 1983.
44 CV6STI 8 = CV G × 6STI × HR8H
HR
[21] J. Martin Bland and D. Altman, “Statistical methods for
45
= CV6STI × HR8
assessing agreement between two methods of clinical
measurement,” Lancet, vol. 327, no. 8476, pp. 307–310,
46
Feb. 1986.
47
corrected STIs (CV6STI 8) is not dependent upon
[22] H. M. Mertens, H. Mannebach, G. Trieb, and U. As equations (A4-a)-(A4-c) indicate, the repeatability of the
48 Gleichmann, “Influence of heart rate on systolic time
49 intervals: Effects of atrial pacing versus dynamic exercise,”
HR . The corrected repeatability is equivalent to
50 Clin. Cardiol., vol. 4, no. 1, pp. 22–27, Jan. 1981.
[23] G. K. Wolf, G. G. Belz, and M. Stauch, “Systolic time correcting the STIs with respect to the HR; i.e. for each record,
51
(STI × HR8.
intervals—correction for heart rate,” Basic Res. Cardiol., the estimated STIs are multiplied by the HR of that record
52 vol. 73, no. 1, pp. 85–96, Jan. 1978.
53 [24] H. Boudoulas et al., “Assessment of ventricular function by
54 combined noninvasive measures: factors accounting for
55
56
57
58 8
59
60

1
2
3
4
5
6
7
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32
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40
41
42
43
44
45
46
47
48
49 Figure 3: The Bland-Altman plots in the consecutive (left side) and 24-hour (right side) experiments, comparing the CV
50 values of our method (SCG and ECG) to the alternative method (ICG and ECG), when the STIs were corrected for heart
51 rate using C2 approach (equations (5) and (6)). Dashed lines indicate the mean (blue) and top/bottom 95% limits of
52 agreement (red). The shadowed areas indicate the corresponding 95% confidence intervals for the mean and limits of
53 agreement.
54
55
56
57
58 9
59
60

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50
51
52
53
54
55 Figure 4: Comparison of the CV values of STIs per subject in the consecutive experiment between C1 (top) and C2
56 (bottom) approaches in our method (SCG & ECG).
57
58 10
59
60

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54
Figure 5: Comparison of the CV values of STIs per subject in the 24-hour experiment between C1 (top) and C2 (bottom)
55
approaches in our method (SCG & ECG).
56
57
58 11
59
60

1
2
4 Heart Rate Using C1 Approach.
5
7 1 74 97 275 0.35 71 94 264 0.36 71 94 264 0.36
8 2 65 88 278 0.32 65 88 281 0.31 63 87 277 0.31
9 3 73 86 300 0.29 70 81 297 0.27 73 85 307 0.28
10 4 81 79 295 0.27 82 80 299 0.27 82 79 298 0.27
11
5 52 83 294 0.28 53 83 300 0.28 52 84 301 0.28
12
13 6 49 88 274 0.32 48 90 267 0.34 61 107 332 0.32
14 7 63 77 330 0.23 59 72 316 0.23 64 76 338 0.22
15 8 66 76 288 0.26 70 86 302 0.28 63 77 278 0.28
16 9 73 73 286 0.26 77 75 300 0.25 84 82 309 0.27
17
10 78 76 311 0.24 76 80 296 0.27 80 75 313 0.24
18
11 74 75 257 0.29 76 75 278 0.27 70 71 264 0.27
19
20 12 65 93 252 0.37 67 96 257 0.37 66 94 256 0.37
21 13 59 86 304 0.28 57 82 300 0.27 60 88 310 0.28
22 14 66 86 312 0.28 62 81 299 0.27 63 81 304 0.27
23 15 74 65 304 0.21 70 63 288 0.22 75 66 305 0.22
24
16 52 90 289 0.31 53 93 295 0.32 50 88 279 0.32
25
26 17 53 90 336 0.27 52 93 332 0.28 53 94 332 0.28
27 18 61 93 275 0.34 62 95 292 0.33 61 91 292 0.31
28 19 55 81 300 0.27 59 89 310 0.29 55 82 300 0.27
29 20 52 88 329 0.27 49 83 310 0.27 49 80 310 0.26
30
31
33 1 68 95 284 0.33 66 100 273 0.37
34 2 64 79 257 0.31 75 93 260 0.36
35
3 72 83 297 0.28 74 83 306 0.27
36
37 4 74 80 314 0.25 72 78 313 0.25
38 5 54 87 311 0.28 52 87 307 0.28
39 6 55 90 326 0.28 49 83 287 0.29
40 7 65 69 311 0.22 73 74 338 0.22
41 8 70 77 294 0.26 69 84 271 0.31
42
9 76 78 298 0.26 79 86 300 0.29
43
44 10 90 79 320 0.25 75 72 285 0.25
45 11 69 71 279 0.25 69 83 273 0.3
46 12 66 89 239 0.37 73 95 265 0.36
47 13 62 93 315 0.3 54 78 306 0.25
48 14 66 82 318 0.26 61 77 283 0.27
49
15 79 78 296 0.26 70 70 299 0.23
50
51 16 49 88 274 0.32 54 95 293 0.32
52 17 60 81 341 0.24 61 89 319 0.28
53 18 62 92 308 0.3 60 89 287 0.31
54 19 62 91 320 0.28 53 81 277 0.29
55
20 52 78 311 0.25 58 87 332 0.26
56
58 Subj. = subject; HR = heart rate; STIs = systolic time intervals. C1 Approach is described by equations (2)-(4)
60

1
2
4 Heart Rate Using C2 Approach
5
7 1 74 124 390 0.32 71 124 389 0.32 71 124 389 0.32
8 2 65 113 386 0.29 65 113 390 0.29 63 115 389 0.3
9 3 73 114 414 0.28 70 112 416 0.27 73 113 420 0.27
10 4 81 113 424 0.27 82 112 428 0.26 82 112 424 0.26
11
5 52 106 386 0.27 53 103 389 0.26 52 105 388 0.27
12
13 6 49 115 381 0.3 48 117 378 0.31 61 117 388 0.3
14 7 63 101 427 0.24 59 100 427 0.23 64 100 427 0.23
15 8 66 102 403 0.25 70 109 404 0.27 63 106 402 0.26
16 9 73 107 421 0.25 77 107 426 0.25 84 110 421 0.26
17
10 78 108 436 0.25 76 112 423 0.26 80 105 432 0.24
18
11 74 104 376 0.28 76 103 397 0.26 70 102 395 0.26
19
20 12 65 120 366 0.33 67 121 369 0.33 66 122 368 0.33
21 13 59 109 398 0.27 57 108 395 0.27 60 111 396 0.28
22 14 66 109 412 0.26 62 108 413 0.26 63 107 413 0.26
23 15 74 94 415 0.23 70 94 410 0.23 75 94 411 0.23
24
16 52 111 374 0.3 53 112 376 0.3 50 112 374 0.3
25
26 17 53 112 418 0.27 52 114 417 0.27 53 115 416 0.28
27 18 61 118 382 0.31 62 118 393 0.3 61 115 392 0.29
28 19 55 104 399 0.26 59 109 400 0.27 55 106 399 0.27
29 20 52 105 403 0.26 49 104 398 0.26 49 103 401 0.26
30
31
33 1 68 120 394 0.3 66 129 389 0.33
34 2 64 111 386 0.29 75 115 368 0.31
35
3 72 113 413 0.27 74 112 420 0.27
36
37 4 74 109 427 0.26 72 109 433 0.25
38 5 54 107 393 0.27 52 110 405 0.27
39 6 55 107 397 0.27 49 109 393 0.28
40 7 65 98 433 0.23 73 99 436 0.23
41 8 70 106 408 0.26 69 112 388 0.29
42
9 76 110 426 0.26 79 115 422 0.27
43
44 10 90 108 437 0.25 75 109 432 0.25
45 11 69 99 396 0.25 69 111 390 0.28
46 12 66 120 363 0.33 73 120 375 0.32
47 13 62 112 394 0.28 54 106 416 0.25
48 14 66 105 418 0.25 61 105 397 0.26
49
15 79 106 406 0.26 70 103 428 0.24
50
51 16 49 112 375 0.3 54 111 369 0.3
52 17 60 106 440 0.24 61 112 414 0.27
53 18 62 115 406 0.28 60 115 392 0.29
54 19 62 110 402 0.27 53 109 389 0.28
55
20 52 103 415 0.25 58 105 411 0.26
56
58 Subj. = subject; HR = heart rate; STIs = systolic time intervals. C2 Approach is described by equations (5) and (6)
60

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Page 1 of 26 AUTHOR SUBMITTED MANUSCRIPT - PMEA-103248.

IOP Publishing Physiological Measurement

Journal XX (XXXX) XXXXXX Zakeri et al

Journal XX (XXXX) XXXXXX Zakeri et al

Journal XX (XXXX) XXXXXX Zakeri et al

Journal XX (XXXX) XXXXXX Zakeri et al

where subscript C2 indicates the corrected STIs in equations

Journal XX (XXXX) XXXXXX Zakeri et al

Journal XX (XXXX) XXXXXX Zakeri et al

average CV values of 1.3%, 0.7%, and 1.8% for PEP ! ,

Journal XX (XXXX) XXXXXX Zakeri et al

numbers and α is a non-negative constant (real number), then,

where σ and μ indicate the standard deviation and the mean,

μ5αX7 α μ5X7 μ5X7

Journal XX (XXXX) XXXXXX Zakeri et al

Journal XX (XXXX) XXXXXX Zakeri et al

Journal XX (XXXX) XXXXXX Zakeri et al

Journal XX (XXXX) XXXXXX Zakeri et al

Journal XX (XXXX) XXXXXX Zakeri et al

IOP Publishing Physiological Measurement

Journal XX (XXXX) XXXXXX Zakeri et al

Journal XX (XXXX) XXXXXX Zakeri et al

Journal XX (XXXX) XXXXXX Zakeri et al

Journal XX (XXXX) XXXXXX Zakeri et al

LVET = 1.6 HR + LVET for females

Journal XX (XXXX) XXXXXX Zakeri et al

Journal XX (XXXX) XXXXXX Zakeri et al

average CV values of 1.3%, 0.7%, and 1.8% for PEP $ ,

Journal XX (XXXX) XXXXXX Zakeri et al

numbers and α is a non-negative constant (real number), then,

where σ and μ indicate the standard deviation and the mean,

μ6αX8 α μ6X8 μ6X8

Journal XX (XXXX) XXXXXX Zakeri et al

Journal XX (XXXX) XXXXXX Zakeri et al

Journal XX (XXXX) XXXXXX Zakeri et al

Journal XX (XXXX) XXXXXX Zakeri et al

Journal XX (XXXX) XXXXXX Zakeri et al

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