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AUTHOR QUERIES

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Q:1 AUTHOR: Snoring patients was changed throughout to patients who snore per style.
Q:2 AUTHOR: Please note that funding information was moved from the Acknowledgments to the Dis-
closure Statement per style.
Q:3 AUTHOR: Please provide supplier and location of supplier for Rooti Rx.
Q:4 AUTHOR: Please provide supplier and location of supplier for Compumedics Grael and ResMed
Embla N7000 and MPR.
Q:5 AUTHOR: The URL http://www.aasmnet.org/resources/pdf/Scoring-manual-update-April-2017.pdf
has been redirected to https://aasm.org/resources/pdf/scoring-manual-update-april-2017.pdf. Please
verify the URL.
Q:6 AUTHOR: Please spell out QRS.
Q:7 AUTHOR: One subhead should not be used. Please provide another subhead under Discussion or delete
subhead here.
https://doi.org/10.5664/jcsm.8462

S C I E N T I F I C I N V E S T I G AT I O N S

Q:1 Screening of obstructive sleep apnea in patients who snore using a patch-type
device with electrocardiogram and 3-axis accelerometer
Ying-Shuo Hsu, MD1,2; Tien-Yu Chen, MD3,4; Dean Wu, MD5,6,7; Chia-Mo Lin, MD8,9,10; Jer-Nan Juang, PhD11;
Wen-Te Liu, MD5,11,12,13,14,15
1
Department of Otolaryngology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; 2School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; 3Department of
Psychiatry, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan; 4 Institute of Brain Science, National Yang-Ming University, Taipei,
Taiwan; 5Sleep Center, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; 6Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei
City, Taiwan; 7Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 8Division of Chest Medicine, Shin Kong Wu Ho-Su Memorial
Hospital, Taipei, Taiwan; 9 Department of Chemistry, Fu-Jen Catholic University, New Taipei City, Taiwan; 10Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen
Catholic University, New Taipei City, Taiwan; 11Department of Engineering Science, National Cheng Kung University, Tainan, Taiwan; 12Division of Pulmonary Medicine, Department of
Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; 13Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical
University, Taipei, Taiwan; 14School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan; 15Sleep Science Center, Taipei Medical University
Hospital, Taipei Medical University, Taipei, Taiwan

Study Objectives: People with obstructive sleep apnea (OSA) remain undiagnosed because of the lack of easy and comfortable screening tools. Through this
study, we aimed to compare the diagnostic accuracy of chest wall motion and cyclic variation of heart rate (CVHR) in detecting OSA by using a single-lead
electrocardiogram (ECG) patch with a 3-axis accelerometer.
Methods: In total, 119 patients who snore simultaneously underwent polysomnography with a single-lead ECG patch. Signals of chest wall motion and CVHR
from the single-lead ECG patch were collected. The chest effort index (CEI) was calculated using the chest wall motion recorded by a 3-axis accelerometer in the
device. The ability of CEI and CVHR indices in diagnosing moderate-to-severe OSA (apnea hypopnea index ≥ 15) was compared using the area under the curve
(AUC) by using the DeLong test.
Results: CVHR detected moderate-to-severe OSA with 52.9% sensitivity and 94.1% specificity (AUC: 0.76, 95% confidence interval: 0.67–0.84, optimal cutoff:
21.2 events/h). By contrast, CEI identified moderate-to-severe OSA with 80% sensitivity and 79.4% specificity (AUC: 0.87, 95% confidence interval: 0.80–0.94,
optimal cutoff: 7.1 events/h). CEI significantly outperformed CVHR regarding the discrimination ability for moderate-to-severe OSA (ΔAUC: 0.11, 95% confidence
interval: 0.009–0.21, P = .032). For determining severe OSA, the performance of discrimination ability was greater (AUC = 0.90, 95% confidence interval:
0.85–0.95) when combining these two signals.
Conclusions: Both CEI and CVHR recorded from a patch-type device with ECG and a 3-axis accelerometer can be used to detect moderate-to-severe OSA.
Thus, incorporation of CEI is helpful in the detection of sleep apnea by using a single-lead ECG with a 3-axis accelerometer.
Keywords: apnea–hypopnea index, cyclic variation of heart rate, chest wall motion, electrocardiogram, sleep apnea, obstructive sleep apnea
sleep-disordered breathing
Citation: Hsu Y-S, Chen T-Y, Wu D, Lin C-M, Juang J-N, Liu W-T. Screening of obstructive sleep apnea in patients who snore using a patch-type device with
electrocardiogram and 3-axis accelerometer. J Clin Sleep Med. 2020;16(0):XXX–XXX.

BRIEF SUMMARY
Current Knowledge/Study Rationale: To determine the accuracy and tolerability of a single electrocardiogram lead to screen for sleep apnea, we collected
the data of 119 patients who snore who simultaneously underwent polysomnography and a single-lead electrocardiogram patch with 3-axis accelerometer.
Chest effort index from the chest wall motion and cyclic variation of heart rate were calculated and compared with the apnea-hypopnea index recorded
through polysomnography.
Study Impact: We found that chest effort index significantly outperformed the cyclic variation of heart rate on the discrimination ability in identifying
moderate-to-severe obstructive sleep apnea. Our study validated that a combination of chest effort index and cyclic variation of heart rate is helpful in
identifying obstructive sleep apnea in sleep tests conducted using a single-lead electrocardiogram with 3-axis accelerometer.

INTRODUCTION excessive daytime sleepiness.5 Therefore, this disease consid-


erably impacts the health and quality of life of affected indi-
Obstructive sleep apnea (OSA) occurs during sleep because of viduals. Benjafield et al6 estimated that globally, 936 million
recurrent upper airway obstruction. Several complications as- adults 30–69 years of age (men and women) have mild-to-se-
sociated with OSA have been detected, such as hypertension,1 vere OSA, and 425 million adults 30–69 years of age have
sudden cardiac death,2 cerebrovascular diseases,3 diabetes,4 and moderate-to-severe OSA. The prevalence is so high that there is

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Y-S Hsu, T-Y Chen, D Wu, et al. Screening of sleep apnea

Figure 1—Rooti Rx, a wireless single-lead ECG monitoring patch.

(A) Appearance of the device. (B) CVHR pattern recorded by Rooti Rx. Cyclic lengthening/shortening in the heart rate during apnea/postapneic
hyperventilation is shown. The airflow and saturation data were derived from the PSG. The response of SpO2 and heart rate falls a little behind air flow in an
apnea event. This phenomenon means that desaturation and heart rate variability are likely an aftermath of sleep apnea. CVHR = cyclic variation of heart rate,
ECG = electrocardiogram, SpO2 = peripheral oxygen saturation.

a growing need for devices that are more accessible to people the diaphragm and intercostal muscle tone remain relatively
to more efficiently and conveniently diagnose new patients the same.17 The difference in muscle function results in upper
with sleep apnea; thus, a comprehensive assessment of novel airway collapse and apnea.18 Staats et al19 suggested that respi-
diagnostic devices for sleep apnea is warranted. ratory efforts against the occlusion cause distortion of the chest
In-laboratory polysomnography (PSG) is the first-line di- wall and result in paradoxical motion of the rib cage, which can
agnostic study for suspected OSA.7 However, this test is adequately characterize apnea in most patients. The authors also
expensive, time consuming, and uncomfortable. Therefore, suggested that recognizing these paradoxical chest wall motions in
several alternatives to PSG were proposed, and home sleep sleep apnea could help avoid the use of invasive sleep monitoring
apnea testing is one of them.7 Oximetry is another less expensive techniques. We hypothesized that chest wall motion, as an indicator
and easier alternative that is widely available.8,9 However, of a sleep apnea episode, can also be simultaneously recorded during
attaching a device to the finger during sleep is uncomfortable recording using a single-lead ECG device.
and may limit natural position change during sleep; moreover, Through this study, we aimed to evaluate the predictive
the device is removed on waking up, which limits its use in performance of chest wall motion and CVHR in detecting OSA
multiday, continuous recordings. with wireless single-lead ECG monitoring patch with 3-axis ac-
Cyclic variation of heart rate (CVHR) was first introduced by celerometer in subjects who snore. We hypothesized that using an
Guilleminault et al10 for screening of OSA. They found that at overnight wireless single-lead ECG monitoring patch with a 3-axis
the onset of sleep apnea, patients showed progressive brady- accelerometer is an accurate method to identify OSA, especially
cardia, followed by abrupt tachycardia on resumption of when simultaneously considering CVHR and chest wall motion.
breathing. As this screening tool has an advantage of comfort
recording in sleep, especially in modern-type single-lead
electrocardiogram (ECG) devices, it is potentially suitable for METHODS
multiday evaluation. Several studies have been conducted to
improve its algorithm and accuracy.11–16 Subjects and study protocol
Chest wall motion is affected in sleep apnea. During sleep In this prospective study, 119 patients who snore were included;
apnea, the muscle tone of the upper airway is reduced. However, they were subjected to in-laboratory PSG examinations at the

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Figure 2—The chest wall motion is translated from the signals of the 3-axis accelerometer.

(A) Placement of Rooti Rx monitoring patch and the axes of the 3-axis accelerometer. (B) Signals from PSG airflow and from 3-axis accelerometer of Rooti
Rx in X, Y, and Z axes (labeled as G-X, G-Y, and G-Z, respectively). The Y-axis signal has the largest fluctuation amplitude during apnea and normal
respiration. PSG = polysomnography.

sleep center. Among them, 97 were from Shin Kong hospital updated standard diagnostic criteria of the American Acad-
(SKH), and 22 were from Shuang Ho Hospital (SHH). The study emy of Sleep Medicine (AASM)20 and AASM 2017 scoring
was approved by the institutional review boards of both hos- guidelines (https://aasm.org/resources/pdf/scoring-manual-
pitals (SKH: 20171003R, SHH: N201709023), and written update-april-2017) by an experienced registered polysomno- Q:5
informed consent was provided by all participants. Adult pa- graphic technologist at the sleep center of SKH and SHH, and
tients aged between 18 and 70 years who complained of snoring these scorings were rechecked by at least 2 technologists to
or those with suspected sleep-disordered breathing were in- ensure further accuracy of sleep apnea events and ECG staging.
cluded. Patients with persistent atrial fibrillation, pacemaker Obstructive apnea was defined as a drop in the peak thermal
implantation, ventricular tachycardia, or those who were sensor excursion by more than 90% from the baseline for at least
Q:3 pregnant were excluded. At the sleep center, a wireless single- 10 seconds, caused by airway obstruction. If these events lacked
F1 lead ECG monitoring patch (Rooti Rx; Figure 1A) was si- respiratory effort, they were defined as central apnea. Hypopnea
multaneously used; it was placed between the midsternal line was defined as more than 30% reduction in airflow for at least
and the left midclavicular line and around the third and fourth 10 seconds with arousal or more than 3% oxygen desaturation.
intercostal space. This device also provides 3-axis acceler- Apnea-hypopnea index (AHI) was determined as the mean
ometer signals, which could represent the motion of chest wall number of apneas and hypopneas per hour of time in sleep for
during respiration. The signals collected by PSG and Rooti Rx each PSG recording. Patients were considered to have mod-
were synchronized, and the measurements derived from the two erate-to-severe OSA when their AHI was more than 15 events/h.
tests were compared. All the PSG recordings were performed during the night, and
split PSG studies were not included. The in-laboratory PSG data
PSG were carefully reviewed by a second sleep technologist. If there
Q:4 The PSG recordings were obtained using Compumedics Grael were differences in their assessments, these were carefully
(SKH) or ResMed Embla N7000 and Embla MPR (SHH). The evaluated by both sleep technologists until a final consensus
sleep stages and respiratory events were scored using the was met.

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Figure 3—Illustration of the calculated peaks and troughs of the chest effort event.

To determine the chest effort event by this diagram, 3 criteria should be achieved (marked in bold). First, peak–trough differences should be greater than the
drop threshold. Second, the trough value should be lower than the block threshold. Third, the duration of each event (start point to end point) should be greater
than 10 seconds.

Table 1—Baseline characteristics of patients according to severity of obstructive sleep apnea.


Variables Total (n = 119) Moderate-to-Severe OSA (n = 85) None-to-Mild OSA (n = 34) P
Age (yr) 42.8 ± 11.6 43.6 ± 11.7 40.9 ± 11.2 .245
Male 96 (80.7) 72 (84.7) 24 (70.6) .069
Height (cm) 169.7 ± 7.5 170.5 ± 7.4 167.9 ± 7.4 .086
Weight (kg) 78.5 ± 16.0 81.8 ± 16.4 70.5 ± 11.4 <.001
BMI (kg/m2) 27.2 ± 4.7 28.0 ± 4.8 25.0 ± 3.6 .001
Neck length (cm) 38.7 ± 3.4 39.4 ± 3.5 37.0 ± 2.7 <.001
Mean heart rate (beats/min) 66.6 ± 10.0 68.1 ± 10.1 62.9 ± 9.0 .011
Mean SpO2 (%) 93.6 ± 4.2 92.4 ± 4.4 96.7 ± 1.0 <.001
Lowest SpO2 (%) 79.5 ± 13.3 76.8 ± 10.7 86.4 ± 16.4 <.001
Desaturation index (events/h) 25.9 ± 28.3 35.1 ± 28.7 2.7 ± 3.1 <.001
Snore index (events/h) 385 ± 238 427 ± 223 281 ± 244 .002
CVHR index (events/h) 22.9 ± 20.6 27.9 ± 21.9 10.4 ± 8.4 <.001
CEI (events/h) 13.5 ± 11.8 16.8 ± 12.3 5.4 ± 3.9 <.001
AHI (events/h) 35.6 ± 26.9 46.6 ± 24.1 7.9 ± 3.8 <.001
Total sleep time (h) 338.6 ± 55.5 342.0 ± 51.8 330.0 ± 63.9 .291
Sleep efficiency (%) 85.1 ± 11.3 85.8 ± 9.7 83.5 ± 14.7 .321
Apnea counts 94.3 ± 125.6 129.8 ± 132.9 5.4 ± 8.2 <.001
Hypopnea counts 112.3 ± 84.5 141.0 ± 83.2 40.7 ± 22.1 <.001

Values are presented as number (%) or mean ± SD. AHI = apnea-hypopnea index, BMI = body mass index, CEI = chest effort index, CVHR = cyclic variation
of heart rate, OSA = obstructive sleep apnea, SpO2 = peripheral oxygen saturation.

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Figure 4—Relationship between (A) CVHR index, (B) CEI, and the severity of obstructive sleep apnea.

AHI = apnea–hypopnea index, CEI = chest effort index, CVHR = cyclic variation of heart rate.

CVHR time-domain dip-detection algorithm.11 Valid CVHR events


CVHR is a characteristic heart rate pattern that often presents were defined as at least 3 consecutive cycles of increase in heart
along with episodes of OSA. CVHR (Figure 1B) is an ECG rate (>6 beats/min) that last for 10–120 seconds. The CVHR
pattern characterized by progressive bradycardia at the onset of index was then calculated as the mean number of CVHR events
sleep apnea, followed by abrupt tachycardia on resumption of per hour of sleep.
breathing. This pattern is identifiable through computer analysis
and can be used as a screening tool for sleep apnea.10 For single- Chest effort
lead ECG, Hayano et al11,16 developed an algorithm called To measure the chest wall motion during respiratory cycles and
autocorrelated wave detection with adaptive threshold for sleep apnea events, the recorded 3-axis accelerometer signals
automated detection of CVHR and demonstrated that this were analyzed using the Rooti Rx monitoring patches, and chest
pattern could be used to screen moderate-to-severe OSA. effort events were calculated (Figure 2). F2
Hence, the analysis of single-lead ECG during sleep could be The chest effort events were automatically detected through 3-axis
considered a screening tool. G-sensor signal recording (Figure 2B). As the most significant
In this study, single-lead ECGs were obtained using wireless chest wall motions were noted on the Y-axis and these signals
single-lead ECG monitoring patches (Rooti Rx; Figure 1A). were less affected by position change, the Y-axis signals contributed
The ECG signals were then analyzed using RootiCare Sleep the most to the chest effort events in this study (Figure 2B).
Monitoring, a certified cloud-based computing software. Using The details of the calculation for chest effort events are shown
this, CVHR was detected through adaptive threshold and its in Figure 3. The Y-axis signals were obtained at a sampling F3

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Table 2—Association between CVHR or CEI and risk of different types of OSA.
Log Value of CVHR Log Value of CEI
Model
OR (95% CI) P OR (95% CI) P
Mild, moderate, and severe OSA
Model 1 1.48 (0.94–2.33) .091 3.82 (1.57–9.27) .003
Model 2 1.53 (0.95–2.45) .080 4.13 (1.59–10.74) .004
Model 3 1.41 (0.85–2.34) .184 3.89 (1.47–10.27) .006
Moderate to severe OSA (primary outcome)
Model 1 2.00 (1.37–2.93) <.001 9.78 (3.99–24.01) <.001
Model 2 2.02 (1.38–2.94) <.001 10.49 (4.09–26.89) <.001
Model 3 1.80 (1.21–2.68) .004 10.50 (3.81–28.92) <.001
Severe OSA
Model 1 5.06 (2.75–9.33) <.001 11.50 (4.83–27.35) <.001
Model 2 4.86 (2.64–8.93) <.001 13.26 (5.20–33.77) <.001
Model 3 4.14 (2.16–7.92) <.001 12.72 (4.51–35.86) <.001

Model 1 is without adjustment for any covariates. Model 2 is adjusted for age and sex. Model 3 is adjusted for age, sex, and body mass index. CEI = chest effort
index, CI = confidence interval, CVHR = cyclic variation of heart rate, OR = odds ratio, OSA = obstructive sleep apnea.

frequency of 31.25 Hz. We initially applied the Butterworth for the categorical variables. The relationships among CVHR,
bandpass filter with a pass band of 0.15–0.4 Hz and then per- CEI, and AHI index were studied using Spearman rank cor-
formed downsampling to 1 Hz by calculating the summation of relation. The outcome of primary interest was moderate-to-
the signal in the moving window of 5 seconds. Then, the severe OSA (AHI ≥ 15 events/h, n = 85), whereas the outcomes
downsampled moving sum signal was used to determine the of secondary interest were mild, moderate, or severe OSA
peaks and troughs. By searching forward and backward from the (AHI ≥ 5 events/h, n = 110), as well as severe OSA (AHI ≥ 30
trough point, the points at which there was 80% peak–trough events/h, n = 58). The association between CVHR or CEI and
difference were also located at the start and the endpoint of the risk of OSA was assessed using bivariate and multivariable
each event. Based on the median of moving sum signal ad- logistic regression analyses. Several known confounders of
justed for each case, the drop threshold value was determined OSA, including age, sex, and body mass index (BMI), were
to detect sharp changes in chest wall motion, and the block adjusted in the multivariable analysis. The values of CVHR or
threshold value was determined to detect blocked chest wall CEI were naturally log-transformed in logistic analyses because
movement. Subsequently, chest effort events could be de- of the lack of normality. The performance of CVHR or CEI to
tected using these three criteria: (1) peak–trough differences detect OSA was evaluated through receiver operating charac-
should be greater than the drop threshold; (2) the trough value teristic curve analysis. The optimal cutoffs were determined by
should be lower than the block threshold; and (3) the duration of Youden index. The positive likelihood ratio (+LR), negative
each event (start point to endpoint) should be greater than likelihood ratio (−LR), positive predictive value (PPV), and
10 seconds. negative predictive value (NPV) were obtained according to the
Events that fulfilled these 3 criteria were considered chest prevalence of patients who snore, in which 40% had moderate-
effort events. The chest effort index (CEI) was calculated as the to-severe OSA.21 The difference in AUCs between CEI and
mean number of chest effort events per hour of sleep. CVHR was compared using the DeLong test. All tests were 2-
A further explanation of a drop threshold and block threshold tailed, and P < .05 was considered statistically significant. No
is described here. A drop threshold is used to check if a sharp adjustment of multiple testing (multiplicity) was made in this
chest movement change occurs (peak-trough difference > drop study. Data were analyzed using SPSS 25 (IBM SPSS Inc.,
threshold), because a sharp chest movement change would be a Chicago, IL).
signal for the start of an obstruction event. A block threshold is a The scale of AHI and CVHR/CEI is different even if their unit
fairly low chest movement level that is used to determine is the same (i.e., the number of events per hour). In other words,
whether the chest movement is blocked, and an even lower chest an AHI value of 1 is not equivalent to a CVHR/CEI value of 1;
movement is considered an obstruction event. Drop threshold likewise, a CVHR value of 1 is also not equivalent to a CEI value
and block threshold were adjusted for each case based on the of 1. Because not every apnea-hypopnea event results in heart
median of the moving sum signal. rate variability or a chest effort change, a suitable screening
threshold for CVHRI and CEI was required in this study. As
Statistical analysis such, the Bland-Altman plot was not appropriate in this sce-
The baseline characteristics of the patients in the moderate-to- nario. Furthermore, neither ECG nor chest effort signals were
severe and none-to-mild OSA groups were compared using the synchronized in this study, so we only compared the final
independent-sample t test for age (continuous variable) or χ 2 test numbers for each patient.

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Table 3—Diagnostic properties of CVHR and CEI in detecting different severities of OSA.
Outcome/Statistics CVHR CEI CVHR + CEI
Mild, moderate or severe OSA
AUC (95% CI) 0.71 (0.56–0.85) 0.80 (0.64–0.96) 0.75 (0.61–0.89)
a
Cutoff >18.6 >6.6 CVHR>18.6 and CEI>6.6
Sensitivity, % (95% CI) 47.3 (37.7–57.0) 70.9 (61.5–79.2) 40.9 (31.6–50.7)
Specificity, % (95% CI) 100 (66.4–100) 88.9 (51.8–99.7) 100 (66.4–100)
+LR (95% CI)b NA 6.4 (1.0–40.7) NA
−LR (95% CI)b 0.5 (0.4–0.6) 0.3 (0.2–0.5) 0.6 (0.5–0.7)
PPV (95% CI)b NA 81 (40.0–96.4) NA
NPV (95% CI)b 74 (70.4–77.2) 82.1 (76.0–86.9) 71.7 (68.5–74.8)
Moderate to severe OSA (primary outcome)
AUC (95% CI) 0.76 (0.67–0.84) 0.87 (0.80–0.94) 0.82 (0.75–0.90)
Cutoffa >21.2 >7.1 CVHR > 21.2 and CEI > 7.1
Sensitivity, % (95% CI) 52.9 (41.8–63.9) 80.0 (69.9–87.9) 48.2 (37.3–59.3)
Specificity, % (95% CI) 94.1 (80.3–99.3) 79.4 (62.1–91.3) 97.1 (84.7–99.9)
+LR (95% CI)b 9 (2.3–35.0) 3.9 (2.0–7.6) 16.4 (2.3–114.5)
−LR (95% CI)b 0.5 (0.4–0.6) 0.3 (0.2–0.4) 0.5 (0.4–0.7)
PPV (95% CI)b 85.7 (60.6–95.9) 72.1 (57.0–83.5) 91.6 (61.0–98.7)
NPV (95% CI)b 75 (70.2–79.2) 85.6 (79.0–90.4) 73.8 (69.4–77.7)
Severe OSA
AUC (95% CI) 0.86 (0.79–0.93) 0.87 (0.81–0.94) 0.91 (0.85–0.96)
Cutoffa >21.9 >11 CVHR > 21.9 and CEI > 11
Sensitivity, % (95% CI) 70.7 (57.3–81.9) 72.4 (59.1–83.3) 58.6 (44.9–71.4)
Specificity, % (95% CI) 91.8 (81.9–97.3) 88.5 (77.8–95.3) 98.4 (91.2–100)
+LR (95% CI)b 8.6 (3.7–20.3) 6.3 (3.1–12.9) 35.8 (5.1–252.8)
−LR (95% CI)b 0.3 (0.2–0.5) 0.3 (0.2–0.5) 0.4 (0.3–0.6)
PPV (95% CI)b 85.2 (71.0–93.1) 80.8 (67.3–89.6) 96.0 (77.1–99.4)
NPV (95% CI)b 82.5 (75.8–87.6) 82.8 (75.9–88.1) 78.1 (72.4–82.9)
a
According to Youden index. bAccording to a prevalence of 40% of moderate-to-severe OSA in patients who snore. AUC = area under the curve, CEI = chest
effort index, CI = confidence interval, CVHR = cyclic variation of heart rate, +LR = positive likelihood ratio, −LR = negative likelihood ratio, NA = not applicable,
NPV = negative predicted value, OSA = obstructive sleep apnea, PPV = positive predicted value.

moderate-to-severe OSA group than in the none-to-mild OSA


RESULTS
group. Significantly lower mean saturation (92.4% in the
Characteristics of the study population moderate-to-severe OSA group vs 96.7% in the none-to-mild
A total of 119 patients who met the inclusion criteria were OSA group) and lowest saturation (76.8% in the moderate-to-
included in this study; of these, 97 patients were from SKH, and severe OSA group vs 86.4% in the none-to-mild OSA group)
T1 22 were from SHH. Table 1 presents the baseline characteristics were also noted in the moderate-to-severe OSA group. In ad-
of the patients according to the severity of OSA. In this study dition, the moderate-to-severe OSA group had more apnea and
population, 85 patients were classified as having moderate-to- hypopnea events.
severe OSA (AHI ≥ 15 events/h), and the other 34 were clas-
sified as having none-to-mild OSA (AHI < 15 events/h). No Association among CVHR, CEI, and severity of OSA
significant difference in age, sex, and height was observed Figure 4 illustrates the relationships among CVHR, CEI, and F4
between the 2 groups. However, patients in the moderate-to- AHI index. The results demonstrated that both CVHR and CEI
severe OSA group had a larger BMI and greater neck length. were significantly positively correlated to AHI values (Spear-
Because the moderate-severe group was predominantly male man rank correlation coefficient = 0.65 and 0.77, respectively;
and the none-to-mild group was predominantly female, sex both P < .001). Table 2 shows the results of bivariate and T2
could explain the differences observed between these 2 groups multivariable logistic regression analyses for the association
in terms of weight, BMI, and neck length. The mean heart between CVHR or CEI and the risk of moderate-to-severe
rate, desaturation index, and snore index, as well as the CVHR, OSA. After adjustment for age, sex, and BMI, both CVHR
CEI, and AHI index, were also significantly higher in the and CEI were significantly associated with higher risks of

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Clinical use
Figure 5—Receiver operating characteristic curves of Figure 6A presents the clinical use of Rooti Rx in the screening F6
CVHR and CEI in detecting moderate-to-severe obstructive of moderate-to-severe OSA. In our study, when CVHR was
sleep apnea. more than 21.2 and CEI was more than 7.1 (42 patients in total),
the detection rate for moderate-to-severe OSA was 97.6% (41 of
42). When one of the indices (CVHR or CEI) was above the
cutoff value (38 patients in total), the detection rate for
moderate-to-severe OSA was 81.6% (31 of 38). When both
indices were under the cutoff value (39 patients in total), only
33.3% (13 of 39) of the patients had moderate-to-severe OSA.
Overall, when CVHR or CEI was found to be above the cutoff
value under the Rooti Rx examination (80 patients in total),
moderate-to-severe OSA was diagnosed in 90% (72 of 80) of
the patients.
Figure 6B illustrates the clinical use of Rooti Rx in the
screening of severe OSA. In our study, when CVHR was more
than 21.9 and CEI was more than 11 (35 patients in total), the
detection rate for severe OSA was 97.1% (34 of 35). When one
of the indices (CVHR or CEI) was above the cutoff value
(25 patients in total), the detection rate for severe OSA was 60%
(15 of 25). When both indices were under the cutoff value
(59 patients in total), only 15.2% (9 of 59) of the patients had
severe OSA. Overall, when CVHR or CEI was found to be
above the cutoff value in the Rooti Rx examination (60 patients
The difference of AUCs between CEI and CVHR was 0.11 (95% CI:
0.009–0.21), with P=.032. AUC = area under the curve, CEI = chest effort in total), 81.6% (49 of 60) of the patients were diagnosed with
index, CI = confidence interval, CVHR = cyclic variation of heart rate. severe OSA.
Figure 7 presents signal waveforms of the parallel trace of F7
cyclical heart rate variations and the chest effort signals dur-
moderate-to-severe OSA (odds ratio [OR] = 1.80, 95% confi- ing apnea.
dence interval [CI]: 1.21–2.68 for CVHR; OR = 10.5, 95% CI:
3.81–28.92 for CEI). In addition, the CVHR was not associated
with higher risks of mild, moderate, and severe OSA, even DISCUSSION
though the CEI was the following: OR = 3.89, 95% CI: 1.47–
10.27. Nonetheless, both CVHR and CEI were significantly This study compared the diagnostic accuracy of detecting
associated with higher risks of severe OSA (OR = 4.14, 95% CI: chest wall motion and CVHR using a single-lead wireless ECG
2.16–7.92 for CVHR; OR = 12.72, 95% CI: 4.51–35.86 patch with a 3-axis accelerometer for the screening of OSA.
for CEI). Based on the survey on 119 patients who snore, a CVHR index
of >21.2 as the criterion to detect moderate-to-severe OSA
Detection performance of CVHR or CEI yielded only 52.9% sensitivity and 94.1% specificity. By
The performance of CVHR in detecting moderate-to-severe contrast, when CEI > 7.1 was used as the criterion, our chest
T3 OSA was satisfactory (Table 3), with an AUC of 0.76 (95% CI: wall motion detection algorithm identified moderate-to-severe
0.67–0.84). The optimal cutoff according to Youden index OSA with 80% sensitivity and 79.4% specificity, which out-
was >21.2 events/h, with a PPV of 85.7% and an NPV of 75%. performed the CVHR index. These observations indicate
By contrast, the performance of CEI in diagnosing moderate-to- that CVHR index and chest wall motion detection using a
severe OSA was significantly better than CVHR (Table 3), with single-lead wireless ECG patch with 3-axis accelerometer
an AUC of 0.87 (95% CI: 0.80–0.94). The optimal cutoff during sleep could be used as a screening tool for moderate-to-
was >7.1 events/h, with a PPV of 72.1% and an NPV of 85.6%. severe OSA.
F5 Figure 5 presents that the CEI significantly outperformed In our study, the measurements of CVHR and CEI were
CVHR with regard to discrimination ability of moderate-to- complementary to each other. When abnormal results were
severe OSA (ΔAUC = 0.11, 95% CI: 0.009–0.21, P = .032). revealed in this device (CEI > 7.1 or CVHR > 21.2), 90% of
However, the combination of the CVHR and CEI did not out- patients who snore were found to have moderate-to-severe
perform CEI alone in discriminating any type of OSA (mild, OSA. Notably, when CVHR was less than the cutoff value,
moderate, or severe OSA) or moderate-to-severe OSA (Table 3). 55.5% (40 of 72) of patients had moderate-to-severe OSA. This
Noticeably, the performance of discrimination ability of se- indicates that CEI evaluation may be necessary for screening
vere OSA was excellent in terms of AUC (AUC = 0.90, 95% CI: moderate-to-severe OSA in this wireless single-lead ECG patch
0.85–0.95) when combining these 2 signals. When using the with 3-axis accelerometer.
optimal cutoffs of both signals, the PPVs of moderate-to-severe This study has several strengths. 22 First, we conducted
OSA (91.6%) and severe OSA (96%) were very high (Table 3). a survey of all patients who snore with both the index

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Y-S Hsu, T-Y Chen, D Wu, et al. Screening of sleep apnea

Figure 6—Clinical use for diagnosis of (A) moderate-to-severe OSA and (B) severe OSA.

CEI = chest effort index, CVHR = cyclic variation of heart rate, OSA = obstructive sleep apnea.

test (CEI and CVHR index) and the reference standard in-laboratory PSG data were carefully reviewed by a second
(AHI by a standard overnight attended PSG). Second, be- sleep technologist, which improved the accuracy of the
cause the CEI, CVHR index, and AHI were simultaneously reference standard.
recorded, no time lag or treatment effect was observed Several previous studies have demonstrated a high performance
between the index test and the reference standard. Third, the of CVHR index in screening OSA both in the PhysioNet sleep

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Y-S Hsu, T-Y Chen, D Wu, et al. Screening of sleep apnea

Figure 7—Signal waveforms during apnea.

Note the response of SpO2 and heart rate falls a little behind air flow and chest effort in an apnea event. CEI = chest effort index, CVHR = cyclic variation
of heart rate, SpO2 = peripheral oxygen saturation.

apnea-ECG database (https://www.physionet.org/physiobank/ Second, their sample size was also smaller than ours. Third, their
database/apnea-ecg/)11–14,23 and in clinical settings.15,16,24–26 study cohort may not be fully representative of the general
Hayano et al16 reported 92% sensitivity and 96% specificity population with sleep apnea, because their cohort comprised
of automated ECG detection algorithms in identifying mod- 71.4% women and only 28.6% men. In our cohort, there were
erate-to-severe OSA among 165 adult male workers. Although only 19.3% women and 80.7% men, which was closer to the
the algorithms were the same as those used in this study, their general epidemiology of individuals with sleep-disordered
performance was much higher than that observed in our study. breathing.30,31 Moreover, the BMI of the patients in their
This difference may be attributed to the difference in the scoring study was higher than the BMI of patients in our study (average
systems used in the 2 studies. The scoring system for AHI BMI for both sexes was 33.9 kg/m2 in their study compared with
has changed extensively, especially in hypopneas.20,27 Many 27.2 kg/m2 in our group). The BMI of patients in our cohort was
studies have shown a higher AHI if updated 2012 AASM re- closer to that of the general population with sleep-disordered
spiratory event criteria were used.28,29 Hayano et al used AASM breathing.32 These differences in study design and patient de-
2007 scoring guidelines, and updated AASM 2017 scoring mographic data may account for the different results of the 2
guidelines were used in our study. This difference may have had studies. Notably, Magnusdottir et al also found that the sen-
a substantial impact on our result regarding sensitivity to CVHR. sitivity of cardiopulmonary coupling–CVHR dropped from
Although the difference in sensitivity and specificity between 100% to 89% when they changed scoring guidelines from 2007
CVHR and CEI for different respiratory event criteria should be and 2017, which proved that different scoring systems strongly
investigated further, it is beyond the scope of this study. affect the accuracy and screening ability of a single-lead ECG
Magnusdottir et al26 used cardiopulmonary coupling to im- test. In our study, detection of chest wall motion may have been
prove CVHR performance and reported 89% sensitivity and better than CVHR for identifying moderate-to-severe OSA with
79% specificity in identifying moderate-to-severe OSA by updated AASM respiratory event criteria.
cardiopulmonary coupling–CVHR algorithms among 47 pa- As this single-lead wireless ECG patch is very comfortable
tients. There are some differences between their study and ours. and could be easily hidden under clothes during the daytime,
First, cardiopulmonary coupling–CVHR was calculated using it is suitable for multiday examination. Analysis of mul-
heart rate variability and ECG-derived respiration. ECG- tiday data could lead to higher sensitivity and enable a more
Q:6 derived respiration referred to amplitude variations in the QRS accurate diagnosis. Sleep hygiene and circadian rhythm
complex because of shifts in the cardiac electrical axis during analysis could also be reviewed in this manner, and more
respiration and changes in thoracic impedance. It was not the information other than sleep apnea numbers could be provided
direct measurement of chest wall motion, as used in this study. to the patients.

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Y-S Hsu, T-Y Chen, D Wu, et al. Screening of sleep apnea

In primary care settings, screening and assessment for OSA still suggested for symptomatic patients who do not meet the
is a priority. Primary care providers need accurate screening cutoffs of this screening tool.
tools to predict the presence of OSA.33 Although the STOP-
Bang and Berlin questionnaires have the highest sensitivity
(97.7% for STOP-Bang and 95.5% for Berlin questionnaires),
CONCLUSIONS
not only is their specificity very low (3.7% for STOP-Bang and
7.4% for Berlin questionnaires) but so is their NPV (20% for Our study validated the effectiveness of screening for OSA
STOP-Bang and 20% for Berlin questionnaires).34 Moreover, using a patch-type device with ECG and 3-axis accelerometer.
the STOP-Bang and Berlin questionnaires do not perform very We also proposed a new method for the quantification of chest
well when excluding low-risk OSA.33 Our patch-type device wall motion, namely chest effort index, to identify moderate-to-
with an ECG and a 3-axis accelerometer could serve as a severe OSA, which outperformed CVHR index in our study.
supplemental screening tool to exclude low-risk OSA with A CVHR index ≥21.2 or CEI ≥ 7.1 after screening suggests
higher specificity and NPV in the diagnosis of moderate-severe moderate-to-severe OSA, and such patients should be re-
OSA (specificity for CVHR and CEI is 94.1% and 79.4%, re- ferred for further studies. Furthermore, compared with ques-
spectively, and NPV for CVHR and CEI is 74% and 82.1%, tionnaires, the device has higher specificity and NPV; therefore,
respectively). When using the optimal cutoffs of both signals, it could serve as a supplemental screening tool to exclude
the specificity and NPV for moderate-severe OSA were low-risk OSA.
also very satisfactory (specificity of 97.1% and NPV of
73.8%; Table 3).

Q:7 Limitations ABBREVIATIONS


This study has several limitations. First, patients with atrial
AASM, American Academy of Sleep Medicine
fibrillation, pacemaker implantation, ventricular tachycardia, or
AHI, apnea–hypopnea index
those who were pregnant were excluded because we could not
AUC, area under the curve
determine CVHR in these patients. Pregnant women were
BMI, body mass index
excluded because arrhythmias in pregnancy are common,
CEI, chest effort index
and analysis of CVHR is often difficult under excessive
CI, confidence interval
arrhythmias.35 Furthermore, CEI is difficult to interpret in
CVHR, cyclic variation of heart rate
women who are pregnant, particularly in the second and third
ECG, electrocardiogram
trimesters, given the effect of the gravid uterus on chest wall
+LR, positive likelihood ratio
motion. Further studies for these subgroups should be per-
−LR, negative likelihood ratio
formed to evaluate the use of chest wall motion in detecting
NPV, negative predicted value
OSA. Second, the influence of medical treatment for our pa-
OSA, obstructive sleep apnea
tients should be evaluated, although they were mostly healthy
PLM, periodic leg movement
other than the snoring habit. Third, several studies reported that
PPV, positive predicted value
automated ECG detection algorithms tend to overestimate AHI
PSG, polysomnography
in patients with central apnea and those with periodic leg
SHH, Shuang Ho Hospital
movements (PLMs).11–14,36 PLMs may overlap CVHR and
SKH, Shin Kong Wu Ho-Su Memorial Hospital
affect its accuracy. During PLM episodes, autonomic activa-
SpO2, peripheral oxygen saturation
tions and heart rate changes could occur, resulting in CVHR.37,38
PLM-related changes in CVHR are reported to have a briefer
duration and shorter cycle length than those of CVHR changes
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SUBMISSION & CORRESPONDENCE INFORMATION
22. Bossuyt PM, Reitsma JB, Bruns DE, et al. Towards complete and accurate Submitted for publication October 16, 2019
reporting of studies of diagnostic accuracy: the STARD initiative. BMJ. Submitted in final revised form March 25, 2020
2003;326(7379):41–44. Accepted for publication March 25, 2020
23. Hilmisson H, Lange N, Duntley SP. Sleep apnea detection: accuracy of using Address correspondence to: Wen-Te Liu, MD, 250 Wuxing St., Taipei 11031, Taiwan;
automated ECG analysis compared to manually scored polysomnography (apnea Tel: 886 2 2736 1661; Fax: 886 2 2739 1143; Email: b7801077@tmu.edu.tw
hypopnea index). Sleep Breath. 2019;23(1):125–133.
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Use of high-frequency peak in spectral analysis of heart rate increment to improve DISCLOSURE STATEMENT
screening of obstructive sleep apnoea. Sleep Breath. 2011;15(4):837–843.
25. Zamarrón C, Hornero R, del Campo F, Abásolo D, Alvarez D. Heart rate All authors have read and approved the manuscript. Work for this study was performed
regularity analysis obtained from pulse oximetric recordings in the diagnosis of at the Shin Kong Wu Ho-Su Memorial Hospital and Shuang Ho Hospital. This study
obstructive sleep apnea. Sleep Breath. 2006;10(2):83–89. was funded by grants from Shin Kong Wu-Ho-Su Memorial Hospital (2018SKHADR017)
26. Magnusdottir S, Hilmisson H. Ambulatory screening tool for sleep apnea: and Shuang Ho Hospital (106TMU-SHH-17). The funders had no role in the study Q:2
analyzing a single-lead electrocardiogram signal (ECG). Sleep Breath. design, data collection and analysis, decision to publish, or preparation of the
2018;22(2):421–429. manuscript. The authors report no conflicts of interest.

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