<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article PUBLIC "-//NLM//DTD Journal Publishing DTD v2.0 20040830//EN" "journalpublishing.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" dtd-version="2.0" xml:lang="en" article-type="research-article"><front><journal-meta><journal-id journal-id-type="nlm-ta">JMIR Cardio</journal-id><journal-id journal-id-type="publisher-id">cardio</journal-id><journal-id journal-id-type="index">26</journal-id><journal-title>JMIR Cardio</journal-title><abbrev-journal-title>JMIR Cardio</abbrev-journal-title><issn pub-type="epub">2561-1011</issn><publisher><publisher-name>JMIR Publications</publisher-name><publisher-loc>Toronto, Canada</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">v9i1e78075</article-id><article-id pub-id-type="doi">10.2196/78075</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Paper</subject></subj-group></article-categories><title-group><article-title>Photoplethysmography-Based Machine Learning Approaches for Atrial Fibrillation Burden: Algorithm Development and Validation</article-title></title-group><contrib-group><contrib contrib-type="author"><name name-style="western"><surname>Wang</surname><given-names>Hong</given-names></name><degrees>MM</degrees><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Liu</surname><given-names>Binbin</given-names></name><degrees>MM</degrees><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Zhang</surname><given-names>Hui</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Zhang</surname><given-names>Zheqi</given-names></name><degrees>MM</degrees><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Jin</surname><given-names>Zhigeng</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Wang</surname><given-names>Hao</given-names></name><degrees>Prof Dr</degrees><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author" corresp="yes"><name name-style="western"><surname>Guo</surname><given-names>Yu-Tao</given-names></name><degrees>Prof Dr</degrees><xref ref-type="aff" rid="aff1">1</xref></contrib></contrib-group><aff id="aff1"><institution>Department of Pulmonary Vessel and Thrombotic Disease, Sixth Medical Center, Chinese PLA General Hospital</institution><addr-line>6 Fucheng Road, Haidian District</addr-line><addr-line>Beijing</addr-line><country>China</country></aff><aff id="aff2"><institution>Graduate School of PLA General Hospital</institution><addr-line>Beijing</addr-line><country>China</country></aff><aff id="aff3"><institution>Department of Cardiology, Second Medical Centre, National Clinical Research Centre for Geriatric Diseases, Chinese PLA General Hospital</institution><addr-line>Beijing</addr-line><country>China</country></aff><contrib-group><contrib contrib-type="editor"><name name-style="western"><surname>Wong</surname><given-names>Kam Cheong</given-names></name></contrib></contrib-group><contrib-group><contrib contrib-type="reviewer"><name name-style="western"><surname>Lin</surname><given-names>Fan</given-names></name></contrib><contrib contrib-type="reviewer"><name name-style="western"><surname>Romiti</surname><given-names>Giulio</given-names></name></contrib><contrib contrib-type="reviewer"><name name-style="western"><surname>Lee</surname><given-names>Po-Tseng</given-names></name></contrib></contrib-group><author-notes><corresp>Correspondence to Yu-Tao Guo, Prof Dr, Department of Pulmonary Vessel and Thrombotic Disease, Sixth Medical Center, Chinese PLA General Hospital, 6 Fucheng Road, Haidian District, Beijing, 100048, China, +86-10-66957703; <email>dor_guoyt@hotmail.com</email></corresp></author-notes><pub-date pub-type="collection"><year>2025</year></pub-date><pub-date pub-type="epub"><day>10</day><month>11</month><year>2025</year></pub-date><volume>9</volume><elocation-id>e78075</elocation-id><history><date date-type="received"><day>26</day><month>05</month><year>2025</year></date><date date-type="rev-recd"><day>23</day><month>08</month><year>2025</year></date><date date-type="accepted"><day>04</day><month>09</month><year>2025</year></date></history><copyright-statement>&#x00A9; Hong Wang, Binbin Liu, Hui Zhang, Zheqi Zhang, Zhigeng Jin, Hao Wang, Yu-Tao Guo. Originally published in JMIR Cardio (<ext-link ext-link-type="uri" xlink:href="https://cardio.jmir.org">https://cardio.jmir.org</ext-link>), 10.11.2025. </copyright-statement><copyright-year>2025</copyright-year><license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/"><p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">https://creativecommons.org/licenses/by/4.0/</ext-link>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Cardio, is properly cited. The complete bibliographic information, a link to the original publication on <ext-link ext-link-type="uri" xlink:href="https://cardio.jmir.org">https://cardio.jmir.org</ext-link>, as well as this copyright and license information must be included.</p></license><self-uri xlink:type="simple" xlink:href="https://cardio.jmir.org/2025/1/e78075"/><abstract><sec><title>Background</title><p>Atrial fibrillation (AF) burden is associated with cardiovascular events such as stroke and heart failure. Recent advancements in photoplethysmography (PPG) technology have provided new insights into noninvasive and convenient AF burden detection.</p></sec><sec><title>Objective</title><p>This study aimed to establish an AF burden model based on smartwatch-monitored PPG technology to track the progression of AF.</p></sec><sec sec-type="methods"><title>Methods</title><p>This prospective pilot study (January 2024 to January 2025) at the Chinese PLA General Hospital enrolled patients with paroxysmal AF. Participants underwent simultaneous rhythm monitoring using smartwatch PPG and 24-hour Holter electrocardiogram monitoring (the gold standard). Five PPG-derived AF burden metrics were defined: (1) ratio of AF episode duration to total monitoring time (M1), (2) ratio of AF episode frequency to total measurements (M2), (3) AF episode density (M3), (4) AF episode variability (M4), and (5) proportion of rapid ventricular rate in AF episodes (&#x003E;120 beats per minute; M5). Smartwatch PPG signals were collected once per minute. Sensitivity, specificity, accuracy, precision, and <italic>F</italic><sub>1</sub> score were used to evaluate the PPG algorithm&#x2019;s AF detection capability through comparison with the gold standard (24-hour Holter monitoring). The mean absolute error (MAE) and Spearman rank correlation coefficient (<italic>r<sub>s</sub></italic>) were used to assess the correlation between the PPG-based AF burden metrics and the gold standard.</p></sec><sec sec-type="results"><title>Results</title><p>A total of 145 participants with paroxysmal AF (n=96, 66.2% male; mean age 63.28, SD 14.23 years) were included. Compared to the gold standard, the PPG-based AF burden model demonstrated a sensitivity of 91.5% (95% CI 87.9%-95.1%), specificity of 97.2% (95% CI 95.9%-98.5%), precision of 92.9% (95% CI 88.6%-97.3%), accuracy of 93.3% (95% CI 88.2%-98.5%), and <italic>F</italic><sub>1</sub> score of 90.5% (95% CI 86.3%-94.7%). The AF burden model exhibited strong discriminatory power in the test cohort (area under the curve=89.5%, 95% CI 89.4%&#x2010;89.7%). For M1, the MAE for the model of AF episode duration as a proportion of total monitoring time was 0.0400 (<italic>P</italic>=.008), with a correlation coefficient (<italic>r<sub>s</sub></italic>) of 0.8788 (<italic>P</italic>&#x003C;.001). For M4, the MAE for the AF episode variability model was 3.9967 (<italic>P</italic>&#x003C;.001), with a correlation coefficient (<italic>r<sub>s</sub></italic>) of 0.7876 (<italic>P</italic>&#x003C;.001). The MAE for the average real variability model was 4.6436 (<italic>P</italic>&#x003C;.001), with a correlation coefficient (<italic>r</italic><sub><italic>s</italic></sub>) of 0.8127 (<italic>P</italic>&#x003C;.001). The MAE for the average AF change model was 0.3893 (<italic>P</italic>=.27), with a correlation coefficient (<italic>r<sub>s</sub></italic>) of 0.7246 (<italic>P</italic>&#x003C;.001).</p></sec><sec sec-type="conclusions"><title>Conclusions</title><p>The PPG-based AF burden model demonstrated high concordance with the gold standard of 24-hour Holter monitoring in tracking AF episode duration and variability, providing new perspectives for exploring AF progression dynamics.</p></sec><sec><title>Trial Registration</title><p>Chinese Clinical Trial Registry ChiCTR2300075516; https://www.chictr.org.cn/showproj.html?proj=200976</p></sec></abstract><kwd-group><kwd>atrial fibrillation</kwd><kwd>photoplethysmography</kwd><kwd>atrial fibrillation burden</kwd><kwd>wearable devices</kwd><kwd>arrhythmia</kwd></kwd-group></article-meta></front><body><sec id="s1" sec-type="intro"><title>Introduction</title><p>Atrial fibrillation (AF) is one of the most common arrhythmias, associated with an increased risk of cardiovascular adverse events such as stroke and heart failure, and causes significant health, social, and economic burdens [<xref ref-type="bibr" rid="ref1">1</xref>]. Numerous studies have found a dose-response relationship between AF burden and cardiovascular event risk, making early assessment of AF burden critical to reduce AF complications [<xref ref-type="bibr" rid="ref2">2</xref>-<xref ref-type="bibr" rid="ref4">4</xref>]. However, there is currently no standardized definition for AF burden. It generally refers to the percentage of time spent in AF during total monitoring duration. Other studies have alternatively quantified the number of AF episodes by using episode density to define AF burden to explore the relationship between AF burden and cardiovascular adverse events [<xref ref-type="bibr" rid="ref2">2</xref>,<xref ref-type="bibr" rid="ref5">5</xref>].</p><p>Currently, devices for monitoring AF burden include cardiovascular implantable electronic devices and noninvasive rhythm recorders (such as 24-hour Holter electrocardiograms [ECGs]), both of which demonstrate high diagnostic accuracy. However, these devices face limitations, including requiring hospital-based monitoring under clinician supervision, high costs, and labor-intensive data interpretation by physicians. Recently, photoplethysmography (PPG) has been developed for AF screening and has shown promising accuracy [<xref ref-type="bibr" rid="ref6">6</xref>,<xref ref-type="bibr" rid="ref7">7</xref>]. PPG devices for AF screening are commercially available in various formats, including handheld devices, smartwatches, or wristbands. They use built-in optical sensors to monitor blood volume changes in skin capillary beds and estimate heart rhythm via reflected light wavelengths, offering greater comfort and convenience and providing potential opportunities for out-of-hospital ambulatory AF burden assessment [<xref ref-type="bibr" rid="ref8">8</xref>]. However, the accuracy of PPG-based AF burden detection algorithms in smartwatches remains uncertain [<xref ref-type="bibr" rid="ref9">9</xref>].</p><p>Our study aimed to evaluate the accuracy of smartwatch integrated PPG algorithms in assessing AF burden.</p></sec><sec id="s2" sec-type="methods"><title>Methods</title><sec id="s2-1"><title>Study Population</title><p>Between January 1, 2024, and January 1, 2025, consecutive patients diagnosed with paroxysmal AF were recruited from the Chinese PLA General Hospital. Inclusion criteria were patients aged &#x2265;18 years who provided written informed consent. Exclusion criteria were inability to use wearable devices, cognitive impairment, or presence of implanted cardiac devices (pacemakers or implantable cardioverter-defibrillators).</p></sec><sec id="s2-2"><title>Ethical Considerations</title><p>This study complied with the World Medical Association&#x2019;s Declaration of Helsinki and was approved by the Institutional Review Board of the Chinese People&#x2019;s Liberation Army General Hospital (HZKY-PJ-2023-23). It was also registered with the Chinese Clinical Trial Registry (ChiCTR2300075516). All participants signed the informed consent form before participating in this study. This study strictly adhered to privacy protection protocols in accordance with the Declaration of Helsinki. No financial compensation was provided to participants.</p></sec><sec id="s2-3"><title>Signal Acquisition and Processing</title><p>This study involved collecting baseline clinical data and PPG signals. Clinical data included demographics, comorbidities, and medications. PPG signals were obtained as follows: after attaching 24-hour Holter ECG electrodes, participants wore smartwatches (Huawei Watch GT2 Pro; Huawei Technologies Co., Ltd.). Simultaneous recordings of cardiac rhythm from both devices were initiated.</p></sec><sec id="s2-4"><title>Development and Optimization of the Primary PPG-Based AF Burden Model</title><p>The PPG-based AF burden algorithm was developed using 3698 PPG data segments from the previous Mobile Atrial Fibrillation Application (mAFA) study as the training and validation sets [<xref ref-type="bibr" rid="ref10">10</xref>]. Each data segment had a duration of 1 minute. The classification of the training data is shown in <xref ref-type="table" rid="table1">Table 1</xref>. The training data segments were each divided into varying durations (8, 16, 24, 32, 40, and 48 seconds) with random start times determined by a random number generator. During model development, we maintained a balanced representation of AF and non-AF episodes across all duration categories, enforced strict subject-level segregation to prevent any overlap between the training and validation datasets, and carefully preserved comparable AF to non-AF ratios in both sets. The raw PPG signal from the sensor module was processed using a bandpass Butterworth digital filter to eliminate low-frequency baseline drift and high-frequency noise, thereby obtaining clear and effective pulsatile PPG waveforms. To overcome limitations of single-time-AF detection algorithms, which exhibit low motion tolerance due to strict signal quality requirements and are inadequate for AF burden assessment, this study proposes a multiscale fusion AF burden detection algorithm featuring continuous PPG acquisition with minute-by-minute interpretation (defining AF burden as &#x003E;40% of AF beats per minute), high-quality signal extraction from motion corrupted segments, an adaptive length machine learning model for variable duration PPG signals, and context-aware fusion calibration leveraging AF episode continuity to refine single time predictions, thereby achieving accurate AF burden quantification. In this study, we enrolled 145 patients as a test cohort to validate the detection accuracy of the AF burden algorithm compared to 24-hour Holter monitoring.</p><table-wrap id="t1" position="float"><label>Table 1.</label><caption><p>The classification of the training data.</p></caption><table id="table1" frame="hsides" rules="groups"><thead><tr><td align="left" valign="bottom">Training data category</td><td align="left" valign="bottom">Record (1-minute segment)</td></tr></thead><tbody><tr><td align="left" valign="top">Atrial fibrillation</td><td align="left" valign="top">1090</td></tr><tr><td align="left" valign="top">Premature contraction</td><td align="left" valign="top">540</td></tr><tr><td align="left" valign="top">Sinus rhythm</td><td align="left" valign="top">2067</td></tr></tbody></table></table-wrap></sec><sec id="s2-5"><title>Definition of AF Burden</title><p>Metric M1 is the proportion of AF episode duration detected through PPG monitoring relative to the total monitoring time, quantifying temporal AF dynamics (<xref ref-type="fig" rid="figure1">Figure 1</xref>).</p><fig position="float" id="figure1"><label>Figure 1.</label><caption><p>A schematic diagram of metric M1. AF: atrial fibrillation; ECG: electrocardiogram; PPG: photoplethysmography; SR: sinus rhythm.</p></caption><graphic alt-version="no" mimetype="image" position="float" xlink:type="simple" xlink:href="cardio_v9i1e78075_fig01.png"/></fig><p>Metric M2 is the proportion of AF episodes detected through PPG monitoring relative to the total number of monitoring epochs, assessing frequency-based AF variations (<xref ref-type="fig" rid="figure2">Figure 2</xref>).</p><fig position="float" id="figure2"><label>Figure 2.</label><caption><p>A schematic diagram of metric M2. AF: atrial fibrillation; ECG: electrocardiogram; PPG: photoplethysmography; SR: sinus rhythm.</p></caption><graphic alt-version="no" mimetype="image" position="float" xlink:type="simple" xlink:href="cardio_v9i1e78075_fig02.png"/></fig><p>Metric M3 is the area between the actual AF burden progression curve (derived from PPG monitoring) and the theoretical uniform AF burden development curve, evaluating AF episode clustering (<xref ref-type="fig" rid="figure3">Figure 3</xref>).</p><fig position="float" id="figure3"><label>Figure 3.</label><caption><p>A schematic diagram of metric M3. AF: atrial fibrillation; ECG: electrocardiogram; PPG: photoplethysmography; SR: sinus rhythm.</p></caption><graphic alt-version="no" mimetype="image" position="float" xlink:type="simple" xlink:href="cardio_v9i1e78075_fig03.png"/></fig><p>Metric M4 is a composite metric integrating 3 variability parameters derived from PPG monitoring: AF episode variability (SD of hourly AF counts normalized by 24-hour mean AF frequency), mean real variability (average of SD and mean absolute deviation of hourly AF counts), and mean AF variation (day-night difference in AF counts normalized by overall mean AF frequency). This model quantifies hourly AF burden fluctuations (<xref ref-type="fig" rid="figure4">Figure 4</xref>).</p><fig position="float" id="figure4"><label>Figure 4.</label><caption><p>A schematic diagram of metric M4. AF: atrial fibrillation; ECG: electrocardiogram; PPG: photoplethysmography; SR: sinus rhythm.</p></caption><graphic alt-version="no" mimetype="image" position="float" xlink:type="simple" xlink:href="cardio_v9i1e78075_fig04.png"/></fig><p>Metric M5 quantifies rapid ventricular rate (RVR) AF episodes, defined as the proportion of AF episodes with heart rates of &#x003E;120 beats per minute (bpm) relative to total monitored AF episodes or the cumulative duration of RVR AF episodes relative to the total monitoring time. This dual parameter model enables characterizing high rate AF burden (<xref ref-type="fig" rid="figure5">Figure 5</xref> and <xref ref-type="fig" rid="figure6">Figure 6</xref>).</p><fig position="float" id="figure5"><label>Figure 5.</label><caption><p>A schematic diagram of metric M5. AF: atrial fibrillation; bpm: beats per minute; ECG: electrocardiogram; PPG: photoplethysmography; SR: sinus rhythm.</p></caption><graphic alt-version="no" mimetype="image" position="float" xlink:type="simple" xlink:href="cardio_v9i1e78075_fig05.png"/></fig><fig position="float" id="figure6"><label>Figure 6.</label><caption><p>A schematic diagram of metric M5. AF: atrial fibrillation; bpm: beats per minute; ECG: electrocardiogram; PPG: photoplethysmography; SR: sinus rhythm.</p></caption><graphic alt-version="no" mimetype="image" position="float" xlink:type="simple" xlink:href="cardio_v9i1e78075_fig06.png"/></fig></sec><sec id="s2-6"><title>Statistical Analysis</title><p>Data with a normal distribution were presented as means and SDs. Data with a nonnormal distribution were presented as medians and IQRs and were analyzed using the Mann-Whitney <italic>U</italic> test. Categorical variables were expressed as percentages. Algorithm performance (sensitivity, specificity, accuracy, precision, <italic>F</italic><sub>1</sub> score, and area under the receiver operating characteristic curve) was validated against Holter ECG values to assess its capability for continuous AF detection. Correlation between the PPG-based AF burden model and 24-hour Holter ECG monitoring was assessed using the mean absolute error (MAE) and Spearman rank correlation coefficient (<italic>r<sub>s</sub></italic>; <xref ref-type="table" rid="table2">Table 2</xref>)</p><table-wrap id="t2" position="float"><label>Table 2.</label><caption><p>Clinical significance of each metric.</p></caption><table id="table2" frame="hsides" rules="groups"><thead><tr><td align="left" valign="bottom">Performance metric</td><td align="left" valign="bottom">Formula</td><td align="left" valign="bottom">Clinical significance</td></tr></thead><tbody><tr><td align="left" valign="top">Sensitivity</td><td align="left" valign="top">TP<sup><xref ref-type="table-fn" rid="table2fn1">a</xref></sup>/(TP + FN<sup><xref ref-type="table-fn" rid="table2fn2">b</xref></sup>)</td><td align="left" valign="top">Proportion of actual positive cases correctly identified</td></tr><tr><td align="left" valign="top">Specificity</td><td align="left" valign="top">TN<sup><xref ref-type="table-fn" rid="table2fn3">c</xref></sup>/(TN + FP<sup><xref ref-type="table-fn" rid="table2fn4">d</xref></sup>)</td><td align="left" valign="top">Proportion of actual negative cases correctly excluded</td></tr><tr><td align="left" valign="top">Accuracy</td><td align="left" valign="top">(TP + TN)/(TP + FP + FN + TN)</td><td align="left" valign="top">Proportion of correctly classified cases</td></tr><tr><td align="left" valign="top">Precision</td><td align="left" valign="top">TP/(TP + FP)</td><td align="left" valign="top">Proportion of TPs among all positive test results</td></tr><tr><td align="left" valign="top"><italic>F</italic><sub>1</sub>-score</td><td align="left" valign="top">2 &#x00D7; TP/(2 &#x00D7; TP + FP + FN)</td><td align="left" valign="top">Balances FNs and FPs when their clinical consequences are comparable</td></tr><tr><td align="left" valign="top">AUC-ROC<sup><xref ref-type="table-fn" rid="table2fn5">e</xref></sup></td><td align="left" valign="top">&#x2014;<sup><xref ref-type="table-fn" rid="table2fn6">f</xref></sup></td><td align="left" valign="top">Overall discriminative ability across all thresholds (0.9=excellent; 0.7&#x2010;0.9=moderate)</td></tr><tr><td align="left" valign="top">MAE<sup><xref ref-type="table-fn" rid="table2fn7">g</xref></sup></td><td align="left" valign="top"><inline-formula><mml:math id="ieqn1"><mml:mfrac><mml:mrow><mml:mrow><mml:munderover><mml:mo stretchy="false">&#x2211;</mml:mo><mml:mrow><mml:mi>i</mml:mi><mml:mo>=</mml:mo><mml:mn>1</mml:mn></mml:mrow><mml:mrow><mml:mi>n</mml:mi></mml:mrow></mml:munderover><mml:mrow><mml:mo>|</mml:mo><mml:msub><mml:mrow><mml:mi>p</mml:mi></mml:mrow><mml:mrow><mml:mi>i</mml:mi></mml:mrow></mml:msub><mml:mo>&#x2212;</mml:mo><mml:msub><mml:mrow><mml:mi>g</mml:mi></mml:mrow><mml:mrow><mml:mi>i</mml:mi></mml:mrow></mml:msub><mml:mo>|</mml:mo></mml:mrow></mml:mrow></mml:mrow><mml:mrow><mml:mi mathvariant="normal">n</mml:mi></mml:mrow></mml:mfrac></mml:math></inline-formula>,<inline-formula><mml:math id="ieqn2"><mml:msub><mml:mrow><mml:mi>p</mml:mi></mml:mrow><mml:mrow><mml:mi>i</mml:mi></mml:mrow></mml:msub><mml:mo>:</mml:mo><mml:mi>P</mml:mi><mml:mi>P</mml:mi><mml:mi>G</mml:mi><mml:mi> </mml:mi><mml:mi> </mml:mi><mml:msub><mml:mrow><mml:mi>g</mml:mi></mml:mrow><mml:mrow><mml:mi>i</mml:mi></mml:mrow></mml:msub><mml:mo>:</mml:mo><mml:mi>E</mml:mi><mml:mi>C</mml:mi><mml:mi>G</mml:mi></mml:math></inline-formula></td><td align="left" valign="top">Quantifies the average prediction error; smaller MAE indicates higher clinical utility for risk stratification or treatment timing</td></tr><tr><td align="left" valign="top"><italic>r<sub>s</sub></italic><sup><xref ref-type="table-fn" rid="table2fn8">h</xref></sup></td><td align="left" valign="top">&#x2014;f</td><td align="left" valign="top">Measures monotonic association; high <italic>r</italic><sub><italic>s</italic></sub> (<italic>r</italic><sub><italic>s</italic></sub>&#x003E;0.6) suggests that the model captures clinically relevant trends, even if they are nonlinear</td></tr></tbody></table><table-wrap-foot><fn id="table2fn1"><p><sup>a</sup>TP: true positive.</p></fn><fn id="table2fn2"><p><sup>b</sup>FN: false negative.</p></fn><fn id="table2fn3"><p><sup>c</sup>TN: true negative.</p></fn><fn id="table2fn4"><p><sup>d</sup>FP: false positive.</p></fn><fn id="table2fn5"><p><sup>e</sup>AUC-ROC: area under the receiver operating characteristic curve.</p></fn><fn id="table2fn6"><p><sup>f</sup>Not applicable.</p></fn><fn id="table2fn7"><p><sup>g</sup>MAE: mean absolute error.</p></fn><fn id="table2fn8"><p><sup>h</sup><italic>r<sub>s</sub></italic>: Spearman rank correlation coefficient.</p></fn></table-wrap-foot></table-wrap><p>A 2-sided <italic>P</italic> value of &#x003C;.05 was considered statistically significant. The 95% CIs were calculated using the Wilson score method without continuity correction. Analyses were conducted using SPSS Statistics (version 22; IBM Corp) and OpenEpi (version 3.01).</p></sec></sec><sec id="s3" sec-type="results"><title>Results</title><sec id="s3-1"><title>Overview</title><p>From January 1, 2024, to January 1, 2025, a total of 148 participants were initially enrolled in the study. Of these 148 participants, after excluding 2 (1.4%) with atrial flutter and 1 (0.7%) with atrioventricular block, 145 (98%) were ultimately included in the final analysis (n=96, 66.2% male; mean age 63.28, SD 14.23; range 19 to 90 years). On the basis of expert-reviewed 24-hour Holter ECG monitoring, 75 patients exhibited AF episodes during the monitoring period, including 35 (47%) cases of paroxysmal AF and 40 (53%) cases of persistent AF lasting 24 hours (<xref ref-type="fig" rid="figure7">Figure 7</xref>).</p><fig position="float" id="figure7"><label>Figure 7.</label><caption><p>A flowchart of the study. AF: atrial fibrillation; ECG: electrocardiogram; PPG: photoplethysmography; SR: sinus rhythm.</p></caption><graphic alt-version="no" mimetype="image" position="float" xlink:type="simple" xlink:href="cardio_v9i1e78075_fig07.png"/></fig></sec><sec id="s3-2"><title>Baseline Characteristics</title><p>The study population comprised patients with paroxysmal AF with a mean age of 63.28 (SD 14.23) years, including 66.2% (96/145) male individuals. Baseline characteristics are detailed in <xref ref-type="table" rid="table3">Table 3</xref>.</p><table-wrap id="t3" position="float"><label>Table 3.</label><caption><p>Baseline characteristics of the participants (N=145).</p></caption><table id="table3" frame="hsides" rules="groups"><thead><tr><td align="left" valign="bottom">Characteristic</td><td align="left" valign="bottom">Values</td></tr></thead><tbody><tr><td align="left" valign="top" colspan="2">Demographics</td></tr><tr><td align="left" valign="top">&#x2003;Age (y), mean (SD)</td><td align="left" valign="top">63.28 (14.23)</td></tr><tr><td align="left" valign="top">&#x2003;Male sex, n (%)</td><td align="left" valign="top">96 (66.2)</td></tr><tr><td align="left" valign="top" colspan="2">Medical history, n (%)</td></tr><tr><td align="left" valign="top">&#x2003;Coronary artery disease</td><td align="left" valign="top">31 (21.4)</td></tr><tr><td align="left" valign="top">&#x2003;Heart failure</td><td align="left" valign="top">4 (2.8)</td></tr><tr><td align="left" valign="top">&#x2003;Hypertension</td><td align="left" valign="top">75 (51.7)</td></tr><tr><td align="left" valign="top">&#x2003;Hyperlipidemia</td><td align="left" valign="top">66 (45.5)</td></tr><tr><td align="left" valign="top">&#x2003;Diabetes mellitus</td><td align="left" valign="top">31 (21.4)</td></tr><tr><td align="left" valign="top">&#x2003;Previous stroke, SE<sup><xref ref-type="table-fn" rid="table3fn1">a</xref></sup>, or TIA<sup><xref ref-type="table-fn" rid="table3fn2">b</xref></sup></td><td align="left" valign="top">3 (2.1)</td></tr><tr><td align="left" valign="top">&#x2003;Vascular disease</td><td align="left" valign="top">47 (32.4)</td></tr><tr><td align="left" valign="top">&#x2003;Renal dysfunction</td><td align="left" valign="top">7 (4.8)</td></tr><tr><td align="left" valign="top">&#x2003;COPD<sup><xref ref-type="table-fn" rid="table3fn3">c</xref></sup></td><td align="left" valign="top">9 (6.2)</td></tr><tr><td align="left" valign="top">&#x2003;Hyperthyroidism</td><td align="left" valign="top">3 (2.1)</td></tr><tr><td align="left" valign="top">&#x2003;OSA<sup><xref ref-type="table-fn" rid="table3fn4">d</xref></sup></td><td align="left" valign="top">15 (10.3)</td></tr><tr><td align="left" valign="top" colspan="2">Anticoagulants, n (%)</td></tr><tr><td align="left" valign="top">&#x2003;Warfarin</td><td align="left" valign="top">2 (1.4)</td></tr><tr><td align="left" valign="top">&#x2003;Dabigatran</td><td align="left" valign="top">14 (9.7)</td></tr><tr><td align="left" valign="top">&#x2003;Rivaroxaban</td><td align="left" valign="top">21 (14.5)</td></tr><tr><td align="left" valign="top">&#x2003;Apixaban</td><td align="left" valign="top">3 (2.1)</td></tr><tr><td align="left" valign="top">&#x2003;Edoxaban</td><td align="left" valign="top">24 (16.6)</td></tr><tr><td align="left" valign="top">&#x2003;Low&#x2013;molecular weight heparin</td><td align="left" valign="top">3 (2.1)</td></tr><tr><td align="left" valign="top" colspan="2">Antiarrhythmic drugs, n (%)</td></tr><tr><td align="left" valign="top">&#x2003;Propafenone</td><td align="left" valign="top">28 (19.3)</td></tr><tr><td align="left" valign="top">&#x2003;Amiodarone</td><td align="left" valign="top">16 (11.0)</td></tr><tr><td align="left" valign="top">&#x2003;Dronedarone</td><td align="left" valign="top">7 (4.8)</td></tr><tr><td align="left" valign="top">&#x2003;Bisoprolol</td><td align="left" valign="top">17 (11.7)</td></tr><tr><td align="left" valign="top">&#x2003;Metoprolol</td><td align="left" valign="top">39 (26.9)</td></tr></tbody></table><table-wrap-foot><fn id="table3fn1"><p><sup>a</sup>SE: systemic arterial embolism.</p></fn><fn id="table3fn2"><p><sup>b</sup>TIA: transient ischemic attack.</p></fn><fn id="table3fn3"><p><sup>c</sup>COPD: chronic obstructive pulmonary disease.</p></fn><fn id="table3fn4"><p><sup>d</sup>OSA: obstructive sleep apnea.</p></fn></table-wrap-foot></table-wrap><p>The AF burden algorithm demonstrated high performance, with a daily model output rate of 86.6% (95% CI 85.2%-88%). The confusion matrix yielded true positive, false negative, false positive, and true negative counts for PPG signals of 106,975, 11,941, 8787, and 308,082, respectively. Compared to the gold standard, the PPG-based AF burden model demonstrated a sensitivity of 91.5% (95% CI 87.9%-95.1%), specificity of 97.2% (95% CI 95.9%-98.5%), precision of 92.9% (95% CI 88.6%-97.3%), accuracy of 93.3% (95% CI 88.2%-98.5%), and <italic>F</italic><sub>1</sub>-score of 90.5% (95% CI 86.3%-94.7%). The AF burden model exhibited strong discriminatory power in the test cohort (area under the curve=89.5%, 95% CI 89.4%-89.7%; <xref ref-type="table" rid="table4">Table 4</xref>). The receiver operating characteristic curve is shown in <xref ref-type="fig" rid="figure8">Figure 8</xref>. The performance metrics of the PPG-based AF burden model across varying threshold values are shown in <xref ref-type="table" rid="table5">Table 5</xref>.</p><p><xref ref-type="fig" rid="figure9">Figure 9</xref> shows the strong concordance between the PPG and Holter ECG waveforms.</p><table-wrap id="t4" position="float"><label>Table 4.</label><caption><p>The performance metrics of the photoplethysmography-based atrial fibrillation burden model.</p></caption><table id="table4" frame="hsides" rules="groups"><thead><tr><td align="left" valign="bottom">Performance metric</td><td align="left" valign="bottom">Performance (%; 95% CI)</td></tr></thead><tbody><tr><td align="left" valign="top">Sensitivity</td><td align="left" valign="top">90.0 (87.9&#x2010;95.1)</td></tr><tr><td align="left" valign="top">Specificity</td><td align="left" valign="top">97.2 (95.9&#x2010;98.5)</td></tr><tr><td align="left" valign="top">Precision</td><td align="left" valign="top">92.9 (88.6&#x2010;97.3)</td></tr><tr><td align="left" valign="top">Accuracy</td><td align="left" valign="top">93.3 (88.2&#x2010;98.5)</td></tr><tr><td align="left" valign="top"><italic>F</italic><sub>1</sub>-score</td><td align="left" valign="top">90.5 (86.3&#x2010;94.7)</td></tr><tr><td align="left" valign="top">AUC<sup><xref ref-type="table-fn" rid="table4fn1">a</xref></sup></td><td align="left" valign="top">89.5 (89.4&#x2010;89.7)</td></tr></tbody></table><table-wrap-foot><fn id="table4fn1"><p><sup>a</sup>AUC: area under the receiver operating characteristic curve.</p></fn></table-wrap-foot></table-wrap><fig position="float" id="figure8"><label>Figure 8.</label><caption><p>Receiver operating characteristic curves for photoplethysmography&#x2013;based atrial fibrillation burden model. AUC: area under the curve; ROC: receiver operating characteristic.</p></caption><graphic alt-version="no" mimetype="image" position="float" xlink:type="simple" xlink:href="cardio_v9i1e78075_fig08.png"/></fig><table-wrap id="t5" position="float"><label>Table 5.</label><caption><p>The performance metrics of the photoplethysmography-based atrial fibrillation burden model across varying threshold values.</p></caption><table id="table5" frame="hsides" rules="groups"><thead><tr><td align="left" valign="bottom">Cutoff point for AF burden threshold</td><td align="left" valign="bottom">Accuracy</td><td align="left" valign="bottom">Precision</td><td align="left" valign="bottom">Sensitivity</td><td align="left" valign="bottom">Specificity</td><td align="left" valign="bottom"><italic>F</italic><sub>1</sub> score</td></tr></thead><tbody><tr><td align="left" valign="top">40%</td><td align="left" valign="top">0.91</td><td align="left" valign="top">0.85</td><td align="left" valign="top">0.84</td><td align="left" valign="top">0.94</td><td align="left" valign="top">0.84</td></tr><tr><td align="left" valign="top">45%</td><td align="left" valign="top">0.92</td><td align="left" valign="top">0.85</td><td align="left" valign="top">0.84</td><td align="left" valign="top">0.94</td><td align="left" valign="top">0.85</td></tr><tr><td align="left" valign="top">50%</td><td align="left" valign="top">0.92</td><td align="left" valign="top">0.84</td><td align="left" valign="top">0.85</td><td align="left" valign="top">0.94</td><td align="left" valign="top">0.85</td></tr><tr><td align="left" valign="top">55%</td><td align="left" valign="top">0.92</td><td align="left" valign="top">0.84</td><td align="left" valign="top">0.86</td><td align="left" valign="top">0.94</td><td align="left" valign="top">0.85</td></tr><tr><td align="left" valign="top">60%</td><td align="left" valign="top">0.92</td><td align="left" valign="top">0.83</td><td align="left" valign="top">0.87</td><td align="left" valign="top">0.94</td><td align="left" valign="top">0.85</td></tr><tr><td align="left" valign="top">65%</td><td align="left" valign="top">0.92</td><td align="left" valign="top">0.83</td><td align="left" valign="top">0.87</td><td align="left" valign="top">0.94</td><td align="left" valign="top">0.85</td></tr><tr><td align="left" valign="top">70%</td><td align="left" valign="top">0.92</td><td align="left" valign="top">0.82</td><td align="left" valign="top">0.88</td><td align="left" valign="top">0.93</td><td align="left" valign="top">0.85</td></tr></tbody></table></table-wrap><fig position="float" id="figure9"><label>Figure 9.</label><caption><p>Representative pulse waveform recording from a patient. AF: atrial fibrillation; PPG: photoplethysmography; SR: sinus rhythm.</p></caption><graphic alt-version="no" mimetype="image" position="float" xlink:type="simple" xlink:href="cardio_v9i1e78075_fig09.png"/></fig></sec><sec id="s3-3"><title>Evaluation of AF Burden Quantification Performance by the AF Burden Model</title><sec id="s3-3-1"><title>Metric M1 Evaluation</title><p>For the ratio of AF duration to the total monitoring time, the PPG median was 0.0402 (IQR 0.0086&#x2010;0.8671) versus 0.0020 (IQR 0.0086&#x2010;0.8671) for 24-hour Holter monitoring, with model performance metrics of MAE=0.0400 (<italic>P</italic>=.008) and <italic>r<sub>s</sub></italic>=0.8788 (<italic>P</italic>&#x003C;.001; <xref ref-type="fig" rid="figure10">Figure 10</xref>A). For the ratio of AF episodes of &#x003E;6 minutes to the total monitoring time, the PPG median was 0.0093 (IQR 0.0000&#x2010;0.7330) versus 0.0000 (IQR 0.0000&#x2010;1.0000) for 24-hour Holter monitoring, with model performance metrics of MAE=0.0582 (<italic>P</italic>=.44) and <italic>r<sub>s</sub></italic>=0.9233 (<italic>P</italic>&#x003C;.001; <xref ref-type="fig" rid="figure10">Figure 10</xref>B). Regarding the ratio of AF episodes of &#x003E;1 hour to the total monitoring time, the PPG median was 0.0000 (IQR 0.0000&#x2010;0.2947) versus 0.0000 (IQR 0.0000&#x2010;1.0000) for 24-hour Holter monitoring, with model performance of MAE=0.1204 (<italic>P</italic>=.04) and <italic>r<sub>s</sub></italic>=0.9293 (<italic>P</italic>&#x003C;.001; <xref ref-type="fig" rid="figure10">Figure 10</xref>C).</p><fig position="float" id="figure10"><label>Figure 10.</label><caption><p>Scatter plot and regression line of AF burden estimated by PPG compared to AF burden estimated by ECG. Each dot represents the AF burden by each method for each patient with AF. Dashed line is the regression line. Solid gray line is line of equality. AF: atrial fibrillation; ECG: electrocardiogram; PPG: photoplethysmography.</p></caption><graphic alt-version="no" mimetype="image" position="float" xlink:type="simple" xlink:href="cardio_v9i1e78075_fig10.png"/></fig></sec><sec id="s3-3-2"><title>Metric M2 Evaluation</title><p>The ratio of AF episodes to the total measurements showed a PPG median of 0.0033 (IQR 0.0009&#x2010;0.0056) versus 0.0001 (IQR 0.0000&#x2010;0.0008) for 24-hour Holter monitoring, with model performance metrics of MAE=0.0320 (<italic>P</italic>&#x003C;.001) and <italic>r<sub>s</sub></italic>=&#x2013;0.0807 (<italic>P</italic>=.33) compared to the gold standard. For the ratio of AF episodes of &#x003E;6 minutes to the total measurements, the PPG median was 0.0010 (IQR 0.0007&#x2010;0.0028) versus 0.0000 (IQR 0.0000&#x2010;0.0007) for 24-hour Holter monitoring, with model performance metrics of MAE=0.0015 (<italic>P</italic>&#x003C;.001) and <italic>r<sub>s</sub></italic>=0.2360 (<italic>P</italic>=.004). Regarding the ratio of AF episodes of &#x003E;1 hour to the total measurements, the PPG median was 0.0004 (IQR 0.0000&#x2010;0.0009) versus 0.0000 (IQR 0.0000&#x2010;0.0007) for 24-hour Holter monitoring, with model performance of MAE=0.0005 (<italic>P</italic>&#x003C;.001) and <italic>r<sub>s</sub></italic>=0.7092 (<italic>P</italic>&#x003C;.001; <xref ref-type="fig" rid="figure11">Figure 11</xref>).</p><fig position="float" id="figure11"><label>Figure 11.</label><caption><p>Scatter plot and regression line of AF burden estimated by PPG compared to AF burden estimated by ECG. Each dot represents the AF burden by each method for each patient with AF. Dashed line is the regression line. Solid gray line is line of equality. AF: atrial fibrillation; ECG: electrocardiogram; PPG: photoplethysmography.</p></caption><graphic alt-version="no" mimetype="image" position="float" xlink:type="simple" xlink:href="cardio_v9i1e78075_fig11.png"/></fig></sec><sec id="s3-3-3"><title>Metric M3 Evaluation</title><p>The PPG-derived AF density showed a median of 0.2700 (IQR 0.1700-0.4725) compared to 0.0000 (IQR 0.0000-0.5900) for 24-hour Holter monitoring. When validated against the gold standard, the model demonstrated an MAE of 0.1725 (<italic>P&#x003C;</italic>.001) with an <italic>r<sub>s</sub></italic> of 0.6576 (<italic>P</italic>&#x003C;.001; <xref ref-type="fig" rid="figure12">Figure 12</xref>)</p><fig position="float" id="figure12"><label>Figure 12.</label><caption><p>Scatter plot and regression line of AF burden estimated by PPG compared to AF burden estimated by ECG. Each dot represents the AF burden by each method for each patient with AF. Dashed line is the regression line. Solid gray line is line of equality. AF: atrial fibrillation; ECG: electrocardiogram; PPG: photoplethysmography.</p></caption><graphic alt-version="no" mimetype="image" position="float" xlink:type="simple" xlink:href="cardio_v9i1e78075_fig12.png"/></fig></sec><sec id="s3-3-4"><title>Metric M4 Evaluation</title><p>The SD of hourly AF episodes measured through PPG showed a median of 5.3229 (IQR 1.0375-15.9058) versus 0.4390 (IQR 0.0000-12.8558) for Holter monitoring, with MAE=5.6009 (<italic>P</italic>&#x003C;.001) and <italic>r<sub>s</sub></italic>=0.8135 (<italic>P</italic>&#x003C;.001; <xref ref-type="fig" rid="figure13">Figure 13</xref>A). AF variability assessment revealed a median PPG value of 3.3478 (IQR 0.6957-9.2174) compared to 0.1739 (IQR 0.0000-5.2174) for 24-hour Holter monitoring, with MAE=3.9967 (<italic>P</italic>&#x003C;.001) and <italic>r<sub>s</sub></italic>=0.7876 (<italic>P</italic>&#x003C;.001; <xref ref-type="fig" rid="figure13">Figure 13</xref>B). Daytime (6 AM-10 PM) variability showed a median PPG value of 3.6000 (IQR 0.8667-11.4667) versus 0.0000 (IQR 0.0000-5.600) for 24-hour Holter monitoring, with MAE=4.8425 (<italic>P</italic>&#x003C;.001) and <italic>r<sub>s</sub></italic>=0.7659 (<italic>P</italic>&#x003C;.001; <xref ref-type="fig" rid="figure13">Figure 13</xref>C), whereas nighttime (10 PM-6 AM) variability showed a median PPG value of 1.000 (IQR 0.0000-6.0000) versus 0.0000 (IQR 0.0000-0.2857) for 24-hour Holter monitoring, with MAE=2.6171 (<italic>P</italic>&#x003C;.001) and <italic>r<sub>s</sub></italic>=0.6712 (<italic>P</italic>&#x003C;.001; <xref ref-type="fig" rid="figure13">Figure 13</xref>D). Mean real variability measurements yielded a median value of 4.5282 (IQR 0.9031-12.4119) for PPG versus 0.3499 (IQR 0.0000-8.9325) for 24-hour Holter monitoring, with MAE=4.6436 (<italic>P</italic>&#x003C;.001) and <italic>r<sub>s</sub></italic>=0.8127 (<italic>P</italic>&#x003C;.001; <xref ref-type="fig" rid="figure13">Figure 13</xref>E). Mean AF variation assessment yielded a median PPG value of 0.0466 (IQR &#x2013;0.2987 to 1.3361) versus &#x2013;0.0142 (IQR &#x2013;0.1249 to 0.0654) for 24-hour Holter monitoring, with MAE=0.3893 (<italic>P</italic>=.27) and <italic>r<sub>s</sub></italic>=0.7246 (<italic>P</italic>&#x003C;.001; <xref ref-type="fig" rid="figure13">Figure 13</xref>F).</p><fig position="float" id="figure13"><label>Figure 13.</label><caption><p>Scatter plot and regression line of AF burden estimated by PPG compared to AF burden estimated by ECG. Each dot represents the AF burden by each method for each patient with AF. Dashed line is the regression line. Solid gray line is line of equality. AF: atrial fibrillation; ECG: electrocardiogram; PPG: photoplethysmography. VOM: variation of the mean (VOM=[&#x2223;average AF episode at day&#x2212;average AF episodes at night&#x2223;/average 24-h AF episodes] &#x00D7;100%).</p></caption><graphic alt-version="no" mimetype="image" position="float" xlink:type="simple" xlink:href="cardio_v9i1e78075_fig13.png"/></fig></sec><sec id="s3-3-5"><title>Metric M5 Evaluation</title><p>For the proportion of AF episodes with a ventricular rate of &#x003E;120 bpm to total monitored episodes, PPG measurements showed a median of 0.0007 (IQR 0.0007-0.0027) compared to 0.0000 (IQR 0.0000-0.0070) for 24-hour Holter monitoring, with model performance metrics of MAE=0.0151 (<italic>P</italic>=.76) and <italic>r<sub>s</sub></italic>=0.3435 (<italic>P</italic>&#x003C;.001). Similarly, for the proportion of time in AF with a ventricular rate of &#x003E;120 bpm to total monitoring time, the median PPG value was 0.0007 (IQR 0.0007-0.0027) versus 0.0000 (IQR 0.0000-0.0070) for 24-hour Holter monitoring, yielding an identical model performance (MAE=0.0151 and <italic>P</italic>=.76; <italic>r<sub>s</sub></italic>=0.3435 and <italic>P</italic>&#x003C;.001). <xref ref-type="table" rid="table6">Table 6</xref> summarizes the quantification performance of the AF burden model.</p><table-wrap id="t6" position="float"><label>Table 6.</label><caption><p>Photoplethysmography (PPG)&#x2013;monitored atrial fibrillation (AF) progression features compared to 24-hour electrocardiogram (ECG) monitoring (N=145).</p></caption><table id="table6" frame="hsides" rules="groups"><thead><tr><td align="left" valign="bottom"/><td align="left" valign="bottom">PPG, median (IQR)</td><td align="left" valign="bottom">ECG, median (IQR)</td><td align="left" valign="bottom">MAE<sup><xref ref-type="table-fn" rid="table6fn1">a</xref></sup></td><td align="left" valign="bottom"><italic>P</italic> value</td><td align="left" valign="bottom"><italic>r</italic><sub><italic>s</italic></sub><sup><xref ref-type="table-fn" rid="table6fn2">b</xref></sup></td><td align="left" valign="bottom"><italic>P</italic> value</td></tr></thead><tbody><tr><td align="left" valign="top" colspan="7">Duration feature</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Ratio of AF duration to total monitoring time (%)</td><td align="left" valign="top">0.0402 (0.0086 to 0.8671)</td><td align="left" valign="top">0.0020 (0.0086 to 0.8671)</td><td align="left" valign="top">0.0400</td><td align="left" valign="top">.008</td><td align="left" valign="top">0.8788</td><td align="left" valign="top">&#x003C;.001</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Ratio of AF episodes lasting over 6 min to total monitoring time (%)</td><td align="left" valign="top">0.0093 (0.0000 to 0.7330)</td><td align="left" valign="top">0.0000 (0.0000 to 1.0000)</td><td align="left" valign="top">0.0582</td><td align="left" valign="top">.44</td><td align="left" valign="top">0.9223</td><td align="left" valign="top">&#x003C;.001</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Ratio of AF episodes lasting over 1 h to total monitoring time (%)</td><td align="left" valign="top">0.0000 (0.0000 to 0.2947)</td><td align="left" valign="top">0.0000 (0.0000 to 1.0000)</td><td align="left" valign="top">0.1204</td><td align="left" valign="top">.04</td><td align="left" valign="top">0.9293</td><td align="left" valign="top">&#x003C;.001</td></tr><tr><td align="left" valign="top" colspan="7">Number feature</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Ratio of AF episodes to total measurements (%)</td><td align="left" valign="top">0.0033 (0.0009 to 0.0056)</td><td align="left" valign="top">0.0001 (0.0000 to 0.0008)</td><td align="left" valign="top">0.0032</td><td align="left" valign="top">&#x003C;.001</td><td align="left" valign="top">&#x2013;0.0807</td><td align="left" valign="top">.33</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Ratio of AF episodes lasting over 6 min to total measurements (%)</td><td align="left" valign="top">0.0010 (0.0007 to 0.0028)</td><td align="left" valign="top">0.0000 (0.0000 to 0.0007)</td><td align="left" valign="top">0.0015</td><td align="left" valign="top">&#x003C;.001</td><td align="left" valign="top">0.2360</td><td align="left" valign="top">.004</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Ratio of AF episodes lasting over 1 h to total measurements (%)</td><td align="left" valign="top">0.0004 (0.0000 to 0.0009)</td><td align="left" valign="top">0.0000 (0.0000 to 0.0007)</td><td align="left" valign="top">0.0005</td><td align="left" valign="top">&#x003C;.001</td><td align="left" valign="top">0.7092</td><td align="left" valign="top">&#x003C;.001</td></tr><tr><td align="left" valign="top" colspan="7">Aggregation feature</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>AF density</td><td align="left" valign="top">0.2700 (0.1700 to 0.4725)</td><td align="left" valign="top">0.0000 (0.0000 to 0.5900)</td><td align="left" valign="top">0.1725</td><td align="left" valign="top">.13</td><td align="left" valign="top">0.6576</td><td align="left" valign="top">&#x003C;.001</td></tr><tr><td align="left" valign="top" colspan="7">Circadian rhythm feature</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>SD per h of AF episodes</td><td align="left" valign="top">5.3229 (1.0375 to 15.9058)</td><td align="left" valign="top">0.4390 (0.0000 to 12.8558)</td><td align="left" valign="top">5.6009</td><td align="left" valign="top">&#x003C;.001</td><td align="left" valign="top">0.8135</td><td align="left" valign="top">&#x003C;.001</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Variability of AF episodes</td><td align="left" valign="top">3.3478 (0.6957 to 9.2174)</td><td align="left" valign="top">0.1739 (0.0000 to 5.2174)</td><td align="left" valign="top">3.9967</td><td align="left" valign="top">&#x003C;.001</td><td align="left" valign="top">0.7876</td><td align="left" valign="top">&#x003C;.001</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Daytime AF variability</td><td align="left" valign="top">3.6000 (0.8667 to 11.4667)</td><td align="left" valign="top">0.0000 (0.0000 to 5.6000)</td><td align="left" valign="top">4.8425</td><td align="left" valign="top">&#x003C;.001</td><td align="left" valign="top">0.7659</td><td align="left" valign="top">&#x003C;.001</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Nighttime AF variability</td><td align="left" valign="top">1.0000 (0.0000 to 6.0000)</td><td align="left" valign="top">0.0000 (0.0000 to 0.2857)</td><td align="left" valign="top">2.6171</td><td align="left" valign="top">&#x003C;.001</td><td align="left" valign="top">0.6712</td><td align="left" valign="top">&#x003C;.001</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Average real variability<sup><xref ref-type="table-fn" rid="table6fn3">c</xref></sup></td><td align="left" valign="top">4.5282 (0.9031 to 12.4119)</td><td align="left" valign="top">0.3499 (0.0000 to 8.9325)</td><td align="left" valign="top">4.6436</td><td align="left" valign="top">&#x003C;.001</td><td align="left" valign="top">0.8127</td><td align="left" valign="top">&#x003C;.001</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>VOM<sup><xref ref-type="table-fn" rid="table6fn4">d</xref></sup> of AF episodes (%)</td><td align="left" valign="top">0.0466 (&#x2013;0.2987 to 1.3361)</td><td align="left" valign="top">&#x2013;0.0142 (&#x2013;0.1249 to 0.0654)</td><td align="left" valign="top">0.3893</td><td align="left" valign="top">.27</td><td align="left" valign="top">0.7246</td><td align="left" valign="top">&#x003C;.001</td></tr><tr><td align="left" valign="top" colspan="7">Heart rate feature</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Ratio of duration of pulse rate of &#x003E;120 bpm<sup><xref ref-type="table-fn" rid="table6fn5">e</xref></sup> to monitoring time (min)</td><td align="left" valign="top">0.0007 (0.0000 to 0.0027)</td><td align="left" valign="top">0.0000 (0.0000 to 0.0070)</td><td align="left" valign="top">0.0151</td><td align="left" valign="top">.76</td><td align="left" valign="top">0.3435</td><td align="left" valign="top">&#x003C;.001</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Ratio of number of pulse rates of &#x003E;120 bpm to total measurements</td><td align="left" valign="top">0.0007 (0.0000 to 0.0027)</td><td align="left" valign="top">0.0000 (0.0000 to 0.0070)</td><td align="left" valign="top">0.0151</td><td align="left" valign="top">.76</td><td align="left" valign="top">0.3435</td><td align="left" valign="top">&#x003C;.001</td></tr></tbody></table><table-wrap-foot><fn id="table6fn1"><p><sup>a</sup>MAE: mean absolute error; <inline-formula><mml:math id="ieqn3"><mml:mi mathvariant="normal">m</mml:mi><mml:mi mathvariant="normal">a</mml:mi><mml:mi mathvariant="normal">e</mml:mi><mml:mo>=</mml:mo><mml:mfrac><mml:mrow><mml:mrow><mml:munderover><mml:mo stretchy="false">&#x2211;</mml:mo><mml:mrow><mml:mi>i</mml:mi><mml:mo>=</mml:mo><mml:mn>1</mml:mn></mml:mrow><mml:mrow><mml:mi>n</mml:mi></mml:mrow></mml:munderover><mml:mrow><mml:mo>|</mml:mo><mml:msub><mml:mrow><mml:mi>p</mml:mi></mml:mrow><mml:mrow><mml:mi>i</mml:mi></mml:mrow></mml:msub><mml:mo>&#x2212;</mml:mo><mml:msub><mml:mrow><mml:mi>g</mml:mi></mml:mrow><mml:mrow><mml:mi>i</mml:mi></mml:mrow></mml:msub><mml:mo>|</mml:mo></mml:mrow></mml:mrow></mml:mrow><mml:mrow><mml:mi mathvariant="normal">n</mml:mi></mml:mrow></mml:mfrac></mml:math></inline-formula><inline-formula><mml:math id="ieqn4"><mml:msub><mml:mrow><mml:mi>p</mml:mi></mml:mrow><mml:mrow><mml:mi>i</mml:mi></mml:mrow></mml:msub><mml:mo>:</mml:mo><mml:mi>P</mml:mi><mml:mi>P</mml:mi><mml:mi>G</mml:mi><mml:mi> </mml:mi><mml:mi> </mml:mi><mml:msub><mml:mrow><mml:mi>g</mml:mi></mml:mrow><mml:mrow><mml:mi>i</mml:mi></mml:mrow></mml:msub><mml:mo>:</mml:mo><mml:mi>E</mml:mi><mml:mi>C</mml:mi><mml:mi>G</mml:mi></mml:math></inline-formula>.</p></fn><fn id="table6fn2"><p><sup>b</sup>Spearman rank correlation coefficient.</p></fn><fn id="table6fn3"><p><sup>c</sup>Average real variability: average AF episodes, SD, and mean absolute deviation per hour were calculated over 24 hours; average real variability was then equal to the average SD and mean absolute deviation over 24 hours.</p></fn><fn id="table6fn4"><p><sup>d</sup>VOM: variation of the mean ([&#x2223;average AF episodes during the day &#x2212; average AF episodes at night&#x2223;/average 24-hour AF episodes] &#x00D7; 100%; daytime AF variability: 6 AM-10 PM; nighttime AF variability: 10 PM-6 AM).</p></fn><fn id="table6fn5"><p><sup>e</sup>bpm: beats per minute.</p></fn></table-wrap-foot></table-wrap></sec></sec></sec><sec id="s4" sec-type="discussion"><title>Discussion</title><sec id="s4-1"><title>Principal Findings</title><p>This study confirmed that the PPG-based AF burden model demonstrated strong agreement in tracking AF burden variations, with metric M1 showing optimal performance: for the ratio of AF duration to the total monitoring time, it achieved an MAE of 0.0400 (<italic>P</italic>=.008) and <italic>r<sub>s</sub></italic> of 0.8788 (<italic>P</italic>&#x003C;.001); for the ratio of &#x2265;6-minute AF episodes to the total monitoring time, it achieved an MAE of 0.0582 (<italic>P</italic>=.44) and <italic>r<sub>s</sub></italic> of 0.9233 (<italic>P</italic>&#x003C;.001); and for the ratio of &#x2265;1-hour AF episodes to the total monitoring time, it achieved an MAE of 0.1204 (<italic>P</italic>=.04) and <italic>r<sub>s</sub></italic> of 0.9293 (<italic>P</italic>&#x003C;.001).</p><p>The current clinical classification of AF largely relies on symptomatic presentation and ECG findings, categorizing AF into paroxysmal, persistent, long-standing persistent, and permanent types. The management of AF involves CHA<sub>2</sub>DS<sub>2</sub>-VASc (congestive heart failure; hypertension; age of &#x2265;75 years; diabetes mellitus; previous stroke, transient ischemic attack, or thromboembolism; vascular disease; age of 65-74 years; and sex category)&#x2013;guided thrombotic risk stratification for anticoagulation decisions. However, current classifications inadequately capture AF progression dynamics [<xref ref-type="bibr" rid="ref9">9</xref>,<xref ref-type="bibr" rid="ref11">11</xref>]. For instance, in real-world settings, it remains unclear whether frequent, short-duration AF episodes confer a higher thrombotic risk than infrequent but prolonged episodes. Currently, no universally accepted AF burden definition exists, although it is commonly quantified as the percentage of time in AF during monitoring [<xref ref-type="bibr" rid="ref12">12</xref>]. Alternative definitions incorporate AF episode frequency, density, and temporal variability [<xref ref-type="bibr" rid="ref2">2</xref>,<xref ref-type="bibr" rid="ref5">5</xref>,<xref ref-type="bibr" rid="ref13">13</xref>], reflecting methodological heterogeneity. While implantable loop recorders and 24-hour Holter monitoring are widely used for AF burden assessment, implantable loop recorders are invasive, costly, and may overestimate AF burden by misclassifying atrial arrhythmias as AF [<xref ref-type="bibr" rid="ref14">14</xref>]. Conversely, 24-hour Holter monitoring underestimates burden due to short duration and tolerability limitations, restricting its utility in daily practice [<xref ref-type="bibr" rid="ref15">15</xref>]. This study leveraged PPG integrated smartwatches to enable multidimensional ambulatory AF monitoring, innovatively characterizing AF burden across 5 distinct dimensions: temporal duration, episode frequency, density, variability, and RVR. This approach offers novel insights for establishing a PPG-based definition of AF burden.</p><p>In recent years, wearable PPG devices have gained traction for AF screening owing to affordability and usability [<xref ref-type="bibr" rid="ref8">8</xref>,<xref ref-type="bibr" rid="ref16">16</xref>]. Previous studies have validated PPG&#x2019;s diagnostic accuracy in AF detection [<xref ref-type="bibr" rid="ref17">17</xref>-<xref ref-type="bibr" rid="ref20">20</xref>]. Our team&#x2019;s previous research (N=187,912) confirmed the feasibility and utility of PPG-based wristbands and smartwatches in population level AF screening, facilitating early AF identification and intervention [<xref ref-type="bibr" rid="ref7">7</xref>]. In a large cohort (N=1,187,381; mean follow-up 255 days), 93.6% of PPG suspected AF cases were verified, demonstrating the reliability and accuracy of this approach [<xref ref-type="bibr" rid="ref21">21</xref>]. Despite PPG&#x2019;s utility in AF screening, its burden monitoring potential is underexplored. V&#x00E4;liaho et al [<xref ref-type="bibr" rid="ref8">8</xref>] evaluated PPG-based algorithms for continuous AF burden assessment in 173 participants, finding 30-minute intervals as optimal (<italic>F</italic><sub>1</sub> score=0.95; sensitivity=94.9%; specificity=98.6%) when comparing 10-, 20-, 30-, and 60-minute reporting intervals. Avram et al [<xref ref-type="bibr" rid="ref22">22</xref>] evaluated a Samsung smartwatch algorithm (5-minute intervals: sensitivity=87.8%, 95% CI 83.6%-91%; specificity=97.4%, 95% CI 97.1%-97.7%; area under the curve=93.3%), showing strong AF burden correlation (<italic>R</italic><sup>2</sup>=0.986). These findings suggest PPG&#x2019;s potential for AF burden quantification, although detection precision for brief AF episodes requires refinement. In this study, we developed a PPG-based AF burden algorithm integrated into smartwatch devices. When evaluated via 1-minute analysis epochs against standard 24-hour Holter monitoring as the reference, the algorithm demonstrated a sensitivity of 91.5% (95% CI 87.9%-95.1%), specificity of 97.2% (95% CI 95.9%-98.5%), and overall accuracy of 95.7% (95% CI 94%-97.4%). Previous studies have reported PPG signal limitations from motion artifacts and other interfering factors, leading to substantial data exclusion. Reissenberger et al [<xref ref-type="bibr" rid="ref23">23</xref>] reported that approximately 50.7% of PPG signals were classified as noise, necessitating exclusion. To address these challenges, we implemented algorithm optimizations through a novel multiscale fusion approach for AF burden detection, achieving a daily model output rate of 0.86 (95% CI 0.852-0.880) and markedly improving data usability. In this study, metric M1 demonstrated optimal performance in tracking AF duration, consistent with previous findings, showing an MAE of 0.0400 (<italic>P</italic>=.008) and <italic>r</italic><sub><italic>s</italic></sub> of 0.8788 (<italic>P</italic>&#x003C;.001) for the ratio of AF duration to total monitoring time and an MAE of 0.1204 (<italic>P</italic>=.04) and <italic>r<sub>s</sub></italic>=0.9293 (<italic>P</italic>&#x003C;.001) for the ratio of episodes of &#x003E;1 hour to total monitoring time. While current studies typically use invasive devices or 24-hour Holter monitoring to define AF burden through episode frequency and density, our study pioneered PPG-based AF burden models integrated into smartwatches. Compared with standard 24-hour Holter monitoring, the AF burden model exhibited higher MAE values, along with a weaker <italic>r</italic><sub><italic>s</italic></sub>, in assessing metrics M2 and M5. This may be attributed to PPG signal interference caused by poor pulse waveform quality, motion artifacts, and noise, which could reduce the models&#x2019; accuracy in evaluating AF episode frequency. However, metric M3 demonstrated good correlation and a weaker MAE, with an MAE of 0.1725 (<italic>P</italic>=.13) and <italic>r<sub>s</sub></italic>=0.6576 (<italic>P</italic>&#x003C;.001), although further optimization is still needed in the future. Notably, metric M4 demonstrated excellent agreement with the gold standard in tracking AF variability, providing novel insights for assessing temporal AF fluctuations.</p><p>AF&#x2019;s rising prevalence and mortality exacerbate global health burdens, with its association to adverse cardiovascular events including stroke, heart failure, and death potentially linked to AF burden [<xref ref-type="bibr" rid="ref1">1</xref>,<xref ref-type="bibr" rid="ref24">24</xref>]. The Catheter Ablation Versus Standard Conventional Treatment in Patients With Left Ventricular Dysfunction and Atrial Fibrillation trial demonstrated that an AF burden threshold of 50% was associated with significant functional and structural changes in cardiomyocytes [<xref ref-type="bibr" rid="ref25">25</xref>]. There is accumulating evidence suggesting that AF burden is correlated with adverse cardiovascular events, including stroke and heart failure [<xref ref-type="bibr" rid="ref2">2</xref>,<xref ref-type="bibr" rid="ref4">4</xref>,<xref ref-type="bibr" rid="ref26">26</xref>]. A large-scale study (N=39,710) defined AF burden as the ratio of daily AF duration percentage to total monitoring time [<xref ref-type="bibr" rid="ref13">13</xref>] and the longest single AF episode duration, revealing dose-dependent associations between increasing baseline AF burden and adverse outcomes at the 1- and 3-year follow-ups. A high AF burden may be a significant risk factor for mortality. However, the causal role of AF burden in stroke events and the optimal threshold (ranging from 1 minute to 24 hours) remain unclear. Moreover, the relationship between AF episode frequency, AF density, AF episode variability, and the proportion of RVR AF and adverse cardiovascular events remains unexplored. However, in this study, metrics M1 and M4 demonstrated strong correlation compared to 24-hour Holter monitoring. This provides a novel methodological foundation for future research into the association between PPG-based AF burden detection and adverse cardiovascular events.</p><p>While there is evidence suggesting that anticoagulation therapy may be considered based on atrial high rate episode burden [<xref ref-type="bibr" rid="ref27">27</xref>], the optimal treatment strategy according to specific AF burden thresholds requires further investigation. Our study&#x2019;s metric M1 for temporal AF burden monitoring showed strong correlation with 24-hour Holter monitoring, potentially offering a novel methodology for future large-scale clinical trials investigating anticoagulant guidance by AF burden quantification. Current AF guidelines recommend active rhythm control to alleviate symptoms in patients with AF, with antiarrhythmic drug therapy and more effective catheter ablation techniques demonstrating the capability to prevent AF recurrence, improve symptoms, and reduce AF burden [<xref ref-type="bibr" rid="ref28">28</xref>-<xref ref-type="bibr" rid="ref30">30</xref>]. Drexler et al [<xref ref-type="bibr" rid="ref31">31</xref>] retrospectively demonstrated that early postprocedural low root mean square of successive differences values following pulmonary vein isolation independently predicted AF recurrence (hazard ratio=0.50; <italic>P</italic>&#x003C;.001), whereas Zhu et al [<xref ref-type="bibr" rid="ref32">32</xref>] prospectively identified postablation root mean square of successive differences and percentage of successive normal sinus intervals that differ by more than 50 milliseconds as independent predictors of recurrence in 102 patients with paroxysmal AF. Collectively, recent randomized trials support the beneficial impact of dynamic AF burden monitoring and reduction on clinical outcomes [<xref ref-type="bibr" rid="ref33">33</xref>]. Our study&#x2019;s metric M4 exhibited strong correlation with 24-hour Holter monitoring in assessing AF variability, providing a potential technical foundation for future rhythm management strategies guided by AF burden quantification and prediction of postablation recurrence risk.</p><p>There is emerging evidence suggesting that AF burden may contribute to adverse cardiovascular outcomes, including stroke and heart failure, necessitating refined assessment methods for optimized risk prediction. While real-world evaluation of AF burden remains uncertain, incorporating this parameter into clinical decision making could enable more precise risk stratification and therapeutic selection. Our study developed a novel smartwatch-based PPG algorithm showing strong concordance with 24-hour Holter monitoring in long-term AF burden assessment. This innovative model incorporates 5 dimensions&#x2014;temporal AF duration, episode density, frequency, variability, and proportion with rapid ventricular response&#x2014;enabling multidimensional AF evaluation. This approach provides new insights for investigating PPG-derived AF burden&#x2019;s relationship with cardiovascular outcomes, potentially informing early intervention strategies, anticoagulation decisions, and rhythm management protocols.</p></sec><sec id="s4-2"><title>Limitations</title><p>This study has several limitations that should be acknowledged. First, the relatively modest sample size warrants validation in larger, real-world cohorts to ensure generalizability. In addition, PPG technology remains significantly susceptible to motion artifacts and noise interference, particularly during daily activities and hand movements, which may compromise accurate quantification of AF episodes. This technical limitation presents a notable challenge in assessing RVR AF. However, ongoing advancements in wearable device technology and detection algorithms are expected to mitigate these limitations. Second, while current PPG applications are limited to AF screening and cannot provide definitive diagnosis, our preliminary research demonstrated the diagnostic feasibility of integrated single-lead electrocardiograph technology. Future investigations should prioritize large-scale, multicenter randomized controlled trials to systematically evaluate the clinical utility of combining PPG with iECG technology for comprehensive AF burden monitoring.</p></sec><sec id="s4-3"><title>Conclusions</title><p>A PPG-based AF burden model incorporating dimensions such as duration, frequency, density, variability, and RVR demonstrated good consistency compared to 24-hour Holter monitoring, with optimal tracking performance observed in the duration and variability dimensions. This approach provides technical support for the at-home multidimensional quantification of AF occurrence and progression, offering new insights for defining PPG-based AF burden. However, further optimization and validation are required for the real-world application of this PPG-based AF burden model.</p></sec></sec></body><back><ack><p>The authors thank the Huawei Heart Health Research Team for their technical support during the research process. They are grateful to Yu Cao, Hongli Zhang, Yubo You, Teng Xu, Shuai Zhao, and Jie Zhou (Huawei Heart Health Research Team) for the development and optimization of the photoplethysmography-based atrial fibrillation burden model. This study was funded by the National Natural Science Foundation of China (grant 82170309) and the Beijing Natural Science Foundation (grant L232117).</p></ack><notes><sec><title>Data Availability</title><p>The datasets generated or analyzed during this study are available from the corresponding author on reasonable request.</p></sec></notes><fn-group><fn fn-type="con"><p>Hao Wang and YTG are joint corresponding authors and contributed equally to conceptualization, project administration, funding acquisition, resources, supervision, and writing&#x2014;review and editing. Hong Wang played a role in the acquisition, analysis, and interpretation of the data. Hong Wang drafted the manuscript. Hong Wang, HZ, ZJ, BL, and ZZ performed data preprocessing. All authors approved the final version of the manuscript.</p></fn><fn fn-type="conflict"><p>None declared.</p></fn></fn-group><glossary><title>Abbreviations</title><def-list><def-item><term id="abb1">AF</term><def><p>atrial fibrillation</p></def></def-item><def-item><term id="abb2">bpm</term><def><p>beats per minute</p></def></def-item><def-item><term id="abb3">ECG</term><def><p>electrocardiogram</p></def></def-item><def-item><term id="abb4">MAE</term><def><p>mean absolute error</p></def></def-item><def-item><term id="abb5">mAFA</term><def><p>Mobile Atrial Fibrillation Application</p></def></def-item><def-item><term id="abb6">pNN50</term><def><p>percentage of successive normal sinus intervals that differ by more than 50 milliseconds</p></def></def-item><def-item><term id="abb7">PPG</term><def><p>photoplethysmography</p></def></def-item><def-item><term id="abb8">RVR</term><def><p>rapid ventricular rate</p></def></def-item></def-list></glossary><ref-list><title>References</title><ref 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