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<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Cardiovasc. Med.</journal-id>
<journal-title-group>
<journal-title>Frontiers in Cardiovascular Medicine</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Cardiovasc. Med.</abbrev-journal-title>
</journal-title-group>
<issn pub-type="epub">2297-055X</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
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<article-meta>
<article-id pub-id-type="doi">10.3389/fcvm.2025.1617872</article-id>
<article-version article-version-type="Version of Record" vocab="NISO-RP-8-2008"/>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Original Research</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Core and bridging symptoms in patients with atrial fibrillation: a network analysis</article-title>
</title-group>
<contrib-group>
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<name><surname>Sun</surname><given-names>Dingce</given-names></name>
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<contrib contrib-type="author">
<name><surname>Yang</surname><given-names>Xue</given-names></name>
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<contrib contrib-type="author">
<name><surname>Li</surname><given-names>Hong</given-names></name>
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<name><surname>Li</surname><given-names>Guirong</given-names></name>
<xref ref-type="aff" rid="aff4"><sup>4</sup></xref>
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<name><surname>Lin</surname><given-names>Hairong</given-names></name>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
<xref ref-type="corresp" rid="cor1">&#x002A;</xref>
<uri xlink:href="https://loop.frontiersin.org/people/2743732/overview"/>
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<aff id="aff1"><label>1</label><institution>Department of Urology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China</institution>, <city>Mianyang</city>, <country country="cn">China</country></aff>
<aff id="aff2"><label>2</label><institution>School of Nursing, Chengdu Medical College</institution>, <city>Chengdu</city>, <country country="cn">China</country></aff>
<aff id="aff3"><label>3</label><institution>Department of Gastroenterology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China</institution>, <city>Mianyang</city>, <country country="cn">China</country></aff>
<aff id="aff4"><label>4</label><institution>Department of Nursing, Mianyang Central Hospital; School of Medicine, University of Electronic Science and Technology of China</institution>, <city>Mianyang</city>, <country country="cn">China</country></aff>
<author-notes>
<corresp id="cor1"><label>&#x002A;</label><bold>Correspondence:</bold> Hairong Lin <email xlink:href="mailto:1273373111@qq.com">1273373111@qq.com</email></corresp>
</author-notes>
<pub-date publication-format="electronic" date-type="pub" iso-8601-date="2025-11-07"><day>07</day><month>11</month><year>2025</year></pub-date>
<pub-date publication-format="electronic" date-type="collection"><year>2025</year></pub-date>
<volume>12</volume><elocation-id>1617872</elocation-id>
<history>
<date date-type="received"><day>27</day><month>04</month><year>2025</year></date>
<date date-type="accepted"><day>14</day><month>10</month><year>2025</year></date>
</history>
<permissions>
<copyright-statement>&#x00A9; 2025 Sun, Yang, Li, Li and Lin.</copyright-statement>
<copyright-year>2025</copyright-year><copyright-holder>Sun, Yang, Li, Li and Lin</copyright-holder><license><ali:license_ref start_date="2025-11-07">https://creativecommons.org/licenses/by/4.0/</ali:license_ref>
<license-p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License (CC BY)</ext-link>. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</license-p></license>
</permissions>
<abstract><sec><title>Background</title>
<p>Atrial fibrillation symptoms are diverse and complex, but symptom networks can visually map the relationships between symptoms and influencing factors, identifying key symptoms and offering better targets for symptom management. However, research on establishing symptom networks in Atrial fibrillation patients is limited.</p>
</sec><sec><title>Aim</title>
<p>We aimed to construct a symptom network for patients with atrial fibrillation, understand its characteristics, and identify core and bridging symptoms.</p>
</sec><sec><title>Methods</title>
<p>This cross-sectional study enrolled 384 patients with atrial fibrillation from November 2021 to August 2022 at Tianjin Medical University General Hospital of China. Network analysis methods were utilized to construct the symptom network. Centrality metrics were used to identify important symptoms.</p>
</sec><sec><title>Results</title>
<p>By incorporating covariates into the symptom network, we revealed that the Mental Health Inventory-5 score was most closely related to &#x201C;fatigue at rest&#x201D;. Sex influenced all symptoms except &#x201C;dizziness&#x201D; and &#x201C;shortness of breath at rest&#x201D;. Left ventricular ejection fraction was closely connected to &#x201C;exercise intolerance&#x201D; and &#x201C;shortness of breath at rest&#x201D;, while the frail score was closely linked to &#x201C;exercise intolerance&#x201D; and &#x201C;dizziness&#x201D;. Controlling for covariates, &#x201C;shortness of breath during physical activity&#x201D; and &#x201C;shortness of breath at rest&#x201D; are atrial fibrillation patients&#x0027; core symptoms. &#x201C;Shortness of breath at rest&#x201D;, &#x201C;palpitations&#x201D;, and &#x201C;chest pain&#x201D; served as bridging symptoms between symptom clusters.</p>
</sec><sec><title>Conclusion</title>
<p>Symptom networks can help us understand the relationships between symptoms and influencing factors, as well as the interactions between different atrial fibrillation symptoms.</p>
</sec>
</abstract>
<kwd-group>
<kwd>atrial fibrillation</kwd>
<kwd>symptom network</kwd>
<kwd>symptom cluster</kwd>
<kwd>frail</kwd>
<kwd>mental health</kwd>
</kwd-group><funding-group>
<funding-statement>The author(s) declare that financial support was received for the research and/or publication of this article. This study received funding from The Incubation Project Fund of Mianyang Central Hospital (2023FH004), China&#x0027;s National Clinical Key Specialty Project (XHZDZK013), and Humanities Research Center of Zigong Key Research Base for Philosophy and Social Sciences(JKRWY24-14).</funding-statement>
</funding-group>
<counts>
<fig-count count="5"/>
<table-count count="4"/><equation-count count="0"/><ref-count count="45"/><page-count count="10"/><word-count count="45845"/></counts><custom-meta-group><custom-meta><meta-name>section-at-acceptance</meta-name><meta-value>General Cardiovascular Medicine</meta-value></custom-meta></custom-meta-group>
</article-meta>
</front>
<body><sec id="s1" sec-type="intro"><label>1</label><title>Introduction</title>
<p>Atrial fibrillation (AF) is a common cardiac arrhythmia (<xref ref-type="bibr" rid="B1">1</xref>) affecting about 1.6&#x0025; of Chinese adults (<xref ref-type="bibr" rid="B2">2</xref>). Atrial fibrillation is associated with increased morbidity, mortality, and a significant economic burden (<xref ref-type="bibr" rid="B1">1</xref>). The development of AF is influenced by multiple factors. Conditions such as hyperthyroidism (<xref ref-type="bibr" rid="B3">3</xref>) and hypertrophic cardiomyopathy (<xref ref-type="bibr" rid="B4">4</xref>) are known to predispose individuals to AF. Additionally, modifiable lifestyle factors are significantly associated with AF risk. Research indicates that smoking more than doubles the risk of AF (<xref ref-type="bibr" rid="B5">5</xref>), while endurance exercise training may increase the probability of developing AF by 2- to 10-fold (<xref ref-type="bibr" rid="B6">6</xref>). Furthermore, cardiac channelopathies are also closely linked to the occurrence of arrhythmias (<xref ref-type="bibr" rid="B7">7</xref>). Further, many atrial fibrillation patients experience symptoms like fatigue, shortness of breath, palpitations (<xref ref-type="bibr" rid="B8">8</xref>),, leading to emotional distress and poor quality of life (<xref ref-type="bibr" rid="B9">9</xref>, <xref ref-type="bibr" rid="B10">10</xref>). Atrial fibrillation symptoms were strongly associated with multiple factors such as depression, sex, coronary artery disease, diabetes mellitus, and sleep disturbances (<xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B12">12</xref>). However, it remains unclear how these factors influence individual or multiple symptoms of atrial fibrillation.</p>
<p>Network analysis is a new approach that offers a comprehensive view by visually representing and quantifying the complex connections between variables in a network graph (<xref ref-type="bibr" rid="B13">13</xref>). This method can help visualize the relationships between variables and symptoms, as well as the interactions between different symptoms (<xref ref-type="bibr" rid="B14">14</xref>). For example, Bard and colleagues used this method to explore the detailed relationship between insomnia and anxiety or depression symptoms (<xref ref-type="bibr" rid="B15">15</xref>). Henneghan and colleagues applied it to examine the detailed connections between symptoms in breast cancer survivors and pro-inflammatory and anti-inflammatory cytokines, suggesting interleukin-2 as a potential mechanism for symptom co-occurrence (<xref ref-type="bibr" rid="B16">16</xref>). These examples illustrate that this method can help clarify the relationship between factors and symptoms, aiding in the discovery of symptom mechanisms.</p>
<p>In addition, symptoms of atrial fibrillation are interconnected and mutually influence each other. Different symptoms also play distinct roles and functions within the symptom network (<xref ref-type="bibr" rid="B14">14</xref>, <xref ref-type="bibr" rid="B17">17</xref>). Network analysis can help identify core symptoms and bridge symptoms linked to symptom clusters, aiding in understanding the key symptoms driving symptom occurrence and impact, and providing targets for tailored interventions (<xref ref-type="bibr" rid="B13">13</xref>). Studies on symptom networks in atrial fibrillation patients are limited; we aim to visualize and analyze the relationships between factors like sleep quality, physiological indicators, psychological health status, and atrial fibrillation symptoms using network analysis. We further seek to explore important symptoms to help understand the mechanisms of symptom interaction to pinpoint intervention targets.</p>
</sec>
<sec id="s2"><label>2</label><title>Design, materials, and methods</title>
<sec id="s2a"><label>2.1</label><title>Participants and methods</title>
<p>This cross-sectional study enrolled 384 patients with atrial fibrillation from November 2021 to August 2022 via convenient sampling at Tianjin Medical University General Hospital. Patients diagnosed with non-valvular atrial fibrillation (<xref ref-type="bibr" rid="B18">18</xref>) were included. Patients with active tumors and reversible atrial fibrillation associated with hyperthyroidism or electrolyte imbalances were excluded.</p>
</sec>
<sec id="s2b"><label>2.2</label><title>Sample size</title>
<p>When the network structure contains fewer than 20 nodes, sample sizes ranging from 250 to 350 are generally sufficient to observe moderate sensitivity, high specificity, and strong correlations between edge weights (<xref ref-type="bibr" rid="B19">19</xref>). Ultimately, we included 360 participants, meeting the required sample size.</p>
</sec>
<sec id="s2c"><label>2.3</label><title>Data collection</title>
<sec id="s2c1"><label>2.3.1</label><title>Demographics and clinical data</title>
<p>Socio-demographic data such as age, sex, and body mass index; disease details like atrial fibrillation type and atrial fibrillation duration; laboratory indicators including high-sensitivity C-reactive protein and B-type natriuretic peptide; echocardiographic measurements including left atrial anteroposterior diameter, right atrial transverse diameter, left ventricular end-diastolic diameter, right ventricular transverse diameter, and left ventricular ejection fraction. Echocardiographic and laboratory data were collected on the admission day.</p>
</sec>
<sec id="s2c2"><label>2.3.2</label><title>Symptom, mental health status, sleep quality, and frailty evaluation tools</title>
<p>Symptoms were evaluated using the University of Toronto Atrial Fibrillation Severity Scale (AFSS), which assesses symptoms such as palpitations, shortness of breath, fatigue, dizziness, and chest pain at rest and during activity. Each item is scored from 0 to 5, with 0 meaning &#x201C;no symptoms&#x201D; and 5 meaning &#x201C;always present.&#x201D; The total score ranges from 0 to 35. The Cronbach&#x0027;s <italic>&#x03B1;</italic> coefficient for this scale in our study was 0.74 (<xref ref-type="bibr" rid="B20">20</xref>).</p>
<p>Mental health was assessed using the Mental Health Inventory-5 (MHI-5), which measures emotional well-being, including anxiety, depression, vitality, happiness, and tranquility over the past month. Scores are transformed to a scale of 0 to 100, with higher scores reflecting better mental health. The Cronbach&#x0027;s <italic>&#x03B1;</italic> coefficient ranged from 0.72 to 0.88 (<xref ref-type="bibr" rid="B21">21</xref>).</p>
<p>The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality over the past month, with scores ranging from 0 to 21. Higher scores indicate poorer sleep quality. The Chinese version of the PSQI had a Cronbach&#x0027;s <italic>&#x03B1;</italic> coefficient of 0.71 (<xref ref-type="bibr" rid="B22">22</xref>).</p>
<p>Frailty was measured using the Chinese version of the FRAIL scale, which assesses fatigue, resistance, ambulation, illness, and weight changes. Each item is scored from 0 to 1, and a total score of 3 or higher indicates frailty. This scale demonstrated good reliability with a Cronbach&#x0027;s <italic>&#x03B1;</italic> coefficient of 0.826 (<xref ref-type="bibr" rid="B23">23</xref>).</p>
</sec>
<sec id="s2c3"><label>2.3.3</label><title>Data collection methods</title>
<p>Upon admission, informed consent was obtained, and a thorough assessment was conducted, covering sociodemographic, clinical, symptom, sleep quality, and mental health information. Patients were fully informed about the study&#x0027;s goals and guidelines. To reduce bias, survey questions were worded consistently and impartially. Of the 400 questionnaires distributed, 384 valid responses were returned, after excluding incomplete forms or those completed in under 5&#x2005;min, resulting in a 96&#x0025; response rate.</p>
<p>This study received approval from the Ethics Committee for Clinical Research at Tianjin Medical University General Hospital [Approval No. (IRB2023-WZ-111)]. All procedures adhered to ethical standards and complied with the Declaration of Helsinki.</p>
</sec>
</sec>
<sec id="s2d"><label>2.4</label><title>Statistical analysis</title>
<p>Statistical analysis utilized SPSS 19.0 and R 4.1.3 software. Missing values for physiological and laboratory data (less than 4&#x0025; of the sample) were addressed by replacing them with the mean or median. Continuous variables were expressed as mean&#x2009;&#x00B1;&#x2009;standard deviation or median, while categorical variables were presented as frequencies and percentages. For assessing factors influencing symptom burden in atrial fibrillation patients, we utilized bivariate analysis and linear regression.</p>
<sec id="s2d1"><label>2.4.1</label><title>Symptom network visualization</title>
<p>Two symptom networks were constructed using distinct graphical approaches: a Mixed Graphical Model (MGM) enrolling covariates which incorporated both continuous (clinical symptoms&#x3001;left ventricular ejection fraction&#x3001;frail score&#x3001;MHI-5 score) and categorical variables (sex), while the &#x201C;Gaussian Graph&#x201D; model focused only on continuous variables after controlling for covariates. Covariates were controlled by performing regression analysis on the seven symptom variables, with the residuals from this analysis used as the data for further analysis (<xref ref-type="bibr" rid="B24">24</xref>).</p>
<p>The &#x201C;<italic>qgraph</italic>&#x201D; package was used for network visualization. The &#x201C;Fruchterman-Reingold&#x201D; algorithm positioned highly connected and numerous symptom nodes at the center of the network and less connected and fewer symptom nodes at the periphery. The &#x201C;pcor&#x201D; algorithm was used to reduce false positive results in the symptom network visualization. The accuracy and stability of the network were assessed using the &#x201C;bootnet&#x201D; package in R. Accuracy was evaluated by calculating 95&#x0025; confidence intervals for edge weights based on 1,000 nonparametric bootstrap samples. The stability of node centrality was assessed via 1,000 case-dropping bootstrap samples, which were used to compute the correlation stability coefficient (CS).</p>
</sec>
<sec id="s2d2"><label>2.4.2</label><title>Core and bridge symptoms identification</title>
<p>We used three centrality measures: &#x201C;Betweenness,&#x201D; &#x201C;Closeness,&#x201D; and &#x201C;Strength&#x201D; to identify key symptoms. &#x201C;Betweenness&#x201D; counts how often a node lies on the shortest path between other nodes. &#x201C;Closeness&#x201D; calculates the average distance from a node to all others, highlighting influential nodes. &#x201C;Strength&#x201D; measures network connectivity, with higher values indicating more frequent co-occurrence. High centrality nodes were identified as core symptoms. Symptom clusters were identified with the &#x201C;EGAnet&#x201D; package&#x0027;s walktrap algorithm, and &#x201C;bridge strength&#x201D; was used to find symptoms linking clusters. The &#x201C;walktrap&#x201D; algorithm is a built-in function of the &#x201C;EGAnet&#x201D; package in R software. It works by calculating the distances between nodes in a graph to identify community structures.</p>
</sec>
</sec>
</sec>
<sec id="s3" sec-type="results"><label>3</label><title>Results</title>
<sec id="s3a"><label>3.1</label><title>Participant characteristics</title>
<p>The average age of participants was 66.19&#x2009;&#x00B1;&#x2009;9.38 years, with 54.7&#x0025; male. Of the participants, 58.3&#x0025; had paroxysmal atrial fibrillation, and the median duration was 18 months (IQR: 7&#x2013;65). Hypertension and coronary heart disease were present in 62&#x0025; and 36.5&#x0025; of participants, respectively (<xref ref-type="table" rid="T1">Table&#x00A0;1</xref>). The average PSQI and MHI-5 scores were 7.85 and 74.64, respectively, with 61.9&#x0025; of participants experiencing impaired sleep quality (PSQI&#x2009;&#x003E;&#x2009;5).</p>
<table-wrap id="T1" position="float"><label>Table&#x00A0;1</label>
<caption><p>Demographic and clinical characteristics of patients with atrial fibrillation (<italic>N</italic>&#x2009;&#x003D;&#x2009;384).</p></caption>
<table>
<thead>
<tr>
<th valign="top" align="left">Item</th>
<th valign="top" align="center"><italic>&#x0060;x</italic>&#x2009;<italic>&#x00B1;</italic>&#x2009;<italic>S/n(&#x0025;)/M(IQR)</italic></th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Age (year)</td>
<td valign="top" align="center">66.19&#x2009;&#x00B1;&#x2009;9.38</td>
</tr>
<tr>
<td valign="top" align="left">Sex (male)</td>
<td valign="top" align="center">210 (54.7&#x0025;)</td>
</tr>
<tr>
<td valign="top" align="left">BMI (Kg/m<sup>2)</sup></td>
<td valign="top" align="center">25.68&#x2009;&#x00B1;&#x2009;3.41</td>
</tr>
<tr>
<td valign="top" align="left">AF Duration (month)</td>
<td valign="top" align="center">18 (7,65)</td>
</tr>
<tr>
<td valign="top" align="left">paroxysmal AF</td>
<td valign="top" align="center">224 (58.3&#x0025;)</td>
</tr>
<tr>
<td valign="top" align="left">Diabetes</td>
<td valign="top" align="center">75 (19.5&#x0025;)</td>
</tr>
<tr>
<td valign="top" align="left">Hypertension</td>
<td valign="top" align="center">238 (62&#x0025;)</td>
</tr>
<tr>
<td valign="top" align="left">Coronary heart disease</td>
<td valign="top" align="center">140 (36.5&#x0025;)</td>
</tr>
<tr>
<td valign="top" align="left">Ischemic stroke</td>
<td valign="top" align="center">91 (23.7&#x0025;)</td>
</tr>
<tr>
<td valign="top" align="left">COPD</td>
<td valign="top" align="center">7 (1.8&#x0025;)</td>
</tr>
<tr>
<td valign="top" align="left">OSA</td>
<td valign="top" align="center">10 (2.6&#x0025;)</td>
</tr>
<tr>
<td valign="top" align="left">Heart failure</td>
<td valign="top" align="center">46 (12&#x0025;)</td>
</tr>
<tr>
<td valign="top" align="left" colspan="2" style="background-color:#d9d9d9">Medication history</td>
</tr>
<tr>
<td valign="top" align="left">None</td>
<td valign="top" align="center">227 (59.3&#x0025;)</td>
</tr>
<tr>
<td valign="top" align="left">AADs</td>
<td valign="top" align="center">65 (17&#x0025;)</td>
</tr>
<tr>
<td valign="top" align="left">Rate control</td>
<td valign="top" align="center">76 (19.6&#x0025;)</td>
</tr>
<tr>
<td valign="top" align="left">AADs&#x2009;&#x002B;&#x2009;rate control</td>
<td valign="top" align="center">16 (4.1&#x0025;)</td>
</tr>
<tr>
<td valign="top" align="left">RFCA history</td>
<td valign="top" align="center">75 (19.6&#x0025;)</td>
</tr>
<tr>
<td valign="top" align="left">Hs-CRP (mg/L)</td>
<td valign="top" align="center">1.41&#xFF08;0.70, 3.46&#xFF09;</td>
</tr>
<tr>
<td valign="top" align="left">BNP (pg/ml)</td>
<td valign="top" align="center">138 (65, 276&#xFF09;</td>
</tr>
<tr>
<td valign="top" align="left">LA-ap (mm)</td>
<td valign="top" align="center">42.07&#x2009;&#x00B1;&#x2009;5.70</td>
</tr>
<tr>
<td valign="top" align="left">LVEDD (mm)</td>
<td valign="top" align="center">48.25&#x2009;&#x00B1;&#x2009;4.42</td>
</tr>
<tr>
<td valign="top" align="left">RA-t (mm)</td>
<td valign="top" align="center">40.08&#x2009;&#x00B1;&#x2009;5.21</td>
</tr>
<tr>
<td valign="top" align="left">RV-b (mm)</td>
<td valign="top" align="center">32.17&#x2009;&#x00B1;&#x2009;3.42</td>
</tr>
<tr>
<td valign="top" align="left">LVEF (&#x0025;)</td>
<td valign="top" align="center">62&#x0025;&#xFF08;60&#x0025;, 64&#x0025;&#xFF09;</td>
</tr>
<tr>
<td valign="top" align="left">MHI-5 score</td>
<td valign="top" align="center">74.64&#x2009;&#x00B1;&#x2009;16.31</td>
</tr>
<tr>
<td valign="top" align="left">PSQI score</td>
<td valign="top" align="center">7.85&#x2009;&#x00B1;&#x2009;4.33</td>
</tr>
<tr>
<td valign="top" align="left">Frail score</td>
<td valign="top" align="center">1.47&#x2009;&#x00B1;&#x2009;1.30</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="TF1"><p>M, median; IQR, interquartile range; BMI, body mass index; RFCA, radiofrequency catheter ablation; AF, atrial fibrillation; BNP, B-type natriuretic peptide; LVEF, left ventricular ejection fraction; RA-t, right atrial transverse diameter; LA-ap, left atrial anteroposterior diameter; LVEDD, left ventricular end-diastolic diameter; RV-b, right ventricular transverse diameter; Hs-CRP, high-sensitivity C-reactive protein; AADs, anti-arrhythmic drugs; OSA, obstructive sleep apnea; COPD, chronic obstructive pulmonary disease; MHI-5, Mental Health Inventory-5; PSQI, The Pittsburgh Sleep Quality Index.</p></fn>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="s3b"><label>3.2</label><title>Analysis of the current status and influencing factors of symptom burden in patients with atrial fibrillation</title>
<p>The AFSS score was 9.28&#x2009;&#x00B1;&#x2009;5.19, with 24 patients (6.3&#x0025;) reporting no symptoms. A total of 360 patients were included in the analysis after excluding non-symptom patients. The bivariate analysis revealed statistical differences in sex, coronary heart disease, heart failure, chronic obstructive pulmonary disease, and atrial fibrillation classification. Variables such as a B-type natriuretic peptide, left ventricular ejection fraction(LVEF), sleep quality, frailty, mental health status, high-sensitivity C-reactive protein, and left atrial diameter showed a correlation with symptom burden (<italic>p</italic>&#x2009;&#x003C;&#x2009;0.05), as detailed in <xref ref-type="table" rid="T2">Table&#x00A0;2</xref>. Multiple linear regression indicated that sex (<italic>&#x03B2;</italic>&#x2009;&#x003D;&#x2009;18.8, <italic>p</italic>&#x2009;&#x003D;&#x2009;0.007), MHI-5 score (<italic>&#x03B2;</italic>&#x2009;&#x003D;&#x2009;&#x2212;0.06, <italic>p</italic>&#x2009;&#x003D;&#x2009;0.001), left ventricular ejection fraction (<italic>&#x03B2;</italic>&#x2009;&#x003D;&#x2009;&#x2212;13.56, <italic>p</italic>&#x2009;&#x003D;&#x2009;0.010), and frail score (<italic>&#x03B2;</italic>&#x2009;&#x003D;&#x2009;0.68, <italic>p</italic>&#x2009;&#x003D;&#x2009;0.005) were identified as independent influencing factors of symptom burden (<xref ref-type="table" rid="T3">Table&#x00A0;3</xref>).</p>
<table-wrap id="T2" position="float"><label>Table&#x00A0;2</label>
<caption><p>The bivariate analysis of symptom burden in atrial fibrillation patients (<italic>N</italic>&#x2009;&#x003D;&#x2009;360).</p></caption>
<table>
<thead>
<tr>
<th valign="top" align="left">Item</th>
<th valign="top" align="center"><italic>t/F/r</italic></th>
<th valign="top" align="center"><italic>p</italic></th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Age (year)</td>
<td valign="top" align="center">0.05</td>
<td valign="top" align="center">0.322</td>
</tr>
<tr>
<td valign="top" align="left">Sex (male)</td>
<td valign="top" align="center">&#x2212;3.84</td>
<td valign="top" align="center">&#x003C;0.001&#x002A;</td>
</tr>
<tr>
<td valign="top" align="left">BMI (Kg/m2)</td>
<td valign="top" align="center">&#x2212;0.04</td>
<td valign="top" align="center">0.427</td>
</tr>
<tr>
<td valign="top" align="left">AF Duration (month)</td>
<td valign="top" align="center">0.07</td>
<td valign="top" align="center">0.209</td>
</tr>
<tr>
<td valign="top" align="left">paroxysmal AF</td>
<td valign="top" align="center">&#x2212;1.95</td>
<td valign="top" align="center">0.051</td>
</tr>
<tr>
<td valign="top" align="left">Diabetes</td>
<td valign="top" align="center">0.17</td>
<td valign="top" align="center">0.867</td>
</tr>
<tr>
<td valign="top" align="left">Hypertension</td>
<td valign="top" align="center">&#x2212;0.53</td>
<td valign="top" align="center">0.595</td>
</tr>
<tr>
<td valign="top" align="left">Coronary heart disease</td>
<td valign="top" align="center">&#x2212;2.91</td>
<td valign="top" align="center">0.004&#x002A;</td>
</tr>
<tr>
<td valign="top" align="left">Ischemic stroke</td>
<td valign="top" align="center">0.57</td>
<td valign="top" align="center">0.572</td>
</tr>
<tr>
<td valign="top" align="left">COPD</td>
<td valign="top" align="center">&#x2212;2.44</td>
<td valign="top" align="center">0.015&#x002A;</td>
</tr>
<tr>
<td valign="top" align="left">OSA</td>
<td valign="top" align="center">&#x2212;0.19</td>
<td valign="top" align="center">0.848</td>
</tr>
<tr>
<td valign="top" align="left">Heart failure</td>
<td valign="top" align="center">&#x2212;2.89</td>
<td valign="top" align="center">0.004&#x002A;</td>
</tr>
<tr>
<td valign="top" align="left">Medication history</td>
<td valign="top" align="center">0.46</td>
<td valign="top" align="center">0.708</td>
</tr>
<tr>
<td valign="top" align="left" colspan="3" style="background-color:#d9d9d9">None</td>
</tr>
<tr>
<td valign="top" align="left" colspan="3" style="background-color:#d9d9d9">AADs</td>
</tr>
<tr>
<td valign="top" align="left" colspan="3" style="background-color:#d9d9d9">Rate control</td>
</tr>
<tr>
<td valign="top" align="left" colspan="3" style="background-color:#d9d9d9">AADs&#x2009;&#x002B;&#x2009;rate control</td>
</tr>
<tr>
<td valign="top" align="left">RFCA history</td>
<td valign="top" align="center">&#x2212;1.59</td>
<td valign="top" align="center">0.113</td>
</tr>
<tr>
<td valign="top" align="left">Hs-CRP (mg/L)</td>
<td valign="top" align="center">0.16</td>
<td valign="top" align="center">0.002&#x002A;</td>
</tr>
<tr>
<td valign="top" align="left">BNP (pg/ml)</td>
<td valign="top" align="center">0.17</td>
<td valign="top" align="center">0.001&#x002A;</td>
</tr>
<tr>
<td valign="top" align="left">LA-ap (mm)</td>
<td valign="top" align="center">0.08</td>
<td valign="top" align="center">0.138</td>
</tr>
<tr>
<td valign="top" align="left">LVEDD (mm)</td>
<td valign="top" align="center">0.05</td>
<td valign="top" align="center">0.305</td>
</tr>
<tr>
<td valign="top" align="left">RA-t (mm)</td>
<td valign="top" align="center">0.01</td>
<td valign="top" align="center">0.882</td>
</tr>
<tr>
<td valign="top" align="left">RV-b (mm)</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">0.999</td>
</tr>
<tr>
<td valign="top" align="left">LVEF (&#x0025;)</td>
<td valign="top" align="center">&#x2212;0.19</td>
<td valign="top" align="center">&#x003C;0.001&#x002A;</td>
</tr>
<tr>
<td valign="top" align="left">MHI-5 score</td>
<td valign="top" align="center">&#x2212;0.28</td>
<td valign="top" align="center">&#x003C;0.001&#x002A;</td>
</tr>
<tr>
<td valign="top" align="left">PSQI score</td>
<td valign="top" align="center">0.20</td>
<td valign="top" align="center">&#x003C;0.001&#x002A;</td>
</tr>
<tr>
<td valign="top" align="left">Frail score</td>
<td valign="top" align="center">0.33</td>
<td valign="top" align="center">&#x003C;0.001&#x002A;</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="TF2"><p>BMI, body mass index; RFCA, radiofrequency catheter ablatsion; AF, atrial fibrillation; BNP, B-type natriuretic peptide; LVEF, left ventricular ejection fraction; RA-t, right atrial transverse diameter; LA-ap, left atrial anteroposterior diameter; LVEDD, left ventricular end-diastolic diameter; RV-b, right ventricular transverse diameter; Hs-CRP, high-sensitivity C-reactive protein; AADs, anti-arrhythmic drugs; OSA, obstructive sleep apnea; COPD, chronic obstructive pulmonary disease; MHI-5:Mental Health Inventory-5; PSQI, The Pittsburgh Sleep Quality Index.</p></fn>
<fn id="table-fn2a"><p>&#x002A;<italic>p</italic>&#x2009;&#x003C;&#x2009;0.05.</p></fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="T3" position="float"><label>Table&#x00A0;3</label>
<caption><p>Multiple linear regression for symptom burden of atrial fibrillation patients (<italic>N</italic>&#x2009;&#x003D;&#x2009;360).</p></caption>
<table>
<thead>
<tr>
<th valign="top" align="left">Characteristic</th>
<th valign="top" align="center"><italic>&#x03B2;</italic></th>
<th valign="top" align="center"><italic>SE</italic></th>
<th valign="top" align="center"><italic>&#x03B2;&#x2019;</italic></th>
<th valign="top" align="center"><italic>t</italic></th>
<th valign="top" align="center"><italic>p</italic></th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Common</td>
<td valign="top" align="center">18.80</td>
<td valign="top" align="center">4.59</td>
<td valign="top" align="center"/>
<td valign="top" align="center">4.09</td>
<td valign="top" align="center">0.000</td>
</tr>
<tr>
<td valign="top" align="left">Sex (female)</td>
<td valign="top" align="center">1.51</td>
<td valign="top" align="center">0.56</td>
<td valign="top" align="center">0.14</td>
<td valign="top" align="center">2.70</td>
<td valign="top" align="center">0.007&#x002A;</td>
</tr>
<tr>
<td valign="top" align="left">LVEF (&#x0025;)</td>
<td valign="top" align="center">&#x2212;13.56</td>
<td valign="top" align="center">5.25</td>
<td valign="top" align="center">&#x2212;0.15</td>
<td valign="top" align="center">&#x2212;2.58</td>
<td valign="top" align="center">0.010&#x002A;</td>
</tr>
<tr>
<td valign="top" align="left">MHI-5 score</td>
<td valign="top" align="center">&#x2212;0.06</td>
<td valign="top" align="center">0.02</td>
<td valign="top" align="center">&#x2212;0.17</td>
<td valign="top" align="center">&#x2212;3.29</td>
<td valign="top" align="center">0.001&#x002A;</td>
</tr>
<tr>
<td valign="top" align="left">Frail score</td>
<td valign="top" align="center">0.68</td>
<td valign="top" align="center">0.24</td>
<td valign="top" align="center">0.17</td>
<td valign="top" align="center">2.83</td>
<td valign="top" align="center">0.005&#x002A;</td>
</tr>
<tr>
<td valign="top" align="left">Heart failure</td>
<td valign="top" align="center">0.72</td>
<td valign="top" align="center">0.87</td>
<td valign="top" align="center">0.05</td>
<td valign="top" align="center">0.83</td>
<td valign="top" align="center">0.406</td>
</tr>
<tr>
<td valign="top" align="left">COPD</td>
<td valign="top" align="center">2.52</td>
<td valign="top" align="center">1.86</td>
<td valign="top" align="center">0.07</td>
<td valign="top" align="center">1.35</td>
<td valign="top" align="center">0.177</td>
</tr>
<tr>
<td valign="top" align="left">Coronary heart disease</td>
<td valign="top" align="center">0.56</td>
<td valign="top" align="center">0.60</td>
<td valign="top" align="center">0.05</td>
<td valign="top" align="center">0.94</td>
<td valign="top" align="center">0.351</td>
</tr>
<tr>
<td valign="top" align="left">AF type</td>
<td valign="top" align="center">0.53</td>
<td valign="top" align="center">0.60</td>
<td valign="top" align="center">0.05</td>
<td valign="top" align="center">0.88</td>
<td valign="top" align="center">0.380</td>
</tr>
<tr>
<td valign="top" align="left">BNP (pg/ml)</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">0.03</td>
<td valign="top" align="center">0.44</td>
<td valign="top" align="center">0.663</td>
</tr>
<tr>
<td valign="top" align="left">PSQI score</td>
<td valign="top" align="center">0.09</td>
<td valign="top" align="center">0.07</td>
<td valign="top" align="center">0.07</td>
<td valign="top" align="center">1.28</td>
<td valign="top" align="center">0.201</td>
</tr>
<tr>
<td valign="top" align="left">Hs-CRP (mg/L)</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">0.04</td>
<td valign="top" align="center">&#x2212;0.01</td>
<td valign="top" align="center">&#x2212;0.10</td>
<td valign="top" align="center">0.923</td>
</tr>
<tr>
<td valign="top" align="left">LA-ap (mm)</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">0.06</td>
<td valign="top" align="center">0.00</td>
<td valign="top" align="center">&#x2212;0.03</td>
<td valign="top" align="center">0.973</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="TF3"><p>R<sup>2</sup>&#x2009;&#x003D;&#x2009;21.3&#x0025;, adjusted R<sup>2</sup>&#x2009;&#x003D;&#x2009;18.4&#x0025;, F&#x2009;&#x003D;&#x2009;7.344, P&#x2009;&#x003C;&#x2009;0.001.</p></fn>
<fn id="TF4"><p>AF, atrial fibrillation; BNP, B-type natriuretic peptide; LVEF, left ventricular ejection fraction; LA-ap, left atrial anteroposterior diameter; Hs-CRP, high-sensitivity C-reactive protein; COPD, chronic obstructive pulmonary disease; PSQI, The Pittsburgh Sleep Quality Index.</p></fn>
<fn id="table-fn4a"><p>&#x002A;<italic>p</italic>&#x2009;&#x003C;&#x2009;0.05.</p></fn>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="s3c"><label>3.3</label><title>Symptom network of atrial fibrillation patients after incorporating covariates</title>
<p>Symptoms and codes are named in <xref ref-type="table" rid="T4">Table&#x00A0;4</xref>. After incorporating covariates such as MHI-5 score, sex, left ventricular ejection fraction, and frail score into the symptom network, it was observed that the MHI-5 score was most closely related to S5 (edge weight&#x2009;&#x003D;&#x2009;0.2). Sex influenced all symptoms except S7 and S2. left ventricular ejection fraction was closely connected to S4 (edge weight&#x2009;&#x003D;&#x2009;0.13) and S2 (edge weight&#x2009;&#x003D;&#x2009;0.07). Frail score was closely linked to S4 (edge weight&#x2009;&#x003D;&#x2009;0.14) and S6 (edge weight&#x2009;&#x003D;&#x2009;0.04). There were also significant correlations between frail score, MHI-5 score, and sex (<xref ref-type="fig" rid="F1">Figure&#x00A0;1</xref>).</p>
<table-wrap id="T4" position="float"><label>Table&#x00A0;4</label>
<caption><p>Symptom code.</p></caption>
<table>
<thead>
<tr>
<th valign="top" align="left">Symptoms</th>
<th valign="top" align="center"><italic>Item</italic></th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Palpitation</td>
<td valign="top">S1</td>
</tr>
<tr>
<td valign="top">Shortness of breath at rest</td>
<td valign="top">S2</td>
</tr>
<tr>
<td valign="top">Shortness of breath during physical activity</td>
<td valign="top">S3</td>
</tr>
<tr>
<td valign="top">Exercise intolerance</td>
<td valign="top">S4</td>
</tr>
<tr>
<td valign="top">Fatigue at rest</td>
<td valign="top">S5</td>
</tr>
<tr>
<td valign="top">Dizziness</td>
<td valign="top">S6</td>
</tr>
<tr>
<td valign="top">Chest pain</td>
<td valign="top">S7</td>
</tr>
</tbody>
</table>
</table-wrap>
<fig id="F1" position="float"><label>Figure&#x00A0;1</label>
<caption><p>Symptom network of atrial fibrillation patients after incorporating covariates. Red and green line segments represent the association between continuity variables, with red line segments representing a negative correlation between nodes and green representing a positive correlation between nodes. Gray line segments indicate the relationship between categorical covariates and other nodes. Wider segments indicate stronger connectivity between the two.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="fcvm-12-1617872-g001.tif"><alt-text content-type="machine-generated">A network graph depicting relationships between impact factors and atrial fibrillation symptoms. Nodes are color-coded: orange for impact factors (F1-F4) and blue for symptoms (S1-S7). Lines represent connections with varying thickness indicating strength, labeled with numerical values. Impact factors include MHI-5 score, frail score, gender, and left ventricular ejection fraction. Symptoms include palpitations, shortness of breath, exercise intolerance, fatigue, dizziness, and chest pain. The graph highlights connections such as S3 strongly linked to S4 and S5, and F4 linked to S2 and S1.</alt-text>
</graphic>
</fig>
</sec>
<sec id="s3d"><label>3.4</label><title>The symptom network of atrial fibrillation patients after controlling for the covariates</title>
<p>We identified the top three symptom connections in the network: S4 with S5 (edge weight &#x2009;&#x003D;&#x2009;0.48), S2 with S3 (edge weight&#x2009;&#x003D;&#x2009;0.46), and S3 with S4 (edge weight&#x2009;&#x003D;&#x2009;0.28). Most symptoms showed positive correlations, except for the negative correlations between S2 and S4, S3 and S6, and S1 and S4 (<xref ref-type="fig" rid="F2">Figure&#x00A0;2</xref>). The three strongest &#x201C;Strength&#x201D; indicators were S3 (node strength&#x2009;&#x003D;&#x2009;0.96), S2 (node strength&#x2009;&#x003D;&#x2009;0.88), and S4 (node strength&#x2009;&#x003D;&#x2009;0.86). This suggests that the core symptoms of atrial fibrillation patients are shortness of breath during physical activity and at rest (<xref ref-type="fig" rid="F3">Figure&#x00A0;3A</xref>).</p>
<fig id="F2" position="float"><label>Figure&#x00A0;2</label>
<caption><p>Symptom network and clusters of atrial fibrillation patients. Red line segments represent a negative correlation between nodes, and green represents a positive correlation between nodes. Wider segments indicate stronger connectivity between the two nodes.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="fcvm-12-1617872-g002.tif"><alt-text content-type="machine-generated">Network diagram depicting connections between symptoms related to breathlessness, fatigue, and cardiac issues. Orange nodes (S2 to S5) represent breathlessness and fatigue symptoms, while blue nodes (S1, S6, S7) represent cardiac symptoms. Thick green lines indicate stronger connections, with numerical values showing correlation strengths. A legend explains each symptom.</alt-text>
</graphic>
</fig>
<fig id="F3" position="float"><label>Figure&#x00A0;3</label>
<caption><p><bold>(A)</bold> Centrality indices of &#x201C;Strength&#x201D;, &#x201C;Closeness&#x201D;, and &#x201C;Betweenness&#x201D; for 7 symptoms ordered by &#x201C;Strength&#x201D;. <bold>(B)</bold> Bridge strength of symptom nodes.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="fcvm-12-1617872-g003.tif"><alt-text content-type="machine-generated">Four line graphs displaying different metrics: \"Strength\", \"Closeness\", \"Betweenness\", and \"Bridge Strength\". Graphs A (Strength, Closeness, Betweenness) and B (Bridge Strength) plot points S1 through S7 with varying trends, showing differences in values across these metrics.</alt-text>
</graphic>
</fig>
<p>We identified two symptom clusters: &#x201C;cardiac cluster&#x201D; (S1, S6, S7) and &#x201C;breathlessness and fatigue cluster&#x201D; (S2, S3, S4, S5) (<xref ref-type="fig" rid="F2">Figure&#x00A0;2</xref>). The top three symptoms with the highest bridge strength were S2 (node bridge strength&#x2009;&#x003D;&#x2009;0.21), S1 (node bridge strength&#x2009;&#x003D;&#x2009;0.16), and S7 (node bridge strength&#x2009;&#x003D;&#x2009;0.15), indicating their role in linking the clusters (<xref ref-type="fig" rid="F3">Figure&#x00A0;3B</xref>).</p>
</sec>
<sec id="s3e"><label>3.5</label><title>Accuracy and stability of the symptom network</title>
<p>Bootstrap confidence intervals for edge weights were relatively narrow, indicating good accuracy of the symptom network (<xref ref-type="fig" rid="F4">Figure&#x00A0;4</xref>). In this study, the CS values for symptom network &#x201C;strength&#x201D; centrality were 0.75. These values indicate good stability for symptom node centrality (<xref ref-type="fig" rid="F5">Figure&#x00A0;5</xref>).</p>
<fig id="F4" position="float"><label>Figure&#x00A0;4</label>
<caption><p>Bootstrap analysis results of edge weights.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="fcvm-12-1617872-g004.tif"><alt-text content-type="machine-generated">Line graph showing sample data and bootstrap mean values along various edges from S4-S5 to S3-S6. The sample line is red, and the bootstrap mean is black, with a shaded confidence interval area. The x-axis represents numeric values from 0 to 0.4.</alt-text>
</graphic>
</fig>
<fig id="F5" position="float"><label>Figure&#x00A0;5</label>
<caption><p>Correlation stability coefficient for strength, betweenness, and closeness of symptom network.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="fcvm-12-1617872-g005.tif"><alt-text content-type="machine-generated">Line graph depicting average correlation with original sample against sampled cases. Three lines represent betweenness (red), closeness (green), and strength (blue). Betweenness decreases significantly, closeness moderately, while strength remains relatively stable.</alt-text>
</graphic>
</fig>
</sec>
</sec>
<sec id="s4" sec-type="discussion"><label>4</label><title>Discussion</title>
<p>We observed that worsening mental health status was linked to a higher symptom burden, which aligns with previous research (<xref ref-type="bibr" rid="B25">25</xref>). Negative emotions were found to be strong predictors of symptom severity in atrial fibrillation patients (<xref ref-type="bibr" rid="B26">26</xref>), affecting symptom perception through attentional bias (<xref ref-type="bibr" rid="B27">27</xref>) and psychological rumination (<xref ref-type="bibr" rid="B28">28</xref>), often leading to an overestimation of symptom frequency and severity. The study also found a strong association between mental health status and Shortness of breath at rest, similar to Yu (<xref ref-type="bibr" rid="B29">29</xref>). This may be related to the chronic low-grade inflammation in atrial fibrillation, which sensitizes the amygdala circuit, activates the neuroimmune network, and induces autonomic hyperreactivity, resulting in difficulty breathing and intolerance to exercise (<xref ref-type="bibr" rid="B30">30</xref>). Therefore, healthcare professionals should recognize the impact of emotional distress on symptomatology in atrial fibrillation patients and provide proactive psychological support.</p>
<p>Female patients experience a more severe symptom burden compared to males, a phenomenon supported by numerous studies (<xref ref-type="bibr" rid="B31">31</xref>). This may be due to them less likely to be treated with rhythm control strategies (<xref ref-type="bibr" rid="B32">32</xref>), more extensive low-voltage areas in the left atrium, higher rates of complex fractionated atrial electrograms (<xref ref-type="bibr" rid="B33">33</xref>), and more severe atrial fibrosis in females (<xref ref-type="bibr" rid="B34">34</xref>), leading to more pronounced atrial remodeling and increased symptom burden. Furthermore, the study finds that sex has a broad impact on atrial fibrillation symptoms, although the mechanisms remain unclear and require further exploration.</p>
<p>Left ventricular ejection fraction is closely associated with symptoms of exercise intolerance and shortness of breath at rest. The left ventricular ejection fraction reflects the heart&#x0027;s ability to pump blood and its overall function. During atrial fibrillation episodes, hemodynamic changes lead to inadequate blood ejection, causing symptoms like dyspnea and exercise intolerance (<xref ref-type="bibr" rid="B35">35</xref>&#x2013;<xref ref-type="bibr" rid="B39">39</xref>). In addition, lower left ventricular ejection fraction is closely linked to persistent atrial fibrillation which experiences more pronounced symptoms of fatigue and exercise intolerance (<xref ref-type="bibr" rid="B40">40</xref>).</p>
<p>The more severe the frailty, the heavier the symptom burden, similar to findings in the Slawuta study (<xref ref-type="bibr" rid="B41">41</xref>). Frailty, caused by factors such as metabolic and neuroimmune dysfunction, may contribute to increased symptom burden by promoting atrial remodeling through chronic inflammatory responses (<xref ref-type="bibr" rid="B42">42</xref>). Covariate-controlled symptom networks show a closer association between frailty and exercise intolerance, as well as chest pain. One possible reason is the similarity between symptoms of atrial fibrillation and frailty, with impaired physical activity and mobility being key features of frailty. Moreover, both conditions share pathological mechanisms such as inflammation and oxidative stress (<xref ref-type="bibr" rid="B43">43</xref>). Frailty is also often characterized by a decline in skeletal muscle quantity and quality, which may contribute to exercise intolerance (<xref ref-type="bibr" rid="B42">42</xref>). Additionally, covariate-controlled symptom networks indicate a strong association between frailty and mental health status, as well as sex, highlighting the need for multidisciplinary interventions addressing various aspects such as sex and psychological factors to effectively manage symptoms in atrial fibrillation patients with frailty and improve the symptom network.</p>
<p>After controlling for confounding factors and covariates, the network shows that palpitations are negatively correlated with exercise intolerance, while dizziness and exercise intolerance are negatively correlated with shortness of breath. This may be due to atrial fibrillation reducing cardiac output (<xref ref-type="bibr" rid="B35">35</xref>&#x2013;<xref ref-type="bibr" rid="B39">39</xref>), leading to symptoms such as exercise intolerance and dizziness. At the same time, reduced cardiac output may decrease pulmonary circulation congestion, which could, in turn, alleviate shortness of breath at rest.</p>
<p>We found that the core symptoms in atrial fibrillation patients were shortness of breath during physical activity and at rest. This is consistent with our previous study (<xref ref-type="bibr" rid="B17">17</xref>), highlighting the stability of core symptoms and their representative role in symptomatology. Core symptoms can trigger a range of connected symptoms that can signal the start or worsening of other issues (<xref ref-type="bibr" rid="B14">14</xref>). During atrial fibrillation episodes, irregular atrial contractions and reduced ventricular diastolic time decrease effective cardiac output, causing compensatory shortness of breath (<xref ref-type="bibr" rid="B35">35</xref>, <xref ref-type="bibr" rid="B36">36</xref>). Hemodynamic changes may increase left ventricular filling pressure, contributing to exercise intolerance (<xref ref-type="bibr" rid="B37">37</xref>). Furthermore, atrial fibrillation patients often have endothelial dysfunction and impaired peripheral muscle oxygen uptake, which, along with hemodynamic changes, can result in fatigue and weakness due to altered muscle sensing (<xref ref-type="bibr" rid="B38">38</xref>, <xref ref-type="bibr" rid="B39">39</xref>). We identified two symptom clusters involving &#x201C;cardiac cluster&#x201D; and &#x201C;breathlessness and fatigue cluster&#x201D; in patients with atrial fibrillation, similar to Streur (<xref ref-type="bibr" rid="B44">44</xref>). &#x201C;Shortness of breath at rest&#x201D;, &#x201C;palpitations&#x201D; and &#x201C;chest pain&#x201D; were a bridge of clusters with high &#x201C;bridge strength&#x201D;. These symptoms can be targeted to improve overall symptom management (<xref ref-type="bibr" rid="B14">14</xref>). Breathing difficulties can worsen chest pain by affecting the sympathetic nervous system (<xref ref-type="bibr" rid="B37">37</xref>), triggering a cardiac symptom cluster. Additionally, palpitations and chest pain may decrease the desire for physical activity in atrial fibrillation patients, potentially leading to long-term muscle changes and exercise intolerance.</p>
<p>Our study suggests that focusing solely on controlling heart rate and rhythm in atrial fibrillation patients may not be enough (<xref ref-type="bibr" rid="B1">1</xref>). Paying attention to core symptoms like shortness of breath could help improve the entire symptom network. Although evidence is limited, treatments such as an ablation procedure and moderate exercise may help ease core symptoms and improve overall symptom management (<xref ref-type="bibr" rid="B35">35</xref>, <xref ref-type="bibr" rid="B45">45</xref>).</p>
<sec id="s4a"><label>4.1</label><title>Strengths and limitations</title>
<p>Using network analysis, we identified the mechanisms linking symptoms and influencing factors. By calculating centrality measures and bridge strength, we were able to pinpoint core and bridging symptoms, which helps in understanding the emergence of symptoms. This approach provides a better understanding of atrial fibrillation symptoms. However, this study has several limitations: it was a single-center investigation with a small sample size, limiting generalizability; its cross-sectional design reduces the strength of evidence regarding relationships between atrial fibrillation symptoms and other factors; and the use of convenience sampling may have introduced selection bias. Longitudinal studies would better elucidate symptom progression and causal relationships with influencing factors.</p>
</sec>
</sec>
<sec id="s5" sec-type="conclusions"><label>5</label><title>Conclusion</title>
<p>Employing symptom networks helps uncover the underlying mechanisms behind symptom occurrence, providing a clearer path for identifying targets for symptom management. Mental health was most closely related to &#x201C;fatigue at rest&#x201D;. Sex influenced all symptoms except &#x201C;dizziness&#x201D; and &#x201C;shortness of breath at rest&#x201D;. Left ventricular ejection fraction was closely connected to &#x201C;exercise intolerance&#x201D; and &#x201C;shortness of breath at rest&#x201D;, while the frail score was closely linked to &#x201C;exercise intolerance&#x201D; and &#x201C;dizziness&#x201D;. Shortness of breath during physical activity and at rest are identified as core symptoms, while &#x201C;shortness of breath at rest&#x201D;, &#x201C;palpations&#x201D; and &#x201C;chest pain&#x201D; serve as bridging symptoms.</p>
</sec>
</body>
<back>
<sec id="s6" sec-type="data-availability"><title>Data availability statement</title>
<p>The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.</p>
</sec>
<sec id="s7" sec-type="ethics-statement"><title>Ethics statement</title>
<p>The studies involving humans were approved by Tianjin Medical University General Hospital [Approval No. (IRB2023-WZ-111)]. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.</p>
</sec>
<sec id="s8" sec-type="author-contributions"><title>Author contributions</title>
<p>DS: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. XY: Conceptualization, Data curation, Formal analysis, Software, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. HL: Conceptualization, Investigation, Methodology, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. GL: Data curation, Investigation, Methodology, Project administration, Software, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. HL: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing.</p>
</sec>
<ack><title>Acknowledgements</title>
<p>We thank all the participants for their contribution to the study.</p>
</ack>
<sec id="s10" sec-type="COI-statement"><title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec id="s11" sec-type="ai-statement"><title>Generative AI statement</title>
<p>The author(s) declare that no Generative AI was used in the creation of this manuscript.</p>
<p>Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.</p>
</sec>
<sec id="s12" sec-type="disclaimer"><title>Publisher&#x0027;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
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<fn-group>
<fn id="n1" fn-type="custom" custom-type="edited-by"><p>Edited by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/53244/overview">Junjie Xiao</ext-link>, Shanghai University, China</p></fn>
<fn id="n2" fn-type="custom" custom-type="reviewed-by"><p>Reviewed by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/1551354/overview">Giuseppe Mascia</ext-link>, University of Genoa, Italy</p>
<p><ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/727421/overview">Dimitrios Tachmatzidis</ext-link>, Aristotle University of Thessaloniki, Greece</p>
<p><ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/2001308/overview">Jheng-Yan Wu</ext-link>, Chi Mei Medical Center, Taiwan</p></fn>
</fn-group>
</back>
</article>