Abstract
The key drivers of symptom severity in atrial fibrillation (AF) patients remain unclear. The study aimed to explore associations between anxious and depressive status and AF-related symptoms as expressed by the modified European Heart Rhythm Association (mEHRA) score. The study enrolled 182 AF patients admitted to the Cardiology Department of Peking University Third Hospital between February 2017 to January 2020. Anxious and depressive status were assessed by “Generalized Anxiety Disorder-7” and “Patient Health Questionnaire-9,” respectively. The severity of AF-related symptoms was scored by mEHRA and classified into 2 groups: low mEHRA group (mEHRA = 1 or 2a) and high mEHRA group (mEHRA ≥ 2b), according to whether they were troubled or affected by AF-related symptoms. In all 182 AF patients, 56.0% (n = 102) patients presented mEHRA ≥ 2b. The high mEHRA group had significantly higher Patient Health Questionnaire-9 score [4.0 (2.0–7.0) vs 2.5 (0–4.8), P < .001] and Generalized Anxiety Disorder-7 score [3 (0–5) vs 0 (0–3), P < .001]. After adjusted for other covariates, persistent AF (odds ratio, OR = 0.48, 95% confidence interval [CI]: 0.23, 0.99), heart failure (OR = 2.91, 95% CI: 1.08, 8.43), depressive status (OR = 2.15, 95% CI: 1.01, 4.65), and anxious status (OR = 2.83, 95% CI: 1.17, 7.38) were independently associated with high mEHRA score (≥2b). Increased anxiety and depression levels was associated with feeling troubled or limited by AF-related symptoms scored by mEHRA.
Keywords: anxiety, atrial fibrillation, depression, modified European Heart Rhythm Association score, symptom
1. Introduction
Atrial fibrillation (AF) is the most common cardiac arrhythmia in the world, the estimated prevalence of which is 1% to 4% in Australia, Europe, and the USA, and 0.49% to 1.9% in Asia.[1] It is independently associated with increased mortality, especially due to stroke or heart failure,[2] representing a major public health challenge worldwide. There are a variety of symptoms in AF patients, such as fatigue, palpitations, dyspnea, and chest tightness. Some patients have severe or disabling symptoms, while some are asymptomatic.[2,3] Many studies attempt to explain this variation. Interestingly, some researches have revealed there is no correlation between symptom severity and clinical factors including AF burden, heart rate, heart rhythm (sinus or not), premature atrial contraction, or premature ventricular contraction burden.[4,5] Moreover, some AF patients could still feel uncomfortable symptoms, or even some severe symptoms, although without any AF episode on a 7-day monitor.[4]
In recent years, more and more studies have focused on the factors influencing symptom conception in AF patients. Since objective clinic features cannot fully explain AF-related symptoms, psychological elements may participate in the process. Thrall et al[6] found that approximately one-third of patients with AF had elevated levels of depression and anxiety. A study of AF population with preserved left ventricular (LV) systolic function indicated psychological functioning, including stress, negative affectivity, and social inhibition, rather than LV diastolic function, AF burden, or ventricular rate, could predict AF-related symptoms.[5] Also, Thompson et al[7] found that increasing anxiety and depression levels were associated with higher AF-related symptom severity. However, the conclusions were inconsistent, with 1 study showing that after adjusting for other confounders, anxiety and depression were not independent predictors of AF-related symptoms improvement after catheter ablation.[8]
AF-related symptom questionnaires are designed to access the health status of AF patients with detailed content, high specificity, and sensitivity, further to identify recurrent events. Some representative questionnaires are as follows: the AF-specific Atrial Fibrillation Effect on Quality of life questionnaire, Atrial Fibrillation-Quality of life questionnaire, and University of Toronto Atrial Fibrillation Severity Scale questionnaire, etc. But most of these questionnaires are relatively time-consuming for routine diagnosis and treatment, thus limited in clinical practice. However, the European Heart Rhythm Association (EHRA) score, which was first published in 2007[9] for clinical trials and recommended by ESC guidelines,[10] is simple, convenient, and intuitive, and can be considered a useful semi-quantitative classification. It can be used to access AF-related symptoms in clinical practice without prior training. Nevertheless, there is only 1 study using EHRA score to access AF-related symptoms and simultaneously explore predictive value of negative emotions, indicating that anxiety and stress were associated with higher AF-related symptom severity.[11] The modified EHRA (mEHRA) score, which was proposed and validated in 2014,[3] separates class 2 into 2 groups based on whether the patients were troubled by their AF (Class 2b) or not (Class 2a). The mEHRA score has a clearer separation in health utility when assessing the cost efficacy of interventions, where Class 2b symptoms appear to be the appropriate treatment threshold.[3] This study aimed to explore factors influencing AF-related symptoms accessed by mEHRA score, and further study the correlation between anxious and depressive status and these symptoms.
2. Materials and methods
2.1. Patient enrollment
We prospectively recruited 182 consecutive AF patients admitted to the Department of Cardiology of Peking University Third Hospital between February 2017 to January 2020. Clinical information was collected on admission. The inclusion criteria were: (1) patients with AF validated by any electrocardiographic (ECG) documentation such as 12-lead ECG and 24-hour Holter; (2) Chinese people who have sufficient knowledge of Chinese language to fill out self-reported questionnaires; (3) age 18 years or older. The exclusion criteria were patients who cannot respond due to limited useful sight or hearing or other disabilities. Written informed consent was obtained from all participants or a legal guardian for illiterate individuals. The study was approved by the Ethics Review Boards of Peking University Third Hospital.
2.2. Collection of clinical information
The demographic and clinical information of all patients were collected, including age, sex, education, AF type, and previous history. CHA2DS2-VASc and HAS-BLED staging systems for stroke and bleeding risk were also calculated. CHA2DS2-VASc score was categorized into 2 groups: men with CHA2DS2-VASc ≥ 2 and women with CHA2DS2-VASc ≥ 3 were classified into high CHA2DS2-VASc score group.[10] The beginning of AF was defined as the first time when the patient felt related symptoms, or the first time when ECG/Holter reported AF onset. AF duration time was counted from the onset day. The comorbidities were reckoned present if there was a former diagnosis or the patient met the diagnostic criteria when recruited. AF that terminates spontaneously or with intervention within 7 days of onset is defined as paroxysmal AF. AF that is continuously sustained beyond 7 days is defined as persistent AF, including episodes terminated by cardioversion (drugs or electrical cardioversion) after ≥7 days.[10]
2.3. Instrumentations
Our study used the following questionnaire tools to quantify the symptom severity, anxious and depressive status, and cognition. The questionnaires on anxiety and depression were filled out by the participants, while others were scored by a cardiologist according to the patient’s situation and response.
2.4. mEHRA
To evaluate the severity of these symptoms and their impact on daily life, EHRA suggested the mEHRA symptom scale for use, which was first published in 2007[9] for clinical trials and was modified and validated in 2014.[3] Five levels of the mEHRA scale reflect physicians’ perspectives of patients’ symptom severity (1 = asymptomatic, 2a = mild, 2b = moderate, 3 = severe, 4 = disabling). Class 2 (symptomatic AF not limiting daily activities) is separated into 2 groups based on whether the patients were troubled by their AF (Class 2b) or not (Class 2a) (Table S1, Supplemental Digital Content, https://links.lww.com/MD/P489).[10]
2.5. Patient Health Questionnaire-9 (PHQ-9)
PHQ-9 is a brief measure of depressive severity. It comprises 9 diagnostic symptom criteria and the score of each item ranges from “0” (not at all) to “3” (nearly every day). Scores of 5, 10, and 15 represented mild, moderate, and severe depression, respectively.[12] Those with a total score of more than 4 were considered as presenting depressive symptoms. PHQ-9 has been widely used and has shown good reliability and validity in China.[13]
2.6. Generalized Anxiety Disorder-7 (GAD-7)
GAD-7 contains 7 typical anxious symptoms and investigates the frequency of each symptom AF patients are bothered by during the last 2 weeks. Each item is scored from 0 to 3 and the GAD-7 scale score ranges from 0 to 21. Cut points of 5, 10, and 15 represent mild, moderate, and severe levels of anxiety, respectively.[14] Those with a total score of more than 4 were regarded as reporting anxious symptoms. Likewise, GAD-7 performs well in China.[15]
2.7. Montreal Cognitive Assessment (MoCA)
The MoCA is a one-page cognitive screening scale ranging from 0 to 30. In comparison with Mini-Mental Status Examination, MoCA has greater sensitivity and specificity by examining more cognitive domains: visuospatial/executive functions, naming, verbal memory registration and learning, attention, abstraction, 5-min delayed verbal recall, and orientation.[16] A point is added to the total score if the subject has 12 years of education or fewer.[17] In mainland China, the cutoff points for screening mild cognitive impairment and early dementia are 13/14 for illiterate individuals, 19/20 for individuals with 1 to 6 years of education, and 24/25 for individuals with 7 or more years of education.[18]
2.8. Statistical analysis
Normally distributed data were presented as mean ± SD and non-normally ones as a median with 25th to 75th percentiles within brackets. Categorical variables were expressed as percentages. Continuous variables that showed normal distribution were compared using Student t test between 2 groups and one-way ANOVA among 4 groups. Non-normally distributed samples were compared using Mann–Whitney U test between 2 groups and Kruskal–Wallis H test among 4 groups. Chi-square test was used for categorical data. Multiple logistic analyses were performed to predict high mEHRA scores (≥2b). Results were expressed as a P value and odds ratio (OR) in confidence interval (CI) of 95%. All statistical analyses were computed using R version 4.1.2. Figures were analyzed using GraphPad Prism version 8.2.0. All reported P values were 2-sided, and a P value < .05 was considered statistically significant.
3. Results
3.1. Baseline characteristics
Of the 182 participants in our study, we divided all people into 2 groups according to whether they were troubled or affected by AF-related symptoms: the low mEHRA group (mEHRA = 1 or 2a) and the high mEHRA group (mEHRA ≥ 2b). The baseline information was presented in Table 1. Eighty (44.0%) patients were asymptomatic or had mild but not troubling symptoms (mEHRA = 1 or 2a). The total number of moderate, severe, or disabling symptom severity was 102 (56.0%). The high mEHRA group had a higher percentage of females (45.1% vs 23.8%, P = .01) and a lower percentage of persistent AF (34.3% vs 50.5%, P = .047) than the low mEHRA group. Other characteristics including age, education, AF duration time, CHA2DS2-VASc score, HAS-BLED score, comorbidities, and cognition score did not show significant relevance to symptom severity.
Table 1.
Baseline characteristics of the total population.
| Characteristics | Total | mEHRA 1or 2a (n = 80) |
mEHRA ≥ 2b (n = 102) | P |
|---|---|---|---|---|
| Clinical characters | ||||
| Age (years) | 68.2 ± 11.3 | 68.2 ± 11.1 | 68.1 ± 11.5 | .96 |
| Female, n (%) | 65 (35.7%) | 19 (23.8%) | 46 (45.1%) | .01* |
| Education | .10 | |||
| Below high school | 56 (30.8%) | 27 (33.8%) | 29 (28.4%) | |
| High school | 51 (28.0%) | 16 (20.0%) | 35 (34.3%) | |
| College and above | 75 (41.2%) | 37 (46.3%) | 38 (37.3%) | |
| AF duration | .63 | |||
| ≤1 year | 74 (40.7%) | 33 (41.3%) | 41 (40.2%) | |
| 1–5 years | 63 (34.6%) | 25 (31.3%) | 38 (37.3%) | |
| >5 years | 45 (24.7%) | 22 (27.5%) | 23 (22.5%) | |
| Persistent AF, n (%) | 75 (41.2%) | 40 (50.0%) | 35 (34.3%) | .047* |
| CHA2DS2-VASc score | 3.0 (1.3–4.0) | 2.5 (1.0–4.0) | 3.0 (2.0–4.0) | .22 |
| High CHA2DS2-VASc | 126 (69.2%) | 55 (68.8%) | 71 (69.6%) | 1.00 |
| HAS-BLED score | 1.0 (1.0–2.0) | 1.0 (1.0–2.0) | 1.0 (1.0–2.0) | .64 |
| HAS-BLED score ≥ 2 | 75 (41.2%) | 36 (45.0%) | 39 (38.2%) | .44 |
| Comorbidities | ||||
| Hypertension, n (%) | 118 (64.8%) | 52 (65.0%) | 66 (64.7%) | .97 |
| Diabetes, n (%) | 35 (19.2%) | 16 (20.0%) | 19 (18.6%) | .97 |
| Heart failure, n (%) | 29 (15.9%) | 10 (12.5%) | 19 (18.6%) | .36 |
| Stroke, n (%) | 20 (11.0%) | 6 (7.5%) | 14 (13.7%) | .27 |
| Vascular disease, n (%) | 44 (24.2%) | 19 (23.8%) | 25 (24.5%) | .91 |
| Cognition | ||||
| MoCA score | 24 (23–26) | 24 (23–26) | 24 (23–27) | .89 |
| MCI or worse | 92 (50.5%) | 41 (51.3%) | 51 (50.0%) | .99 |
AF = atrial fibrillation, MCI = mild cognitive impairment, mEHRA = modified European Heart Rhythm Association symptom scale, MoCA = Montreal Cognitive Assessment.
P < .05.
3.2. Relation between AF-related symptom severity and depressive status
As seen in Table 2, the high mEHRA group had a significantly higher PHQ-9 score than the low mEHRA group [4.0 (2.0–7.0) vs 2.5 (0–4.8), P < .001]. Also, the high mEHRA group had more patients with mild, moderate, and severe depressive status, respectively, with a significant difference in the whole distribution (P = .003). There was also a greater proportion of patients presenting depressive symptoms (PHQ-9 > 4) in the high mEHRA group (49.0% vs 25.0%, P = .001). We further divided all patients into 4 groups: asymptomatic (mEHRA = 1), mild (mEHRA = 2a), moderate (mEHRA = 2b), and severe and disabling symptom severity (mEHRA = 3–4). The difference among PHQ-9 scores of 4 mEHRA groups showed great significance (P < .001). According to the PHQ-9 severity classification, 26.9% (n = 49) of patients with AF had mild depressive symptoms and 5.5% (n = 10) had moderate depressive symptoms. There were 11 (6.0%) patients with severe depressive symptoms, 7 of which belonged to the group “mEHRA3 to 4.” The difference comparing 4 depressive classifications in 4 groups showed great significance (P = .007). The distribution of depressive severity in each group is presented in Table 2 and Figure 1.
Table 2.
Depressive status measured by PHQ-9 score in mEHRA groups.
| Total | mEHRA score | P | ||||
|---|---|---|---|---|---|---|
| 1–2a (n = 80) | ≥2b (n = 102) | |||||
| PHQ-9 score | 3.5 (1.0–6.0) | 2.5 (0–4.8) | 4.0 (2.0–7.0) | <.001* | ||
| None, 0–4 | 112 (61.5%) | 60 (75.0%) | 52 (51%) | .003* | ||
| Mild, 5–9 | 49 (26.9%) | 17 (21.3%) | 32 (31.4%) | |||
| Moderate, 10–14 | 10 (5.5%) | 2 (2.5%) | 8 (7.8%) | |||
| Severe, ≥15 | 11 (6.0%) | 1 (1.3%) | 10 (9.8%) | |||
| PHQ-9 > 4 | 70 (38.5%) | 20 (25.0%) | 50 (49.0%) | .001* | ||
| Total | mEHRA score | P | ||||
|---|---|---|---|---|---|---|
| 1 (n = 39) | 2a (n = 41) | 2b (n = 60) | 3–4 (n = 42) | |||
| PHQ-9 score | 3.5 (1.0–6.0) | 3.0 (0–6.0) | 2.0 (0–4.0) | 4.0 (1.25–6.0) | 5.5 (3.0–9.75) | <.001* |
| None, 0–4 | 112 (61.5%) | 28 (71.8%) | 32 (78.0%) | 36 (60.0%) | 16 (38.1%) | .007* |
| Mild, 5–9 | 49 (26.9%) | 10 (25.6%) | 7 (17.1%) | 16 (26.7%) | 16 (38.1%) | |
| Moderate, 10–14 | 10 (5.5%) | 1 (2.6%) | 1 (2.4%) | 5 (8.3%) | 3 (7.1%) | |
| Severe, ≥15 | 11 (6.0%) | 0 (0.0%) | 1 (2.4%) | 3 (5.0%) | 7 (16.7%) | |
| PHQ-9 > 4 | 70 (38.5%) | 11 (28.2%) | 9 (22.0%) | 24 (40%) | 26 (61.9%) | .001* |
mEHRA = modified European Heart Rhythm Association symptom scale, PHQ-9 = Patient Health Questionnaire-9.
P < .05.
Figure 1.
The distribution of depressive symptoms in groups. mEHRA = modified European Heart Rhythm Association symptom scale, PHQ-9 = Patient Health Questionnaire-9.
3.3. Relation between AF-related symptom severity and anxious status
As seen in Table 3, the high mEHRA group had a significantly higher GAD-7 score than the low mEHRA group [3 (0–5) vs 0 (0–3), P < .001]. Also, the high mEHRA group had more patients with mild, moderate, and severe anxious status than the low mEHRA group, respectively (P = .001). There was a greater proportion of patients reporting anxious symptoms (GAD-7 > 4) in the high mEHRA group (32.4% vs 11.3%, P = .001). Moreover, the GAD-7 scores of the 4 mEHRA groups existed significant difference (P = .004). The mild, moderate, severe anxious status account for 17.6% (n = 32), 4.4% (n = 8), 1.1% (n = 2) of AF patients, respectively. There was a significant difference in GAD-7 score distribution among 4 mEHRA groups (P = .049) (Table 3 and Fig. 2). More than 90% of asymptomatic patients showed no evidence of anxious symptoms while nearly one-third of the group “mEHRA3 to 4” had varying degrees of anxious symptoms.
Table 3.
Anxious status measured by GAD-7 score in mEHRA groups.
| Total | mEHRA score | P | ||||
|---|---|---|---|---|---|---|
| 1–2a (n = 80) | ≥2b (n = 102) | |||||
| GAD-7 score | 1 (0–4) | 0 (0–3) | 3 (0–5) | <.001* | ||
| None, 0–4 | 140 (76.9%) | 71 (88.8%) | 69 (67.6%) | .001* | ||
| Mild, 5–9 | 32 (17.6%) | 9 (11.3%) | 23 (22.5%) | |||
| Moderate, 10–14 | 8 (4.4%) | 0 (0%) | 8 (7.8%) | |||
| Severe, 15–21 | 2 (1.1%) | 0 (0%) | 2 (2.0%) | |||
| GAD-7 > 4 | 42 (23.1%) | 9 (11.3%) | 33 (32.4%) | .001* | ||
| Total | mEHRA score | P | ||||
|---|---|---|---|---|---|---|
| 1 (n = 39) | 2a (n = 41) | 2b (n = 60) | 3–4 (n = 42) | |||
| GAD-7 score | 1 (0–4) | 0 (0–3) | 1 (0–3) | 3 (0–5) | 2 (0–5) | .004* |
| None, 0–4 | 140 (76.9%) | 36 (92.3%) | 35 (85.4%) | 40 (66.7%) | 29 (69.0%) | .049* |
| Mild, 5–9 | 32 (17.6%) | 3 (7.7%) | 6 (14.6%) | 14 (23.3%) | 9 (21.4%) | |
| Moderate, 10–14 | 8 (4.4%) | 0 (0.0%) | 0 (0.0%) | 5 (8.3%) | 3 (7.1%) | |
| Severe, 15–21 | 2 (1.1%) | 0 (0.0%) | 0 (0.0%) | 1 (1.7%) | 1 (2.4%) | |
| GAD-7 > 4 | 42 (23.1%) | 3 (7.7%) | 6 (14.6%) | 20 (33.3%) | 13 (31%) | .007* |
GAD-7 = Generalized Anxiety Disorder-7, mEHRA = modified European Heart Rhythm Association symptom scale.
P < .05.
Figure 2.
The distribution of anxious symptoms in groups. GAD-7 = Generalized Anxiety Disorder-7, mEHRA = modified European Heart Rhythm Association symptom scale.
3.4. Multiple logistic regression for symptom severity
Multiple logistic regression results for mEHRA score ≥ 2b were shown in Table 4. Patients with persistent AF had lower odds of being troubled by AF-related symptoms, compared to patients with paroxysmal AF (OR = 0.48, 95% CI: 0.23, 0.99, P = .049). Patients with HF had higher odds of being troubled by AF-related symptoms (OR = 2.91, 95% CI: 1.08, 8.43, P = .04). Patients with depressive status had 115% increased odds of being troubled by AF-related symptoms (OR = 2.15, 95% CI: 1.01, 4.65, P = .049), and patients with anxious status had 183% increased odds of being troubled by AF-related symptoms (OR = 2.83, 95% CI: 1.17, 7.38, P = .03).
Table 4.
Multiple logistic analysis for mEHRA score ≥ 2b.
| OR | 95% CI | P | |
|---|---|---|---|
| Age (years) | 1.01 | (0.97, 1.06) | .51 |
| Female | 2.01 | (0.96, 4.26) | .07 |
| Education | |||
| Below high school | Ref | – | – |
| High school | 1.90 | (0.75, 4.90) | .18 |
| College and above | 1.03 | (0.46, 2.33) | .94 |
| AF duration | |||
| ≤1 year | Ref | – | – |
| 1–5 years | 0.96 | (0.44, 2.13) | .93 |
| >5 years | 0.59 | (0.24, 1.42) | .24 |
| Persistent AF | 0.48 | (0.23, 0.99) | .049* |
| High CHA2DS2-VASc | 0.68 | (0.20, 2.29) | .54 |
| HAS-BLED score ≥ 2 | 0.66 | (0.29, 1.45) | .30 |
| Hypertension, n (%) | 0.97 | (0.43, 2.18) | .95 |
| Diabetes, n (%) | 0.73 | (0.30, 1.76) | .49 |
| Heart failure, n (%) | 2.91 | (1.08, 8.43) | .04* |
| Vascular disease, n (%) | 1.20 | (0.49, 3.00) | .69 |
| MCI or worse | 0.75 | (0.37, 1.49) | .42 |
| Depressive status (PHQ-9 > 4) | 2.15 | (1.01, 4.65) | .049* |
| Anxious status (GAD-7 > 4) | 2.83 | (1.17, 7.38) | .03* |
AF = atrial fibrillation, CI = confidence interval, GAD-7 = Generalized Anxiety Disorder-7, MCI = mild cognitive impairment, mEHRA = modified European Heart Rhythm Association symptom scale, OR = odds ratio, PHQ-9 = Patient Health Questionnaire-9, Ref = reference.
P < .05.
4. Discussion
In this study, we found AF type, anxious and depressive status were significantly associated with AF-related symptoms as indicated by mEHRA score. Increasing anxious and depressive levels were related to feeling troubled or limited by AF-related symptoms. To the best of our knowledge, this is the first study investigating factors influencing AF-related symptoms scored by mEHRA, which considered the influence of subjective emotion.
Psychological distress is increasingly prevalent nowadays. Several aspects of personality style, such as anxiety sensitivity, negative personality, stress perception, neuroticism, and somatization, are related to the subjective experience of AF.[5] Some studies have demonstrated a strong correlation between AF symptoms and anxiety, although it was unclear whether anxiety was a consequence of AF symptom or a driving force.[7,19] Our study showed that depressive status was also an important determinant of subjective AF-related symptom. A study of 118 patients with persistent AF showed that AF patients experienced significantly higher levels of anxiety and depression than the general population. Also, AF patients with higher depression levels reported significantly more AF symptoms, and reported symptoms to occur with a higher frequency during the AF episode.[20] Thompson et al demonstrated that increased anxiety or depression was associated with increased AF symptom severity.[7] Depression and anxiety were also correlated with AF recurrence after ablation.[21] However, many of these prior studies are limited by their use of general quality of life instruments or complicated AF-related symptom questionnaires. The mEHRA score might serve as a more appropriate way to be used in clinical work because of its simplicity and convenience.
Several possible mechanisms behind this relationship have been suggested, although it remains unclear. Inflammation is 1 vital mechanism of AF occurrence and development, and relates to AF recurrence after ablation. Biomarkers of inflammation, such as inflammatory cytokines and acute-phase proteins, are also expressed significantly higher in patients with depression and anxiety.[22] Stress response and immune system activation play a role in the development of depression and anxiety. Stress-induced inflammation harms brain function and ultimately affects mental health, facilitating depression and anxiety emerging.[23] Moreover, depression and anxiety increase people’s focus on bodily sensation, which in turn may influence the report of somatic complaints. Another potential mechanism between psychological comorbidities and AF-related complaints is the activation of the sympathetic system. The increased sympathetic tone could augment inflammation and further contribute to increased symptoms by having direct effects on brain regions critical for the regulation of depression and anxiety.[24] Sympathetic overactivation can also induce significant and heterogeneous changes in atrial electrophysiology and increase vulnerability to AF.[25] Further research is needed on ways to reduce the body-centered attentional bias in AF patients with emotional distress. For some highly distressed AF patients, they should be recommended to a psychologist to get more professional treatment. For cardiologists, there are also some methods they could do that may help, such as taking more time answering questions from anxious patients, and timely and appropriate provision of different levels of information tailored to a patient’s coping styles and preferences,[26] thus reducing the degree of anxiety and depression, and relieving symptomatic burden of AF to some extent.
We also found persistent AF patients were less likely to report AF-related symptoms, in agreement with other studies. A study of 3119 patients showed permanent AF was around threefold more common in asymptomatic than in symptomatic patients.[27] Data of 6196 AF patients manifested that a higher proportion of asymptomatic patients were found to have non-paroxysmal AF.[28] Commonly, the onset of AF is continuous in persistent and permanent AF patients. Therefore, it is likely that they live with and get accustomed to AF presence. This could be 1 reason why their subjective reports of AF symptoms are less than paroxysmal AF patients. Our study also found that women were reported to have higher symptom burdens indicated by mEHRA score. Previous research has also shown that there were gender differences in AF-related symptoms, indicating female was associated with symptomatic AF.[27,28] Women with AF reported poorer functional status and poorer AF-related quality of life, higher anxiety, higher symptoms of depression, and AF symptom severity, compared with men.[29] Women tend to be more symptomatic, and the higher symptoms of anxiety and depression among women may contribute to higher AF symptom severity. However, it is reported that women were less likely to receive invasive rhythm control therapy such as electrical cardioversion or ablation to reduce symptom severity.[30] Therefore it is crucial to engage with patients to identify their values, needs and preferences for care, and then articulate a tailored treatment strategy that incorporates personal values and guidance recommendations.[31] In addition, a different chest wall conformation may be associated with a different symptom perception in AF patients. Recent findings indicate that asymptomatic persistent AF patients are typically older males with a more circular thoracic shape. Conversely, symptomatic AF patients tend to be younger females presenting with a concave-shaped chest wall conformation characterized by a narrow antero-posterior thoracic diameter.[32] However, our study did not include any assessment of chest wall shape, indicating that our future research should incorporate this factor to further elucidate its role in AF-related symptom perception.
The pathophysiologic mechanisms of AF-related symptoms also contain decreased LV function and impaired myocardial perfusion,[33] consistent with our results that HF patients had a higher AF symptom burden. AF is often accompanied by HF, which may present similar symptoms; HF may also aggravate AF symptoms and functional status. We further conducted the multiple logistic regression in patients without HF, and the results suggested that anxious and depressive status were still associated with AF-related symptoms. Interestingly, 1 previous study revealed that asymptomatic AF patients are more frequently with increased cardiovascular disease burden, comorbidities, thromboembolic risks, and mortality.[27] Unlike our work, however, it defined “cardiovascular disease burden” mainly as previous myocardial infarction rather than heart failure. These findings highlight the need for further research into the relationship between cardiovascular disease and AF symptoms while underscoring the importance of monitoring asymptomatic AF patients given their elevated long-term risk.
AF could also increase the risk of cognitive decline and dementia through multiple ways, containing cerebral hypoperfusion, brain ischemia, silent brain infarcts, brain atrophy, and changes in homeostasis favoring thrombosis, especially with a long AF duration time.[34] However, there was no data exploring the association between cognition and AF-related symptoms yet, and our study didn’t find a significant association between mild cognitive impairment (defined by MoCA) and AF symptom burden. It was worth further study enrolling more participants to explore this relationship.
There are some inherent limitations in our study. Firstly, the sample size was relatively small and all came from a single center, which may cause a statistical bias. Secondly, it is only an observational cross-sectional study, without following up with these AF patients after treatments such as catheter ablation or antiarrhythmic drugs to evaluate their effects on anxiety and depression change. Finally, studies should further explore whether psychological comorbidities are a trigger or a result of AF-related symptoms, or whether these conditions develop concurrently, and which psychophysiological processes play a role.
5. Conclusions
In conclusion, our study confirmed and extended the relationship between psychological comorbidities and AF-related symptoms. It suggested that AF type, previous heart failure, gender, anxious, and depressive status played a central role in AF-related symptoms. These findings call for clinicians’ attention to the levels of depression and anxiety in AF patients. It also helps clinicians to assess the cost efficacy of interventions such as ablation, according to the mEHRA score. This evaluation might allow identification of patients who are most likely to benefit from interventions.
Author contributions
Conceptualization: Ying Wei, Danlei Zheng, Lei Li.
Data curation: Danlei Zheng, Ning Zhao, Yi Li, Chen Wang.
Formal analysis: Ying Wei, Danlei Zheng.
Funding acquisition: Lei Li.
Investigation: Ying Wei, Danlei Zheng, Ning Zhao, Lei Li.
Methodology: Ying Wei, Danlei Zheng, Ning Zhao, Yi Li, Chen Wang, Lei Li.
Project administration: Ming Cui, Lei Li.
Resources: Ming Cui, Lei Li.
Software: Ying Wei, Danlei Zheng.
Supervision: Ming Cui, Lei Li.
Validation: Ying Wei.
Visualization: Ying Wei.
Writing – original draft: Ying Wei, Danlei Zheng.
Writing – review & editing: Ning Zhao, Yi Li, Chen Wang, Ming Cui, Lei Li.
Supplementary Material
Abbreviations:
- AF
- atrial fibrillation
- CI
- confidence interval
- ECG
- electrocardiographic
- EHRA
- European Heart Rhythm Association
- GAD-7
- Generalized Anxiety Disorder-7
- LV
- left ventricular
- mEHRA
- modified European Heart Rhythm Association
- MoCA
- Montreal Cognitive Assessment
- OR
- odds ratio
- PHQ-9
- Patient Health Questionnaire-9
This work was supported by the National Natural Science Foundation of China (Grant No. 31700674 to Lei Li).
The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Review Boards of Peking University Third Hospital. Informed consent was obtained from all subjects or a legal guardian for illiterate individuals involved in the study.
The authors have no conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request.
Supplemental Digital Content is available for this article.
How to cite this article: Wei Y, Zheng D, Zhao N, Li Y, Wang C, Cui M, Li L. Association between atrial fibrillation-related symptoms scored by modified European Heart Rhythm Association (mEHRA) and anxious and depressive status. Medicine 2025;104:29(e43511).
YW and DZ contributed equally to this work.
Contributor Information
Ying Wei, Email: weiying@bjmu.edu.cn.
Danlei Zheng, Email: zhengdanlei@pku.edu.cn.
Ning Zhao, Email: zhaoning1997@pku.edu.cn.
Yi Li, Email: dr_lilei@bjmu.edu.cn.
Chen Wang, Email: pumc_wangchen@student.pumc.edu.cn.
Ming Cui, Email: mingcui@bjmu.edu.cn.
References
- [1].Zulkifly H, Lip GYH, Lane DA. Epidemiology of atrial fibrillation. Int J Clin Pract. 2018;72:e13070. [DOI] [PubMed] [Google Scholar]
- [2].Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37:2893–962. [DOI] [PubMed] [Google Scholar]
- [3].Wynn GJ, Todd DM, Webber M, et al. The European Heart Rhythm Association symptom classification for atrial fibrillation: validation and improvement through a simple modification. Europace. 2014;16:965–72. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [4].Patel N, Chung EH, Mounsey JP, Schwartz JD, Pursell I, Gehi AK. Effectiveness of atrial fibrillation monitor characteristics to predict severity of symptoms of atrial fibrillation. Am J Cardiol. 2014;113:1674–8. [DOI] [PubMed] [Google Scholar]
- [5].Walters TE, Wick K, Tan G, et al. Symptom severity and quality of life in patients with atrial fibrillation: psychological function outweighs clinical predictors. Int J Cardiol. 2019;279:84–9. [DOI] [PubMed] [Google Scholar]
- [6].Thrall G, Lip GY, Carroll D, Lane D. Depression, anxiety, and quality of life in patients with atrial fibrillation. Chest. 2007;132:1259–64. [DOI] [PubMed] [Google Scholar]
- [7].Thompson TS, Barksdale DJ, Sears SF, Mounsey JP, Pursell I, Gehi AK. The effect of anxiety and depression on symptoms attributed to atrial fibrillation. Pacing Clin Electrophysiol. 2014;37:439–46. [DOI] [PubMed] [Google Scholar]
- [8].Barmano N, Charitakis E, Karlsson JE, Nystrom FH, Walfridsson H, Walfridsson U. Predictors of improvement in arrhythmia-specific symptoms and health-related quality of life after catheter ablation of atrial fibrillation. Clin Cardiol. 2019;42:247–55. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [9].Kirchhof P, Auricchio A, Bax J, et al. Outcome parameters for trials in atrial fibrillation: executive summary. Eur Heart J. 2007;28:2803–17. [DOI] [PubMed] [Google Scholar]
- [10].Hindricks G, Potpara T, Dagres N, et al. 2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J. 2021;42:373–498. [DOI] [PubMed] [Google Scholar]
- [11].Sadlonova M, Senges J, Nagel J, et al. Symptom severity and health-related quality of life in patients with atrial fibrillation: findings from the observational ARENA Study. J Clin Med. 2022;11:1140. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [12].Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16:606–13. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [13].Chen S, Chiu H, Xu B, et al. Reliability and validity of the PHQ-9 for screening late-life depression in Chinese primary care. Int J Geriatr Psychiatry. 2010;25:1127–33. [DOI] [PubMed] [Google Scholar]
- [14].Spitzer RL, Kroenke K, Williams JB, Löwe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006;166:1092–7. [DOI] [PubMed] [Google Scholar]
- [15].Wu Q, Luo X, Chen S, et al. Stigmatizing attitudes towards mental disorders among non-mental health professionals in six general hospitals in hunan province. Front Psychiatry. 2019;10:946. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [16].Finney GR, Minagar A, Heilman KM. Assessment of mental status. Neurol Clin. 2016;34:1–16. [DOI] [PubMed] [Google Scholar]
- [17].FAQ | MoCA - Cognitive Assessment. MoCA cognitive assessment. Available at: https://www.mocatest.org/faq/ [Access date August 20, 2022]. [Google Scholar]
- [18].Lu J, Li D, Li F, et al. Montreal cognitive assessment in detecting cognitive impairment in Chinese elderly individuals: a population-based study. J Geriatr Psychiatry Neurol. 2011;24:184–90. [DOI] [PubMed] [Google Scholar]
- [19].Charitakis E, Barmano N, Walfridsson U, Walfridsson H. Factors predicting arrhythmia-related symptoms and health-related quality of life in patients referred for radiofrequency ablation of atrial fibrillation: an observational study (the SMURF Study). JACC Clin Electrophysiol. 2017;3:494–502. [DOI] [PubMed] [Google Scholar]
- [20].Kupper N, van den Broek KC, Widdershoven J, Denollet J. Subjectively reported symptoms in patients with persistent atrial fibrillation and emotional distress. Front Psychol. 2013;4:192. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [21].Efremidis M, Letsas KP, Lioni L, et al. Association of quality of life, anxiety, and depression with left atrial ablation outcomes. Pacing Clin Electrophysiol. 2014;37:703–11. [DOI] [PubMed] [Google Scholar]
- [22].Felger JC. Imaging the role of inflammation in mood and anxiety-related disorders. Curr Neuropharmacol. 2018;16:533–58. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [23].Peirce JM, Alviña K. The role of inflammation and the gut microbiome in depression and anxiety. J Neurosci Res. 2019;97:1223–41. [DOI] [PubMed] [Google Scholar]
- [24].Michopoulos V, Powers A, Gillespie CF, Ressler KJ, Jovanovic T. Inflammation in fear- and anxiety-based disorders: PTSD, GAD, and Beyond. Neuropsychopharmacology. 2017;42:254–70. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [25].Chen PS, Chen LS, Fishbein MC, Lin SF, Nattel S. Role of the autonomic nervous system in atrial fibrillation: pathophysiology and therapy. Circ Res. 2014;114:1500–15. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [26].Bellani ML. Psychological aspects in day-case surgery. Int J Surg. 2008;6(Suppl 1):S44–6. [DOI] [PubMed] [Google Scholar]
- [27].Boriani G, Laroche C, Diemberger I, et al. Asymptomatic atrial fibrillation: clinical correlates, management, and outcomes in the EORP-AF Pilot General Registry. Am J Med. 2015;128:509–18.e2. [DOI] [PubMed] [Google Scholar]
- [28].Bakhai A, Darius H, De Caterina R, et al. Characteristics and outcomes of atrial fibrillation patients with or without specific symptoms: results from the PREFER in AF registry. Eur Heart J Qual Care Clin Outcomes. 2016;2:299–305. [DOI] [PubMed] [Google Scholar]
- [29].Gleason KT, Dennison Himmelfarb CR, Ford DE, et al. Association of sex and atrial fibrillation therapies with patient-reported outcomes. Heart. 2019;105:1642–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [30].Schnabel RB, Pecen L, Ojeda FM, et al. Gender differences in clinical presentation and 1-year outcomes in atrial fibrillation. Heart. 2017;103:1024–30. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [31].Hendriks J, Strömberg A. Gender differences in atrial fibrillation: patient-reported outcomes beyond symptom management alone. Heart. 2019;105:1614–5. [DOI] [PubMed] [Google Scholar]
- [32].Sonaglioni A, Grasso E, Nicolosi GL, Lombardo M. Modified Haller Index is inversely associated with asymptomatic status in atrial fibrillation patients undergoing electrical cardioversion: a preliminary observation. Minerva Cardiol Angiol. 2024;72:190–203. [DOI] [PubMed] [Google Scholar]
- [33].Rienstra M, Lubitz SA, Mahida S, et al. Symptoms and functional status of patients with atrial fibrillation: state of the art and future research opportunities. Circulation. 2012;125:2933–43. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [34].Ladwig KH, Goette A, Atasoy S, Johar H. Psychological aspects of atrial fibrillation: a systematic narrative review: Impact on incidence, cognition, prognosis, and symptom perception. Curr Cardiol Rep. 2020;22:137. [DOI] [PMC free article] [PubMed] [Google Scholar]
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