Abstract
Background
Disease-specific patient reported outcome measures (PROMs) are widely used to evaluate not only a patient’s view of their symptoms, functional status, and health related quality of life, but also clinical benefit of treatments. The Patient Perspective of Arrhythmia Questionnaire (PPAQ) was initially developed as a self-administered, disease-specific PROM for patients with supraventricular tachycardia (SVT) assessing the impact of the arrhythmia and symptoms on patients’ daily activities and physical, emotional, and social functioning. Preliminary evidence of content and construct validity has been previously demonstrated, but only in SVT patients in the U.S. and Poland. The aim of this study was to further evaluate the concurrent validity of the PPAQ in patients having a variety of arrhythmias and to explore whether differences in symptoms existed by gender.
Methodology
In this cross-sectional study, adult cardiac arrhythmia outpatients from a tertiary care, academic medical center completed the 6-item PPAQ, the SF-12, a Fatigue Visual Analog Scale (VAS), the Brief Symptom Inventory (BSI), and the Patient Health Questionnaire (PHQ-9). Included were patients with atrial fibrillation (82.4%), ventricular tachycardia (15.7%), and atrial tachycardia (2%). Descriptive statistics and independent t-tests, pairwise comparisons with Pearson correlations, Goodman Kruskal gamma statistic for ordinal associations, Cronbach’s alpha, and Kuder-Richardson-20 (KR-20) were used to determine concurrent construct validity and internal consistency reliability.
Results
Participants (n=51) had a mean age of 59.4 years (± 12.6), were majority male (66.7%) and Caucasian (75%). Preliminary evidence of concurrent construct validity was found based on moderate to strong correlations (range from 0.4 to 0.7) between the PPAQ and other validated measures, as well as strong internal reliability (KR-20 of 0.80 and Cronbach’s alpha of 0.91). The most common symptoms reported were fatigue (60.8%) and heart fluttering (52.9%). Blurred vision (p<0.04), dizziness (p<0.01), and fatigue (p<0.04) were seen significantly more frequently in men compared to women.
Conclusions
Results present additional evidence of the validity and reliability of the PPAQ. The PPAQ comprehensively measures the burden of the disease from cardiac arrhythmia patients’ perspective. Validated, reliable, disease-specific PROMs are needed to direct personalized clinical decision-making.
Keywords: Cardiac arrhythmias, Patient Perspective of Arrhythmia Questionnaire, Symptoms, Reliability and validity, Atrial fibrillation
Background
Cardiac arrhythmias are experienced by millions of individuals globally and include supraventricular tachycardia (SVT), atrial fibrillation (AF), and ventricular tachycardia (VT) [1, 2]. AF is the most common irregular, rapid heart rhythm seen in clinical practice affecting over 6 million people in the U.S. and is a rising epidemic as the population ages [3]. Other narrow complex SVTs, typically seen in younger adults, are estimated to have a prevalence of 2.25 per 1,000 individuals, and VT is thought to occur in about 6% of people [2, 4–6]. Diagnosis by ECG is often difficult due to the sporadic nature and short duration of episodes [4, 7, 8]. The paroxysmal and unpredictable nature of occurrences, the frequency, severity, and duration of symptoms, as well as any necessary hospitalizations negatively affect patient quality of life. In addition to the actual disruptions caused by the episodes, patients’ lives may be further impaired by activity, dietary, and/or job restrictions, as well as medication side effects [7, 9, 10].
Women with arrhythmias are misdiagnosed with panic disorders 33% more often than men, resulting in delay of care for women [4, 8, 11]. Women experience delays in access to treatment because of misdiagnosis, [4, 8, 11–13] causing severe adverse effects as patients struggle to manage arrhythmia episodes over time. Anxiety and depression are associated with changes in symptoms and increased morbidity and mortality in other cardiac patients, yet the prevalence of these symptoms has not been routinely measured in arrhythmia patients [14–16].
Patient reported outcomes measures (PROMs) evaluate a patient’s view of their functional status, their symptoms, and health related quality of life, as well as the clinical benefit of various treatments and their use is becoming recognized as an important part of personalized medicine and patient centered care [17–19]. Disease-specific PROMs include specific aspects of conditions that are more sensitive to change after treatment. Unfortunately, in chronic illnesses such as cardiac arrhythmias, these data often go unreported due to lack of disease-specific measurement tools [20].
The Patient Perspective of Arrhythmia Questionnaire (PPAQ) was initially developed in 2009 as a disease-specific PROM for patients with SVT assessing the impact of the arrhythmia and symptoms on patients’ daily activities and physical, emotional, and social functioning [21]. The complete questionnaire is included in that publication as an Appendix [21]. Preliminary evidence of content and construct validity was previously demonstrated using qualitative patient interviews, exploratory factor analysis and revision, expert physician, nurse, and SVT patient review, pilot study testing after revisions, and regression analysis, but only in SVT patient cohorts [21–24]. The aim of this study was to further examine concurrent validity of the PPAQ in patients with a variety of cardiac arrhythmias to build further evidence of validity and reliability in these additional patient groups and to explore whether differences existed in symptoms by gender.
Methods
Design and sample
This was a descriptive, cross-sectional study including outpatients with a variety of cardiac arrhythmias. Patients were recruited from a large, western U.S. academic medical center’s outpatient clinic. Inclusion criteria were age > 18 years, willing/able to participate and speak/read English and having symptomatic arrhythmias. Exclusion criteria included the following: having structural heart disease or unstable angina; myocardial infarction or coronary bypass surgery within the past six months; NYHA ≥ Class 2 heart failure; a reversible cause of arrhythmia (including temporary electrolyte imbalances, hyperthyroidism, or pericarditis); an acute, life-threatening condition or a life expectancy of < 6-months; any hemodynamic instability; or any cognitive limitations preventing accurate completion of the questionnaire. Cognitive function was assessed by the research team based on our review of subjects’ clinical history and the subject being asked to look at their watch or the clinic wall clock to tell us the time. The study protocol received expedited approval by the University of California, San Francisco Committee on Human Subjects prior to recruitment of participants and data collection. All patients provided written informed consent. This study was conducted in accordance with the ethical norms and standards set forward in the Declaration of Helsinki and received no grant award from any funding agency in the public, commercial or not-for-profit sectors.
Study procedures
Patients were identified as potential subjects from electrophysiology outpatient clinic schedules and were approached in the exam room by the physician. Subjects were given verbal and written information about the details of the study by members of the study team. Those enrolled completed the questionnaires in the clinic while they waited between tests. To establish concurrent validity, scores from the new questionnaire are compared with scores from already established, valid questionnaires measuring similar concepts administered at the same time.
Clinical measures
Patient Perception of Arrhythmia Questionnaire (PPAQ)
Preliminary validity and reliability of the PPAQ has been previously reported for patients with SVT, but not other arrhythmias [21–24]. The 6-item PPAQ addresses four main concepts pertaining to arrhythmia patient experiences such as: frequency and duration of the arrhythmia episodes, a symptom list (presence/absence of symptoms and the severity of the symptoms present), the range of daily activities affected by the arrhythmia symptoms (Impact of Arrhythmia 10-item subscale), and restricted activity days (indicating the number of days to which daily activities are interrupted or limited each month). Patients are asked to recall the past four weeks to provide responses. Two questions on the PPAQ address the frequency and duration of arrhythmia episodes and these are scored at the item level. The frequency response options range from ‘not at all’ (0) to ‘three or more times daily’ (9). The duration response options range from ‘not applicable’ (0) to ‘longer than one hour’ (8).
The PPAQ includes a symptom list with 18 symptoms listed and an additional blank option of ‘other symptoms’ for patients to write in symptoms not addressed by the symptoms listed (scores range from 0 −19). Patients are asked to check “yes/no” if present and then rank the severity of those symptoms present on a Likert-type scale from “not at all” (0) to “extremely bothersome” (4). The number of symptoms is a sum of items marked ‘yes’ and scores range from 0–19, with higher scores indicating a larger symptom burden. Prevalence of symptoms marked ‘yes’ are reported as frequencies. Severity score is reported as mean +/- SD and ranges from 0–76, with higher scores indicating more severity.
The Impact of Arrhythmia (Impact subscale) is a 10-item subscale of the PPAQ including a range of daily or social activities potentially curtailed by the arrhythmia. The Likert-type response options for the Impact subscale items range from ‘not at all’ (0) to ‘extremely’ (4). The subscale items are summed and then transformed to a 0–100 scale, with higher scores indicating more adverse effect of the arrhythmia on one’s life (lowered quality of life) [21]. Finally, there are two restricted activity day questions asking how many days per month the patient took off from work, school, or usual activities due to the arrhythmia, with scores ranging from 0–31 days per month with higher scores indicating more activity restrictions due to the arrhythmia.
Fatigue Visual Analog Scale (VAS)
The one-item fatigue visual analog scale was used for concurrent construct validity purposes to correlate with the symptom of fatigue/no energy on the PPAQ symptom list. Scores on the fatigue VAS ranged from 0 (no fatigue) to 10 (highest fatigue) and participants were asked to rank severity of feelings of fatigue/tiredness they perceived was associated with their arrhythmia episodes.
Short Form-12 (SF-12) survey
Additionally, we used the SF-12 generic quality of life questionnaire to correlate with the PPAQ for concurrent construct validity analysis. The SF-12 is a 12-item survey developed from the original Medical Outcomes Study SF-36 item tool [25]. The SF-12 is typically scored using two component summary scores (physical, mental) ranging from 0–100, with higher scores indicating better quality of life. Higher scores on the SF-12 subscales denote better quality of life, mental and physical health. Both physical and mental component summary scores (PCS and MCS) use a mean scale of 50 with standard deviation of 10 [25]. The physical function domain scale and overall quality of life scores were correlated with the PPAQ number of symptoms from the symptom list and the Impact subscale of the PPAQ for one analysis of concurrent validity of the PPAQ. We also scored the SF-12 in eight SF-12 subscale scores (ranging from 0 to 100) to use the SF-12 Energy/Vitality domain subscale (item 6b) in concurrent validity analysis to compare to the PPAQ scores. The SF-12 item 6b question stem is: “How much time during the past 4 weeks did you have a lot of energy?”. The Likert-type item response options range from “all of the time” (1) to “none of the time” (5), with higher scores indicating less energy/more fatigue and a worse quality of life. We correlated scores from the PPAQ fatigue symptom (presence/absence of fatigue) with item 6b scores from the SF-12 with the fatigue VAS score for concurrent validity testing.
Brief Symptom Inventory (BSI)
The BSI anxiety and depression subscale scores (each six-item scales) measure symptoms of anxiety and depression. Patients are requested to recall the past week and record their symptoms on a scale ranging from “none at all” (0) to “extremely frequently” (4). The items are summed and averaged for the total score ranging from 0 to 4, with higher scores indicating higher levels of psychologic distress [26]. Mean scores reported for the depression subscale are reported as 0.28 for healthy individuals and 1.77 for inpatient psychiatric patients [26]. We chose a cut point of 0.28 or higher to demonstrate the presence of depressive symptoms for this study. We expected to see less physical activity in arrhythmia patients who had more depressive symptoms; therefore, we correlated the BSI depressive symptom total score with the number of restricted activity days reported on the PPAQ and the PPAQ’s Impact subscale score as one step to establish evidence of concurrent construct validity of the PPAQ.
Patient Health Questionnaire (PHQ-9)
The PHQ-9 is a 9-item survey measuring depressive symptoms. Patients were asked to reflect on the prior two weeks and note the frequency with which they experienced any of the depressive symptoms listed from “not at all” to “nearly every day.” Total scores could range from 0 to 27, with 0 representing no depressive symptoms and 27 representing severe depression [27]. To establish preliminary evidence of concurrent construct validity, we wanted to compare the total PHQ-9 depressive symptom score to the number of restricted activity days reported on the PPAQ and the PPAQ’s Impact subscale score. From the PHQ-9, we also used question 4, “Have you experienced feeling tired or having little energy?” with response options in a Likert type scale ranging from “not at all” (0) to “nearly every day” (3) [27]. Higher scores on this item indicated less energy and more fatigue. The scores on this item were correlated with scores on the Fatigue VAS and the PPAQ fatigue symptom (presence/absence).
Statistical analysis
Descriptive statistics were conducted for all baseline demographic and clinical variables. All continuous variables are described as mean +/- SD, while categorical variables are presented as proportions. Psychometric properties of the questionnaires were assessed with a focus on validity and reliability analyses. Validity is whether a questionnaire measures what it is supposed to measure and whether it does not measure what it is not supposed to measure. Concurrent validity demonstrates how well the questionnaire correlates with another measure considered to be an acceptable, previously validated standard. For supporting the concurrent construct validity of the PPAQ, we provided pairwise comparison using Pearson correlation for two following sets: (i) the SF-12 PCS score with total number of symptoms on PPAQ and Impact subscale score; (ii) PPAQ Impact subscale score and scores from two restricted activity day questions on the PPAQ with BSI depression and PHQ-9 total scores. Concurrent validity was determined using Pearson correlation coefficients with correlation strengths ranging from 0 to 1, with those closer to 1 indicating a stronger relationship and better concurrent validity between the new measure and established questionnaires. Generally, a correlation coefficient above 0.5 is considered good concurrent validity [28]. Absolute values should be used because the strength, not the direction of the correlation, indicates concurrent validity. Additionally, we assessed the association for ordinal responses using Goodman Kruskal's gamma statistic among four fatigue related measurements: PPAQ symptom of fatigue, the Fatigue VAS score, the SF-12 energy subscale (item 6b) and the PHQ-9 item 4 “feeling tired or having little energy”. Reliability refers mainly to aspects of internal consistency, stability, and equivalence. Cronbach’s alpha and Kuder Richardson-20 tests were reported in this study for the PPAQ Impact subscale, BSI and PHQ-9 questionnaires. All analyses were conducted using R packages “DescTools,” “gtsummary” and “tidyverse” under R version 4.2.2.
Results
Descriptive statistics
As presented in Table 1, participants were primarily older, male (66.7%), and Caucasian (64.7%). Diagnoses included: AF (82.4%), VT (15.7%), and atrial tachycardia (2.0%). Comorbidities were reported as: hypertension (51.0%), joint pain (31.4%), other heart diseases (33.3%), chest pain (25.5%), anxiety (27.5%), and depression (23.5%).
Table 1.
Demographic and clinical characteristics of the sample (N = 51)
| Characteristic | Overall, N=511 |
|---|---|
| Age (years) | |
| Mean (SD) | 59.37 (12.58) |
| Range | 27- 80 |
| Gender | |
| Male | 34 (66.67%) |
| Female | 17 (33.33%) |
| Race | |
| Hispanic, Latino or Latin American | 3 (5.88%) |
| Asian or Pacific Islander | 6 (11.76%) |
| Black or African American | 1 (1.96%) |
| White/Caucasian | 33 (64.71%) |
| Other | 1 (1.96%) |
| Unknown | 7 (13.73%) |
| Marital Status | |
| Married or permanent partnership | 27 (52.94%) |
| Widowed | 3 (5.88%) |
| Divorced | 4 (7.84%) |
| Never married | 8 (15.69%) |
| Unknown | 9 (17.65%) |
| Highest Education Level | |
| Below 11 th grade | 3 (5.88%) |
| High school graduate or equivalent | 4 (7.84%) |
| Some college, vocational school or junior college | 20 (39.21%) |
| College degree (4 year) | 9 (17.65%) |
| Graduate or professional degree | 7 (13.73%) |
| Unknown | 8 (15.69%) |
| Arrhythmia Diagnosis | |
| Atrial Fibrillation | 42 (82.35%) |
| Ventricular tachycardia | 8 (15.69%) |
| Atrial Tachycardia | 1 (1.96%) |
| Hypertension | 26 (50.98%) |
| Joint Pain | 16 (31.37%) |
| Chest Pain | 13 (25.49%) |
| Other Heart Diseases | 17 (33.33%) |
| Anxiety | 14 (27.45%) |
| Depression | 12 (23.53%) |
1“n (%)” for categorical variables
“Mean (SD)” for continuous variables
Results for individual symptom questionnaires
The PPAQ
As outlined in Table 2, over the past month, 35% of participants experienced a fast heart rhythm at least once every week. The most prevalent symptoms reported were fatigue (60.8%), heart fluttering (52.9%), heart racing (51.0%), dizziness (49%), trouble sleeping (49%), and heart skipping (45.1%). Based on the Impact subscale, the majority of patients reported their arrhythmias did not alter their daily activities such as driving (86.3%), relationships with a significant other (72.5%), sexual relationships (66.7%), social activities (60.8%), mood (52.9%) and walking (52.9%). The average score for the Impact subscale from the PPAQ was 19.2 (range: 0–80), with higher values indicating a more adverse effect of the arrhythmia on the patient’s quality of life. On average, participants indicated a reduction in their activities by 2.8 days per month (+/- 6.4; range: 0–28 days).
Table 2.
Symptoms reported on patient perspective of arrhythmia questionnaire (N=51)
| Gender | |||
|---|---|---|---|
| Symptoms in past 4 weeks | Overall 1 N = 51 |
Male 1 N=34 |
Female 1 N=17 |
| Fatigue/No energy | 31 (60.8%) | 24 (70.6%) | 7 (41.2%) |
| Heart flutters | 27 (52.9%) | 21 (61.8%) | 6 (35.3%) |
| Heart racing | 26 (51.0%) | 19 (55.9%) | 7 (41.2%) |
| Trouble sleeping | 25 (49.0%) | 18 (52.9%) | 7 (41.2%) |
| Dizziness/lightheadedness | 25 (49.0%) | 21 (61.8%) | 4 (23.5%) |
| Heart skipping | 23 (45.1%) | 16 (47.1%) | 7 (41.2%) |
| Feeling warm/flushed | 16 (31.4%) | 11 (32.4%) | 5 (29.4%) |
| Trouble concentrating | 16 (31.4%) | 12 (35.3%) | 4 (23.5%) |
| Hard to catch breath | 13 (25.5%) | 9 (26.5%) | 4 (23.5%) |
| Passing a lot of urine | 13 (25.5%) | 8 (23.5%) | 5 (29.4%) |
| Headache | 10 (19.6%) | 7 (20.6%) | 3 (17.6%) |
| Blurred vision | 8 (15.7%) | 8 (23.5%) | 0 (0.0%) |
| Sweating | 8 (15.7%) | 4 (11.8%) | 4 (23.5%) |
| Nausea | 8 (15.7%) | 6 (17.6%) | 2 (11.8%) |
| Pounding feeling in neck | 7 (13.7%) | 6 (17.6%) | 1 (5.9%) |
| Chest pressure as heart was racing | 6 (11.8%) | 5 (14.7%) | 1 (5.9%) |
| Loss of appetite | 4 (7.8%) | 3 (8.8%) | 1 (5.9%) |
| Passing out | 1 (2.0%) | 0 (0.0%) | 1 (5.9%) |
n (%) for participants who answered “yes” to specific symptoms
The fatigue VAS scale
The mean score for the symptom of fatigue on the VAS was 3.9 (+/- 2.9; range: 0–10) indicating moderately low severity of fatigue when it occurred.
The SF-12
The eight domain subscale scores were: Physical Functioning of 66.2 (+/- 34.2), Role Physical of 63.0 (+/−27.7), Bodily Pain of 83.8 (+/−27.8), General Health of 57.4 (+/- 23.6), Vitality of 25.5 (+/−28.9), Social Functioning of 77.9 (+/- 26.3), Role Emotional of 76.7 (+/- 26.9), and Mental Health of 55.6 (+/- 14.4).
The Brief Symptom Inventory
The mean BSI anxiety subscale was 3.4 (+/- 4.6; range: 0–24), while the mean BSI depressive subscale was 3.2 (+/- 4.9, range: 0–24), where lower scores indicated a milder effect of the arrhythmia with less anxiety or depression.
The PHQ-9
The mean depressive symptom score on the PHQ-9 was 4.9 (+/−4.7, range: 0–19), where a score of 0 to 3 represents minimal depressive symptom severity.
Validity evaluations
Preliminary evidence of content and construct validity using Pearson correlation and Goodman Kruskal's gamma for validity of the PPAQ in the sample of a variety of arrhythmia patients was demonstrated in this study (Table 3), building on the accumulation of prior preliminary evidence of validity in SVT samples. However, some of the gold standard questionnaires we used for establishing concurrent validity pf the PPAQ did not show as strong a relationship as we had expected. The Pearson’s correlation between the SF-12 PCS and the total number of symptoms reported on the PPAQ symptom checklist and on the PPAQ’s Impact subscale are −0.136 and −0.157, respectively. These findings indicate a weak negative relationship in that the participants with higher total number of symptoms or higher PPAQ Impact subscale scores had slightly, and not statistically significant, lower amounts of physical activity as measured by the PCS. Poor concurrent validity was demonstrated in this comparison indicating that the PPAQ is not capturing the construct about physical activity as strongly as seen in the PCS (Table 3).
Table 3.
Concurrent validity via Pearson’s correlation among instruments
| Comparison | ||||
|---|---|---|---|---|
| PPAQ vs. SF-12 | SF-12 PCS | |||
| PPAQ total number of symptoms | −0.136 | |||
| PPAQ Impact subscale | −0.157 | |||
| Activity Reduction with depression | BSI depression subscale | PHQ-9 total score | ||
| PPAQ - “Cut down” activity | 0.170 | 0.279 | ||
| PPAQ – Miss work | 0.087 | 0.247 | ||
| Average PPAQ Impact subscale | 0.346 (*) | 0.351 (*) |
PPAQ Patient Perspective of Arrhythmia Questionnaire, SF-12 Short Form 12 (item 6b), Fatigue, VAS Visual Analog Scale, BSI Brief Symptom Inventory–Depression, and PHQ-9 Patient Health Questionnaire-9 item survey. Correlations from 0–0.25, 0.25–0.50, 0.50–0.75, and >0.75 are considered weak, fair, moderate-to-good, and good-to-excellent concurrent validity, respectively. A significance code follows each correlation, indicating whether it differs from zero, with ‘*’ for p<0.05. All correlations in Table 3 used Pearson’s correlation.
We did find evidence of concurrent validity linking participants’ reduction in activities to their depression status. All pairwise Pearson’s correlations between items measured in the PPAQ and BSI/PHQ-9 are presented in Table 3. All the correlations are positive, indicating participants experiencing higher depression subscale scores in both BSI and PHQ-9 reported greater limitations in activities. The low Pearson correlations between the two PPAQ restricted activity day items and the BSI depression scale or PHQ-9 total scores indicate poor concurrent validity in this comparison. The PPAQ Impact subscale had a moderately strong positive correlation with depressive symptoms as measured by the BSI-depression or the PHQ-9 questionnaires (Table 3). Although the correlation between the PPAQ Impact subscale and the two depression scales did show evidence of moderate concurrent validity, our expectations of a correlation between decreased physical activity and increased depressive symptoms was not as strong as we expected.
Evidence of strong concurrent validity was found when we evaluated the consistency of fatigue reported by patients across four questionnaires: PPAQ, Fatigue VAS, SF-12 and PHQ-9 (Table 3). Positive gamma statistics indicate a positive relationship between any two questionnaires demonstrating that the PPAQ was measuring a similar concept of fatigue to the Fatigue VAS and the PHQ-9 (item 4). For example, people who reported higher levels of fatigue severity on the PPAQ symptom list tended to score higher on the PHQ-9 for question 4 indicating more tiredness and feeling of little energy. The gamma statistic showed a small concurrence between the PPAQ and the SF-12 energy question (item 6b).
Internal consistency reliability
There was also preliminary evidence of strong internal consistency reliability of the symptom list and Impact subscale of the PPAQ. Internal consistency reliability of the PPAQ symptom list and Impact subscale were supported by Cronbach’s alpha of 0.786 and 0.914, respectively. In comparison, the internal consistency of both PCS and MCS for this cohort was evaluated by Cronbach’s alpha of 0.686 and 0.896; results for the BSI anxiety and depressive symptoms scale was 0.888; and results for the PHQ-9 in this sample was 0.766. All support the relatively high internal consistency of the PPAQ (Table 4).
Table 4.
Concurrent validity via Goodman Kruskal’s gamma among instruments
| Comparison | ||||
|---|---|---|---|---|
| Fatigue Consistency | PPAQ Fatigue | Fatigue VAS | SF-12 “Energy” | |
| Fatigue VAS | 0.728 (***) | - | - | |
| SF-12 “Energy” | 0.311 | 0.193 | - | |
| PHQ-9 “Tired” | 0.664 (**) | 0.475 (**) | 0.457 (**) |
PPAQ Patient Perspective of Arrhythmia Questionnaire, SF-12 Short Form 12 (item 6b), Fatigue, VAS Visual Analog Scale, BSI Brief Symptom Inventory–Depression, and PHQ-9 Patient Health Questionnaire-9 item survey (item 4). Correlations from 0–0.25, 0.25–0.50, 0.50–0.75, and >0.75 are considered weak, fair, moderate-to-good, and good-to-excellent concurrent validity, respectively. A significance code follows each correlation, indicating whether it differs from zero, with ‘**’ for p<0.01, and ‘***’ for p<0.001. All correlations in Table 4 used Goodman Kruskal’s gamma.
Gender differences
We further investigated if any gender differences existed for the PPAQ symptoms, the SF-12 PCS/MCS, 1-item Fatigue VAS, the BSI Anxiety/Depression and PHQ-9 total scores (Table 5). The symptoms of blurred vision (p=0.040), dizziness (p=0.010) and fatigue (p=0.043) were reported significantly more frequently by males than by females. The total number of symptoms from the PPAQ was 5.8 (+/−3.3) in males which is slightly higher than 4.1 (+/−3.7) in females (p=0.069). No other noteworthy gender disparities were identified as assessed by the five questionnaires.
Table 5.
Gender differences in symptoms across five questionnaires of interest
| Questionnaire | Variable | Overall1 | Gender | p-value2 | |
|---|---|---|---|---|---|
| Female1 | Male1 | ||||
| PPAQ | Total Number of Symptoms | 5.2 (3.5) | 4.1 (3.7) | 5.8 (3.3) | 0.069 |
| Blurred Vision | 8 (16%) | 0 (0%) | 8 (24%) | 0.040 | |
| Dizziness | 26 (51%) | 13 (76%) | 13 (38%) | 0.010 | |
| Fatigue | 31 (61%) | 7 (41%) | 24 (71%) | 0.043 | |
| SF-12 | PCS | 46.3 (10.8) | 45.3 (12.9) | 46.8 (9.8) | 0.857 |
| MCS | 43.2 (6.8) | 41.8 (7.9) | 43.9 (6.2) | 0.194 | |
| VAS | Fatigue | 3.9 (2.9) | 3.4 (3.1) | 4.1 (2.9) | 0.401 |
| BSI | Anxiety | 3.4 (4.6) | 4.2 (6.6) | 3.1 (3.3) | 0.485 |
| Depression | 3.2 (4.9) | 3.7 (6.1) | 2.9 (4.3) | 0.933 | |
| PHQ-9 | Total score | 4.9 (4.7) | 4.5 (5.4) | 5.0 (4.4) | 0.233 |
1For categorical variable: n (%) for participants who answer “yes”; for continuous variable: mean(SD)
2Wilcoxon rank sum test; Pearson's Chi-squared test; Fisher's exact test
Discussion
The validation of any questionnaire is an ongoing process of building evidence that the questionnaire performs as expected. The aim of our study was met with findings providing evidence of the concurrent validity of the PPAQ in a cohort of adults with a variety of arrhythmias, suggesting the PPAQ could be useful in clinical practice and future research. In this convenience sample of mostly older, White men, having a range of cardiac arrhythmias including AF, VT, and atrial tachycardia, we found the PPAQ exhibited moderate to strong concurrent validity when correlated to other well-established, validated questionnaires. These findings are supported by other prior findings in solely SVT patient cohorts [22, 23]. Our expectations of a strong relationship between an increase in PPAQ number of symptoms or higher Impact subscale scores with lower SF-12 PCS scores (less physical activity) did not prove true. The correlations did show an inverse, but extremely weak relationship. This result could be because of the sporadic nature of arrhythmia occurrences that would only temporarily affect the patient’s ability to do physical activities. Our expectations of a strong relationship between an increase in days off of work or normal activities on the PPAQ and an increase in depressive symptom scores was partially met. While the Pearson correlations were statistically significant between the PPAQ Impact subscale and the two depression tools showing moderate concurrent validity, there was essentially no correlation between the PPAQ restricted activity day items and the two depression scales. We found significant, strong concurrent validity between the PPAQ fatigue symptom checklist item and both the Fatigue VAS and the PHQ-9 “tired” item (item 4) indicating they were all measuring the same concept. However, we found only a small, non-significant correlation between the PPAQ fatigue item and the SF-12 “energy” question (item 6b), indicating the two questionnaires were measuring different concepts of fatigue. The SF-12 includes many items focused on physical activity and the energy to do physical chores, whereas the PPAQ is more focused on the presence and severity of fatigue as a symptom and the corresponding interruptions in daily life that symptom would cause.
The findings from this study of the PPAQ’s validity and reliability are supported by a recent scoping review comparing the PPAQ to five other arrhythmia patient questionnaires and finding the PPAQ to be the most comprehensive disease-specific instrument for arrhythmia patients [29]. Different from the Atrial Fibrillation Effect on Quality of life Questionnaire (AFEQT) [30], designed to measure AF patient outcomes after cardiac procedures listing only five potential symptoms, the PPAQ comprehensively lists 18 potential symptoms that patients living with arrhythmias typically report and includes aspects of the arrhythmia also deemed important to patients such as the frequency and duration of episodes and the impact of the arrhythmia on patients’ lives. While all 18 symptoms on the PPAQ were not each reported with great occurrence and severity, all symptoms were experienced by at least one individual in our sample, so no symptoms were removed from the PROM based on these findings. The Cardiff Cardiac Ablation PROM (C-CAP) questionnaire also includes a symptom checklist along with items inquiring about patient expectations and health care utilization before and after ablation procedures but is specific to measuring these concepts around ablation treatment [31]. The Arrhythmia-Specific Questionnaire in Tachycardia and Arrhythmia (ASTA) questionnaire for arrhythmia patients includes a symptom scale and also includes items asking about current medications and factors influencing the occurrence of the arrhythmia and has been validated in patients with a variety of arrhythmias [32].
We noted fatigue was the most prevalent symptom reported in patients with AF (60%) or VT (75%). Patients with AF reported fatigue to be more severe with a higher impact on their daily activities than those patients with VT. This could be due to associated heart failure and/or reduced ejection fraction seen more often in patients with VT where those patients may normally not be as active as patients with AF. The majority of patients in this study reported minimal anxiety and depressive symptoms. Besides fatigue, the other most prevalent symptoms noted in this study (heart fluttering, dizziness, trouble sleeping, and heart skipping) align with findings from a recent state-of the-science report on cardiovascular symptoms in arrhythmia patients [33] and other reports of symptom studies in atrial fibrillation [9, 10, 34, 35]. Women experienced more of an emotional impact with their arrhythmia than men in the current study, while men reported more lightheadedness/dizziness and blurred vision, perhaps associated with vasomotor factors or faster heart rates during some tachycardias in men [7, 36]. Our findings of gender distinctions contradict reports in the current literature, which state that women with atrial fibrillation and cardiovascular disease tend to report higher symptom severity and frequency than men [33, 37].
Strengths and limitations
These findings provide preliminary data of concurrent validity and reliability of the PPAQ a variety of arrhythmia patients. Clinicians and researchers should interpret these findings in light of some methodological limitations. Sampling bias may be present as this was a convenience sample recruited from the arrhythmia clinic at one urban, academic center in California, which would be expected to include more symptomatic, cardiac arrhythmia patients. Therefore, these subjects may not be representative of arrhythmia patients from the general population or those who are asymptomatic with their arrhythmias which limits external reliability. Because of the small sample size and only one patient with ATACH, we could not compare differences in symptoms between the types of arrhythmia patients. But these findings can be hypothesis generating for future studies with larger samples who seek to identify differences in symptom clusters or profiles between groups of arrhythmia patients.
Another limitation was no data about the length of time any individual had been living with their arrhythmia. The sample may have included both newly diagnosed patients with those who had been living with the symptoms and arrhythmias for many years. This was a cross-sectional study, so we were not able to measure the responsiveness of the PPAQ and how the scores changed over time. Future longitudinal research with larger samples is needed to explore how symptoms change over time and if gender or racial/ethnic differences exist in symptoms of arrhythmia patients. There are strengths however, of these findings, in that we presented additional evidence of moderate to good concurrent validity and reliability of the PPAQ to extend use of the questionnaire to an AF and VT population for measurement of the symptom of fatigue. The process of building evidence of concurrent validity is an iterative process and future studies testing the validity of the PPAQ should include patients with a wider variety of arrhythmias and more ethnic diversity. Although our sample was mostly Caucasian which reflects the nature of AF, we were also able to include 13% Asian and 7% Hispanic individuals to give a broader reflection of symptoms in a wider range of ethnicities.
Conclusion
Disease-specific PROMs provide evidence of the efficacy of treatments and are important to establish the burden of disease and inform clinical decision making about treatment outcomes. These findings establish additional evidence that the PPAQ is an easy to administer, valid, and reliable disease-specific PROM for adults diagnosed with a variety of cardiac arrhythmias to measure arrhythmia-related episode frequency and duration, symptom occurrence and severity, and impact on one’s daily life activities. The PPAQ is the most comprehensive disease-specific PROM for cardiac arrhythmia patients, and we have demonstrated clear evidence of content, construct, and now beginning evidence of concurrent validity for using this tool in a broad range of arrhythmia patients.
Acknowledgements
The authors wish to thank the participants who willingly contributed their time and experiences of living with a cardiac arrhythmia to the data used in this study.
Abbreviations
- SVT
Supraventricular tachycardia
- AF
Atrial fibrillation
- ATACH
Atrial tachycardia
- VT
Ventricular tachycardia
- PROs
Patient reported outcomes
- PROMs
Patient reported outcome measures
- PPAQ
Patient Perspective of Arrhythmia Questionnaire
- IoA
Impact of Arrhythmia subscale
- NYHA
New York Heart Association classification
- SD
Standard deviation
- VAS
Fatigue Visual Analog Scale
- SF-12
Medical Outcome Study Short Form-12 Survey
- PCS
Physical component summary scores of the SF-12
- MCS
Mental component summary scores of the SF-12
- BSI
Brief Symptom Inventory
- PHQ-9
Patient Health Questionnaire
- AFEQT
Atrial Fibrillation Effect on Quality-of-life Questionnaire
- C-CAP
Cardiff Cardiac Ablation PROM
- ASTA
Arrhythmia-Specific Questionnaire in Tachycardia and Arrhythmia
Authors’ contributions
KW and NB conceived the study. KW researched literature and KW, JJ, SI, and NB were involved in protocol development, ethics approval, patient recruitment, and data collection. KW, YJ, and RK were involved in data analysis and drafting the initial manuscript and all Tables. All authors reviewed and edited the manuscript and approved the final version of the manuscript.
Funding
This research received no specific grant award from any funding agency in the public, commercial or not-for-profit sectors.
Data availability
The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
Ethical approval for this study was obtained from the University of California, San Francisco Committee on Human Subjects (approval # 11-05704) prior to recruitment of participants and any data collection. Written informed consent was obtained from each subject for their participation in the study and their anonymized information to be published in this article.
This research study was conducted in accordance with the ethical norms and standards set forward in the Declaration of Helsinki.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.