Abstract
Background:
Surviving cardiac arrest is characterized by cognitive, psychological, and functional impairments and apprehension over long-term prognosis. We first estimated the proportion of clinically significant depression and anxiety in cardiac arrest survivors and their informal caregivers, then examined the association between depression and anxiety with worse quality of life (QoL).
Methods:
In an online survey, cardiac arrest survivors and caregivers reported demographic and arrest characteristics, the Patient Health Questionnaire-4 (PHQ-4), and the WHOQOL-BREF physical, psychological, and social QoL subscales. Six multiple regression models (three for survivors and three for caregivers) tested associations between PHQ-4 scores with each QoL subscale, adjusted for the following: for survivors – functional dependence, self-reported memory problems, sex, income, months since arrest, and age; for caregivers – months since arrest, age, and income.
Results:
We included 169 survivors (mean age: 50.8 years, 49.7% women, positive depression screen: 21.3%, anxiety: 29.6%) and 52 caregivers (mean age: 48.7 years, 86.5% women, positive depression screen: 21.2%, anxiety: 36.5%). In adjusted models, depression and anxiety were associated with worse QoL on each subscale (β: −0.39—0.7, p < .01).
Limitations:
We assessed depression and anxiety and QoL cross-sectionally, which cannot exclude bi-directionality. Further, there was a selection bias in our survey, as the majority of survivors were of good neurologic recovery.
Conclusion:
Depression and anxiety were moderately associated with worse QoL over functional dependence and memory problems in survivors, and worse QoL in caregivers. Future study should explore the feasibility of dyadic interventions in cardiac arrest survivors and informal caregivers.
Keywords: Cardiac arrest, Depression, Anxiety, Quality of life, Caregivers, Survey
1. Introduction
Cardiac arrest is the cessation of the heart’s mechanical activity, confirmed by the absence of signs of circulation (i.e., pulse or heart rate) (Virani et al., 2020), resulting in disrupted blood flow to the brain and major organs. Surviving a cardiac arrest is characterized by uncertainty over long-term prognosis, chronic cognitive, functional, and psychological symptoms, and an unclear direction for post-discharge follow-up care (Sawyer et al., 2020), which can be stressful for both survivors and their informal caregivers (i.e., family or friends who provide instrumental and emotional care) (National Alliance for Caregiving). Unsurprisingly, rates of clinically significant depression (14–45%) and anxiety symptoms (13–61%) are high in survivors (Wilder Schaaf et al., 2013), and may be high in informal caregivers, though informal caregivers are largely understudied. As more people are surviving cardiac arrest now than ever before, the many different post-arrest challenges (i.e., cognitive, functional, and psychological) are becoming more evident. However, it remains unclear which challenges (cognitive, functional, and psychological) are most strongly associated with poor quality of life (QoL).
Clinically significant depression symptoms involve persistent low mood characterized by sadness, emptiness, and or hopelessness, as well diminished interest and/or pleasure (American Psychiatric Association, 2013). Clinically significant anxiety symptoms involve persistent, intense worry (expectant apprehension) concurrent with sympathetic arousal (American Psychiatric Association, 2013). The implications of depression and anxiety symptoms may be serious for both cardiac arrest survivors and informal caregivers. Previous studies in critical illness have found clinically significant depression and anxiety symptoms to remain long after hospitalization in both patients and caregivers (Hatch et al., 2018, Nikayin et al., 2016, Meyers et al., 2020, Meyers et al., 2020). Further, among post-myocardial infarction and post-cardiac surgery patients, anxiety has been associated with greater risk of major adverse cardiovascular and cerebrovascular events (Roest et al., 2010, Cserép et al., 2010). Similarly, in stroke survivors, depression has been linked to greater risk of mortality (Bartoli et al., 2013). In caregivers, chronic anxiety has been linked to caregiver strain, depression, and earlier onset cardiovascular disease (Denno et al., 2013, Mausbach et al., 2007).
QoL is a patient-centered construct defined by the World Health Organization as an individual’s perceived position in life in the context of their culture and value systems, and in relation to their goals, expectations, standards, and concerns (WHOQOL Group, 1994). Due to improved survival from cardiac arrest, the American Heart Association has prioritized patient-centered outcomes such as QoL in these survivors (Sawyer et al., 2020). Understanding relative contributions to QoL in survivors could, in turn, help inform systematic interventions/recommendations. Further, QoL of informal caregivers of cardiac arrest survivors is also of importance, as they must juggle their own life responsibilities with those of caring for the post-arrest survivor.
In this study we first estimated the proportion of clinically significant depression and anxiety in a sample of cardiac arrest survivors with good neurological recovery and informal caregivers of cardiac arrest survivors. Next, we tested the following hypotheses: (1) greater depression and anxiety symptoms are associated with worse QoL over and above functional dependence and memory problems in survivors and (2) greater depression and anxiety symptoms are associated with worse QoL in informal caregivers of cardiac arrest survivors.
2. Method
This study is part of an online survey study distributed between October and November 2019 to cardiac arrest survivors and informal caregivers of cardiac arrest survivors who were registered as members of the Sudden Cardiac Arrest Foundation (SCAF). SCAF offers an online support group whose membership is free and open to all cardiac arrest survivors and informal caregivers of cardiac arrest survivors. Survivors and caregivers completed the surveys independently, and thus, we did not collect paired, dyadic data. All survivor participants were of good neurologic recovery such that they were able to independently complete their surveys. The surveys were conducted through REDCap, a secure data capture software. This study was approved by the local Institutional Review Board.
2.1. Measures
Survivor Characteristics
Survey items varied slightly for survivors and informal caregivers. For survivors, we examined demographic variables such as age at arrest, sex, income (categorized as low: <$50,000, medium: $50,000–$99,999, and high: >$99,999) and race, as well as cardiac arrest characteristics such as months since initial cardiac arrest, comorbidities at the time of the arrest (which were then used to calculate the Charlson Comorbidity Index) (Charlson et al., 1987), provision of cooling therapy, and arrest location.
We assessed functional status via the Lawton Instrumental Activities of Daily Living scale (Lawton and Brody, 1969). The Lawton is an 8-point scale with higher scores indicating greater independence and lower scores indicating greater dependence. Because the majority of survivor respondents were fully independent (Lawton score 8 = 83.4%) we dichotomized survivors as being either functionally independent (Lawton score 8) or functionally dependent (Lawton score <8). Additionally, survivors reported whether they presently experience daily memory problems.
Finally, we collected zip code data which we used to characterize the geographic make-up of participants.
2.2. Informal caregiver characteristics
Informal caregivers reported the same demographic variables as survivors did, as well as their relationship to the survivor that they care for. For the income variable, we dichotomized responses at a cut-off of $99,999 because the majority of responses below $99,999 were greater than $50,000. Arrest characteristics included months since initial cardiac arrest of the survivor and arrest location. Informal caregivers also reported whether the survivor they care for presently experiences daily memory problems. Finally, we collected zip code data to characterize the geographic make-up of caregivers.
2.3. Depression and anxiety symptoms
We measured depression and anxiety symptoms through the Patient Health Questionnaire-4 (PHQ-4) which probes for symptoms experienced in the previous two weeks (Kroenke et al., 2009). Total scores range from of 0–12, with higher scores indicating greater depression and anxiety severity. A total symptom severity score is yielded by summing individual items.
The PHQ-4 is comprised of two separate depression and anxiety subscales which each range from 0–6; the PHQ-4 authors suggest a cut-off of 3 on each subscale as being indicative of clinically significant depression and anxiety (Kroenke et al., 2009). Because depression and anxiety are frequently co-morbid, we utilized the PHQ-4 total score for our main analyses. We do, however, report the proportion of clinically significant depression and anxiety based on their respective subscale scores. The PHQ, while brief, has good psychometrics, namely, strong factorial and criterion validity (Kroenke et al., 2009).
2.4. Quality of life
We measured three domains of QoL (i.e., physical, psychological, and social QoL) through the WHOQOL-BREF (Skevington et al., 2004). The physical QoL subscale measures perceived independence in activities of daily living, utilization of medical treatments, pain, mobility, sleep quality, fatigue, and work capacity. The psychological QoL subscale assesses experience of positive and negative emotions, cognitive function, self-esteem, meaning making, and body image. The social QoL subscale measures quality and availability of social support and satisfaction with sex life. Individual items are rated on a 5-point scale, with higher scores indicating greater QoL. From these ratings, we calculated domain scores according to published scoring recommendations (range 4–20) (World Health Organization, 1996).
2.5. Statistical analysis
We followed an identical but separate analytic plan for survivors and informal caregivers. First, we calculated measures of central tendency to describe participant characteristics, PHQ-4 scores, proportion of clinically significant depression and anxiety, and QoL subscales. Next, we ran six adjusted multiple regression models (three for patients and three for caregivers) to test associations between clinically significant anxiety scores with each QoL domain. We adjusted for covariates that were previously associated with QoL in our survey study (Presciutti et al., 2020); for survivors these included functional dependence (calculated via Lawton scores), self-reported daily memory problems, sex, income, months since arrest, and age at arrest; for caregivers, months since arrest, age at arrest, and income. We used Bonferroni correction for multiple tests to limit Type I error.
3. Results
3.1. Participant characteristics
A total of 179 cardiac arrest survivors initiated the survey, 169 survivors (mean age: 50.8 years, 49.7% women, 95.9% white, mean months since arrest: 62.8) provided full data on the measures included in this analysis. A total of 36 (21.3%) survivors screened positively for clinically significant depression, and 50 (29.6%) survivors screened positively for clinically significant anxiety.
A total of 53 informal caregivers initiated the survey, 52 informal caregivers (mean age: 48.7 years, 86.5% women, 88.5% white, mean months since arrest: 43.2, 82.7% spousal caregivers) provided full data on the measures included in this analysis. A total of 11 (21.2%) caregivers screened positively for clinically significant depression and 19 (36.5%) screened positively for clinically significant anxiety. Full descriptive statistics for survivors and caregivers are presented in Table 1.
Table 1.
Demographic and participant characteristics included in this analysis.
| Demographics | Survivors | Caregivers | Scale Range |
|---|---|---|---|
| Age at arrest, mean ± SD1 | 50.8 ± 11.5 | 48.7 ± 13.7 | |
| Gender—Female, % (n) | 49.7 (84) | 86.5 (45) | |
| Race, % (n) | |||
| -White | 95.9 (162) | 88.5 (46) | |
| -Non-white | 4.1 (7) | 11.5 (6) | |
| Spousal caregiver, % (n) | 82.7 (43) | ||
| Income, % (n) | |||
| -Low (<$50,000) | 17.8 (30) | 3.8 (2) | |
| -Medium ($50,000 - $99,999) | 25.4 (43) | 36.5 (19) | |
| -High (>$99,999) | 53.8 (91) | 57.7 (30) | |
| Participant Characteristics | |||
| Pre-arrest Charlson Comorbidity Index, median (IQR2) | 1 (0–2) | ||
| Out-of-hospital arrest, % (n) | 84.6 (143) | 92.3 (48) | |
| Therapeutic hypothermia, % (n) | 40.8 (69) | ||
| Months since arrest, mean (IQR) | 62.8 (26–91) | 43.2 (17–55) | |
| Self-reported presence of daily memory problems % (n) | 47.3 (80) | 34.6 (18) | |
| Lawton IADLs3, median (IQR) | 8 (8–8) | 0–8 | |
| Functional dependence, % (n) | 16.6 (28) | ||
| PHQ-44 median, (IQR) | 2 (0–6) | 2 (0–6) | 0–12 |
| Clinically significant depression5, % (n) | 21.3 (36) | 21.2 (11) | |
| Clinically significant anxiety, % (n) | 29.6 (50) | 36.5 (19) | |
| Geographic Region, % (n) | |||
| United States East | 17.8 (30) | 9.6 (5) | |
| United States South | 34.3 (58) | 21.2 (11) | |
| United States Midwest | 20.1 (34) | 28.8 (15) | |
| United States West | 20.7 (35) | 34.6 (18) | |
| Non-United States | 7.1 (12) | 5.8 (3) | |
| WHOQOL-BREF Subscales 6 | |||
| Physical QoL mean, ± SD | 15.2 ± 3.1 | 16.1 ± 2.3 | 4–20 |
| Psychological QoL mean, ± SD | 14.4 ± 3.3 | 14.7 ± 3 | 4–20 |
| Social QoL mean, ± SD | 13.9 ± 3.7 | 14.1 ± 3.5 | 4–20 |
Note:
Standard Deviation
Interquartile Range
Lawton Instrumental Activities of Daily Living (scale range 0–8). Lower scores = more functional dependence.
Patient Health Questionnaire – 4 (scale range 0–12). Higher scores = more severe depression and anxiety symptoms.
Clinically significant depression and anxiety is based on a score of ≥3 on their respective PHQ subscales.
World Health Organization Quality of Life Scale – Brief (subscale ranges 4–20). Lower scores = lower QoL.
3.2. Associations between anxiety and quality of life subscales
Full details on multiple regression models are presented in Tables 2 and 3 for survivors and informal caregivers respectively.
Table 2.
Associations between depression and anxiety symptoms with quality of life subscales in survivors.
| Variable | Physical QoL β (p-value) | Psychological QoL β (p-value) | Social QoL β (p-value) |
|---|---|---|---|
| Depression and anxiety symptoms | −0.39 (<0.001) * | −0.62 (<0.001) * | −0.43 (<0.001) * |
| Functional dependence | −0.24 (<0.001) * | −0.01 (0.88) | 0.05 (0.47) |
| Daily memory problems | −0.22 (0.001) * | −0.24 (<0.001) * | −0.14 (0.08) |
| Male sex | 0.09 (0.14) | 0.05 (0.32) | −0.05 (0.48) |
| Months since arrest | 0.06 (0.34) | 0.07 (0.16) | 0.03 (0.69) |
| Age at arrest | −0.05 (0.39) | 0.07 (0.19) | 0.03 (0.69) |
| Income <$50,000 | −0.14 (0.02) | 0.02 (0.75) | −0.17 (0.02) |
Note:
= significant after Bonferroni correction for multiple tests (p < .005)
Table 3.
Associations between depression and anxiety symptoms with quality of life subscales in caregivers.
| Variable | Physical QoL β (p-value) | Psychological QoL β (p-value) | Social QoL β (p-value) |
|---|---|---|---|
| Depression and anxiety symptoms | −0.7 (< 0.001) * | −0.7 (0.001) * | −0.39 (0.007) * |
| Age at arrest | −0.35 (0.003) * | −0.04 (0.97) | 0.08 (0.55) |
| Months since arrest | −0.14 (0.22) | 0.05 (0.65) | 0.24 (0.08) |
| Income <$99,999 | −0.08 (0.51) | 0.11 (0.3) | 0.09 (0.5) |
Note:
= significant after Bonferroni correction for multiple tests (p < .013)
3.3. Survivors
For survivors, in adjusted models corrected for multiple tests (p < 0.005), greater depression and anxiety symptoms (β: −0.39, p < 0.001), functional dependence (β: −0.24, p < 0.001), and presence of daily memory problems (β: −0.22, p = 0.001), were associated with worse physical QoL; greater depression and anxiety symptoms (β: −0.62, p < 0.001) and presence of daily memory problems (β: −0.24, p < 0.001) were associated with worse psychological QoL; and greater depression and anxiety symptoms (β: −0.43, p < 0.001) were associated with worse social QoL.
3.4. Informal caregivers
For informal caregivers, in adjusted models corrected for multiple tests (p < 0.013), greater depression and anxiety symptoms (β: −0.7, p < 0.001) and age at arrest (β: −0.35, p = 0.003) were associated with worse physical QoL. Further, greater depression and anxiety symptoms were associated with worse psychological QoL (β: −0.7, p = 0.001) and social QoL (β: −0.39, p = 0.007)
4. Discussion
This study highlights important areas for improvement in post-cardiac arrest survivorship by (1) indicating a high proportion of depression and anxiety symptoms in cardiac arrest survivors and their caregivers and (2) establishing a link between depression and anxiety with quality of life, years after the initial cardiac arrest event. Our results indicate that approximately 1 in 5 survivors and caregivers experienced clinically significant depression years after the initial cardiac arrest event. Further, nearly 1 in 3 survivors and over 1 in 3 informal caregivers experienced clinically significant anxiety years after the initial arrest. Additionally, in survivors, greater depression and anxiety symptoms were moderately-strongly associated with all three QoL domains, over and above functional dependence and presence of daily memory problems. In informal caregivers, greater depression and anxiety symptoms were moderately-strongly associated with all three QoL domains.
It has become apparent that post-cardiac arrest recovery is characterized by ambiguity, such that survivors and their caregivers are unaware of and unprepared to confront the many post-arrest challenges (Sawyer et al., 2020, Sawyer et al., 2016). Indeed, in cardiac arrest survivors, low readiness for discharge, more threatening illness perceptions (i.e. cognitive and emotional appraisals of illness status and recovery), and low quality communication with their providers have each been associated with worse QoL (Presciutti et al., 2020). Given that post-arrest recovery contains many unknowns, and that clinically significant anxiety symptoms are comprised of intense expectant apprehensions, it is no surprise that rates of significant anxiety are high in cardiac arrest survivors and informal caregivers. Similarly, the loss of function and lack of post-discharge support may lead to a learned helplessness and persistent depressive symptoms in both survivors and caregivers.
Our results contribute to existing evidence indicating the problematic nature of depression and anxiety in critical illness. Previously, significant depression and anxiety symptoms have been associated with greater likelihood of adverse clinical outcome in post-myocardial infarction, post-cardiac surgery, and post-stroke patients (Roest et al., 2010, Cserép et al., 2010, Bartoli et al., 2013). Potential mechanisms mays be a dysregulated hypothalamic-pituitary-axis in response to chronic sympathetic activation in anxiety, as well as inflammation in depression. Additionally, in caregivers of stroke patients, anxiety has been associated with greater caregiver strain and depression (Denno et al., 2013). In caregivers of dementia patients, depression symptoms have led to earlier onset of cardiovascular disease (Mausbach et al., 2007).
There is a need to identify and treat depression and anxiety symptoms early, as they appear to endure well beyond the initial experience of life-threatening medical events. In neurocritical care patient-caregiver dyads, elevated depression and anxiety symptoms reported during hospital admission persisted through 3- and 6-month follow-up (Meyers et al., 2020, Meyers et al., 2020). These symptoms were interdependent between patients and caregivers, such that patients’ depression and anxiety influenced caregivers’ depression and anxiety and vice versa. In the present study, a high proportion of clinically significant depression and anxiety symptoms were present approximately 5- and 3.5-years post-event on average in survivors and caregivers respectively. Taken together, depression and anxiety symptoms persist over time, are interdependent between patient-caregiver dyad members, and impact clinical, psychological, and quality of life outcomes. As such, a future research direction could be to study an early, in-hospital dyadic intervention for cardiac arrest survivors and their informal caregivers.
4.1. Limitations
We identified four limitations that warrant consideration. First, we assessed depression and anxiety and QoL cross-sectionally, which cannot exclude the possibility of a bi-directional relationship such that poor QoL could lead to worse depression and anxiety symptoms. In theory, however, psychological symptoms typically precede worse QoL, though they mutually reinforce each other over time. Second, to limit survey fatigue we utilized a brief screener to measure depression and anxiety symptoms, via the PHQ-4. Future study should utilize more comprehensive depression and anxiety measures. Third, our survey was prone to selection bias given that the majority of survivors were functionally independent and of sufficient mental status to complete our measures. Fourth, our participant pool lacked racial diversity and representation from low income individuals. Despite these limitations, the contents of our survey provide a potential framework for future assessments in more diverse participant populations.
5. Conclusion
Years after the initial cardiac arrest event, approximately 1 in 5 cardiac arrest survivors and informal caregivers of arrest survivors report clinically significant depression symptoms, while nearly 1 in 3 survivors and over 1 in 3 caregivers report clinically significant anxiety symptoms. Additionally, greater depression and anxiety symptoms were moderately-strongly associated with worse QoL in both cardiac arrest survivors and informal caregivers. Future study should examine the feasibility of dyadic psychological intervention for cardiac arrest survivors and their informal caregivers to address persistent depression and anxiety symptoms.
Acknowledgements
We would like to thank the members of the Sudden Cardiac Arrest Foundation for participating in this research. We also thank the Sudden Cardiac Arrest Foundation leadership for making this research possible.
Role of the funding source
Alex Presciutti acknowledges support by NIH/NCATS Colorado CTSA Grant Number TL1 TR002533 which provided fellowship funds and study expenses to complete this study.
Financial disclosures
Alex Presciutti is supported by NIH/NCATS Colorado CTSA Grant Number TL1 TR002533.
Footnotes
Declaration of Competing Interest
The authors whose names are listed in the title page certify that they have no affiliations with or involvement in any organization or entity with any financial interest, or non-financial interest in the subject matter or materials discussed in this manuscript.
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