Heart failure (HF) is a heterogeneous clinical syndrome characterized by symptoms of exercise intolerance. Peak oxygen consumption (VO2peak) is considered the gold-standard measurement of exercise/functional capacity in participants with HF; however, self-report questionnaires are frequently used to evaluate exercise/functional capacity and symptom burden for ease and clinical efficiency.1,2 Depression, or depressive symptoms, is a common comorbidity observed in HF, which may be altered during significant changes in health status.3 Psychophysiological manifestations of depressive symptoms may result in differences between perceived functional ability and objective functional capacity. The aim of this study was to explore the relationships between depressive symptoms and both subjective and objective measures of exercise/functional capacity in adult patients following recent hospitalization for decompensated HF with reduced ejection fraction (HFrEF).
Secondary analysis was performed on baseline data obtained for a randomized controlled trial (NCT03797001) at a single urban academic center. Patients were recruited during hospital admission with a primary diagnosis of decompensated HFrEF and identified based on HF signs/symptoms and transthoracic echocardiogram left-ventricular ejection fraction ≤ 40%. Secondary analysis inclusion criteria consisted of completion of cardiopulmonary exercise testing and self-administered questionnaires, including the Participant Health Questionnaire-9 (PHQ-9), Kansas City Cardiomyopathy Questionnaire (KCCQ), and the Duke Activity Status Index (DASI). Objective exercise/functional capacity was measured by VO2peak and exercise time during a symptom-limited cardiopulmonary exercise test. A peak respiratory exchange ratio (RERpeak) ≥1.0 was used to quantify acceptable effort. Additional included clinical characteristics were extracted from the study record.
Depressive symptoms were measured with the PHQ-9, a 9-item tool where higher scores indicate greater severity of depressive symptoms, with a score ≥10 considered clinically-significant for depressive symptoms.4 Subjective functional capacity was assessed using the KCCQ-physical limitation (PL) domain and the DASI. The KCCQ is a 23-item tool separated into multiple subdomains that assess different aspects of health status with each subdomain scaled from 0–100.5 The KCCQ-clinical summary and overall summary scores were also included in the analysis.5 The DASI is a 12-item tool consisting of specific activities of daily living weighted based on the metabolic cost and scaled from 0–58.2.6 For both KCCQ and DASI, higher scores indicate better-perceived exercise/functional capacity. All participants provided written informed consent before study entry as approved by the local Institutional Review Board.
Data are presented as mean (SD) or number (%). Pearson’s correlation coefficients were used to assess relationships between continuous variables. Analysis of covariance was used for group comparisons between participants with PHQ-9 scores < or ≥ 10 for VO2peak, exercise time, RERpeak, KCCQ-PL, and DASI scores (reported as adjusted mean difference [95%CI]). Data were analyzed using IBM SPSS Statistics-v29.0 with significance set at p≤0.05.
A total of 101 patients (56 [SD=12] years, 36% female sex, 74% Black Americans) were included in the study. The mean PHQ-9 score was 7.97 (SD=6.7) and 34 patients (34%) met criteria for clinically-significant depressive symptoms (Figure 1).
Figure 1.
Distribution of patients with HFrEF following recent HF hospitalization according to PHQ-9 scores for depressive symptoms.
#=clinically-significant scores for depressive symptoms. Abbreviations: HFrEF=heart failure with reduced ejection fraction; PHQ-9=Participant Health Questionnaire-9.
Seven participants (7%) were taking antidepressant medications at baseline visit. The mean DASI score was 28.4 (SD=15.8), KCCQ-PL score was 63.6 (SD=25.7), and VO2peak was 13.6 (SD=4.1) mL·kg−1·min−1. The PHQ-9 scores had a moderate inverse correlation with the DASI (R= −0.355, p<0.001), KCCQ-PL, KCCQ-clinical summary, and KCCQ-overall summary scores (R= −0.437, R= −0.629, R= −0.560, all p<0.001, respectively). No association was observed between PHQ-9 and effort-dependent exercise variables (VO2peak [R= −0.065, p=0.517], RERpeak [R= 0.039, p=0.702], or exercise time [R= −0.079, p=0.430]). Peak VO2 was moderately correlated with the KCCQ-PL (R= 0.322, p=0.001) and DASI (R= 0.320, p=0.001) scores.
When grouped as those without or with clinically-significant depressive symptoms (Table 1), there was a significant group difference for DASI (10.1, 95%CI [4.0–16.1]; p=0.001) and KCCQ-PL scores (22.1, 95%CI [12.8–31.4]; p<0.001), but not for VO2peak (−0.6, 95%CI [−2.4–1.2] mL·kg−1·min−1; p= 0.536), RERpeak (−0.03, 95%CI [−0.08–0.02], p= 0.238), or exercise time (21, 95%CI [−102–60] seconds, p= 0.605).
Table 1.
Group comparisons in those with and without moderate-severe depressive symptoms.
| Total | PHQ-9 <10 | PHQ-9 ≥10 | |
|---|---|---|---|
| Variables | N=101 | n=67 | n=34 |
|
| |||
| Left-ventricle ejection fraction (%) | 28 (8) | 29 (7) | 26 (8)* |
| Body Mass Index (kg/m2) | 33.7 (8.0) | 33.7 (8.2) | 33.8 (7.8) |
| Cardiopulmonary Exercise Test variables | |||
| Peak respiratory exchange ratio | 1.16 (0.10) | 1.15 (0.10) | 1.17 (0.11) |
| Exercise time, seconds | 450 (182) | 462 (197) | 422 (147) |
| Physical activity (MET/min/week) | 1669 (3637) | 1267 (1988) | 2461 (5588) |
| Duke Activity Status Index | 28.4 (15.8) | 32.2 (15.0) | 21.1 (15.1)* |
| Kansas City Cardiomyopathy Questionnaire | |||
| Physical Limitation domain | 63.6 (25.7) | 71.5 (23.8) | 47.9 (22.0)* |
| Overall Summary Score | 50.7 (21.6) | 59.9 (19.5) | 33.2 (12.9)* |
| Clinical Summary Score | 57.9 (22.8) | 66.7 (20.5) | 40.9 (16.8)* |
| Medications | |||
| Antidepressants | 7 (6.9%) | 3 (4.5%) | 4 (11.8%) |
| Beta Blockers | 56 (55%) | 37 (55%) | 19 (56%) |
| ACE/ARB/ARNI | 63 (63%) | 41 (61%) | 20 (59%) |
| MRA | 25 (25%) | 15 (22%) | 9 (27%) |
| SGLT2 inhibitor | 14 (14%) | 9 (13%) | 4 (12%) |
| Hydralazine | 16 (16%) | 12 (18%) | 3 (9%) |
| Isosorbide nitrates | 15 (15%) | 14 (21%) | 2 (6%)* |
Data are presented as mean (SD) or number (%).
statistically significant group difference (p= <0.05).
Abbreviations: ACE=angiotensin-converting enzyme inhibitor; ARB=angiotensin receptor blocker; ARNI=angiotensin receptor/neprilysin inhibitor; MET=metabolic equivalents of task; MRA= mineralocorticoid receptor antagonist; PHQ-9=Participant Health Questionnaire-9 question version; SGLT2=sodium-glucose cotransporter-2.
In patients with recent decompensated HFrEF, depressive symptoms quantified by PHQ-9 scores were inversely related to subjective assessments of exercise/functional capacity, as assessed by the KCCQ-PL and DASI scores. However, no significant associations were observed with objective measures of exercise/functional capacity. As previously shown, subjective assessments of exercise/functional capacity were moderately correlated with objective measures of functional capacity in patients with cardiovascular disease compared to strong correlations observed in healthy participants in validation studies.6,7 Also, while our current findings did not show a significant relationship between depressive symptoms and effort-dependent exercise variables, previous research has shown weak correlations between depressive symptoms (measured using the Beck Depression Index) and effort-dependent exercise variables in a chronic HF cohort.8
Compared to previous reports, differences observed in this study may be attributed to the smaller cohort and the majority of Black Americans.8 Furthermore, the current study evaluated patients within 14 days of a hospital discharge for HFrEF decompensation. This recent change in health status may have impacted the relationship between depressive symptoms and the perception of exercise/functional capacity seen in this study. Current findings indicate the perception of health status, as assessed by KCCQ-clinical summary and overall summary scores, was also correlated with depressive symptoms, similar to observations with the KCCQ-PL domain. Lastly, patients in acute care settings are more likely to have transient changes in depression symptoms compared to patients in the outpatient setting.9 Future research is needed to assess changes in depressive symptoms over time and how these changes impact perceptions of functional ability and measured functional capacity. Other potential variables that may have impacted our result include that only 11% of patients with clinically-significant depressive symptoms reported treatment with antidepressant medication. This secondary analysis study does not have a priori power calculations and its single center cross-sectional design may not represent the entire HFrEF population, thus causation cannot be proven due to the inability to assess the bi-directionality of relationships between variables.
In conclusion, these findings suggest that depressive symptom severity plays a significant role in perceptions of subjective functional ability more than objectively measured functional capacity. Understanding this relationship may assist clinicians in the most appropriate use of functional capacity assessments and improve the quality of treatment decisions in participants with HF.
Acknowledgments:
This study was funded by a National Heart, Lung, and Blood Institute award from the National Institute of Health award (R61/R33 HL139943) to Drs. Van Tassell and Abbate. The study is also supported by a Clinical and Translational Science award to Virginia Commonwealth University (UM1TR004360) from the National Center for Advancing Translational Sciences. J. Canada is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number K23HL159270.
Footnotes
Conflict of Interest Statements: None of the authors have conflicts of interests related to this manuscript.
Declaration of Competing Interests
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:
Antonio Abbate reports financial support was provided by National Heart Lung and Blood Institute. Benjamin Van Tassell reports financial support was provided by National Heart Lung and Blood Institute. Justin M. Canada reports financial support was provided by National Heart Lung and Blood Institute. Michele Golino reports financial support was provided by National Heart Lung and Blood Institute. Josh West reports financial support was provided by National Heart Lung and Blood Institute. Azita Talasaz reports financial support was provided by National Heart Lung and Blood Institute. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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