Abstract
Background
Depression is a common comorbidity in heart failure (HF) and is strongly associated with increased mortality, morbidity, and reduced health status. Whether depression treatment may result in improvement of health status in HF patients with comorbid depression remains unknown.
Methods and Results
The SADHART-CHF study randomized 469 participants with chronic HF (LVEF 45% and NYHA class II) and major depressive disorder (MDD) DSM-IV criteria) to sertraline or placebo for 12 weeks. The Kansas City Cardiomyopathy Questionnaire (KCCQ), Short Form Health Survey (SF-36), and 6-minute walk test (6MWT) were used to assess health status. Health status changes between treatment arms and remission status were evaluated adjusting for baseline variables and treatment assignment. The final HDRS scores were 3.50±2.08 and 12.97±4.33 in the remission and non-remission groups, respectively (p-value = 0.0001). Of 469 total participants, 378 (80.6%) completed the 6MWT and 285 (70.1%) completed KCCQ and SF-36, at baseline and at week-12. Depression remission was significantly associated with higher improvements in KCCQ subscale scores (p < 0.001) except on the Self-Efficacy (p=0.18) and Symptom Stability (p=0.91). On the SF-36, depression remission was associated with significant improvement in subscales of the Physical and Mental Component Summary except the Pain Index (p=0.34). The 6MWT improved more in depression remission compared to non-remission group (difference from baseline: 63.51±238.78 vs. 16.24±115.70 meters, p=0.03).
Conclusions
HF patients whose depressive symptoms remitted had significantly greater improvement in physical function, social function, and quality of life.
Keywords: heart failure, depression, health status, Kansas City Cardiomyopathy Questionnaire, 6-Minute Walk Test
In addition to increased mortality, heart failure (HF) results in functional disability and lower quality-of-life.1–3 In HF, the prevalence of depression is at least 20%.4 The World Health Organization World Health Survey across 60 countries found that depression comorbid with one or more chronic diseases had the worst health function scores of all the disease states, even after adjusting for socioeconomic factors.5 Depression is an independent risk factor for worsening health status and reduced quality of life in patients with HF.6–11To elucidate the temporal relationship between depression and health status in patients with HF, this study examined whether antidepressant intervention and successful depression treatment (i.e., remission from depression), affect the health status. A secondary analysis is conducted from the Sertraline Against Depression and Heart Disease in Chronic Heart Failure (SADHART-CHF) database to examine predetermined health status outcomes that were assessed via the Kansas City Cardiomyopathy Questionnaire (KCCQ), the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), and the 6-minutes walk test (6MWT). We hypothesize that depression remission will result in significant improvement of health status in HF patients with comorbid major depressive disorder (MDD).
Methods
Study Description
A complete description of the SADHART-CHF trial design and primary findings has been published in detail elsewhere.12–14 In brief, SADHART-CHF is the first and the largest randomized clinical trial examining the effects of a selective serotonin reuptake inhibitor (SSRI) on depression and cardiac outcomes in patient with HF and comorbid MDD. The protocol was reviewed and approved by the institutional review board for each center. The study recruited 469 participants (N=234 sertraline, N=235 placebo), from 3 centers in the United States between 8/13/2003 and 3/3/2008. Participants were ≥45 years of age with LVEF ≤45% (within the previous 6 months), NYHA class II-IV HF symptoms, and had MDD based on Diagnostic Statistics Manual 4th Edition (DSM-IV) criteria. The intervention was sertraline vs. matched placebo for 12-week. Additionally, all participants received nurse facilitated support that was to build rapport and trust with the study participants, to ascertain compliance with the study protocol, re-evaluate depression status, monitor suicidal ideation, and consult with study physicians on appropriate patient management. Trial intervention was terminated after week 12.13–14 For the primary outcome of depression remission, sertraline treatment did not significantly differ from placebo. Of 469 participants, 208 (44.3% achieved remission, 194 (41.4%) remained depressed, and 67 (14.3%) dropped out or died without any repeat HDRS assessment.14
Depression Measurement and Comparison
The 17-item Hamilton Depression Rating Scale (HDRS) was completed at baseline and at 2 week intervals during the 12-week treatment phase and at the end of the 12-week intervention. Depression remission was defined as HDRS <8 during the last depression assessment. Patients whose HDRS remained ≥8 were considered non-remission. Participants (n=67, 14.3%) who dropped out without having a repeat HDRS were excluded.
Patient-reported Outcomes (PRO) for Health Status
In addition to the primary outcome of depression remission, a priori outcome measurements included patient-reported health status outcomes.12 The health status outcomes were ascertained at baseline prior to randomization and the end of 12-week intervention via the Kansas City Cardiomyopathy Questionnaire (KCCQ), total and subscale scores, the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) Mental Component Summary (MCS) and Physical Component Summary (PCS) scores, and the 6-minute walk test (6MWT). KCCQ is a 23-item self-administered disease specific questionnaire, scored from 0 to 100 with higher scores corresponding to better health status. In addition to the overall summary score, we also examined score from the subscales for Social Limitation, Quality-Of-Life, Symptom Frequency, Total Symptom Score, and Clinical Summary. A 5-point change in the KCCQ summary score had been previously used to correspond to minimal clinical significance.15–17 The SF-36 was designed to measure general health status with higher scores indicating a better health state. The results are expressed in terms of 8 subscores. The Physical Component Summary (PCS) consists of a 10-item Physical Functioning, 4-item Role Physical, 2-item Pain index, and 5-item General Health Perception.18 Mental Component Summary (MCS) consists of 4-item Vitality, 2-item Social Functioning, 3-item Emotional Role, and 5-item Mental Health Index.19,20 The 6MWT reflects a global and integrated response of the body systems to exercise testing and closely mimics everyday activity. It examines overall functional capacity and serves as a simple prognosticator.21–24
Statistical Analysis
Statistical analyses were performed using SAS, version 9.1 (SAS Incorporated, Cary, NC). Descriptive statistics were reported for the depression remission and non-remission groups. Differences of depression treatment, and remission on health status scores with categorical variables (e.g. gender, race etc) were examined using chi-squared test, while for the continuous variables Wilcoxon test were used. Linear regression models with model based standard errors were used to test if the changes scores (final minus baseline) of health status between groups were associated with or without covariates including age, gender, race, history of depression, baseline HDSR score, New York Heart Association (NYHA) class, ejection fraction, history of depression, ischemia, coronary artery disease, history of coronary artery bypass grafting (CABG) surgery, implanted cardioverter defibrillator, angina, myocardial infarction, arrhythmia, hypertension, diabetes, and baseline medications ace inhibitors, statins, beta-blockers, and loop diuretics. Judging by standard models of fit, there was no empirical evidence to support any non-linear relationships with the outcomes; hence, we employed linear regression models. Prior to fitting the final model, we looked for multicollinearity as well as for extreme values using the standard techniques (Rosner, 2000).25 The change scores are obtained from participants who completed both baseline and final measurements. Treatment assignment (sertraline vs. placebo) was additionally added as a covariate to examine the effects of depression remission vs. nonremission. Since a total of 10 KCCQ and 8 SF-36 outcomes were examined, a p-value <0.001 was set as statistical significance to account for examination of multiple dependent variables. Statistical significance for 6MWT was set at p<0.05 because that was the only outcome examined in this category.
Results
Participant Characteristics
A total of 469 participants were enrolled, and 402 (85.7%) had least one HDRS evaluation during the trial intervention phase. Of them, a total of 378 (80.6%) participants completed the 6MWT at baseline and at week-12, and 285 (70.1%) completed both baseline and 12-week KCCQ and SF-36. Of the participants who completed both the KCCQ and SF-36, 73 (54.1%) of 135 participants received sertraline and achieved remission, while 80 (53.3%) of 150 received placebo and achieved remission (p=0.91). Treatment with sertraline vs. placebo did not correspond to difference in KCCQ, SF-36 subscale scores (for KCCQ Overall Summary: p=0.88, KCCQ Quality of Life: p=0.83, SF-36 Physical Function: p=0.40, and 6MWT: p=0.53).
Table 1 displays the baseline characteristics between the remission and non-remission groups who completed both baseline and 12-week KCCQ and SF-36 measurements (n=285). The final HDRS scores were 3.50±2.08 and 12.97±4.33 in the remission and non-remission groups, respectively (p-value < 0.001). For KCCQ changes at week 12 from baseline (Table 2), depression remission was significantly associated with higher score improvements in Social Limitation (p<0.001), Physical Limitation (p<0.001) Quality-Of-Life (p<0.001), Symptom Frequency (p<0.001), Total Symptom (p<0.001), Clinical Summary (p<0.001), and Overall Summary (p<0.001) scores. Depression remission was not associated with improvements in Self-efficacy and (p=0.18) Symptom Stability (p=0.91) measurements.
Table 1.
Baseline Characteristics between remission vs. nonremission groups
| Remission (n=132) | Nonremission (n=152) | p-value | |
|---|---|---|---|
| History of antidepressant treatment | 119 (45.25%) | 144 (54.75%) | 0.27 |
| Age | 60.5±10.1 | 62.3±9.40) | 0.10 |
| Women | 58 (43.94%) | 51 (33.33%) | 0.07 |
| White | 76 (57.58%) | 90 (58.82%) | 0.90 |
| African American | 56 (42.42%) | 63 (41.18%) | |
| Ischemic cause | 90 (68.18%) | 103 (67.32%) | 0.71 |
| NYHA Classification | 3.0±0.8 | 2.92±0.70) | 0.39 |
| Ejection Fraction (%) | 31.2±10.3 | 30.22±9.56 | 0.45 |
| Previous coronary bypass surgery | 35 (26.52%) | 53 (34.64%) | 0.16 |
| Implantable cardioverter-defibrillator | 27 (20.45%) | 21 (13.73%) | 0.15 |
| History of angina | 82 (62.12%) | 79 (51.63%) | 0.09 |
| History of myocardial infarction | 58 (43.94%) | 69 (45.10%) | 0.91 |
| History of arrhythmia | 51 (38.64%) | 62 (40.52%) | 0.81 |
| Hypertension | 112 (84.85%) | 136 (88.89%) | 1.00 |
| Diabetes | 70 (53.03%) | 82 (53.59%) | 1.00 |
| ACE Inhibitor | 95 (71.97%) | 115 (75.16%) | 0.59 |
| Beta-blocker | 114 (86.36%) | 132 (86.27%) | 1.00 |
| Loop Diuretic | 83 (62.88%) | 95 (62.50%) | 1.00 |
| Statin | 89 (67.42%) | 105 (68.63%) | 0.90 |
| Sertraline | 62 (46.97%) | 73 (47.71%) | 0.91 |
Table 2.
Comparison of Kansas City Cardiomyopathy Questionaire (KCCQ) base, final, and change scores between depression and remission groups
| Remission (n=153) | Non-remission (n=132) | |||||||
|---|---|---|---|---|---|---|---|---|
| Mean (SD) | Mean (SD) | Unadjusted | Adjusted | |||||
| Baseline | Final | Change* | Baseline | Final | Change* | p-value | p-value | |
| Social Limitation | 40.6 (31.2) | 68.5 (28.8) | 28.1 (32.9) | 33.9 (30.4) | 43.8 (31.9) | 9.6 (30.0) | <0.001 | <0.001 |
| Physicial Limitation | 44.7 (25.5) | 60.5 (25.9) | 15.7 (26.0) | 36.2 (27.1) | 41.9 (24.6) | 5.6 (22.7) | 0.002 | <0.001 |
| Symptom Stability | 42.3 (33.7) | 54.1 (21.4) | 11.8 (36.4) | 37.1 (28.7) | 49.6 (20.7) | 12.5 (35.2) | 0.8 | 0.91 |
| Quality of Life | 41.7 (25.2) | 72.1 (22.5) | 30.3 (26.3) | 37.2 (24.3) | 50.8 (25.0) | 13.6 (25.0) | <0.001 | <0.001 |
| Self Efficacy | 79.7 (25.0) | 90.1 (16.9) | 10.4 (23.4) | 82.4 (21.1) | 89.0 (17.8) | 6.6 (19.6) | 0.3 | 0.18 |
| Symptom Burden | 50.5 (26.3) | 74.6 (24.0) | 24.1 (32.9) | 40.8 (28.7) | 52.4 (25.5) | 11.6 (26.7) | 0.009 | 0.001 |
| Symptom Frequency | 45.8 (25.9) | 71.8 (24.9) | 26.9 (29.3) | 37.5 (25.1) | 50 (25.4) | 12.6 (24.8) | <0.002 | <0.001 |
| Total Symptom Score | 48.1 (24.6) | 73.2 (23.4) | 25.1 (29.6) | 39.2 (25.5) | 51.2 (24.0) | 12.1 (23.9) | <0.001 | <0.001 |
| Clinical Summary | 46.5 (22.4) | 66.9 (22.5) | 20.4 (25.0) | 37.9 (23.0) | 46.7 (21.2) | 8.8 (18.5) | <0.001 | <0.001 |
| Overall Summary | 43.9 (22.1) | 68.7 (21.5) | 24.7 (23.8) | 36.7 (21.2) | 47.0 (20.9) | 10.4 (17.7) | <0.001 | 0.001 |
Table 3 displays the SF-36 PCS and MCS changes in subscale scores between depression remission and nonremission. In the PCS subscales, there was significant improvement in the depression remission group on General Health Perception (p<0.001), Physical Function (p<0.001) and Role Physical (p<0.001) but not Pain Index (p=0.34). For the MCS subscales, the depression remission group had significant improvement in all 4 subscales including Role Emotional, Mental Health Index, Social Functioning, and Vitality (Table 3).
Table 3.
Comparision of 36-Item Short-Form (SF-36) baseline, final, and change scores between depression remission vs. nonremission groups
| Remission (n=153) Mean±SD |
Non-remission (n=132) Mean±SD |
|||||||
|---|---|---|---|---|---|---|---|---|
| Baseline | Final | Change* | Baseline | Final | Change* | Unadjusted | Adjusted | |
| Physican Component Summary | ||||||||
| Pain Index | 51.6 (30.8) | 66.3 (28.4) | 14.7 (35.8) | 40.7 (29.4) | 50.6 (28.6) | 9.9 (29.0) | 0.25 | 0.34 |
| General Health Perception | 38.1 (19.4) | 47.6 (20.9) | 9.6 (20.2) | 29.8 (17.3) | 32.4 (15.9) | 2.5 (17.8) | 0.005 | 0.0005 |
| Physical Function | 28.6 (22.9) | 45.2 (27.9) | 16.6 (25.1) | 23.3 (21.4) | 25.9 (22.9) | 2.5 (19.7) | <0.001 | <0.001 |
| Role Physical | 14.2 (28.6) | 38.4 (40.7) | 24.5 (45.3) | 7.9 (22.0) | 12.6 (28.3) | 4.7 (28.5) | <0.001 | <0.001 |
| Mental Component Summary | ||||||||
| Role Emotional | 41.5 (42.9) | 84.3 (31.5) | 43.1 (45.3) | 31.1 (41.5) | 46.8 (43.6) | 16.5 (49.9) | <0.001 | <0.001 |
| Mental Health Index | 60.7 (19.9) | 80.9 (13.9) | 20.2 (19.64) | 27.1 (19.4) | 52.6 (20.2) | 8.9 (24.4) | <0.001 | <0.001 |
| Social Functioning | 46.4 (29.4) | 76.4 (26.2) | 30.0 (32.7) | 39.6 (29.7) | 49.9 (28.0) | 10.3 (30.9) | <0.001 | <0.001 |
| Vitality | 28.9 (19.7) | 49.5 (50.0) | 20.6 (25.2) | 23.9 (19.6) | 26.0 (19.0) | 2.1 (20.2) | <0.001 | <0.001 |
Table 4 reports remission and nonremission groups with both baseline and 12-week 6MWT measurements. At baseline, the depression remission group had higher 6MWT compared to depression nonremission group (p=0.007). At the conclusion of the study, the final from baseline change of 6MWT results was higher in the depression remission compared to nonremission group (63.51+238.78 m vs. 16.24±115.70 m, p=0.03).
Table 4.
Comparison of 6-Minute Walk Test Between Depression Remission and Nonremission Groups
| Remission (n=192) | Nonremission (n=186) | ||||
|---|---|---|---|---|---|
| Mean | SD | Mean | SD | p-value | |
| Baseline (meters) | 88.8 | 126.02 | 59.40 | 115.44 | 0.007 |
| Week 12 (meters) | 152.3 | 263.85 | 75.64 | 132.43 | 0.05 |
| Difference (meters) | 63.51 | 238.78 | 16.24 | 115.70 | 0.03 |
The baseline HDRS scores were 16.83 ± 5.33 and 19.51 ± 5.50, in the remission and non-remission groups, respectively (p < 0.001). The health status outcomes associated with depression remission were not significantly associated with measured baseline conditions including baseline HDRS score.
Discussion
Depression is considered a major determinant of health status in patients with HF.26,27 However, few studies have examined depression treatment on health status in HF. In a placebo-controlled pilot study (n=28), Gottlieb et al. found that paroxetine was associated with higher SF-36 psychological quality-of-life but not with physical quality-of-life.28 In contrast, the SADHART-CHF study found that sertraline treatment did not differ from placebo in terms of depression remission and health status outcomes, although depression remission was associated with significant improvement in health status.
For the self-reported KCCQ measurements, depression remission was associated with improvement in Social Limitation, Physical Limitation, and Symptom Frequency. A 5-point change in the KCCQ is considered of minimal clinical significance17. In this study, the KCCQ overall summary score was about 13 point higher in the depression remission group compared to depression non-remission group. The largest difference was observed on the KCCQ Quality of Life and Social Limitation subscales, where the differences were nearly 20 points between the two groups, indicating moderate to large clinical difference. The observed finding on the KCCQ was verified by the SF-36 measurements, in that depression remission was associated with improvements in General Health Perception and Physical Function subscales. On the 6MWT, patients with depression remission were able to walk 47 meters more than those patients with continued to have depression (p=0.03). These findings highlight the fact that depression remission was associated with improvements in physical health measurements. On the other hand depression remission was not associated with improvements in KCCQ Symptom Stability and Self Efficacy subscales, and SF-36 Pain Index.
The strength of this study includes the use of rigorous instruments (KCCQ, SF-36, and 6MWT) to measure health status in HF, which had been extensively studied to evaluate the health impact of exercise training in HF.29–32 Most of these studies used one or two of these outcome instruments and not all three. We were able to demonstrate that health performance on the three outcomes measures consistently improved with depression remission.
There were limitations to this study, however. First, this study was a secondary analysis where the primary outcome of SADHART-CHF was depression remission. The health status instruments were secondary outcomes. The study was further limited by the low completion rate of KCCQ and SF-36 of 60.1% (n=282), and 6MWT of 80.6% (n=378) in 469 total participants. Therefore the conclusion of this study may not be generlizable to participants who dropout or who did not complete the health status measurements. Non-completers were older (64.29 (11.6) vs 61.45 (9.8) p= 0.02), had larger incidence of MI (40.38% vs30.88%, p=0.04) and CABG (54.5 vs 44.5% p = 0.044). Also, the outcomes were not measured beyond the first 12-week during long-term follow-up, therefore whether the improvement persisted after 12 weeks remained unknown. Finally, we did not examine interaction effects between treatments and among independent variables. The conclusions therefore were limited to the variables examined and thus subject to unmeasured confounding effects.
In conclusion, sertraline treatment did not impact health status compared to placebo but depression remission was associated with improved health status in patients with HF and comorbid MDD. Therefore, it is important that future studies that examine the comobidity of depression and HF should include health status as an important outcome. Clinically, depression monitoring and treatment of depression in HF to achieve remission has important impact on physical function and quality-of-life that is beyond just psychological and emotional well-being.
Depression is associated with increase risk of mortality and morbidity in patient with heart failure. This study examined patient-reported health status in patients who participated in the Safety and Efficacy of Sertraline for Depression in Patient with CHF (SADHART-CHF) study. Health status measurements included. The Kansas City Cardiomyopathy Questionnaire (KCCQ), Short Form Health Survey (SF-36), and 6-minute walk test (6MWT). Of 469 total participants, 378 (80.6%) completed 6MWT and 285 (70.1%) completed KCCQ and SF-36, at baseline and at week-12. Depression remission was significantly associated with higher improvements in 1) KCCQ subscale scores (p < 0.001) except on the Self-Efficacy (p=0.18) and Symptom Stability (p=0.91); 2) SF-36 subscales of the Physical and Mental Component Summary except the Pain Index (p=0.34); and 3) 6MWT (difference from baseline: 63.51±238.78 vs. 16.24±115.70 meters, p=0.03). However, treatment with sertraline vs. placebo was not associated with improvement in the health status measurements. This study suggests that depression remission is an important outcome to achieve in CHF patients, and that medication treatment of their depression alone may not predict improvements in health status outcomes.
Acknowledgments
Sources of Funding
The SADHART-CHF study was funded by the National Institute of Mental Health (NIMH) Bethesda, Maryland. Sertraline was supplied by Pfizer, Inc., New York, New York. Pfizer had no other role in any aspect of the study.
Footnotes
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Disclosures
None.
References
- 1.Juenger J, Schellberg D, Kraemer S, Haunstetter A, Zugck C, Herzog W, Haass M. Health related quality of life in patients with congestive heart fialure: comparison with other chronic diseases and relation to functional variables. Heart. 2002;87:235–241. doi: 10.1136/heart.87.3.235. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Lee DTF, Yu DSF, Woo J, Thompason DR. Health-related quality of life in patients with congestive heart failure. Eur J Heart Fail. 2005;7:419–422. doi: 10.1016/j.ejheart.2004.08.004. [DOI] [PubMed] [Google Scholar]
- 3.Dracup K, Walden JA, Stevenson LW, Brecht ML. Quality of life in patients with advanced heart failure. J Heart Lung Transplant. 1992;11:273–279. [PubMed] [Google Scholar]
- 4.Rutledge T, Reis VA, Linke SE, Greenberg BH, Mills PJ. Depression in heart failure a meta-analytic review of prevalence, intervention effects, and associations with clinical outcomes. J Am Coll Cardiol. 2006;48:1527–1537. doi: 10.1016/j.jacc.2006.06.055. [DOI] [PubMed] [Google Scholar]
- 5.Moussavi S, Chatterji S, Verdes E, Tandon A, Patel V, Ustun B. Depression, chronic diseases, and decrement in health: results from the World Health Survyes. Lancet. 2007;370:851–858. doi: 10.1016/S0140-6736(07)61415-9. [DOI] [PubMed] [Google Scholar]
- 6.Jiang W, Alexander J, Christopher E, Kuchibhatla M, Gaulden LH, Cuffe MS, Blazing MA, Davenport C, Califf RM, Krishnan RR, O’Connor CM. Relationship of depresion to increased risk of mortality and rehospitalization in patients with congestive heart fialure. Arch Intern Med. 2001;161:1849–1856. doi: 10.1001/archinte.161.15.1849. [DOI] [PubMed] [Google Scholar]
- 7.Rumsfeld JS, Havranek E, Masoudi FA, Peterson ED, Jones P, Tooley JF, Krumholz HM, Spertus JA. Depressive symptoms are the strongest predictors of short-term declines in health status in patients with heart failure. J Am Coll Cardiol. 2003;42:1811–1817. doi: 10.1016/j.jacc.2003.07.013. [DOI] [PubMed] [Google Scholar]
- 8.Sullivan M, Levy WC, Russo JE, Spertus JA. Depression and health status in patients with advanced heart failure: a prospective study in tertiary care. J Card Fail. 2004;10:390–396. doi: 10.1016/j.cardfail.2004.01.011. [DOI] [PubMed] [Google Scholar]
- 9.Rozzini R, Sabatini T, Frisoni GM, Trabucchi M. Depression and major outcomes in older patients with heart failure. Arch Intern Med. 2002;162:362–363. doi: 10.1001/archinte.162.3.362-a. [DOI] [PubMed] [Google Scholar]
- 10.Muller-Tasch T, Peters-Klimm F, Schellberg D, Holzapfel N, Barth A, Jünger J, Szecsenyi J, Herzog W. Depression is a major determinant of quality of life in patients with chronic systolic heart failure in general practice. J Card Fail. 2007;13:818–824. doi: 10.1016/j.cardfail.2007.07.008. [DOI] [PubMed] [Google Scholar]
- 11.Angermann CE, Gelbrich G, Stork S, Fallgatter A, Deckert J, Faller H, Ertl G MOOD-HF Investigators. Rationale and design of a randomised, controlled, multicenter trial investigating the effects of selective serotonin re-uptake inhibition on morbidity, mortality and mood in depressed heart failure patients (MOOD-HF) Eur J Heart Fail. 2007;9:1212–1222. doi: 10.1016/j.ejheart.2007.10.005. [DOI] [PubMed] [Google Scholar]
- 12.Jiang W, O'Connor C, Silva SG, Kuchibhatla M, Cuff MS, Callwood DD, Zakhary B, Henke, Arias RM, Krishnan R SADHART-CHF Investigators. Safety and efficacy of sertraline for depression in patients with CHF (SADHART-CHF): a randomized, double-blind, placebo-controlled trial of sertraline for major depression with congestive heart failure. Am Heart J. 2008;156:437–444. doi: 10.1016/j.ahj.2008.05.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.O’Connor CM, Jiang W, Kuchibhatla M, Silva SG, Cuffe MS, Callwood DD, Zakhary B, Stough WG, Arias RM, Rivelli SK, Krishnan R SADHART-CHF Investigators. Safety and efficacy of sertraline for depression in patients with heart failure: results of the SADHARTCHF trial. J Am Coll Cardiol. 2010;56:692–699. doi: 10.1016/j.jacc.2010.03.068. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Jiang W, Krishnan R, Kuchibhatla M, Cuff MS, Martzberger C, Arias RM, O’Connor CM SADHART-CHF Investigators. Characteristics of depression remission and its relation with cardiovascular outcome among patients with chronic heart failure (from the SADHART-CHF study) Am J Card. 2011;107:545–551. doi: 10.1016/j.amjcard.2010.10.013. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Green CP, Porter CB, Bresnahan DR, Spertus JA. Development and evaluation of the Kansas City Cardiomyopathy Questionnaire: a new health status measure for heart failure. J Am Coll Cardiol. 2000;35:1245–1255. doi: 10.1016/s0735-1097(00)00531-3. [DOI] [PubMed] [Google Scholar]
- 16.Spertus J, Peterson E, Conard MW, Heidenreich PA, Krumholz HM, Jones P, McCullough PA, Pina I, Tooley J, Weintraub WS, Rumsfeld JS Cardiovascular Outcomes Research Consortium. Monitoring clinical changes in patients with heart failure: a comparison of methods. Am Heart J. 2005;150:707–715. doi: 10.1016/j.ahj.2004.12.010. [DOI] [PubMed] [Google Scholar]
- 17.Flynn KE, Pina IL, Whellan DJ, Lin L, Blumenthal JA, Ellis SJ, Howlett JG, Keteyian SJ, Kitzman DW, Kraus WE, Miller NH, Schulman KA, Spertus JA, O’Connor CM, Weinfurt KP HF-ACTION Investigators. Effects of exercise training on health status in patients with chronic health failure. JAMA. 2009;301:1451–1459. doi: 10.1001/jama.2009.457. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Ware JE, Kosinski M, Bayliss MS, McHorney CA, Rogers WH, Raczek A. Comparison of methods for the scoring and statistical analysis of SF-36 health profile and summary measures: summary of results from the medical outcomes study. Med Care. 1995;33:AS264–AS279. [PubMed] [Google Scholar]
- 19.Ware JE, Kosinski M, Keller SD. SF-36 Physical and Mental Health Summary Scales: A User’s Manual. Boston, Mass: Health Assessment Lab, New England Medical Center; 1994. [Google Scholar]
- 20.Ware JE, Snow KK, Kosinski M, Gandek B. SF-36 Health Survey:Manual and Interpretation Guide. Lincoln, RI: QualityMetric, Inc; 2000. [Google Scholar]
- 21.Olsson LG, Swedberg K, Clark AL,Witte KK, Cleland JG. Six minute corridor walk test as an outcome measure for the assessment of treatment in randomized, blinded intervention trials of chronic heart failure: a systematic review. Eur Heart J. 2005;26:778–793. doi: 10.1093/eurheartj/ehi162. [DOI] [PubMed] [Google Scholar]
- 22.American Thoracic Society Statement: Guidelines for the six-minute walk test. Am J respire Crit Care Med. 2002;166:111–117. doi: 10.1164/ajrccm.166.1.at1102. [DOI] [PubMed] [Google Scholar]
- 23.Faggiano P, D’Aloia A, Gualeni A Lavatelli a, Giordano A. Assessment of oxygen uptake during the 6-minute walking test in patients with heart failure: preliminary experience with a portable device. Am Heart J. 1997;134:203–206. doi: 10.1016/s0002-8703(97)70125-x. [DOI] [PubMed] [Google Scholar]
- 24.Shah MR, Hasselblad V, Gheorghiade M, Adams KF, Jr, Swedberg K, Califf RM, O’Connor CM. Prognostic usefulness of the six-minute walk in patients with advanced congestive heart failure secondary to ischemic of nonischemic cardiomyopathy. Am J Cardiol. 2001;88:987–993. doi: 10.1016/s0002-9149(01)01975-0. [DOI] [PubMed] [Google Scholar]
- 25.Rosner B. Fundamentals of Biostatistics. Duxbury Press; 2000. [Google Scholar]
- 26.Gottlieb SS, Kop WJ, Ellis SJ, Binkley P, Howlett J, O’Connor C, Blumenthal JA, Fletcher G, Swank AM, Cooper L HF-ACTION Investigators. Relation of depression to severity of illness in heart failure (from Heart Failure And a Controlled Trial Investigating Outcomes of Exercise Training [HF-ACTION]) Am J Cardiol. 2009;103:1285–1289. doi: 10.1016/j.amjcard.2009.01.025. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Cohen DJ, Van Hout B, Serruys BW, Mohr FW, Macaya C, den Heijer P, Vrakking MM, Wang K, Mahoney EM, Audi S, Leadley K, Dawkins KD, Kappetein AP Synergy between PCI with Taxus and Cardiac Surgery Investigators. Quality of life after PCI with drug-eluting stents or coronary artery bypass surgery. N Engl J Med. 2011;364:1016–1026. doi: 10.1056/NEJMoa1001508. [DOI] [PubMed] [Google Scholar]
- 28.Gottlieb SS, Kop WJ, Thomas SA, Katzen S, Vesely MR, Greenberg N, Marshall J, Cines M, Minshall S. A double-blind placebo-controlled pilot study of controlled-release paroxetine on depression and quality of life in chronic heart failure. Am Heart J. 2007;153:868–873. doi: 10.1016/j.ahj.2007.02.024. [DOI] [PubMed] [Google Scholar]
- 29.Belardinelli R, Georgiou D, Cianci G, Purcaro A. Randomized, controlled trail of long-term moderate exercise training in chronic heart failure: effects on functional capacity, quality of life, and clinical outcomes. Circulation. 1999;99:1173–1182. doi: 10.1161/01.cir.99.9.1173. [DOI] [PubMed] [Google Scholar]
- 30.Rees K, Taylor RS, Singh S, Coats A, Ebrahim S. Exercise based rehabilitation for heart failure. Cochrane Database Sust Rev. 2004:CD003331. doi: 10.1002/14651858.CD003331.pub2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Gary RA, Sueta CA, Dougherty M, Rosenberg B, Cheek D, Preisser J, Neelon V, McMurray R. Home-based exercise improves functional performance and quality of life in women with diastolic heart failure. Heart Lung. 2004;33:210–218. doi: 10.1016/j.hrtlng.2004.01.004. [DOI] [PubMed] [Google Scholar]
- 32.O’Connor CM, Whellan DJ, Lee KL, Keteyian SJ, Cooper LS, Ellis SJ, Leifer ES, Kraus WE, Kitzman DW, Blumenthal JA, Rendall DS, Miller NH, Fleg JL, Schulman KA, McKelvie RS, Zannad F, Pina IL HF-ACTION Investigators. Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial. JAMA. 2009;301:1439–1450. doi: 10.1001/jama.2009.454. [DOI] [PMC free article] [PubMed] [Google Scholar]