[Skip to Navigation]
Sign In
Visual Abstract. Efficacy of Blended Collaborative Care for Patients With Heart Failure and Comorbid Depression
Efficacy of Blended Collaborative Care for Patients With Heart Failure and Comorbid Depression
Figure 1.  Flowchart of Screening, Enrollment, Randomization, and Follow-upa
Flowchart of Screening, Enrollment, Randomization, and Follow-upa

aStudy participants who missed a 3- or 6-month follow-up assessment remained eligible to complete a later assessment. We display the cumulative number of withdrawn and deceased patients in parentheses. There were no differences in follow-up rates between randomized arms or by baseline depression status (eTable 1 in Supplement 3).

HIPAA indicates Health Insurance Portability and Accountability Act; NYHA, New York Heart Association; PHQ, Patient Health Questionnaire; Tx, treatment; UC, usual care.

Figure 2.  Twelve-Month Adjusted Differences in Mental Component Summary of the 12-Item Short Form Health Survey Scores for All Randomized Patients With Depression and by Sex
Twelve-Month Adjusted Differences in Mental Component Summary of the 12-Item Short Form Health Survey Scores for All Randomized Patients With Depression and by Sex

Subgroup analysis by sex revealed no significant subgroup effect (P = .57 for 3-way interaction). eUC indicates enhanced usual care; UC, usual care.

Figure 3.  Estimated Mental Component Summary of the 12-Item Short Form Health Survey (MCS-12) Scores by Time Point for All Patients, Men, and Women
Estimated Mental Component Summary of the 12-Item Short Form Health Survey (MCS-12) Scores by Time Point for All Patients, Men, and Women

Error bars indicate 95% CIs. eUC indicates enhanced usual care; ND, no depression; UC, usual care.

Table 1.  Baseline Sociodemographic and Clinical Characteristics by Randomization and Baseline Depression Status
Baseline Sociodemographic and Clinical Characteristics by Randomization and Baseline Depression Status
Table 2.  Twelve-Month Care Processes and Health Services Use Following Randomization
Twelve-Month Care Processes and Health Services Use Following Randomization
1.
Virani  SS, Alonso  A, Benjamin  EJ,  et al; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee.  Heart disease and stroke statistics—2020 update: a report from the American Heart Association.   Circulation. 2020;141(9):e139-e596. doi:10.1161/CIR.0000000000000757PubMedGoogle ScholarCrossref
2.
Celano  CM, Villegas  AC, Albanese  AM, Gaggin  HK, Huffman  JC.  Depression and anxiety in heart failure: a review.   Harv Rev Psychiatry. 2018;26(4):175-184. doi:10.1097/HRP.0000000000000162PubMedGoogle ScholarCrossref
3.
Vaccarino  V, Kasl  SV, Abramson  J, Krumholz  HM.  Depressive symptoms and risk of functional decline and death in patients with heart failure.   J Am Coll Cardiol. 2001;38(1):199-205. doi:10.1016/S0735-1097(01)01334-1PubMedGoogle ScholarCrossref
4.
Gottlieb  SS, Kop  WJ, Ellis  SJ,  et al; 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(9):1285-1289. doi:10.1016/j.amjcard.2009.01.025PubMedGoogle ScholarCrossref
5.
Gathright  EC, Dolansky  MA, Gunstad  J,  et al.  The impact of medication nonadherence on the relationship between mortality risk and depression in heart failure.   Health Psychol. 2017;36(9):839-847. doi:10.1037/hea0000529PubMedGoogle ScholarCrossref
6.
Sherwood  A, Blumenthal  JA, Trivedi  R,  et al.  Relationship of depression to death or hospitalization in patients with heart failure.   Arch Intern Med. 2007;167(4):367-373. doi:10.1001/archinte.167.4.367PubMedGoogle ScholarCrossref
7.
Johnson  TJ, Basu  S, Pisani  BA,  et al.  Depression predicts repeated heart failure hospitalizations.   J Card Fail. 2012;18(3):246-252. doi:10.1016/j.cardfail.2011.12.005PubMedGoogle ScholarCrossref
8.
Freedland  KE, Carney  RM, Rich  MW, Steinmeyer  BC, Skala  JA, Dávila-Román  VG.  Depression and multiple rehospitalizations in patients with heart failure.   Clin Cardiol. 2016;39(5):257-262. doi:10.1002/clc.22520PubMedGoogle ScholarCrossref
9.
Rollman  BL, Herbeck Belnap  B, Mazumdar  S,  et al.  A positive 2-item Patient Health Questionnaire depression screen among hospitalized heart failure patients is associated with elevated 12-month mortality.   J Card Fail. 2012;18(3):238-245. doi:10.1016/j.cardfail.2011.11.002PubMedGoogle ScholarCrossref
10.
Frasure-Smith  N, Lespérance  F, Habra  M,  et al; Atrial Fibrillation and Congestive Heart Failure Investigators.  Elevated depression symptoms predict long-term cardiovascular mortality in patients with atrial fibrillation and heart failure.   Circulation. 2009;120(2):134-140, 3p, 140. doi:10.1161/CIRCULATIONAHA.109.851675PubMedGoogle ScholarCrossref
11.
Freedland  KE, Hesseler  MJ, Carney  RM,  et al.  Major depression and long-term survival of patients with heart failure.   Psychosom Med. 2016;78(8):896-903. doi:10.1097/PSY.0000000000000346PubMedGoogle ScholarCrossref
12.
Gathright  EC, Goldstein  CM, Josephson  RA, Hughes  JW.  Depression increases the risk of mortality in patients with heart failure: a meta-analysis.   J Psychosom Res. 2017;94:82-89. doi:10.1016/j.jpsychores.2017.01.010PubMedGoogle ScholarCrossref
13.
Jha  MK, Qamar  A, Vaduganathan  M, Charney  DS, Murrough  JW.  Screening and management of depression in patients with cardiovascular disease: JACC state-of-the-art review.   J Am Coll Cardiol. 2019;73(14):1827-1845. doi:10.1016/j.jacc.2019.01.041PubMedGoogle ScholarCrossref
14.
Gottlieb  SS, Kop  WJ, Thomas  SA,  et al.  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(5):868-873. doi:10.1016/j.ahj.2007.02.024PubMedGoogle ScholarCrossref
15.
Freedland  KE, Carney  RM, Rich  MW, Steinmeyer  BC, Rubin  EH.  Cognitive behavior therapy for depression and self-care in heart failure patients: a randomized clinical trial.   JAMA Intern Med. 2015;175(11):1773-1782. doi:10.1001/jamainternmed.2015.5220PubMedGoogle ScholarCrossref
16.
O’Connor  CM, Jiang  W, Kuchibhatla  M,  et al; SADHART-CHF Investigators.  Safety and efficacy of sertraline for depression in patients with heart failure: results of the SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) trial.   J Am Coll Cardiol. 2010;56(9):692-699. doi:10.1016/j.jacc.2010.03.068PubMedGoogle ScholarCrossref
17.
Gary  RA, Dunbar  SB, Higgins  MK, Musselman  DL, Smith  AL.  Combined exercise and cognitive behavioral therapy improves outcomes in patients with heart failure.   J Psychosom Res. 2010;69(2):119-131. doi:10.1016/j.jpsychores.2010.01.013PubMedGoogle ScholarCrossref
18.
Dekker  RL, Moser  DK, Peden  AR, Lennie  TA.  Cognitive therapy improves three-month outcomes in hospitalized patients with heart failure.   J Card Fail. 2012;18(1):10-20. doi:10.1016/j.cardfail.2011.09.008PubMedGoogle ScholarCrossref
19.
Angermann  CE, Gelbrich  G, Störk  S,  et al; MOOD-HF Study Investigators and Committee Members.  Effect of escitalopram on all-cause mortality and hospitalization in patients with heart failure and depression: the MOOD-HF randomized clinical trial.   JAMA. 2016;315(24):2683-2693. doi:10.1001/jama.2016.7635PubMedGoogle ScholarCrossref
20.
Wagner  EH, Austin  BT, Von Korff  M.  Organizing care for patients with chronic illness.   Milbank Q. 1996;74(4):511-544. doi:10.2307/3350391PubMedGoogle ScholarCrossref
21.
Rich  MW, Beckham  V, Wittenberg  C, Leven  CL, Freedland  KE, Carney  RM.  A multidisciplinary intervention to prevent the readmission of elderly patients with congestive heart failure.   N Engl J Med. 1995;333(18):1190-1195. doi:10.1056/NEJM199511023331806PubMedGoogle ScholarCrossref
22.
Lee  DS, Stukel  TA, Austin  PC,  et al.  Improved outcomes with early collaborative care of ambulatory heart failure patients discharged from the emergency department.   Circulation. 2010;122(18):1806-1814. doi:10.1161/CIRCULATIONAHA.110.940262PubMedGoogle ScholarCrossref
23.
Bekelman  DB, Plomondon  ME, Carey  EP,  et al.  Primary results of the patient-centered disease management (PCDM) for heart failure study: a randomized clinical trial.   JAMA Intern Med. 2015;175(5):725-732. doi:10.1001/jamainternmed.2015.0315PubMedGoogle ScholarCrossref
24.
Bekelman  DB, Allen  LA, McBryde  CF,  et al.  Effect of a collaborative care intervention vs usual care on health status of patients with chronic heart failure: the CASA randomized clinical trial.   JAMA Intern Med. 2018;178(4):511-519. doi:10.1001/jamainternmed.2017.8667PubMedGoogle ScholarCrossref
25.
Rollman  BL, Belnap  BH, LeMenager  MS,  et al.  Telephone-delivered collaborative care for treating post-CABG depression: a randomized controlled trial.   JAMA. 2009;302(19):2095-2103. doi:10.1001/jama.2009.1670PubMedGoogle ScholarCrossref
26.
Davidson  KW, Rieckmann  N, Clemow  L,  et al.  Enhanced depression care for patients with acute coronary syndrome and persistent depressive symptoms: coronary psychosocial evaluation studies randomized controlled trial.   Arch Intern Med. 2010;170(7):600-608. doi:10.1001/archinternmed.2010.29PubMedGoogle ScholarCrossref
27.
Huffman  JC, Mastromauro  CA, Sowden  G, Fricchione  GL, Healy  BC, Januzzi  JL.  Impact of a depression care management program for hospitalized cardiac patients.   Circ Cardiovasc Qual Outcomes. 2011;4(2):198-205. doi:10.1161/CIRCOUTCOMES.110.959379PubMedGoogle ScholarCrossref
28.
Davidson  KW, Bigger  JT, Burg  MM,  et al.  Centralized, stepped, patient preference-based treatment for patients with post-acute coronary syndrome depression: CODIACS vanguard randomized controlled trial.   JAMA Intern Med. 2013;173(11):997-1004. doi:10.1001/jamainternmed.2013.915PubMedGoogle ScholarCrossref
29.
Huffman  JC, Mastromauro  CA, Beach  SR,  et al.  Collaborative care for depression and anxiety disorders in patients with recent cardiac events: the Management of Sadness and Anxiety in Cardiology (MOSAIC) randomized clinical trial.   JAMA Intern Med. 2014;174(6):927-935. doi:10.1001/jamainternmed.2014.739PubMedGoogle ScholarCrossref
30.
Donohue  JM, Belnap  BH, Men  A,  et al.  Twelve-month cost-effectiveness of telephone-delivered collaborative care for treating depression following CABG surgery: a randomized controlled trial.   Gen Hosp Psychiatry. 2014;36(5):453-459. doi:10.1016/j.genhosppsych.2014.05.012PubMedGoogle ScholarCrossref
31.
Huffman  JC, Adams  CN, Celano  CM.  Collaborative care and related interventions in patients with heart disease: an update and new directions.   Psychosomatics. 2018;59(1):1-18. doi:10.1016/j.psym.2017.09.003PubMedGoogle ScholarCrossref
32.
Katon  WJ, Lin  EHB, Von Korff  M,  et al.  Collaborative care for patients with depression and chronic illnesses.   N Engl J Med. 2010;363(27):2611-2620. doi:10.1056/NEJMoa1003955PubMedGoogle ScholarCrossref
33.
Katon  W, Unützer  J, Wells  K, Jones  L.  Collaborative depression care: history, evolution and ways to enhance dissemination and sustainability.   Gen Hosp Psychiatry. 2010;32(5):456-464. doi:10.1016/j.genhosppsych.2010.04.001PubMedGoogle ScholarCrossref
34.
Katon  WJ, Von Korff  M, Lin  EH,  et al.  The Pathways Study: a randomized trial of collaborative care in patients with diabetes and depression.   Arch Gen Psychiatry. 2004;61(10):1042-1049. doi:10.1001/archpsyc.61.10.1042PubMedGoogle ScholarCrossref
35.
Kronish  IM, Moise  N, Cheung  YK,  et al.  Effect of depression screening after acute coronary syndromes on quality of life: the CODIACS-QoL randomized clinical trial.   JAMA Intern Med. 2020;180(1):45-53. doi:10.1001/jamainternmed.2019.4518PubMedGoogle ScholarCrossref
36.
Freedland  KE, Mohr  DC, Davidson  KW, Schwartz  JE.  Usual and unusual care: existing practice control groups in randomized controlled trials of behavioral interventions.   Psychosom Med. 2011;73(4):323-335. doi:10.1097/PSY.0b013e318218e1fbPubMedGoogle ScholarCrossref
37.
Herbeck Belnap  B, Anderson  A, Abebe  KZ,  et al.  Blended collaborative care to treat heart failure and comorbid depression: rationale and study design of the Hopeful Heart Trial.   Psychosom Med. 2019;81(6):495-505. doi:10.1097/PSY.0000000000000706PubMedGoogle ScholarCrossref
38.
Kroenke  K, Spitzer  RL, Williams  JB.  The Patient Health Questionnaire-2: validity of a two-item depression screener.   Med Care. 2003;41(11):1284-1292. doi:10.1097/01.MLR.0000093487.78664.3CPubMedGoogle ScholarCrossref
39.
Callahan  CM, Unverzagt  FW, Hui  SL, Perkins  AJ, Hendrie  HC.  Six-item screener to identify cognitive impairment among potential subjects for clinical research.   Med Care. 2002;40(9):771-781. doi:10.1097/00005650-200209000-00007PubMedGoogle ScholarCrossref
40.
Kroenke  K, Spitzer  RL, Williams  JB.  The PHQ-9: validity of a brief depression severity measure.   J Gen Intern Med. 2001;16(9):606-613. doi:10.1046/j.1525-1497.2001.016009606.xPubMedGoogle ScholarCrossref
41.
Ware  J  Jr, Kosinski  M, Keller  SD.  A 12-item short-form health survey: construction of scales and preliminary tests of reliability and validity.   Med Care. 1996;34(3):220-233. doi:10.1097/00005650-199603000-00003PubMedGoogle ScholarCrossref
42.
Spertus  JA, Jones  PG.  Development and validation of a short version of the Kansas City Cardiomyopathy Questionnaire.   Circ Cardiovasc Qual Outcomes. 2015;8(5):469-476. doi:10.1161/CIRCOUTCOMES.115.001958PubMedGoogle ScholarCrossref
43.
Schalet  BD, Pilkonis  PA, Yu  L,  et al.  Clinical validity of PROMIS Depression, Anxiety, and Anger across diverse clinical samples.   J Clin Epidemiol. 2016;73:119-127. doi:10.1016/j.jclinepi.2015.08.036PubMedGoogle ScholarCrossref
44.
Freedland  KE, Skala  JA, Carney  RM,  et al.  The Depression Interview and Structured Hamilton (DISH): rationale, development, characteristics, and clinical validity.   Psychosom Med. 2002;64(6):897-905.PubMedGoogle Scholar
45.
Knighton  AJ, Savitz  L, Belnap  T, Stephenson  B, VanDerslice  J.  Introduction of an area deprivation index measuring patient socioeconomic status in an integrated health system: implications for population health.   EGEMS (Wash DC). 2016;4(3):1238-1238. doi: doi:10.13063/2327-9214.1238PubMedGoogle Scholar
46.
Schuster  JM, Belnap  BH, Roth  LH, Rollman  BL.  The Checklist Manifesto in action: integrating depression treatment into routine cardiac care.   Gen Hosp Psychiatry. 2016;40:1-3. doi:10.1016/j.genhosppsych.2016.01.005PubMedGoogle ScholarCrossref
47.
Rollman  BL, Belnap  BH, LeMenager  MS, Mazumdar  S, Schulberg  HC, Reynolds  CF  III.  The Bypassing the Blues treatment protocol: stepped collaborative care for treating post-CABG depression.   Psychosom Med. 2009;71(2):217-230. doi:10.1097/PSY.0b013e3181970c1cPubMedGoogle ScholarCrossref
48.
Herbeck Belnap  B, Schulberg  HC, He  F, Mazumdar  S, Reynolds  CF  III, Rollman  BL.  Electronic protocol for suicide risk management in research participants.   J Psychosom Res. 2015;78(4):340-345. doi:10.1016/j.jpsychores.2014.12.012PubMedGoogle ScholarCrossref
49.
Hunkeler  EM, Katon  W, Tang  L,  et al.  Long term outcomes from the IMPACT randomised trial for depressed elderly patients in primary care.   BMJ. 2006;332(7536):259-263. doi:10.1136/bmj.38683.710255.BEPubMedGoogle ScholarCrossref
50.
Frasure-Smith  N, Lespérance  F, Prince  RH,  et al.  Randomised trial of home-based psychosocial nursing intervention for patients recovering from myocardial infarction.   Lancet. 1997;350(9076):473-479. doi:10.1016/S0140-6736(97)02142-9PubMedGoogle ScholarCrossref
51.
Berkman  LF, Blumenthal  J, Burg  M,  et al; Enhancing Recovery in Coronary Heart Disease Patients Investigators (ENRICHD).  Effects of treating depression and low perceived social support on clinical events after myocardial infarction: the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) randomized trial.   JAMA. 2003;289(23):3106-3116. doi:10.1001/jama.289.23.3106PubMedGoogle Scholar
52.
Laird  NM, Ware  JH.  Random-effects models for longitudinal data.   Biometrics. 1982;38(4):963-974. doi:10.2307/2529876PubMedGoogle ScholarCrossref
53.
Little  RJA, Rubin  DB.  Statistical Analysis With Missing Data. 2nd ed. Wiley; 2002. doi:10.1002/9781119013563
54.
Greene  SJ, Fonarow  GC, DeVore  AD,  et al.  Titration of medical therapy for heart failure with reduced ejection fraction.   J Am Coll Cardiol. 2019;73(19):2365-2383. doi:10.1016/j.jacc.2019.02.015PubMedGoogle ScholarCrossref
55.
Havranek  EP, Mujahid  MS, Barr  DA,  et al; American Heart Association Council on Quality of Care and Outcomes Research, Council on Epidemiology and Prevention, Council on Cardiovascular and Stroke Nursing, Council on Lifestyle and Cardiometabolic Health, and Stroke Council.  Social determinants of risk and outcomes for cardiovascular disease: a scientific statement from the American Heart Association.   Circulation. 2015;132(9):873-898. doi:10.1161/CIR.0000000000000228PubMedGoogle ScholarCrossref
56.
McClintock  HF, Bogner  HR.  Incorporating patients’ social determinants of health into hypertension and depression care: a pilot randomized controlled trial.   Community Ment Health J. 2017;53(6):703-710. doi:10.1007/s10597-017-0131-xPubMedGoogle ScholarCrossref
57.
Herrmann-Lingen  C, Albus  C, de Zwaan  M,  et al.  Efficacy of team-based collaborative care for distressed patients in secondary prevention of chronic coronary heart disease (TEACH): study protocol of a multicenter randomized controlled trial.   BMC Cardiovasc Disord. 2020;20(1):520. doi:10.1186/s12872-020-01810-9PubMedGoogle ScholarCrossref
58.
Obama  B.  United States health care reform: progress to date and next steps.   JAMA. 2016;316(5):525-532. doi:10.1001/jama.2016.9797PubMedGoogle ScholarCrossref
59.
McManus  D, Pipkin  SS, Whooley  MA.  Screening for depression in patients with coronary heart disease (data from the Heart and Soul Study).   Am J Cardiol. 2005;96(8):1076-1081. doi:10.1016/j.amjcard.2005.06.037PubMedGoogle ScholarCrossref
60.
Lichtman  JH, Bigger  JT  Jr, Blumenthal  JA,  et al; American Heart Association Prevention Committee of the Council on Cardiovascular Nursing; American Heart Association Council on Clinical Cardiology; American Heart Association Council on Epidemiology and Prevention; American Heart Association Interdisciplinary Council on Quality of Care and Outcomes Research; American Psychiatric Association.  Depression and coronary heart disease: recommendations for screening, referral, and treatment: a science advisory from the American Heart Association Prevention Committee of the Council on Cardiovascular Nursing, Council on Clinical Cardiology, Council on Epidemiology and Prevention, and Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Psychiatric Association.   Circulation. 2008;118(17):1768-1775. doi:10.1161/CIRCULATIONAHA.108.190769PubMedGoogle ScholarCrossref
Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    Original Investigation
    August 30, 2021

    Efficacy of Blended Collaborative Care for Patients With Heart Failure and Comorbid Depression: A Randomized Clinical Trial

    Author Affiliations
    • 1Division of General Internal Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
    • 2Center for Behavioral Health, Media and Technology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
    • 3Center for Research on Health Care Data Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
    • 4Heart and Vascular Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
    • 5Healthy Lifestyle Institute & Physical Activity and Weight Management Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania
    • 6Department of Psychosomatic Medicine and Psychotherapy, University of Göttingen Medical Center, Göttingen, Germany
    • 7Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
    • 8Now with Department of Psychiatry, University of Arizona College of Medicine, Tucson
    JAMA Intern Med. 2021;181(10):1369-1380. doi:10.1001/jamainternmed.2021.4978
    Key Points

    Question  Does blended collaborative care for heart failure and depression improve clinical outcomes more than collaborative care for heart failure alone or physicians’ usual care?

    Findings  In this randomized clinical trial of 629 patients with depression and heart failure, patients received either blended collaborative care, collaborative care for heart failure alone, or usual care. At 12 months, patients receiving blended care reported significantly better mental health–related quality of life (mHRQOL) and mood than those receiving usual care and better mood but not mHRQOL than those receiving care for heart failure alone; physical function, rehospitalizations, and mortality were similar among all 3 groups.

    Meaning  Blended collaborative care for heart failure and depression improved mHRQOL and mood more than usual care, and mood more than collaborative care for heart failure alone.

    Abstract

    Importance  Depression is often comorbid in patients with heart failure (HF) and is associated with worse clinical outcomes. However, depression generally goes unrecognized and untreated in this population.

    Objective  To determine whether a blended collaborative care program for treating both HF and depression can improve clinical outcomes more than collaborative care for HF only and physicians’ usual care (UC).

    Design, Setting, and Participants  This 3-arm, single-blind, randomized effectiveness trial recruited 756 participants with HF with reduced left ventricular ejection fraction (<45%) from 8 university-based and community hospitals in southwestern Pennsylvania between March 2014 and October 2017 and observed them until November 2018. Participants included 629 who screened positive for depression during hospitalization and 2 weeks postdischarge and 127 randomly sampled participants without depression to facilitate further comparisons. Key analyses were performed November 2018 to March 2019.

    Interventions  Separate physician-supervised nurse teams provided either 12 months of collaborative care for HF and depression (“blended” care) or collaborative care for HF only (enhanced UC [eUC]).

    Main Outcomes and Measures  The primary outcome was mental health–related quality of life (mHRQOL) as measured by the Mental Component Summary of the 12-item Short Form Health Survey (MCS-12). Secondary outcomes included mood, physical function, HF pharmacotherapy use, rehospitalizations, and mortality.

    Results  Of the 756 participants (mean [SD] age, 64.0 [13.0] years; 425 [56%] male), those with depression reported worse mHRQOL, mood, and physical function but were otherwise similar to those without depression (eg, mean left ventricular ejection fraction, 28%). At 12 months, blended care participants reported a 4.47-point improvement on the MCS-12 vs UC (95% CI, 1.65 to 7.28; P = .002), but similar scores as the eUC arm (1.12; 95% CI, −1.15 to 3.40; P = .33). Blended care participants also reported better mood than UC participants (Patient-Reported Outcomes Measurement Information System–Depression effect size, 0.47; 95% CI, 0.28 to 0.67) and eUC participants (0.24; 95% CI, 0.07 to 0.41), but physical function, HF pharmacotherapy use, rehospitalizations, and mortality were similar by both baseline depression and randomization status.

    Conclusions and Relevance  In this randomized clinical trial of patients with HF and depression, telephone-delivered blended collaborative care produced modest improvements in mHRQOL, the primary outcome, on the MCS-12 vs UC but not eUC. Although blended care did not differentially affect rehospitalization and mortality, it improved mood better than eUC and UC and thus may enable organized health care systems to provide effective first-line depression care to medically complex patients.

    Trial Registration  ClinicalTrials.gov Identifier: NCT02044211

    Introduction

    Heart failure (HF) affects approximately 6.2 million people in the US and is the leading cause for hospitalizations among Medicare patients.1 Depression is comorbid in 20% to 40% of patients with HF2 and associated with worse health-related quality of life (HRQOL),3,4 reduced adherence with recommended care,5 higher levels of health services utilization,6-8 and increased mortality.9-12 Yet despite the availability of proven-effective treatments, depression is often unrecognized and untreated in patients with HF.13

    Several trials have examined the effect of treating depression as a means to improve clinical outcomes for patients with cardiovascular disease, but they reported mixed benefits on mood symptoms,14-19 and none reduced hospital admissions or mortality.2 Possible explanations include reliance on a single antidepressant that may be ineffective,16,19 small sample sizes,14,17 short follow-up duration, and enrollment of low-risk patients.15,16,19 Given the negative adverse effect of depression, interest remains in identifying effective treatments for depression that can be delivered at scale in routine HF practice.

    One potential treatment strategy is collaborative care. Based on Wagner’s Chronic Care Model,20 it involves active follow-up by nonphysician care managers who support patients with the frequency of contacts necessary to educate them about their illness, impart evidence-based treatment recommendations, consider their prior treatment experiences and current preferences, and proactively monitor their responses to therapy and suggest adjustments in care under supervision of a physician. Trials have demonstrated the effectiveness of this model at improving patient outcomes for a variety of conditions, including HF,21-24 and we and others have demonstrated their clinical effectiveness25-29 and cost-effectiveness30 at treating depression in patients with cardiovascular disease. However, we are unaware of any collaborative care trial that focused on treating patients with depression and HF.2,31

    Given the impracticality of separate collaborative care programs for HF and depression, integrated interventions that provide care for both conditions together may be an ideal means for organized systems of health care to deliver physical and mental health care at scale.32,33 Furthermore, evidence suggests that blended collaborative care may produce greater improvements in cardiovascular risk factors and mood symptoms32 than interventions focused solely on depression.34,35 To examine these issues in patients with HF, we conducted the Hopeful Heart Trial (https://www.hopefulheart.pitt.edu/) to test the effectiveness of a blended collaborative care strategy for treating both HF and depression. Hopeful Heart also included (1) a clinically relevant attention control arm to clarify whether any observed clinical improvements are due to our depression intervention rather than treatment for HF or patient expectations,36 and (2) a randomly selected cohort without depression to evaluate the influence of comorbid depression on the natural course of HF and the benefits derived from our study interventions.

    Methods
    Participants

    Our full study protocol (Supplement 1; the statistical analysis plan is in Supplement 2) has been published37 and was approved by the University of Pittsburgh’s Institutional Review Board prior to the start of recruitment. Nurse-recruiters identified medically stable hospitalized patients aged 21 years and older with a left ventricular ejection fraction (LVEF) of 45% or less at 2 university-affiliated and 6 community Pittsburgh, Pennsylvania, area hospitals. After our study nurses obtained patients’ oral consent through a nurse or physician involved with their care, they confirmed the presence of New York Heart Association class II to IV symptoms and then administered the Patient Health Questionnaire (PHQ-2) depression screen.38

    We classified the PHQ-2 screen as positive when a patient replied “yes” to at least 1 PHQ item and required that patients be medically stable and discharged home; have no current alcohol abuse, substance abuse, or bipolar disorder; not be in treatment with a mental health specialist or report active suicidality; have no communication barrier; and be mentally competent to provide consent.39 Upon verification, the nurse-recruiters obtained patients’ signed consent. Two weeks after hospital discharge, we telephoned patients to administer the PHQ-940 and required they score 10 or higher to remain protocol eligible.

    Comparison Cohort Without Depression

    We randomly sampled approximately 1 PHQ-2 screen-negative patient not using an antidepressant who met all other protocol eligibility criteria for every 4 randomized patients with depression, stratified by hospital and sex and oversampled by race. At the 2-week posthospitalization call, we required they score less than 5 on the PHQ-9 to remain protocol eligible.

    Assessments and Outcome Measures

    Following confirmation of protocol eligibility, a research assessor administered our baseline telephone assessment. It included the Mental and Physical Component Summary of the 12-item Short Form Health Survey to measure mental HRQOL (mHRQOL) and physical HRQOL, respectively (MCS-12 and PCS-12)41; the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12)42; the 8-item fixed-length Patient-Reported Outcomes Measurement Information System–Depression (PROMIS-D) scale43; and the 17-item Hamilton Rating Scale for Depression (HRS-D).44 We also collected information on patients’ race and ethnicity, sex, address,45 and sociodemographic characteristics by self-report; and on comorbid medical conditions, medication use, and laboratory values by detailed medical record review.

    Research assessors blinded to participants’ randomization assignments readministered our assessments by telephone 3, 6, and 12 months later and inquired about any hospitalizations since the previous assessment. When a hospitalization or death was reported, we obtained the relevant medical records and/or death certificates and 2 physicians independently reviewed and classified the event.

    Randomization Procedure

    Following the baseline assessment, we randomized participants with depression using permuted blocks of varying size stratified by hospital type and patient sex prepared in advance by the study statistician (K.Z.A.) in a 2:2:1 ratio to either (1) collaborative care for HF and depression (“blended” care); (2) collaborative care for HF only (enhanced usual care [eUC]), or (3) physicians’ usual care (UC). To maintain our assessors’ blinding for telephone follow-up assessments, the project coordinator notified participants of their treatment assignment.

    Interventions

    We organized our care managers into separate blended care and eUC teams of 2 to 3 nurses. To standardize our interventions and facilitate weekly case review sessions, we developed an electronic registry and checklist46 that systematically prompted each nurse to inquire about and document key aspects of HF care (eg, medications, blood pressure). The blended care registry also included prompts about depression care.37

    Enhanced Usual Care

    Following randomization, care managers scheduled a 1-hour telephone call to review the patient’s cardiac history and medications to identify potential gaps in care; record HF symptoms, weight, and blood pressure; and impart basic HF education. Afterward, they scheduled 20- to 30-minute follow-up calls every 1 to 4 weeks for the first 3 months, and then monthly for the duration of our 12-month intervention. Based on participants’ clinical status, treatment preferences, and their case review discussions with the study cardiologist (R.R.), the care managers typically encouraged (1) adherence to guideline-recommended HF pharmacotherapy; (2) healthy lifestyle (eg, physical activity, tobacco cessation, and other HF self-care); (3) maintaining weight within a narrow range; and (4) keeping follow-up medical appointments.

    Blended Care

    In addition to the eUC protocol, our blended care manager team provided collaborative care for depression based on our prior work.47 Specifically, they (1) inquired about participants’ psychiatric history; (2) provided basic psychoeducation; (3) assessed treatment preferences for depression; and (4) monitored mood symptoms with the PHQ-9. Following case review discussions with the study psychiatrist, they suggested treatment options that included initiation or adjustment of antidepressant pharmacotherapy prescribed by their primary care physician; adequate physical activity and sleep; “watchful waiting” for those with no history of depression and only mild elevations in mood (PHQ-9 score, 10-14); or referral to a mental health specialist if patients needed a higher level of care.

    Case Review

    To minimize the potential for contamination between study arms, we held separate weekly case review meetings with our blended and eUC nurse care management teams and instructed staff to not discuss their patients with the other team. Sessions focused on newly randomized participants and those not doing well or with gaps in evidence-based HF care. Afterward, the care manager typically conveyed 1 to 3 treatment recommendations back to the patient and to their physician(s) via electronic medical record system, telephone, or fax. Patients and physicians could accept or reject our treatment recommendations and/or obtain care outside of the trial.

    Usual Care

    For ethical reasons, we informed both UC participants and their primary care physicians about their baseline depression status. Participants receiving UC continued to receive care from their physicians, which could include referral to specialty cardiac or mental health care. However, we did not provide any treatment advice unless we detected suicidality or cardiac distress during a routine assessment.

    Data and Safety Monitoring

    Whenever suicidal ideation was recorded in our electronic database, it automatically triggered a suicide risk management protocol that systematically guided staff to determine the frequency, chronicity, content, and threat level.48 Afterward, the staff member reviewed the information with the study psychiatrist, who determined the next steps. We also advised participants in possible cardiac distress to immediately telephone their physician, present to an emergency department, or call 911 as indicated. An independent data and safety monitoring board approved by our funding agency also monitored study progress and safety.

    Power and Sample Size

    We designed Hopeful Heart to compare our blended care intervention to both UC and to eUC, the former to compare our findings with other collaborative care trials32 and the latter to control for the effects of HF collaborative care on mood.36 We selected the MCS-12 as our primary outcome measure because it is sensitive to changes in mood,49 clinically meaningful to patients, and permitted measurement of the effect of our interventions on both HF and depression. Because women with cardiovascular disease treated for depression may experience little benefit and perhaps harm vs usual care,25,50,51 we powered our trial to conduct within-sex analyses on our primary outcome measure.

    Based on prior trials,25,26,32 we estimated that blended collaborative care could produce a clinically meaningful moderate 0.50 or greater effect size (ES) improvement on the MCS-12 vs UC at 12-month follow-up. Assuming an 80% 12-month assessment completion rate, intention-to-treat (ITT) analyses, and 2-sided α of .05, 125 blended care and 62 UC women (or men) with depression provided 80% power to detect within-sex 0.50 or greater ES improvement. We estimated that our blended care intervention would produce a smaller but still clinically meaningful 0.30 or greater ES improvement vs eUC. Using similar assumptions, 250 participants per arm provided 85% power to detect 0.30 or greater ES improvement and 80% power to detect 0.40 or greater ES within-sex improvements. We did not adjust for multiple comparisons in our power calculations.

    Statistical Analyses

    We compared baseline sociodemographic, clinical, and functional status measures by baseline depression status using t tests for continuous data and χ2 tests for categorical data. Next we used linear mixed models52 with fixed effects for time, treatment arm, time-by-study arm, sex, hospital type, and a random effect to account for participant-level variability to estimate ITT changes in 12-month scores and ESs on all randomized participants with 95% CIs. We also performed a planned subgroup analysis of MCS-12 by sex and post hoc analysis of MCS-12 restricted to patients with a baseline PHQ-9 score of 15 or higher. Our ITT analyses used repeated measures linear mixed models to include all patients with data at any time point. To assess the effect of missing data, we compared baseline characteristics between those who did vs did not withdraw from the study, and we compared lost-to-follow-up rates between study arms. We assumed all data were missing-at-random and were robust to ignorable missingness assumptions.53 As a sensitivity analysis, we fit shared parameter models on the MCS-12, our primary outcome, and confirmed no association between time to dropout/mortality and scores over time.

    We used Cox proportional hazard models adjusted for hospital recruitment site and sex to analyze time to first hospitalization and death by study arm and repeated these analyses within sex while adjusting for hospital recruitment site. Finally, we examined differences between treatment arms on various process of care measures (eg, pharmacotherapy), and applied similar ITT techniques to compare our cohorts with and without depression. All reported P values are 2-tailed with significance levels at P ≤ .05 with no adjustments for multiplicity, and all analyses were performed with STATA/SE, version 15.0 (StataCorp LLC). This study followed the Consolidated Standards of Reporting Trials (CONSORT) reporting guideline.

    Results

    Of the 7866 hospitalized patients with HF who completed our PHQ-2 depression screening procedure between March 2014 and October 2017, 3644 (46%) screened positive and 2651 (73%) consented to enroll (Figure 1). At 2 weeks posthospitalization, 1677 (63%) remained eligible and completed the PHQ-9; 671 (40%) scored 10 or higher, and we randomized 629 who met all protocol eligibility criteria. Additionally, we enrolled 127 randomly selected patients with HF without depression for a total of 756 study participants. Rates of follow-up assessments were similar by baseline depression status and treatment assignment (eTable 1 in Supplement 3).

    At baseline, participants with depression had similar sociodemographic and clinical characteristics by randomization status. However, compared with participants without depression, they were more likely to be White, have less formal education, be unemployed, smoke, and report lower HRQOL and physical functioning, despite having a similar mean (SD) LVEF (28% [9.4%]) and disease burden (Table 1).

    Primary Outcome Measure

    At 12-month follow-up, patients with HF and depression randomized to blended care reported a 4.47-point improved MCS-12 score vs UC (95% CI, 1.65 to 7.28; P = .002) (Figure 2) (0.34 ES improvement; 95% CI, 0.13 to 0.56; P = .002) (eFigure 1 in Supplement 3). Within-sex analyses confirm the benefits of blended care vs UC for women (6.50-point improvement; 95% CI, 2.46 to 10.55; P = .002) but not men (2.62; 95% CI, −1.27 to 6.52; P = .19), and subgroup analyses by sex revealed no subgroup effect (P = .57 for 3-way interaction). Post hoc analyses restricted to patients with a baseline PHQ-9 score of 15 or higher identified a significant between-arm difference for blended vs UC patients (3.95-point improvement; 95% CI, 0.65 to 7.24; P = .02) but no significant within-sex effects.

    Comparing blended care to eUC patients, we found similar 12-month MCS-12 scores both among our full cohort (1.12-point improvement, 95% CI, −1.15 to 3.40; P = .33) and within each sex (Figure 2), and no significant sex subgroup effect. We display estimated mean MCS-12 scores at each assessment point for all study patients in Figure 3.

    Secondary Outcome Measures
    Mood and Physical Function

    At 12-month follow-up, patients receiving blended care reported improved mood on the PROMIS-D vs those receiving eUC (ES, 0.24; 95% CI, 0.07-0.41; P = .006) and UC (ES, 0.47; 95% CI, 0.28-0.67; P < .001), thus confirming the added benefits of collaborative care for patients with depression and HF (eFigure 1 in Supplement 3). Within-sex analyses confirm these blended vs UC findings for women (PROMIS-D, 0.65; 95% CI, 0.38-0.92; P < .001) and men (PROMIS-D, 0.31; 95% CI, 0.04-0.59; P = .03), and for women receiving blended care vs eUC (PROMIS-D, 0.41; 95% CI, 0.15-0.67; P = .002) but not men. However, analyzing HRS-D scores, we only found a differential improvement in mood symptoms for women receiving blended care vs UC (0.35; 95% CI, 0.02-0.67; P = .04). Patients receiving blended care also reported similar physical function (KCCQ-12) and physical HRQOL (PCS-12) vs both the UC and eUC arms (eFigure 1 in Supplement 3).

    Care Process Measures

    Although participants with depression were more likely to report taking a statin medication at 12 months, pharmacotherapy use was otherwise similar by baseline depression status. Also at 12 months, blended care and eUC participants had similar median numbers of nurse care manager contacts and mental health specialty visits and rates of antidepressant and HF pharmacotherapy use and adjustments (Table 2).

    Rehospitalizations and Mortality

    By November 1, 2018, after the last 12-month follow-up contact, we identified 1145 rehospitalizations (533 cardiovascular-related; eTable 2 in Supplement 3). We ascertained vital status on all 756 participants (100%) and identified 98 deaths, all from nonsuicidal causes (79 cardiovascular-related; eTable 3 in Supplement 3), and found no serious or unexpected adverse events.

    We observed similar patterns for the incidence of all-cause and cardiovascular readmissions (eFigure 2 in Supplement 3) even after calculating incidence rate per person-year to adjust for multiple readmissions within a single patient (all-cause readmissions: 61.2% blended care; 53.1% eUC; 58.2% UC; 56.5% controls without depression) (eTable 2 in Supplement 3). The cumulative incidence of 12-month all-cause and cardiovascular mortality was similar by treatment assignment (all-cause: 13.4% blended care, 10.2% eUC, 13.2% UC), within sex, and by baseline depression status (14.1% controls without depression) (eFigure 3 in Supplement 3).

    Discussion

    At 12-month follow-up, telephone-delivered blended collaborative care for treating both HF and depression improved mHRQOL and mood symptoms on the PROMIS-D more than physicians’ UC, and improved PROMIS-D scores but not mHRQOL compared with collaborative care for HF alone. However, it did not differentially improve HRS-D mood symptoms, physical HRQOL, or function; increase use of HF or antidepressant pharmacotherapy; or affect rates of hospital readmissions and mortality between any of our comparison groups (eUC, UC, or controls without depression).

    To our knowledge, Hopeful Heart is the first trial to apply a blended collaborative care approach to treat depression in patients with HF. Our blended intervention generated similar improvements in mHRQOL vs UC as reported in our collaborative care trial for post-CABG depression (SF-36 MCS ES: 0.30; 95% CI, 0.17 to 0.52)25 and by other investigators.24,26-29 To our knowledge, Hopeful Heart is also the first collaborative care trial for depression that included a potent and clinically relevant attention control arm, thus supporting the effectiveness of this strategy at improving mood.36

    Owing to the mutually exacerbating effects of depression on comorbid medical illness,2 we speculated that our blended care intervention would generate larger improvements in mood symptoms and improve HF outcomes more than if we focused solely on depression. Supporting this hypothesis, the TEAMcare trial by Katon et al32 of blended collaborative care for depression and poorly controlled diabetes reported large improvements in mood (0.67 ES) and diabetes control vs UC. Therefore, we were surprised to find similar usage of guideline-recommended HF pharmacotherapy regardless of treatment assignment. As HF pharmacotherapy use was also similar by baseline depression status (except statin use), our findings may reflect ceiling effects (84% β-blocker use), medication intolerance or contraindication (29% baseline kidney insufficiency), difficulty affording medications (13% employed), or clinical inertia.54 We frequently encountered patients challenged to follow our treatment recommendations owing to out-of-pocket costs for medical services and medications, lack of transportation to medical appointments, and inadequate access to heart-healthy food. These factors could have contributed to the similarities in rehospitalization and mortality rates among all study arms. Thus, we encourage new approaches to treat HF and other medically complex patients that address these barriers55,56 and build on our efforts.57

    The external and internal validity of our findings is supported by recruitment of patients from community and underserved hospitals, application of standardized enrollment criteria, randomization, blinded outcomes assessments, inclusion of both a clinically relevant attention control resembling the HF care provided by many organized health care delivery systems and a UC control, and centralized telephone-delivered intervention. We also included a randomly selected cohort of patients with HF without depression to evaluate the effect of comorbid depression and control for changes in medical care and insurance coverage58 over the duration of our study.

    Limitations

    Our study has several limitations. First, we limited enrollment to hospitalized patients with confirmed systolic dysfunction and excluded those with preserved LVEF to ensure that all study patients had HF and not another condition whose symptoms overlap (eg, emphysema). Second, we enrolled patients hospitalized for new or recurrent episodes of HF decompensation and other medical conditions that could have influenced their risks of rehospitalization and adverse cardiac events and need to adjust their HF medications. Third, we relied on the 2-step PHQ rather than a psychiatric interview to classify patients as having depression.59 Still, an American Heart Association science advisory recommends the PHQ because it can be administered by non–mental health professionals,60 and we rescreened patients following hospital discharge to confirm the persistence of mood symptoms. Finally, there was the potential for treatment contamination, as community clinicians may have cared for patients in different study arms and our single study cardiologist participated in both blended and eUC case review sessions. While a cluster randomized clinical trial involving separate teams of study cardiologists could minimize contamination, this study design would require a much larger sample size and greater expense to conduct.

    Conclusions

    Despite the modest improvements of telephone-delivered blended collaborative care for HF and depression on clinical outcomes vs physicians’ UC and collaborative care for HF alone in this randomized clinical trial, blended strategies such as ours may enable organized health care systems to provide effective first-line care for comorbid depression and other mental health conditions at scale to medically complex patients. Further research is needed to understand the cost-effectiveness of this approach and test adaptations that help patients overcome barriers to recommended treatments.

    Back to top
    Article Information

    Accepted for Publication: July 15, 2021.

    Published Online: August 30, 2021. doi:10.1001/jamainternmed.2021.4978

    Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Rollman BL et al. JAMA Internal Medicine.

    Corresponding Author: Bruce L. Rollman, MD, MPH, University of Pittsburgh School of Medicine, 230 McKee Pl, Ste 600, Pittsburgh, PA 15213 (rollmanbl@upmc.edu).

    Author Contributions: Dr Rollman had full access to all the data in the study and takes responsibility for the integrity of the data and the overall conduct of the trial as Principal Investigator, and for the preparation of this manuscript as its first and corresponding author. All coauthors received a copy of this manuscript and provided Dr Rollman with their comments on earlier drafts prior to its submission for peer review.

    Concept and design: Rollman, Ramani, Muldoon, Jakicic, Herbeck Belnap, Karp.

    Acquisition, analysis, or interpretation of data: Rollman, Anderson, Rothenberger, Abebe, Ramani, Muldoon, Karp.

    Drafting of the manuscript: Rollman, Rothenberger, Abebe, Ramani, Karp.

    Critical revision of the manuscript for important intellectual content: All authors.

    Statistical analysis: Rothenberger, Abebe.

    Obtained funding: Rollman, Herbeck Belnap.

    Administrative, technical, or material support: Rollman, Anderson, Muldoon, Karp.

    Supervision: Rollman, Anderson, Ramani, Muldoon, Herbeck Belnap.

    Conflict of Interest Disclosures: Drs Rollman, Anderson, and Muldoon reported receiving grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Jakicic reported receiving grants from the National Institutes of Health during the conduct of the study; and personal fees from WW International, Inc (scientific advisory board) and Naturally Slim (advisory board) outside the submitted work. Dr Karp reported serving as an adviser for Aifred Health and NightWare; receiving medication supplies for investigator-initiated studies from Pfizer and Indivior; receiving compensation for work on the editorial boards of the Journal of Clinical Psychiatry and American Journal of Geriatric Psychiatry; and preparing and delivering a webinar for Otsuka. No other disclosures were reported.

    Funding/Support: This study was funded by a grant from the National Heart, Lung, and Blood Institute to Dr Rollman (R01 HL114016). The statements in the article are solely the responsibility of the authors and do not necessarily represent the views of the sponsor.

    Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

    Meeting Presentations: Parts of this article were presented at the annual national meetings of the American Psychosomatic Society, March 7, 2019, Vancouver, British Columbia, Canada; American College of Cardiology, March 16, 2019, New Orleans, Louisiana; and Society of General Internal Medicine, May 9, 2019, Washington, DC.

    Data Sharing Statement: See Supplement 4.

    Additional Contributions: We gratefully thank our National Heart, Lung, and Blood Institute project officers Susan Czajkowski, PhD (2013-2015), Katherine Stoney, PhD (2015-2020), and Lawton Cooper, MD (2020-2021) for their long-term support of our efforts. They were employed by National Heart, Lung, and Blood Institute and received employment compensation. We also thank our study consultant and colleague Wayne Katon, MD (deceased 2015) whose seminal contributions to collaborative care inspired our work (he did not receive compensation for these contributions), and the many patients who volunteered their time and efforts to participate in the Hopeful Heart Trial.

    Additional Information: Hopeful Heart Study Team: We wish to thank the members of our dedicated study team for their efforts: Amy Anderson, MS, LPC, Susan I. Antle, RN, Rachel Cohen, BA, RN, Danielle Connor, MPH, Julia Holber, BA, Janet Ingram, BA, Adelina A. Malito, MSW, Shawna McIntyre, BSN, RN, Mary Ann Sieber, RN, Tara Stakich, RN, Caroline Thomas, BSN, MS, Lori G. Thiry, BS, Christopher Wiltrout, BS, MPH (University of Pittsburgh, Pittsburgh, Pennsylvania).

    Data Safety Monitoring Board: John Spertus, MD (chair) (University of Missouri–Kansas City, Kansas City, Missouri), Kenneth E. Freedland, PhD (Washington University, St Louis, Missouri), and Carolyn M. Rutter, PhD (RAND Corporation, Santa Monica, California).

    Endpoint Classification Committee: Ravi Ramani, MD (chair), Etsemaye P. Agonafer, MD, MPH, Nicholas S. Duca, MD, Emily N. Guhl, MD, Andrew Lutz, MD, Amber Makani, MD, Amy Marino, MD, Jaqueline H. Morris, DO, Daniel Nguyen, MD, Adi Shafir, MD, Eloho Ufomata, MD, MS, Margaret Zupa, MD (all: University of Pittsburgh, Pittsburgh, Pennsylvania).

    Center for Research on Health Care Data Center: Kwonho Jeong, MS, Yan Huang, MS, Terry Sefcik, MSIS, Charlene Xie, MSIS (University of Pittsburgh, Pittsburgh, Pennsylvania). Other additional information is available at http://www.hopefulheart.pitt.edu.

    References
    1.
    Virani  SS, Alonso  A, Benjamin  EJ,  et al; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee.  Heart disease and stroke statistics—2020 update: a report from the American Heart Association.   Circulation. 2020;141(9):e139-e596. doi:10.1161/CIR.0000000000000757PubMedGoogle ScholarCrossref
    2.
    Celano  CM, Villegas  AC, Albanese  AM, Gaggin  HK, Huffman  JC.  Depression and anxiety in heart failure: a review.   Harv Rev Psychiatry. 2018;26(4):175-184. doi:10.1097/HRP.0000000000000162PubMedGoogle ScholarCrossref
    3.
    Vaccarino  V, Kasl  SV, Abramson  J, Krumholz  HM.  Depressive symptoms and risk of functional decline and death in patients with heart failure.   J Am Coll Cardiol. 2001;38(1):199-205. doi:10.1016/S0735-1097(01)01334-1PubMedGoogle ScholarCrossref
    4.
    Gottlieb  SS, Kop  WJ, Ellis  SJ,  et al; 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(9):1285-1289. doi:10.1016/j.amjcard.2009.01.025PubMedGoogle ScholarCrossref
    5.
    Gathright  EC, Dolansky  MA, Gunstad  J,  et al.  The impact of medication nonadherence on the relationship between mortality risk and depression in heart failure.   Health Psychol. 2017;36(9):839-847. doi:10.1037/hea0000529PubMedGoogle ScholarCrossref
    6.
    Sherwood  A, Blumenthal  JA, Trivedi  R,  et al.  Relationship of depression to death or hospitalization in patients with heart failure.   Arch Intern Med. 2007;167(4):367-373. doi:10.1001/archinte.167.4.367PubMedGoogle ScholarCrossref
    7.
    Johnson  TJ, Basu  S, Pisani  BA,  et al.  Depression predicts repeated heart failure hospitalizations.   J Card Fail. 2012;18(3):246-252. doi:10.1016/j.cardfail.2011.12.005PubMedGoogle ScholarCrossref
    8.
    Freedland  KE, Carney  RM, Rich  MW, Steinmeyer  BC, Skala  JA, Dávila-Román  VG.  Depression and multiple rehospitalizations in patients with heart failure.   Clin Cardiol. 2016;39(5):257-262. doi:10.1002/clc.22520PubMedGoogle ScholarCrossref
    9.
    Rollman  BL, Herbeck Belnap  B, Mazumdar  S,  et al.  A positive 2-item Patient Health Questionnaire depression screen among hospitalized heart failure patients is associated with elevated 12-month mortality.   J Card Fail. 2012;18(3):238-245. doi:10.1016/j.cardfail.2011.11.002PubMedGoogle ScholarCrossref
    10.
    Frasure-Smith  N, Lespérance  F, Habra  M,  et al; Atrial Fibrillation and Congestive Heart Failure Investigators.  Elevated depression symptoms predict long-term cardiovascular mortality in patients with atrial fibrillation and heart failure.   Circulation. 2009;120(2):134-140, 3p, 140. doi:10.1161/CIRCULATIONAHA.109.851675PubMedGoogle ScholarCrossref
    11.
    Freedland  KE, Hesseler  MJ, Carney  RM,  et al.  Major depression and long-term survival of patients with heart failure.   Psychosom Med. 2016;78(8):896-903. doi:10.1097/PSY.0000000000000346PubMedGoogle ScholarCrossref
    12.
    Gathright  EC, Goldstein  CM, Josephson  RA, Hughes  JW.  Depression increases the risk of mortality in patients with heart failure: a meta-analysis.   J Psychosom Res. 2017;94:82-89. doi:10.1016/j.jpsychores.2017.01.010PubMedGoogle ScholarCrossref
    13.
    Jha  MK, Qamar  A, Vaduganathan  M, Charney  DS, Murrough  JW.  Screening and management of depression in patients with cardiovascular disease: JACC state-of-the-art review.   J Am Coll Cardiol. 2019;73(14):1827-1845. doi:10.1016/j.jacc.2019.01.041PubMedGoogle ScholarCrossref
    14.
    Gottlieb  SS, Kop  WJ, Thomas  SA,  et al.  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(5):868-873. doi:10.1016/j.ahj.2007.02.024PubMedGoogle ScholarCrossref
    15.
    Freedland  KE, Carney  RM, Rich  MW, Steinmeyer  BC, Rubin  EH.  Cognitive behavior therapy for depression and self-care in heart failure patients: a randomized clinical trial.   JAMA Intern Med. 2015;175(11):1773-1782. doi:10.1001/jamainternmed.2015.5220PubMedGoogle ScholarCrossref
    16.
    O’Connor  CM, Jiang  W, Kuchibhatla  M,  et al; SADHART-CHF Investigators.  Safety and efficacy of sertraline for depression in patients with heart failure: results of the SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) trial.   J Am Coll Cardiol. 2010;56(9):692-699. doi:10.1016/j.jacc.2010.03.068PubMedGoogle ScholarCrossref
    17.
    Gary  RA, Dunbar  SB, Higgins  MK, Musselman  DL, Smith  AL.  Combined exercise and cognitive behavioral therapy improves outcomes in patients with heart failure.   J Psychosom Res. 2010;69(2):119-131. doi:10.1016/j.jpsychores.2010.01.013PubMedGoogle ScholarCrossref
    18.
    Dekker  RL, Moser  DK, Peden  AR, Lennie  TA.  Cognitive therapy improves three-month outcomes in hospitalized patients with heart failure.   J Card Fail. 2012;18(1):10-20. doi:10.1016/j.cardfail.2011.09.008PubMedGoogle ScholarCrossref
    19.
    Angermann  CE, Gelbrich  G, Störk  S,  et al; MOOD-HF Study Investigators and Committee Members.  Effect of escitalopram on all-cause mortality and hospitalization in patients with heart failure and depression: the MOOD-HF randomized clinical trial.   JAMA. 2016;315(24):2683-2693. doi:10.1001/jama.2016.7635PubMedGoogle ScholarCrossref
    20.
    Wagner  EH, Austin  BT, Von Korff  M.  Organizing care for patients with chronic illness.   Milbank Q. 1996;74(4):511-544. doi:10.2307/3350391PubMedGoogle ScholarCrossref
    21.
    Rich  MW, Beckham  V, Wittenberg  C, Leven  CL, Freedland  KE, Carney  RM.  A multidisciplinary intervention to prevent the readmission of elderly patients with congestive heart failure.   N Engl J Med. 1995;333(18):1190-1195. doi:10.1056/NEJM199511023331806PubMedGoogle ScholarCrossref
    22.
    Lee  DS, Stukel  TA, Austin  PC,  et al.  Improved outcomes with early collaborative care of ambulatory heart failure patients discharged from the emergency department.   Circulation. 2010;122(18):1806-1814. doi:10.1161/CIRCULATIONAHA.110.940262PubMedGoogle ScholarCrossref
    23.
    Bekelman  DB, Plomondon  ME, Carey  EP,  et al.  Primary results of the patient-centered disease management (PCDM) for heart failure study: a randomized clinical trial.   JAMA Intern Med. 2015;175(5):725-732. doi:10.1001/jamainternmed.2015.0315PubMedGoogle ScholarCrossref
    24.
    Bekelman  DB, Allen  LA, McBryde  CF,  et al.  Effect of a collaborative care intervention vs usual care on health status of patients with chronic heart failure: the CASA randomized clinical trial.   JAMA Intern Med. 2018;178(4):511-519. doi:10.1001/jamainternmed.2017.8667PubMedGoogle ScholarCrossref
    25.
    Rollman  BL, Belnap  BH, LeMenager  MS,  et al.  Telephone-delivered collaborative care for treating post-CABG depression: a randomized controlled trial.   JAMA. 2009;302(19):2095-2103. doi:10.1001/jama.2009.1670PubMedGoogle ScholarCrossref
    26.
    Davidson  KW, Rieckmann  N, Clemow  L,  et al.  Enhanced depression care for patients with acute coronary syndrome and persistent depressive symptoms: coronary psychosocial evaluation studies randomized controlled trial.   Arch Intern Med. 2010;170(7):600-608. doi:10.1001/archinternmed.2010.29PubMedGoogle ScholarCrossref
    27.
    Huffman  JC, Mastromauro  CA, Sowden  G, Fricchione  GL, Healy  BC, Januzzi  JL.  Impact of a depression care management program for hospitalized cardiac patients.   Circ Cardiovasc Qual Outcomes. 2011;4(2):198-205. doi:10.1161/CIRCOUTCOMES.110.959379PubMedGoogle ScholarCrossref
    28.
    Davidson  KW, Bigger  JT, Burg  MM,  et al.  Centralized, stepped, patient preference-based treatment for patients with post-acute coronary syndrome depression: CODIACS vanguard randomized controlled trial.   JAMA Intern Med. 2013;173(11):997-1004. doi:10.1001/jamainternmed.2013.915PubMedGoogle ScholarCrossref
    29.
    Huffman  JC, Mastromauro  CA, Beach  SR,  et al.  Collaborative care for depression and anxiety disorders in patients with recent cardiac events: the Management of Sadness and Anxiety in Cardiology (MOSAIC) randomized clinical trial.   JAMA Intern Med. 2014;174(6):927-935. doi:10.1001/jamainternmed.2014.739PubMedGoogle ScholarCrossref
    30.
    Donohue  JM, Belnap  BH, Men  A,  et al.  Twelve-month cost-effectiveness of telephone-delivered collaborative care for treating depression following CABG surgery: a randomized controlled trial.   Gen Hosp Psychiatry. 2014;36(5):453-459. doi:10.1016/j.genhosppsych.2014.05.012PubMedGoogle ScholarCrossref
    31.
    Huffman  JC, Adams  CN, Celano  CM.  Collaborative care and related interventions in patients with heart disease: an update and new directions.   Psychosomatics. 2018;59(1):1-18. doi:10.1016/j.psym.2017.09.003PubMedGoogle ScholarCrossref
    32.
    Katon  WJ, Lin  EHB, Von Korff  M,  et al.  Collaborative care for patients with depression and chronic illnesses.   N Engl J Med. 2010;363(27):2611-2620. doi:10.1056/NEJMoa1003955PubMedGoogle ScholarCrossref
    33.
    Katon  W, Unützer  J, Wells  K, Jones  L.  Collaborative depression care: history, evolution and ways to enhance dissemination and sustainability.   Gen Hosp Psychiatry. 2010;32(5):456-464. doi:10.1016/j.genhosppsych.2010.04.001PubMedGoogle ScholarCrossref
    34.
    Katon  WJ, Von Korff  M, Lin  EH,  et al.  The Pathways Study: a randomized trial of collaborative care in patients with diabetes and depression.   Arch Gen Psychiatry. 2004;61(10):1042-1049. doi:10.1001/archpsyc.61.10.1042PubMedGoogle ScholarCrossref
    35.
    Kronish  IM, Moise  N, Cheung  YK,  et al.  Effect of depression screening after acute coronary syndromes on quality of life: the CODIACS-QoL randomized clinical trial.   JAMA Intern Med. 2020;180(1):45-53. doi:10.1001/jamainternmed.2019.4518PubMedGoogle ScholarCrossref
    36.
    Freedland  KE, Mohr  DC, Davidson  KW, Schwartz  JE.  Usual and unusual care: existing practice control groups in randomized controlled trials of behavioral interventions.   Psychosom Med. 2011;73(4):323-335. doi:10.1097/PSY.0b013e318218e1fbPubMedGoogle ScholarCrossref
    37.
    Herbeck Belnap  B, Anderson  A, Abebe  KZ,  et al.  Blended collaborative care to treat heart failure and comorbid depression: rationale and study design of the Hopeful Heart Trial.   Psychosom Med. 2019;81(6):495-505. doi:10.1097/PSY.0000000000000706PubMedGoogle ScholarCrossref
    38.
    Kroenke  K, Spitzer  RL, Williams  JB.  The Patient Health Questionnaire-2: validity of a two-item depression screener.   Med Care. 2003;41(11):1284-1292. doi:10.1097/01.MLR.0000093487.78664.3CPubMedGoogle ScholarCrossref
    39.
    Callahan  CM, Unverzagt  FW, Hui  SL, Perkins  AJ, Hendrie  HC.  Six-item screener to identify cognitive impairment among potential subjects for clinical research.   Med Care. 2002;40(9):771-781. doi:10.1097/00005650-200209000-00007PubMedGoogle ScholarCrossref
    40.
    Kroenke  K, Spitzer  RL, Williams  JB.  The PHQ-9: validity of a brief depression severity measure.   J Gen Intern Med. 2001;16(9):606-613. doi:10.1046/j.1525-1497.2001.016009606.xPubMedGoogle ScholarCrossref
    41.
    Ware  J  Jr, Kosinski  M, Keller  SD.  A 12-item short-form health survey: construction of scales and preliminary tests of reliability and validity.   Med Care. 1996;34(3):220-233. doi:10.1097/00005650-199603000-00003PubMedGoogle ScholarCrossref
    42.
    Spertus  JA, Jones  PG.  Development and validation of a short version of the Kansas City Cardiomyopathy Questionnaire.   Circ Cardiovasc Qual Outcomes. 2015;8(5):469-476. doi:10.1161/CIRCOUTCOMES.115.001958PubMedGoogle ScholarCrossref
    43.
    Schalet  BD, Pilkonis  PA, Yu  L,  et al.  Clinical validity of PROMIS Depression, Anxiety, and Anger across diverse clinical samples.   J Clin Epidemiol. 2016;73:119-127. doi:10.1016/j.jclinepi.2015.08.036PubMedGoogle ScholarCrossref
    44.
    Freedland  KE, Skala  JA, Carney  RM,  et al.  The Depression Interview and Structured Hamilton (DISH): rationale, development, characteristics, and clinical validity.   Psychosom Med. 2002;64(6):897-905.PubMedGoogle Scholar
    45.
    Knighton  AJ, Savitz  L, Belnap  T, Stephenson  B, VanDerslice  J.  Introduction of an area deprivation index measuring patient socioeconomic status in an integrated health system: implications for population health.   EGEMS (Wash DC). 2016;4(3):1238-1238. doi: doi:10.13063/2327-9214.1238PubMedGoogle Scholar
    46.
    Schuster  JM, Belnap  BH, Roth  LH, Rollman  BL.  The Checklist Manifesto in action: integrating depression treatment into routine cardiac care.   Gen Hosp Psychiatry. 2016;40:1-3. doi:10.1016/j.genhosppsych.2016.01.005PubMedGoogle ScholarCrossref
    47.
    Rollman  BL, Belnap  BH, LeMenager  MS, Mazumdar  S, Schulberg  HC, Reynolds  CF  III.  The Bypassing the Blues treatment protocol: stepped collaborative care for treating post-CABG depression.   Psychosom Med. 2009;71(2):217-230. doi:10.1097/PSY.0b013e3181970c1cPubMedGoogle ScholarCrossref
    48.
    Herbeck Belnap  B, Schulberg  HC, He  F, Mazumdar  S, Reynolds  CF  III, Rollman  BL.  Electronic protocol for suicide risk management in research participants.   J Psychosom Res. 2015;78(4):340-345. doi:10.1016/j.jpsychores.2014.12.012PubMedGoogle ScholarCrossref
    49.
    Hunkeler  EM, Katon  W, Tang  L,  et al.  Long term outcomes from the IMPACT randomised trial for depressed elderly patients in primary care.   BMJ. 2006;332(7536):259-263. doi:10.1136/bmj.38683.710255.BEPubMedGoogle ScholarCrossref
    50.
    Frasure-Smith  N, Lespérance  F, Prince  RH,  et al.  Randomised trial of home-based psychosocial nursing intervention for patients recovering from myocardial infarction.   Lancet. 1997;350(9076):473-479. doi:10.1016/S0140-6736(97)02142-9PubMedGoogle ScholarCrossref
    51.
    Berkman  LF, Blumenthal  J, Burg  M,  et al; Enhancing Recovery in Coronary Heart Disease Patients Investigators (ENRICHD).  Effects of treating depression and low perceived social support on clinical events after myocardial infarction: the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) randomized trial.   JAMA. 2003;289(23):3106-3116. doi:10.1001/jama.289.23.3106PubMedGoogle Scholar
    52.
    Laird  NM, Ware  JH.  Random-effects models for longitudinal data.   Biometrics. 1982;38(4):963-974. doi:10.2307/2529876PubMedGoogle ScholarCrossref
    53.
    Little  RJA, Rubin  DB.  Statistical Analysis With Missing Data. 2nd ed. Wiley; 2002. doi:10.1002/9781119013563
    54.
    Greene  SJ, Fonarow  GC, DeVore  AD,  et al.  Titration of medical therapy for heart failure with reduced ejection fraction.   J Am Coll Cardiol. 2019;73(19):2365-2383. doi:10.1016/j.jacc.2019.02.015PubMedGoogle ScholarCrossref
    55.
    Havranek  EP, Mujahid  MS, Barr  DA,  et al; American Heart Association Council on Quality of Care and Outcomes Research, Council on Epidemiology and Prevention, Council on Cardiovascular and Stroke Nursing, Council on Lifestyle and Cardiometabolic Health, and Stroke Council.  Social determinants of risk and outcomes for cardiovascular disease: a scientific statement from the American Heart Association.   Circulation. 2015;132(9):873-898. doi:10.1161/CIR.0000000000000228PubMedGoogle ScholarCrossref
    56.
    McClintock  HF, Bogner  HR.  Incorporating patients’ social determinants of health into hypertension and depression care: a pilot randomized controlled trial.   Community Ment Health J. 2017;53(6):703-710. doi:10.1007/s10597-017-0131-xPubMedGoogle ScholarCrossref
    57.
    Herrmann-Lingen  C, Albus  C, de Zwaan  M,  et al.  Efficacy of team-based collaborative care for distressed patients in secondary prevention of chronic coronary heart disease (TEACH): study protocol of a multicenter randomized controlled trial.   BMC Cardiovasc Disord. 2020;20(1):520. doi:10.1186/s12872-020-01810-9PubMedGoogle ScholarCrossref
    58.
    Obama  B.  United States health care reform: progress to date and next steps.   JAMA. 2016;316(5):525-532. doi:10.1001/jama.2016.9797PubMedGoogle ScholarCrossref
    59.
    McManus  D, Pipkin  SS, Whooley  MA.  Screening for depression in patients with coronary heart disease (data from the Heart and Soul Study).   Am J Cardiol. 2005;96(8):1076-1081. doi:10.1016/j.amjcard.2005.06.037PubMedGoogle ScholarCrossref
    60.
    Lichtman  JH, Bigger  JT  Jr, Blumenthal  JA,  et al; American Heart Association Prevention Committee of the Council on Cardiovascular Nursing; American Heart Association Council on Clinical Cardiology; American Heart Association Council on Epidemiology and Prevention; American Heart Association Interdisciplinary Council on Quality of Care and Outcomes Research; American Psychiatric Association.  Depression and coronary heart disease: recommendations for screening, referral, and treatment: a science advisory from the American Heart Association Prevention Committee of the Council on Cardiovascular Nursing, Council on Clinical Cardiology, Council on Epidemiology and Prevention, and Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Psychiatric Association.   Circulation. 2008;118(17):1768-1775. doi:10.1161/CIRCULATIONAHA.108.190769PubMedGoogle ScholarCrossref
    ×