Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure

Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION)

The purpose of this study is to determine the long-term safety and effectiveness of exercise training for individuals with congestive heart failure (CHF).

Study Overview

• Status: Completed
• Conditions: Heart Diseases; Cardiovascular Diseases; Heart Failure, Congestive
• Intervention / Treatment: Behavioral: Supervised Exercise Training Program

Detailed Description

BACKGROUND:

CHF affects approximately five million Americans and is the number one cause of hospital admission in individuals over the age of 65. Although exercise training improves several clinical measures in individuals with CHF (e.g., peak VO2, heart rate variability, and plasma norepinephrine levels), it is not known whether exercise training reduces mortality in individuals with CHF.

DESIGN NARRATIVE:

This multicenter randomized study will determine if exercise training reduces mortality and hospitalization rates in individuals with moderate to severe CHF. The secondary objective is to evaluate whether an exercise program designed for individuals with CHF improves quality of life and functioning, is economically advantageous, and prevents medical complications.

Three thousand individuals with moderate to severe CHF will be randomly assigned to either standard medical therapy and education, or standard medical therapy and education plus a supervised exercise training program. The exercise training will include 36 supervised clinic-based training sessions followed by home-based exercise and periodic supervised sessions for reinforcement. Participants assigned to the supervised exercise training program will use either a treadmill or stationary bicycle, which will be provided for them.

Recruitment Status: As of November 9, 2006, HF-ACTION has enrolled 2180 subjects and will conclude enrollment at the end of February, 2007, with an anticipated enrollment of approximately 2300 subjects.

• Study Type: Interventional
• Enrollment (Actual): 2331
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N1
      • University Of Calgary
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 2A6
      • University of Manitoba Health Sciences Center
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3K6A3
      • Queen Elizabeth II Health Sciences Center
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton General Hospital
    • London, Ontario, Canada, N6A 4G5
      • London Health Sciences Center
    • Toronto, Ontario, Canada, M5B 1W8
      • Saint Michaels Hospital
    • Toronto, Ontario, Canada, M5T 2S8
      • Toronto General Hospital
  • Quebec
    • Montreal, Quebec, Canada, H1T 1N6
      • Montreal Heart Institute
    • Sainte Foy, Quebec, Canada, G1V 4G5
      • Laval Hospital
• France
  • Caen, France, 14000
    • CHU de Caen
  • Clichy, France, 92110
    • Hopital Beaujon Cardiologie
  • Creteil, France, 94010
    • Hopital Henri Mondor-Service de C
  • Paris, France, 75014
    • Hôpital Broussais
  • Saint Denis, France, 93200
    • Centre Cardiologie du Nord
  • Vandoeuvre Les Nancy, France, 54500
    • Hôpital Brabois
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Heart Clinic Arkansas
  • California
    • Long Beach, California, United States, 90806
      • Memorial Heart Institute
    • Los Angeles, California, United States, 90095
      • Ahmanson-University of California Los Angeles
    • Sacramento, California, United States, 95817
      • University of California, Davis Medical Center
    • San Diego, California, United States, 92103
      • University of California at San Diego Medical Center
  • Colorado
    • Denver, Colorado, United States, 80262
      • University of Colorado Health Sciences Center
    • Fort Collins, Colorado, United States, 80528
      • Heart and Vascular Clinic of Northern Colorado
  • Connecticut
    • Hartford, Connecticut, United States, 06102-5037
      • Hartford Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20422
      • Veterans Affairs Medical Center
  • Florida
    • Fort Myers, Florida, United States, 33919
      • Southwest Florida Heart Group
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Jacksonville, Florida, United States, 32216
      • Mayo Clinic
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
    • Atlanta, Georgia, United States, 30310
      • Morehouse School of Medicine
    • Augusta, Georgia, United States, 30901
      • Cardiovascular Associates of Augusta
    • Savannah, Georgia, United States, 31405
      • Heart and Lung Group of Savannah
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Medical Center
    • Chicago, Illinois, United States, 60637
      • University of Chicago Hospitals
    • Winfield, Illinois, United States, 60190
      • Central DuPage Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • The Care Group, Llc
  • Iowa
    • Iowa City, Iowa, United States, 52242-1081
      • University of Iowa Hospital and Clinics
  • Kentucky
    • Louisville, Kentucky, United States, 40292
      • University of Louisville
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
    • Boston, Massachusetts, United States, 02120-1613
      • Brigham and Women's Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Detroit, Michigan, United States, 48236
      • Saint John Hospital and Medical Center
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Mid America Heart Institute-Saint Luke's Hospital
    • St. Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Montana
    • Kalispell, Montana, United States, 59901
      • Glacier View Cardiology, P.C.
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Bryan Lincoln General Hospital
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • University Of Medicine & Dentistry Of New Jersey
    • Westwood, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131-0001
      • University of New Mexico
  • New York
    • Rochester, New York, United States, 14624
      • University of Rochester
    • Roslyn, New York, United States, 11576
      • Saint Francis Hospital
  • North Carolina
    • Chapel Hill, North Carolina, United States, 17517
      • University of North Carolina School of Medicine
    • Concord, North Carolina, United States, 28025
      • Northeast Medical Center
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University School of Medicine
  • Ohio
    • Cincinnati, Ohio, United States, 45267-0542
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44106
      • University Hospitals of Cleveland
    • Columbus, Ohio, United States, 43210-1252
      • Davis Heart and Lung Research Institute
    • Toledo, Ohio, United States, 43614-2598
      • Medical University of Ohio
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Sciences University
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center
    • Nashville, Tennessee, United States, 37205
      • Saint Thomas Hospital
  • Texas
    • Dallas, Texas, United States, 75230
      • Medical City Dallas Hospital
    • Dallas, Texas, United States, 75426
      • Baylor Heart and Vascular Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84143
      • LDS Hospital
  • Virginia
    • Lynchburg, Virginia, United States, 24501
      • Lynchburg General Hospital
  • Washington
    • Seattle, Washington, United States, 98195-6310
      • University of Washington Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Madison
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora Health Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• LVEF less than or equal to 35%
• New York Heart Association (NYHA) class II, III, or IV CHF diagnosis in the 3 months prior to study entry, with a minimum of 6 weeks of treatment
• Must be on optimal heart failure therapy according to American Heart Association (AHA), American College of Cardiology (ACC), and Heart Failure Society of America (HFSA) heart failure guidelines, including treatment with angiotensin II converting enzyme inhibitors (ACEI) and beta-blocker therapy, or have documentation justifying why optimal therapy is not being used, including intolerance, contraindication, participant preference, or physician's judgment
• Must be on stable doses of medications (e.g., beta-blocker, ACEI, and additional medications as listed in the study guidelines) for 6 weeks prior to study entry
• Must be in stable medical condition and able to begin an exercise program, as determined by study physician

Exclusion Criteria:

• Comorbid disease, behavioral limitations, or other limitations that would interfere with exercise training, or would prevent completion of 1 year of exercise training
• Pregnant or planning to become pregnant in the year following study entry
• Major heart event or heart procedure within the 6 weeks prior to study entry
• Heart procedure or hospitalization for any reason planned in the future
• Expecting to receive a heart transplant in the 6 months following study entry
• CHF caused by significant uncorrected primary valvular disease (except mitral regurgitation secondary to left ventricular dysfunction); if valve replacement has been performed, may not participate for 12 months following the procedure
• CHF caused by congenital heart disease or obstructive cardiomyopathy
• Performance of exercise training at regular intervals (more than once per week) at a moderate to vigorous intensity at any time in the 6 weeks prior to study entry
• Exercise testing results that would prevent safe exercise training, as defined by the American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR) guidelines, including abnormal blood pressure response, early ischemic changes, and unexpected life-threatening arrhythmia
• Use of fixed-rate pacemakers, pacemakers with inability to attain target heart rates, or automatic implantable cardioverter defibrillator (AICD) devices with heart rate limits set below the target heart rate for exercise training
• Use of an intracardiac device such as an implantable cardioverter defibrillator (ICD) or a cardiac resynchronization therapy pacemaker in the 6 months prior to study entry (must demonstrate stability for 6 weeks post-procedure)
• Primary physician considers placement of an intracardiac device such as an ICD or a cardiac resynchronization therapy pacemaker probable within 6 months of study entry; will be excluded until such device has been placed and 6 weeks of stabilization have passed
• Participation in another clinical trial that may interfere with study participation, follow-up, or data collection, or that may affect cardiovascular morbidity or mortality

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 2	Behavioral: Supervised Exercise Training Program; Exercise 30 minutes minimum three times per week.
No Intervention: 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Composite of all-cause mortality and all-cause hospitalization rates (measured at Year 3)	Measured as events occur during the lifespan of the trial.

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in peak VO2	Measured at 3 months, 12 months, and 24 months.
Changes in VE/VCO2 slope	Measured at 3 months, 12 months, and 24 months.
Heart rate at a submaximal work load defined as the end of the exercise test's second stage	Measured at 3 months, 12 months, and 24 months.
Changes in 6-minute walk (measured at Month 3 and Year 1)	Measured at 3 months, 12 months, 24 months, 36 months, and at end of study.
Composite of cardiovascular mortality and cardiovascular hospitalization rates	Measured as events occur during the life of the trial.
Composite of cardiovascular mortality and CHF hospitalization rates	Measured as events occur during the life of the trial.
All-cause mortality rates	Measured as events occur during the life of the trial.
Cardiovascular mortality rates	Measured as events occur during the life of the trial.
All-cause hospitalization rates	Measured as events occur during the life of the trial.
CHF hospitalization rates	Measured as events occur during the life of the trial.
Heart attack rates	Measured as events occur during the life of the trial.
Worsening CHF event rates	Measured as events occur during the life of the trial.
Composite of all-cause mortality, all-cause hospitalization, emergency room visit, and urgent clinic visit for CHF exacerbation rates	Measured as events occur during the life of the trial.
Cost	Measured throughout the life of the trial.
Quality of life	Measured at baseline, months 3, 6, 9, 12, 15, 18, 21, 24, 36, and end of study

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Study Chair: Christopher M. O'Connor, Duke University; Study Chair: David J. Whellan, Jefferson Medical College of Thomas Jefferson University

Publications and helpful links

General Publications

• Whellan DJ, O'Connor CM, Lee KL, Keteyian SJ, Cooper LS, Ellis SJ, Leifer ES, Kraus WE, Kitzman DW, Blumenthal JA, Rendall DS, Houston-Miller N, Fleg JL, Schulman KA, Pina IL; HF-ACTION Trial Investigators. Heart failure and a controlled trial investigating outcomes of exercise training (HF-ACTION): design and rationale. Am Heart J. 2007 Feb;153(2):201-11. doi: 10.1016/j.ahj.2006.11.007.
• Hejjaji V, Tang Y, Coles T, Jones PG, Reeve BB, Mentz RJ, Spatz ES, Dunlay SM, Caldwell B, Saha A, Tarver ME, Tran A, Patel KK, Henke D, Pina IL, Spertus JA. Psychometric Evaluation of the Kansas City Cardiomyopathy Questionnaire in Men and Women With Heart Failure. Circ Heart Fail. 2021 Sep;14(9):e008284. doi: 10.1161/CIRCHEARTFAILURE.120.008284. Epub 2021 Sep 1.
• Truby LK, Regan JA, Giamberardino SN, Ilkayeva O, Bain J, Newgard CB, O'Connor CM, Felker GM, Kraus WE, McGarrah RW, Shah SH. Circulating long chain acylcarnitines and outcomes in diabetic heart failure: an HF-ACTION clinical trial substudy. Cardiovasc Diabetol. 2021 Aug 3;20(1):161. doi: 10.1186/s12933-021-01353-z.
• Feng KY, O'Connor CM, Clare R, Alhanti B, Pina IL, Kraus WE, Whellan DJ, Mentz RJ. Greater Pain Severity Is Associated with Worse Outcomes in Patients with Heart Failure. J Cardiovasc Transl Res. 2021 Oct;14(5):984-991. doi: 10.1007/s12265-021-10104-0. Epub 2021 Feb 9.
• Regan JA, Kitzman DW, Leifer ES, Kraus WE, Fleg JL, Forman DE, Whellan DJ, Wojdyla D, Parikh K, O'Connor CM, Mentz RJ. Impact of Age on Comorbidities and Outcomes in Heart Failure With Reduced Ejection Fraction. JACC Heart Fail. 2019 Dec;7(12):1056-1065. doi: 10.1016/j.jchf.2019.09.004.
• Mediano MFF, Leifer ES, Cooper LS, Keteyian SJ, Kraus WE, Mentz RJ, Fleg JL. Influence of Baseline Physical Activity Level on Exercise Training Response and Clinical Outcomes in Heart Failure: The HF-ACTION Trial. JACC Heart Fail. 2018 Dec;6(12):1011-1019. doi: 10.1016/j.jchf.2018.09.012.
• Luo N, O'Connor CM, Cooper LB, Sun JL, Coles A, Reed SD, Whellan DJ, Pina IL, Kraus WE, Mentz RJ. Relationship between changing patient-reported outcomes and subsequent clinical events in patients with chronic heart failure: insights from HF-ACTION. Eur J Heart Fail. 2019 Jan;21(1):63-70. doi: 10.1002/ejhf.1299. Epub 2018 Aug 31.
• Warraich HJ, O'Connor C, Wu A, Coles A, Kraus WE, Pina IL, Whellan DJ, Mentz RJ. Differences Between Patients Enrolled Early and Late During Clinical Trial Recruitment: Insights From the HF-ACTION Trial. Circ Cardiovasc Qual Outcomes. 2018 Jul;11(7):e004643. doi: 10.1161/CIRCOUTCOMES.117.004643. No abstract available.
• Ambrosy AP, Bhatt AS, Stebbins AL, Wruck LM, Fudim M, Greene SJ, Kraus WE, O'Connor CM, Pina IL, Whellan DJ, Mentz RJ. Prevalent digoxin use and subsequent risk of death or hospitalization in ambulatory heart failure patients with a reduced ejection fraction-Findings from the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) randomized controlled trial. Am Heart J. 2018 May;199:97-104. doi: 10.1016/j.ahj.2018.02.004. Epub 2018 Feb 11.
• Pokharel Y, Khariton Y, Tang Y, Nassif ME, Chan PS, Arnold SV, Jones PG, Spertus JA. Association of Serial Kansas City Cardiomyopathy Questionnaire Assessments With Death and Hospitalization in Patients With Heart Failure With Preserved and Reduced Ejection Fraction: A Secondary Analysis of 2 Randomized Clinical Trials. JAMA Cardiol. 2017 Dec 1;2(12):1315-1321. doi: 10.1001/jamacardio.2017.3983. Erratum In: JAMA Cardiol. 2018 Feb 1;3(2):181.
• Sharma A, Stevens SR, Lucas J, Fiuzat M, Adams KF, Whellan DJ, Donahue MP, Kitzman DW, Pina IL, Zannad F, Kraus WE, O'Connor CM, Felker GM. Utility of Growth Differentiation Factor-15, A Marker of Oxidative Stress and Inflammation, in Chronic Heart Failure: Insights From the HF-ACTION Study. JACC Heart Fail. 2017 Oct;5(10):724-734. doi: 10.1016/j.jchf.2017.07.013.
• Ambrosy AP, Cerbin LP, DeVore AD, Greene SJ, Kraus WE, O'Connor CM, Pina IL, Whellan DJ, Wojdyla D, Wu A, Mentz RJ. Aerobic exercise training and general health status in ambulatory heart failure patients with a reduced ejection fraction-Findings from the Heart Failure and A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION)trial. Am Heart J. 2017 Apr;186:130-138. doi: 10.1016/j.ahj.2016.12.017. Epub 2017 Jan 19.
• Luo N, Merrill P, Parikh KS, Whellan DJ, Pina IL, Fiuzat M, Kraus WE, Kitzman DW, Keteyian SJ, O'Connor CM, Mentz RJ. Exercise Training in Patients With Chronic Heart Failure and Atrial Fibrillation. J Am Coll Cardiol. 2017 Apr 4;69(13):1683-1691. doi: 10.1016/j.jacc.2017.01.032.
• Kelly JP, Dunning A, Schulte PJ, Fiuzat M, Leifer ES, Fleg JL, Cooper LS, Keteyian SJ, Kitzman DW, Pina IL, Kraus WE, Whellan DJ, O'Connor CM, Mentz RJ. Statins and Exercise Training Response in Heart Failure Patients: Insights From HF-ACTION. JACC Heart Fail. 2016 Aug;4(8):617-24. doi: 10.1016/j.jchf.2016.05.006. Epub 2016 Jul 6.
• Keteyian SJ, Patel M, Kraus WE, Brawner CA, McConnell TR, Pina IL, Leifer ES, Fleg JL, Blackburn G, Fonarow GC, Chase PJ, Piner L, Vest M, O'Connor CM, Ehrman JK, Walsh MN, Ewald G, Bensimhon D, Russell SD; HF-ACTION Investigators. Variables Measured During Cardiopulmonary Exercise Testing as Predictors of Mortality in Chronic Systolic Heart Failure. J Am Coll Cardiol. 2016 Feb 23;67(7):780-9. doi: 10.1016/j.jacc.2015.11.050. Erratum In: J Am Coll Cardiol. 2016 Apr 26;67(16):1979-80.
• Ahmad T, Kelly JP, McGarrah RW, Hellkamp AS, Fiuzat M, Testani JM, Wang TS, Verma A, Samsky MD, Donahue MP, Ilkayeva OR, Bowles DE, Patel CB, Milano CA, Rogers JG, Felker GM, O'Connor CM, Shah SH, Kraus WE. Prognostic Implications of Long-Chain Acylcarnitines in Heart Failure and Reversibility With Mechanical Circulatory Support. J Am Coll Cardiol. 2016 Jan 26;67(3):291-9. doi: 10.1016/j.jacc.2015.10.079.
• Cooper LB, Mentz RJ, Sun JL, Schulte PJ, Fleg JL, Cooper LS, Pina IL, Leifer ES, Kraus WE, Whellan DJ, Keteyian SJ, O'Connor CM. Psychosocial Factors, Exercise Adherence, and Outcomes in Heart Failure Patients: Insights From Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION). Circ Heart Fail. 2015 Nov;8(6):1044-51. doi: 10.1161/CIRCHEARTFAILURE.115.002327. Erratum In: Circ Heart Fail. 2016 Mar;9(3):e000014.
• Fiuzat M, Wojdyla D, Pina I, Adams K, Whellan D, O'Connor CM. Heart Rate or Beta-Blocker Dose? Association With Outcomes in Ambulatory Heart Failure Patients With Systolic Dysfunction: Results From the HF-ACTION Trial. JACC Heart Fail. 2016 Feb;4(2):109-115. doi: 10.1016/j.jchf.2015.09.002. Epub 2015 Oct 28.
• Ahmad T, O'Brien EC, Schulte PJ, Stevens SR, Fiuzat M, Kitzman DW, Adams KF, Kraus WE, Pina IL, Donahue MP, Zannad F, Whellan DJ, O'Connor CM, Felker GM. Evaluation of the Incremental Prognostic Utility of Increasingly Complex Testing in Chronic Heart Failure. Circ Heart Fail. 2015 Jul;8(4):709-16. doi: 10.1161/CIRCHEARTFAILURE.114.001996. Epub 2015 Jun 1.
• Dardas T, Li Y, Reed SD, O'Connor CM, Whellan DJ, Ellis SJ, Schulman KA, Kraus WE, Forman DE, Levy WC. Incremental and independent value of cardiopulmonary exercise test measures and the Seattle Heart Failure Model for prediction of risk in patients with heart failure. J Heart Lung Transplant. 2015 Aug;34(8):1017-23. doi: 10.1016/j.healun.2015.03.017. Epub 2015 Mar 26.
• Mentz RJ, Babyak MA, Bittner V, Fleg JL, Keteyian SJ, Swank AM, Pina IL, Kraus WE, Whellan DJ, O'Connor CM, Blumenthal JA; HF-ACTION Investigators. Prognostic significance of depression in blacks with heart failure: insights from Heart Failure: a Controlled Trial Investigating Outcomes of Exercise Training. Circ Heart Fail. 2015 May;8(3):497-503. doi: 10.1161/CIRCHEARTFAILURE.114.001995. Epub 2015 Apr 21.
• Ahmad T, Pencina MJ, Schulte PJ, O'Brien E, Whellan DJ, Pina IL, Kitzman DW, Lee KL, O'Connor CM, Felker GM. Clinical implications of chronic heart failure phenotypes defined by cluster analysis. J Am Coll Cardiol. 2014 Oct 28;64(17):1765-74. doi: 10.1016/j.jacc.2014.07.979. Epub 2014 Oct 21.
• Jones LW, Douglas PS, Khouri MG, Mackey JR, Wojdyla D, Kraus WE, Whellan DJ, O'Connor CM. Safety and efficacy of aerobic training in patients with cancer who have heart failure: an analysis of the HF-ACTION randomized trial. J Clin Oncol. 2014 Aug 10;32(23):2496-502. doi: 10.1200/JCO.2013.53.5724. Epub 2014 Jul 7.
• Felker GM, Fiuzat M, Thompson V, Shaw LK, Neely ML, Adams KF, Whellan DJ, Donahue MP, Ahmad T, Kitzman DW, Pina IL, Zannad F, Kraus WE, O'Connor CM. Soluble ST2 in ambulatory patients with heart failure: Association with functional capacity and long-term outcomes. Circ Heart Fail. 2013 Nov;6(6):1172-9. doi: 10.1161/CIRCHEARTFAILURE.113.000207. Epub 2013 Oct 8.
• Piccini JP, Hellkamp AS, Whellan DJ, Ellis SJ, Keteyian SJ, Kraus WE, Hernandez AF, Daubert JP, Pina lL, O'Connor CM; HF-ACTION Investigators. Exercise training and implantable cardioverter-defibrillator shocks in patients with heart failure: results from HF-ACTION (Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing). JACC Heart Fail. 2013 Apr;1(2):142-8. doi: 10.1016/j.jchf.2013.01.005.
• McCullough PA, Barnard D, Clare R, Ellis SJ, Fleg JL, Fonarow GC, Franklin BA, Kilpatrick RD, Kitzman DW, O'Connor CM, Pina IL, Thadani U, Thohan V, Whellan DJ; HF-ACTION Investigators. Anemia and associated clinical outcomes in patients with heart failure due to reduced left ventricular systolic function. Clin Cardiol. 2013 Oct;36(10):611-20. doi: 10.1002/clc.22181. Epub 2013 Aug 8.
• Li Y, Neilson MP, Whellan DJ, Schulman KA, Levy WC, Reed SD. Associations between Seattle Heart Failure Model scores and health utilities: findings from HF-ACTION. J Card Fail. 2013 May;19(5):311-6. doi: 10.1016/j.cardfail.2013.03.008.
• Keteyian SJ, Leifer ES, Houston-Miller N, Kraus WE, Brawner CA, O'Connor CM, Whellan DJ, Cooper LS, Fleg JL, Kitzman DW, Cohen-Solal A, Blumenthal JA, Rendall DS, Pina IL; HF-ACTION Investigators. Relation between volume of exercise and clinical outcomes in patients with heart failure. J Am Coll Cardiol. 2012 Nov 6;60(19):1899-905. doi: 10.1016/j.jacc.2012.08.958. Epub 2012 Oct 10.
• Reed SD, Li Y, Ellis SJ, Isitt JJ, Cheng S, Schulman KA, Whellan DJ. Associations between hemoglobin level, resource use, and medical costs in patients with heart failure: findings from HF-ACTION. J Card Fail. 2012 Oct;18(10):784-91. doi: 10.1016/j.cardfail.2012.08.359.
• Blumenthal JA, Babyak MA, O'Connor C, Keteyian S, Landzberg J, Howlett J, Kraus W, Gottlieb S, Blackburn G, Swank A, Whellan DJ. Effects of exercise training on depressive symptoms in patients with chronic heart failure: the HF-ACTION randomized trial. JAMA. 2012 Aug 1;308(5):465-74. doi: 10.1001/jama.2012.8720. Erratum In: JAMA. 2012 Nov 7;308(17):1742.
• Swank AM, Horton J, Fleg JL, Fonarow GC, Keteyian S, Goldberg L, Wolfel G, Handberg EM, Bensimhon D, Illiou MC, Vest M, Ewald G, Blackburn G, Leifer E, Cooper L, Kraus WE; HF-ACTION Investigators. Modest increase in peak VO2 is related to better clinical outcomes in chronic heart failure patients: results from heart failure and a controlled trial to investigate outcomes of exercise training. Circ Heart Fail. 2012 Sep 1;5(5):579-85. doi: 10.1161/CIRCHEARTFAILURE.111.965186. Epub 2012 Jul 6.
• Fiuzat M, Wojdyla D, Kitzman D, Fleg J, Keteyian SJ, Kraus WE, Pina IL, Whellan D, O'Connor CM. Relationship of beta-blocker dose with outcomes in ambulatory heart failure patients with systolic dysfunction: results from the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial. J Am Coll Cardiol. 2012 Jul 17;60(3):208-15. doi: 10.1016/j.jacc.2012.03.023. Epub 2012 May 2.
• Whellan DJ, Nigam A, Arnold M, Starr AZ, Hill J, Fletcher G, Ellis SJ, Cooper L, Onwuanyi A, Chandler B, Keteyian SJ, Ewald G, Kao A, Gheorghiade M. Benefit of exercise therapy for systolic heart failure in relation to disease severity and etiology-findings from the Heart Failure and A Controlled Trial Investigating Outcomes of Exercise Training study. Am Heart J. 2011 Dec;162(6):1003-10. doi: 10.1016/j.ahj.2011.09.017.
• O'Connor CM, Whellan DJ, Wojdyla D, Leifer E, Clare RM, Ellis SJ, Fine LJ, Fleg JL, Zannad F, Keteyian SJ, Kitzman DW, Kraus WE, Rendall D, Pina IL, Cooper LS, Fiuzat M, Lee KL. Factors related to morbidity and mortality in patients with chronic heart failure with systolic dysfunction: the HF-ACTION predictive risk score model. Circ Heart Fail. 2012 Jan;5(1):63-71. doi: 10.1161/CIRCHEARTFAILURE.111.963462. Epub 2011 Nov 23.
• Felker GM, Fiuzat M, Shaw LK, Clare R, Whellan DJ, Bettari L, Shirolkar SC, Donahue M, Kitzman DW, Zannad F, Pina IL, O'Connor CM. Galectin-3 in ambulatory patients with heart failure: results from the HF-ACTION study. Circ Heart Fail. 2012 Jan;5(1):72-8. doi: 10.1161/CIRCHEARTFAILURE.111.963637. Epub 2011 Oct 20.
• Atchley AE, Iskandrian AE, Bensimhon D, Ellis SJ, Kitzman DW, Shaw LK, Pagnanelli RA, Whellan DJ, Gardin JM, Kao A, Abdul-Nour K, Ewald G, Walsh MN, Kraus WE, O'Connor CM, Borges-Neto S; HF-ACTION Trial Nuclear Ancillary Study Investigators. Relationship of technetium-99m tetrofosmin-gated rest single-photon emission computed tomography myocardial perfusion imaging to death and hospitalization in heart failure patients: results from the nuclear ancillary study of the HF-ACTION trial. Am Heart J. 2011 Jun;161(6):1038-45. doi: 10.1016/j.ahj.2011.02.007. Epub 2011 Apr 6.
• Reed SD, Whellan DJ, Li Y, Friedman JY, Ellis SJ, Pina IL, Settles SJ, Davidson-Ray L, Johnson JL, Cooper LS, O'Connor CM, Schulman KA; HF-ACTION Investigators. Economic evaluation of the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) randomized controlled trial: an exercise training study of patients with chronic heart failure. Circ Cardiovasc Qual Outcomes. 2010 Jul;3(4):374-81. doi: 10.1161/CIRCOUTCOMES.109.907287. Epub 2010 Jun 15.
• Keteyian SJ, Isaac D, Thadani U, Roy BA, Bensimhon DR, McKelvie R, Russell SD, Hellkamp AS, Kraus WE; HF-ACTION Investigators. Safety of symptom-limited cardiopulmonary exercise testing in patients with chronic heart failure due to severe left ventricular systolic dysfunction. Am Heart J. 2009 Oct;158(4 Suppl):S72-7. doi: 10.1016/j.ahj.2009.07.014.
• Flynn KE, Lin L, Ellis SJ, Russell SD, Spertus JA, Whellan DJ, Pina IL, Fine LJ, Schulman KA, Weinfurt KP; HF-ACTION Investigators. Outcomes, health policy, and managed care: relationships between patient-reported outcome measures and clinical measures in outpatients with heart failure. Am Heart J. 2009 Oct;158(4 Suppl):S64-71. doi: 10.1016/j.ahj.2009.07.010.
• Atchley AE, Kitzman DW, Whellan DJ, Iskandrian AE, Ellis SJ, Pagnanelli RA, Kao A, Abdul-Nour K, O'Connor CM, Ewald G, Kraus WE, Borges-Neto S; HF-ACTION Investigators. Myocardial perfusion, function, and dyssynchrony in patients with heart failure: baseline results from the single-photon emission computed tomography imaging ancillary study of the Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing (HF-ACTION) Trial. Am Heart J. 2009 Oct;158(4 Suppl):S53-63. doi: 10.1016/j.ahj.2009.07.009.
• Felker GM, Whellan D, Kraus WE, Clare R, Zannad F, Donahue M, Adams K, McKelvie R, Pina IL, O'Connor CM; HF-ACTION Investigators. N-terminal pro-brain natriuretic peptide and exercise capacity in chronic heart failure: data from the Heart Failure and a Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) study. Am Heart J. 2009 Oct;158(4 Suppl):S37-44. doi: 10.1016/j.ahj.2009.07.011.
• Horwich TB, Leifer ES, Brawner CA, Fitz-Gerald MB, Fonarow GC; HF-ACTION Investigators. The relationship between body mass index and cardiopulmonary exercise testing in chronic systolic heart failure. Am Heart J. 2009 Oct;158(4 Suppl):S31-6. doi: 10.1016/j.ahj.2009.07.016.
• Russell SD, Saval MA, Robbins JL, Ellestad MH, Gottlieb SS, Handberg EM, Zhou Y, Chandler B; HF-ACTION Investigators. New York Heart Association functional class predicts exercise parameters in the current era. Am Heart J. 2009 Oct;158(4 Suppl):S24-30. doi: 10.1016/j.ahj.2009.07.017.
• Pina IL, Kokkinos P, Kao A, Bittner V, Saval M, Clare B, Goldberg L, Johnson M, Swank A, Ventura H, Moe G, Fitz-Gerald M, Ellis SJ, Vest M, Cooper L, Whellan D; HF-ACTION Investigators. Baseline differences in the HF-ACTION trial by sex. Am Heart J. 2009 Oct;158(4 Suppl):S16-23. doi: 10.1016/j.ahj.2009.07.012.
• Whellan DJ, Ellis SJ, Kraus WE, Hawthorne K, Pina IL, Keteyian SJ, Kitzman DW, Cooper L, Lee K, O'Connor CM. Method for establishing authorship in a multicenter clinical trial. Ann Intern Med. 2009 Sep 15;151(6):414-20. doi: 10.7326/0003-4819-151-6-200909150-00006.
• Flynn KE, Pina IL, Whellan DJ, Lin L, Blumenthal JA, Ellis SJ, Fine LJ, 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 heart failure: HF-ACTION randomized controlled trial. JAMA. 2009 Apr 8;301(14):1451-9. doi: 10.1001/jama.2009.457. Erratum In: JAMA. 2009 Dec 2;302(21):2322.
• 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 Apr 8;301(14):1439-50. doi: 10.1001/jama.2009.454.

Study record dates

Study Major Dates

• Study Start: April 1, 2003
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: October 3, 2002
• First Submitted That Met QC Criteria: October 3, 2002
• First Posted (Estimate): October 4, 2002

Study Record Updates

• Last Update Posted (Estimate): March 21, 2013
• Last Update Submitted That Met QC Criteria: March 20, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Failure; Heart Diseases; Cardiovascular Diseases
• Other Study ID Numbers: Pro00017406; U01HL063747 (U.S. NIH Grant/Contract); U01HL064250 (U.S. NIH Grant/Contract); U01HL064257 (U.S. NIH Grant/Contract); U01HL064264 (U.S. NIH Grant/Contract); U01HL064265 (U.S. NIH Grant/Contract); U01HL066461 (U.S. NIH Grant/Contract); U01HL066482 (U.S. NIH Grant/Contract); U01HL066491 (U.S. NIH Grant/Contract); U01HL066494 (U.S. NIH Grant/Contract); U01HL066497 (U.S. NIH Grant/Contract); U01HL066501 (U.S. NIH Grant/Contract); U01HL068973 (U.S. NIH Grant/Contract); U01HL068980 (U.S. NIH Grant/Contract)