Results of a randomized controlled trial demonstrate that a long-term, supervised, moderate-intensity exercise training program for chronic heart failure patients can produce improvements in hospital readmission and survival rates.
Frank J. Domino, MD
Belardinelli R, Georgiou D, Cianci G, Purcaro A. 10-year exercise training in chronic heart failure: A randomized controlled trial. JACC. 2012 Sep 24;60(16):1521-8. http://www.jaccjournaloftheacc.com/article/S0735-1097(12)02811-2/abstract.
This was a randomized controlled trial comparing a trained group (T) of 63 chronic heart failure (CHF) patients who underwent an exercise training (ET) program for 10 years to a non-trained group (NT) of 60 CHF patients who weren’t provided a formal ET program. On study entry and at every 12 months, all patients in both groups underwent a cardiopulmonary exercise test (CPET), an echo-Doppler study, and a quality of life (QOL) assessment.
All patients were recommended to take their usual medications and received counseling on nutrition, stress reduction, smoking cessation, and physical activity.
The mean age of the entire patient population was 59 +/- 14 years old, and 22% of study participants were women. Average left ventricular ejection fraction (LVEF) was 37 +/- 8 % and 39 +/- 7% in CHF patients with ischemic and non-ischemic causes, respectively. All patients were either in New York Heart Association (NYHA) functional class II (59%) or III (41%).
Inclusion criteria comprised of patients who were clinically stability for 3 months before study enrollment, had LVEF of less than 40%, and were able to exercise. The cause of CHF was ischemic in 80% of the participants and non-ischemic in the rest. Exclusion criteria encompassed hemodynamically significant valvular heart disease, uncontrolled diabetes mellitus and hypertension, orthopedic or neurological problems, and renal insufficiency defined as creatinine less than 2.5 mg/dl.
Intervention and Control
The intervention training program consisted of 3 sessions per week at a hospital for 2 months, followed by 2 supervised weekly sessions for the remainder of the year. During the second phase, participants were encouraged to exercise on their own for a third weekly session. Each training session lasted approximately 1 hour, beginning with a 15- to 20-minute warm-up phase of calisthenics and stretching, followed by 40 minutes of aerobic activity on a cycle ergometer, treadmill, or both.
The ET intensity was set at 60% of maximal oxygen consumption (VO2) for the first 2 months, and then at 70% of peak VO2 until the end of the study period.
NT patients were instructed to continue performing their usual daily physical activities at home and to avoid ET in a supervised environment. They were also instructed to avoid high intensity exercise, though they were free to perform aerobic activities such as walking, swimming, and cycling in the home or outside, as long as they kept the duration under 30 minutes.
Medications were adjusted according to each patient’s clinical needs. There were no changes in drug type and dosage among patients whose conditions were clinically stable. Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) were administered in 100% of patients, aspirin in 75%, beta-blockers in 46%, diuretics in 52%, and statins in 60%.
Results and Outcomes
Of 135 patients who initially enrolled, 63 in the T group and 60 in the NT group completed the study protocol.
After 12 months, peak VO2 improved by 14.7% in T patients, while it decreased by 2.5% in NT patients (P< 0.01). At 10 years, the absolute difference in peak VO2 was 3.6 ml/kg per minute (21.8%; P< 0.01 for each comparison).
Ejection fraction (EF) wasn’t significantly different between the 2 groups from baseline until the 4th year. However, at the 5-year mark, there was a significant improvement in EF and resting EF among T patients that was sustained until the completion of the study — suggesting that a training-induced reverse remodeling effect requires a longer period. At 10 years, there was a 28% difference in resting EF between T and NT patients (P< 0.01).
In addition, average QOL score was significantly better in the T group compared to the NT group (P < 0.05), and it was sustained throughout the study for each comparison.
There were no important adverse events in T patients, though at the end of exercise sessions, hypotension occurred in 4 patients over 10 years. Sporadic premature ventricular complexes were occasionally present during exercise sessions in 21 patients, but didn’t require the interruption of any sessions. T patients with an implantable cardioverter defibrillator (ICD) had no discharges.
Adverse events and cardiac deaths occurred more frequently in NT than T patients. In addition, 25 NT patients had hospital readmissions, compared to the 8 T patients who were readmitted for worsening heart failure (HF), which was resolved with medical therapy. In the NT group, 60% of patients were readmitted for ICD firing, atrial arrhythmias, hip fracture, ischemic stroke, or unstable angina, while 40% of NT readmissions resulted from worsening HF.
Multivariate analysis selected peak VO2 and resting heart rate as independent predictors of adverse events (P< 0.0001 for both). The survival model showed an overall effect of ET in predicting all cardiac events, whereas HF cause and patient gender didn’t predict the outcome.
A 10-year supervised, moderate-intensity ET program produced a sustained improvement in functional capacity and QOL in a group of patients with NYHA class II and III CHF. Those improvements were associated with a reduction in hospital readmission for acute HF and improved survival. Cause of CHF didn’t influence patients’ response to ET.
This study was the first to demonstrate that a long-term, supervised, moderate-intensity ET program can produce improvements in hard patient outcomes. Though increased functional capacity and improved QOL scores are logical benefits of ET, there are very few interventions for severe HF patients that reduce both hospitalization and mortality.
Causes of hospitalization among the study’s 2 patient groups differed by both number and quality. Reduced arrhythmias, stroke, HF progression, and hip fracture all resulted from the study’s ET intervention.
Previous research has demonstrated some intermediate benefit from cardiac rehabilitation, but no sustained improvements.1 The critical difference between former studies and the one described here was the degree of supervision during ET and the length of the time period in which the research was carried out.
The authors suggested that increased supervision improved compliance and patient effort. Without this degree of supervision, peak VO2 might not have been reached and patient adherence to continued exercise may have waned over time, rather than maintaining this study’s 88% participation rate at 10 years.
Limits of the study included the fact that the ET program’s cost wasn’t described or even predicted for use on a wider scale. A prediction of quality-adjusted life years (QALYs) would help healthcare insurers and governments determine how coverage of this intensive therapy would compare to the current standard of care. In addition, the study population didn’t include “non-white” persons, and no explanation was given. Plus, the study began in 1994, when the use of beta blockers in CHF was contraindicated.
Heart disease continues to be the most common cause of death in the US, and the rate of HF keeps rising. Though treatment typically focuses on a variety and combination of medications, this study must remind all healthcare providers about the critical role of exercise in treating deadly conditions.
While other recent studies have demonstrated that cardiac rehabilitation improves depression scores2 and mortality after myocardial infarction3, the ET program used in this study lowered other related diseases, such as arrhythmias and hip fractures.
Taking this evidence and previous findings into account, prescribing an aggressive, supervised cardiac rehabilitation program should become the standard of care for HF patients, and organizations that offer such rehabilitation should reconsider their degree of supervision and exercise goals.
1. O’Connor CM, et al. Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial. 2009 Apr 8;301(14):1439-1450. http://jama.jamanetwork.com/article.aspx?articleid=183708.
2. Rutledge T, Redwin LS, Linke SE, Mills PJ. A meta-analysis of mental health treatments and cardiac rehabilitation for improving clinical outcomes and depression among patients with coronary heart disease. Psychosom Med. 2013 May;75(4):335-49. http://www.psychosomaticmedicine.org/content/75/4/335.abstract.
3. Dobson LE, Lewin RJ, Doherty P, Batin PD, Megarry S, Gale CP. Is cardiac rehabilitation still relevant in the new millennium? J Cardiovasc Med. 2012 Jan;13(1):32-7. http://journals.lww.com/jcardiovascularmedicine/Fulltext/2012/01000/Is_cardiac_rehabilitation_still_relevant_in_the.5.aspx.
About the Author
Frank J. Domino, MD, is Professor and Pre-Doctoral Education Director for the Department of Family Medicine and Community Health at the University of Massachusetts Medical School in Worcester, MA. Domino is Editor-in-Chief of the 5-Minute Clinical Consult series (Lippincott Williams & Wilkins). Additionally, he is Co-Author and Editor of the Epocrates LAB database, and author and editor to the MedPearls smartphone app. He presents nationally for the American Academy of Family Medicine and serves as the Family Physician Representative to the Harvard Medical School’s Continuing Education Committee.