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. 2023 Sep 2;103(11):pzad119. doi: 10.1093/ptj/pzad119

Effects of Comprehensive Outpatient Cardiac Rehabilitation on Exercise Capacity, Functional Status, and Quality of Life in People With Heart Failure: A Systematic Review and Meta-Analysis

Shweta Gore 1,✉, Hargun Khanna 2, Amit Kumar 3
PMCID: PMC10630615  PMID: 37658777

Abstract

Purpose

The purpose of this study was to systematically review and conduct a meta-analysis to examine the impact of comprehensive outpatient cardiac rehabilitation on exercise capacity, functional status, and quality of life in patients with heart failure.

Methods

PubMed, Embase, and CINAHL were searched using keywords and MeSH terms on heart failure and cardiac rehabilitation. Randomized clinical trials published in English using outpatient exercise-based cardiac rehabilitation in patients with heart failure were included. The Grading of Recommendations Assessment, Development, and Evaluation was utilized for quality appraisal. Pooled estimates were computed using standardized mean differences (SMDs) and 95% CIs. Primary outcomes were functional status (6-minute walk distance, quality of life, exercise capacity using peak oxygen consumption, muscle strength, and endurance).

Results

Eleven randomized controlled trials including 1523 participants ranging from 45 to 80 years old and an intervention duration ranging from 2 to 26 weeks were analyzed. Pooled results indicated significant improvements with comprehensive cardiac rehabilitation on 6-minute walk distance (SMD = 0.30; 95% CI = 0.06 to 0.54) and oxygen consumption (SMD = 0.23; 95% CI = 0.06 to 0.40). However, there was no additional benefit for the quality of life beyond that seen in the comparison groups.

Conclusion

Results of this study suggest that comprehensive outpatient cardiac rehabilitation is associated with significantly better clinical outcomes than single-component exercise programs in cardiac rehabilitation settings, multicomponent exercise in noncardiac rehabilitation settings, or no exercise.

Impact

Heart failure is significantly associated with an increased risk of poor exercise tolerance. Despite the proven benefit of cardiac rehabilitation on exercise tolerance and physical activities from individual randomized clinical trials, questions regarding its impact on clinical outcomes such as exercise capacity, functional status, and quality of life remain inadequate. This systematic review and meta-analysis provides strong evidence supporting comprehensive outpatient cardiac rehabilitation for improving clinical outcomes in heart failure.

Keywords: Heart Failure, Minnesota Living with Heart Failure, Rehabilitation, Six-Minute Walk Distance

Introduction

With the growing epidemic of heart failure and its burden on health service utilization in the USA and globally, there is a critical need to establish evidence for existing interventions that have a strong potential to influence clinical outcomes.1,2 Heart failure is associated with lowered exercise capacity, physical activity, and functional status.3 All of these factors are strong prognostic indicators of morbidity, quality of life, and mortality.3–8

Cardiac rehabilitation is an evidence-based, cost-effective, and noninvasive intervention that focuses on improving cardiovascular endurance, exercise capacity, and functional status through exercise training, psychological intervention, health education, and lifestyle modification. Cardiac rehabilitation has a class 1A recommendation by the American Heart Association and American College of Cardiology for secondary prevention after myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, stable angina, or peripheral arterial disease.9 In 2014, the Centers for Medicare and Medicaid Services expanded the coverage of cardiac rehabilitation to include patients with chronic heart failure. The changes expanded cardiac rehabilitation services to all “beneficiaries with stable chronic heart failure defined as patients with left ventricular ejection fraction of 35% or less and New York Heart Association (NYHA) class II to IV symptoms despite being on optimal heart failure therapy for at least 6 weeks.”10 Despite the expanded eligibility to include heart failure by the Centers for Medicare and Medicaid Services, the utilization of cardiac rehabilitation in patients with heart failure has been very low.11,12 Between 2005 and 2014, only 10.4% of eligible patients with heart failure were referred for cardiac rehabilitation upon discharge from the hospital.13 Moreover, between 2007 and 2011, only 2.6% of the 243,208 Medicare beneficiaries hospitalized with heart failure attended at least 1 session of cardiac rehabilitation.14

Several clinical trials have been published to specifically evaluate the effectiveness of cardiac rehabilitation on clinical outcomes in heart failure.11,12,15–18 Previously published systematic reviews have shown benefits of cardiac rehabilitation in heart failure; however, the setting in which cardiac rehabilitation was delivered was unclear. The findings in these systematic reviews present the aggregate effectiveness of cardiac rehabilitation provided across multiple settings and included controlled exercise interventions, which are not typically performed in a conventional outpatient cardiac rehabilitation setting (eg, home-based exercise, virtually supervised home exercise, aquatic exercise, or exercise performed in a laboratory) making it challenging to derive a clear consensus on the unique effectiveness of comprehensive outpatient cardiac rehabilitation on specific health-related clinical outcomes, including functional status, exercise capacity, and quality of life. Therefore, to increase the awareness and implementation efforts for improving access to outpatient cardiac rehabilitation for patients with heart failure, it is crucial to strengthen the current evidence by conducting a meta-analysis of randomized controlled trials (RCTs) on the effectiveness of comprehensive outpatient cardiac rehabilitation on specific health-related clinical outcomes. We performed a systematic review and pooled meta-analysis to understand the effectiveness of comprehensive outpatient cardiac rehabilitation programs compared to single-component exercise programs in cardiac rehabilitation settings, multicomponent exercise programs in noncardiac rehabilitation settings, or no exercise on clinical outcomes, including exercise capacity, functional status, and quality of life.

Methods

Protocol and Registration

We utilized the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines19 in conducting this work. The study protocol was registered in the International prospective register of systematic reviews (PROSPERO), registration ID: CRD42022318055.

Literature Search

A systematic search of available literature for all relevant articles published after 2007 was conducted in January 2020 and later updated in January 2023. Electronic databases that were searched included PubMed, Embase, CINAHL, Physiotherapy Evidence Database, and Web of Science. The search strategy included “Cardiac rehabilitation”[mesh] OR “Cardiac Rehabilitation/therapy”[Mesh] OR “Cardiac Rehabilitation/therapeutic use”[Mesh] OR “Cardiac Rehabilitation/instrumentation”[Mesh] OR “Cardiac Rehabilitation/methods”[Mesh] OR “Exercise Therapy”[Mesh] OR “Exercise Therapy/instrumentation”[Mesh] OR “Exercise Therapy/methods”[Mesh] OR “Exercise Therapy/therapeutic use”[Mesh] OR “Exercise Therapy/therapy”[Mesh] OR “cardiac therapy”) AND (“Heart Failure”[Mesh] OR “Heart Failure/rehabilitation”[Mesh] OR “Heart Failure/therapy”[Mesh] OR “congestive heart failure”) NOT (“telemedicine”[Mesh]) NOT (“Complementary Therapies”[Mesh]). The search was conducted using filters to limit studies published on animals and in other languages. In addition to the electronic searches, manual search of back references of articles was also performed. Three independent reviewers (A.K., P.B., and S.G.) who were content experts and researchers in cardiac rehabilitation, heart failure, and/or health services research independently reviewed the titles and abstracts. Screening was performed using a rating form that was developed based on the eligibility criteria to facilitate article retrieval (Suppl. Tab. 1). Following review of titles and abstracts, 2 reviewers (H.K. and B.B.) were trained to independently complete full-text reviews. Disagreements between reviewers were resolved by mutual consensus, and a third reviewer (S.G.) was utilized in case of difficulty achieving consensus.

Study Inclusion Criteria

RCTs published in the English language utilizing outpatient or hospital-based outpatient cardiac rehabilitation as an intervention in patients with heart failure were included in this review. Studies that focused on home-based or telehealth cardiac rehabilitation delivery models were excluded due to the differences in health care delivery compared to conventional care. In addition, studies that focused on a specific type of treatment, such as yoga, tai chi, or aquatic therapy, were excluded. Studies that compared different forms of exercise training in noncardiac rehabilitation settings were also excluded.

Data Extraction

From each study, the following data were extracted: authors’ names, year of publication, sample size, information on participant demographics, heart failure severity, specifics of intervention, length of intervention, and follow-up and outcome measures collected. In case of missing information on specific items within a study, attempts to contact the authors via email were made. When no information was available, the section was labeled as “not available” within the data extraction forms. Extracted outcome measures included functional status of patients measured via the 6-Minute Walk Test and/or muscle strength and muscle endurance; exercise capacity measures, including peak oxygen consumption (Vo2); and quality of life. Different statistical measures utilized for comparing outcomes were recorded. Means and SDs for preintervention, postintervention, and follow-up (if applicable) assessments were recorded.

Quality Assessment and Risk of Bias

All data was extracted and appraised for quality independently by 2 reviewers (H.K. and B.B.), and disagreements were resolved by a third reviewer (S.G.). The interrater reliability of the 2 independent reviewers for quality appraisal scores was examined using weighted κ coefficients and was found to be excellent (κ = 0.91; 95% CI = 0.79 to 1.03). Following this, quality of reporting for each included study was obtained through the Consolidated Standards of Reporting Trials (CONSORT) checklist with 25 items.20 The revised Cochrane risk-of-bias tool for randomized trials was used to assess the quality of the evidence and risk of bias across studies.21–23 This tool includes 5 major domains of bias arising from the randomization process, deviations from intended interventions, missing outcome data, measurement of outcomes, and selection of the reported result. Grading of Recommendations Assessment, Development, and Evaluation guidelines was used to assess the overall quality of evidence for each outcome.24

Analysis

Meta-analysis of RCTs was conducted using the Meta-package in RStudio statistical software (RStudio Inc, Boston, MA, USA). We operationalized the comprehensive outpatient cardiac rehabilitation to focus on a multicomponent program (eg, combinations of aerobic, resistance, high-intensity interval training, education, or stimulation) performed in a conventional outpatient cardiac rehabilitation setting. For studies that included more than 1 comparison group within the cardiac rehabilitation cohort, we included only the group that utilized a multicomponent training program as the intervention group for analysis of outcomes. The comparison group received usual or standard care (with or without exercise) in other settings or a single exercise (aerobic, resistance, or interval only) within a cardiac rehabilitation setting. Standardized mean differences (SMDs) were calculated and reported. We estimated the effect size from studies using SMDs. Forest plots were used to present the results of the meta-analysis. Heterogeneity was estimated by the I2 statistic, which measures the percentage of variation across studies. If I2 was ≤50%, then studies were considered homogeneous, and a fixed-effects model of the meta-analysis was used. If I2 was >50%, then heterogeneity was high, and we used the random-effects model for meta-analysis.

Role of the Funding Source

The funder played no role in the design, conduct, or reporting of this study.

Results

Characteristics of the Studies

Six hundred twenty-eight articles were retrieved from the initial search, of which 51 full-text articles were reviewed for inclusion. Eleven RCTs met the eligibility criteria upon full-text review and were included in the final review. The flowchart of study selection is shown in Figure 1. In total, 11 trials with 1523 participants were included, ranging from 26 to 770 participants per study. The characteristics of participants included in the trials are summarized in the Table. The average age of the participants ranged from 45 to 80 years. Three of the 11 studies included patients with NYHA severity classification I, 10 of the 11 studies enrolled patients with NYHA classes II and III, and 1 study included patients with NYHA class IV. Total intervention duration ranged from 2 to 26 weeks across studies. The frequency of intervention ranged from 1 to 5 days/week and included a combination of aerobic and resistance or high-intensity interval exercises with or with electrical stimulation and patient education. Quality-of-life outcomes included in the studies were the Minnesota Living With Heart Failure Questionnaire (MLHFQ) (4/11),25–28 European Quality of Life Scale (1/11),25 Health Complaints Scale (1/11),29 Heart Failure Needs Assessment Questionnaire (1/11),26 Hospital Anxiety and Depression Scale (2/11),30,31 36-Item Short-Form Health Survey (2/11),31,32 Psychological General Well-Being Index (1/11),33 Subjective Symptoms Assessment Profile (1/11),33 and Health-Related Quality of Life (1/11).27 Exercise capacity outcomes included peak Vo2 (6/11)27–30,33,34 and functional outcomes included the 6-Minute Walk Test (7/11),25,26,28,30,32,34,35 muscle strength (3/11),27,29,34 and muscle endurance (2/11).27 Details of the interventions across studies are described in the Table.

Figure 1.

Figure 1

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Data search record. RCT = randomized controlled trial.

Table 1.

Characteristics of Interventionsa

Study NYHA Class Patient Age, y b Intervention Components Intervention Duration (wk) Session Frequency and Duration Intensity Outcomes Assessed
CON EXP Comparison Intervention Comparison Intervention Comparison Intervention
Austin et al25 II, III 71.8 71.9 Standard care and patient education about heart failure fluid overload, and dietary advice Aerobic endurance training and low-intensity resistance training or highly repetitive muscular strength work 8 Seen regularly 2 times/wk NA 150 min/d MLHFQ, EuroQol, 6MWT, Borg RPE
Beckers et al29 II, III 59 (11) 58 (11) Endurance training Combined endurance training and resistance training (treadmill, bicycle, stair or step, arm cycling, and half-recumbent or reclined cycling) for various muscles (quadriceps, pectoralis major, serratus anterior, and latissimus dorsi), 2 times, 15 repetitions 24 3 times/wk 2 times/wk Endurance training: 5 min of warm-up/cool-down and 8 min on 5 different devices with 2 min of recuperation time between devices; after 4 mo, devices were reduced from 5 to 3 Endurance training: 5-min of warm-up/cool-down and 8 min on 5 different devices with 2 min of recuperation time between devices; after 4 mo, devices were reduced from 5 to 3; resistance training: initial training intensity was set at 50% 1RM and increased from 1 times 10 to 1 times 15, 2 times 10, and 2 times 15 HCS, peak Vo2, MSK strength
Davidson et al26 I, II, III, IV 73.9 71.6 Home-based exercise program, patient education Warm-up/cool down with calisthenics and static stretching; endurance training with treadmills, stationary cycles, and recumbent cycles 12 1 1 NA 5–10 min of warm-up/cool-down and 30 min of endurance training MLHFQ, HFNAQ, 6MWT
Freyssin et al30 NA 55 (12) 54 (9) Balneotherapy (gymnastics in water); gymnastics training consisted of 5 min of warm-up followed by 45 min of strengthening exercises, stretching, and relaxation; the program also included therapeutic educational sessions on risk factors and physical practice After a 10-min warm-up phase at 5 W, IT consisted of 12 repetitions of 30 s of cycling exercise followed by 60 s of complete rest; the exercise intensity was 50% and 80% of the maximal power reached during a steep ramp test during the first 4 wk and the last 4 wk, respectively; each training session consisted of 3 series (12 repetitions of 30 s of exercise) separated by 5 min of rest 8 61 min of CT, 4 h of gymnastics, and 3 h of balneotherapy; 360 min of exercise weekly 2–3 h/d, 5 d/wk; 6 sessions of 71 min of IT; 168 min of exercise weekly CT was composed of 10 min of warm-up followed by 45 min of aerobic exercise corresponding to the heart rate at the VT1 and a final 5 min of active recovery After a 10-min warm-up phase at 5 W, IT consisted of 12 repetitions of 30 s of cycling exercise followed by 60 s of complete rest; the exercise intensity was 50% and 80% of the maximal power reached during a steep ramp test during the first 4 wk and the last 4 wk, respectively; each training session consisted of 3 series (12 repetitions of 30 s of exercise) separated by 5 min of rest HADS, 6MWT, peak Vo2, VT1
Iliou et al34 II–IIIb 59.2 (7.2) 57.6 (9.8) Endurance training: exercises, including resistance training, gymnastics, respiratory exercises, walking, and aqua gymnastics Endurance training of both quadriceps with EMS, which consisted of a low-frequency, 10-Hz biphasic current with a pulse duration of 200 μs, on for 20 s and off for 40 s 8 2.5 sessions/wk, 60 min/session 2.5 sessions/wk, 60 min/session 30–60 min of aerobic exercise with target heart rate determined by initial treadmill test; target was a Borg RPE of 12–14 EMS; the intensity increased until the patient demonstrated a visible contraction 6MWT, peak Vo2, MSK strength
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(Continued)

Risk of Bias

Three studies demonstrated an overall low risk of bias across all categories, 6 studies demonstrated some concern, and 1 study demonstrated a high overall risk of bias (Suppl. Fig. 1). Overall, all included studies had a low risk of bias in domains 3 and 5: missing outcome data and selection of the reported result. Fifty-five percent of included studies demonstrated some concern for bias due to deviations from intended interventions, 36% of studies demonstrated some concern for bias due to measurement of outcomes, and 27% demonstrated some concern for bias arising from the randomization process. One study demonstrated high risk of bias due to the randomization process.33 A detailed summary of bias composite scores is presented in Supplementary Figure 1. Reporting quality varied across studies with differences noted in the reporting of sample size, randomization details, sensitivity analyses, and details of trial registration. The CONSORT scoring is described in Supplementary Table 2.

Synthesis of Results: Meta-Analysis of RCTs

Functional Status

Six-Minute Walk Distance

Seven of the included studies compared 6-minute walk distance between intervention and comparison groups. The intervention duration for these 7 studies ranged from 2 to 12 weeks. Across studies, both intervention and comparison groups showed improvement in the 6-minute walk distance after intervention. However, the comparison group gains were lower than the intervention group (Suppl. Tab. 3). We compared the mean change in the distance in both groups for the meta-analysis. Pooled results across studies showed that the SMD (mean of intervention—mean of comparison) was positive (SMD = 0.30; 95% CI = 0.06 to −0.54), indicating a significant benefit for the intervention group on 6-minute walk distance (Fig. 2).

Figure 2.

Figure 2

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Meta-analysis of 6-minute walk distance across studies. SMD = standardized mean differences.

Table 1.

Continued

Study NYHA Class Patient Age, y b Intervention Components Intervention Duration (wk) Session Frequency and Duration Intensity Outcomes Assessed
CON EXP Comparison Intervention Comparison Intervention Comparison Intervention
Karapolat et al32 II, III 45.16 (13.58) 44.05 (11.49) Flexibility, aerobic, and breathing exercises at home Flexibility, aerobic, and breathing exercises in a comprehensive outpatient CR setting 8 45- to 60-min sessions, 3 times/wk 45- to 60-min sessions, 3 times/wk 60%–70% pVo2, 60%–70% HRR, levels 13–15 on the Borg Scale 60%–70% pVo2, 60%–70% HRR, levels 13–15 on the Borg Scale SF-36, BDI, 6MWT, MSK endurance
Klocek et al33 II, III 55 (9) 57 (8) Usual activities of daily living; individuals were asked not to increase their physical activity 20 min of warm-up; exercise workload gradually increasing (25 W) after each 5-min period for a total of 20 min, with the last 5 min pedaled unloaded; resting and listening to relaxing music for 15 min afterward 26 NA 3 times/wk, 25 min/session NA Started at an RPM of 60 kpm/min for the first 5 min and then gradually increased by 25 W every 5 min; after 2 and 4 mo, the workload increased by 10 W and was limited by patient fatigue or exercise tolerability and heart rate (75% of HRmax for age group) PGWB, SSAP, peak Vo2, LVEF, VT1
Mandic et al27 I, II, III 62 (13) 59 (11) Usual activities of daily living Treadmill and Schwinn Airdyne (arm/leg ergometer), resistance exercise (chest press, shoulder press, vertical row, bicep curl, tricep extension, and leg extension) 12 NA 3 times/wk, 30 min/session NA Moderate intensity (50%–70% HRR); levels 11–14/20 on the Borg Scale; 1 or 2 sets of 10–15 repetitions of each exercise at 50%–70% 1RM MLHFQ, HRQL, peak Vo2, MSK strength, MSK endurance
Ozasa et al35 II, III 79.9 (6.5) 79.0 (7.0) Stretching, very low-intensity resistance training, gait training, and cool-down Stretching, low-intensity resistance training, machine-assisted cycling, and cool-down 2 5 times/wk 5 times/wk NA 30–40 rpm for 15 min 6MWT
Papathanasiou et al28 II–IIIb 63.82 (6.71) 63.65 (6.71) Electromagnetically braked cycle ergometer 3 high-intensity intervals and 2 moderate-intensity intervals (flexibility and strength) 12 2 times/wk 2 times/wk 40 min at 70% HRmax HRmax: 90% high intensity; HRmax: 70% moderate intensity; 40 min total MLHFQ, 6MWT, peak Vo2, Borg RPE, LVEF
Zwisler et al31 I, II, III 66 (29–94)c 66 (33–91)c Usual care Patient education, 12 exercise sessions, dietary counseling, psychosocial support, smoking cessation, risk factor management, and clinical assessment 6 2 times/wk 2 times/wk NA NA HADS, SF-36
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a 1RM = 1 repetition maximum; 6MWT = 6-Minute Walk Test; BDI = Beck Depression Inventory; CON = control; CR = cardiac rehabilitation; CT = continuous training; EMS = electrical muscle stimulation; EuroQol = European Quality of Life Scale; EXP = experimental; HADS = Hospital Anxiety and Depression Scale; HCS = Health Complaints Scale; HFNAQ = Heart Failure Needs Assessment Questionnaire; HRmax = maximum heart rate; HRQL = Health-Related Quality of Life; HRR = heart rate reserve; IT = interval training; kpm = kilopond meter per minute; LVEF = left ventricle ejection fraction; MLHFQ = Minnesota Living With Heart Failure Questionnaire; MSK = musculoskeletal; NA = not available; NYHA = New York Heart Association; PGWB = Psychological General Well-Being Index; pVo2 = maximal oxygen uptake; RPE = rating of perceived exertion; rpm = revolutions/min; SF-36 = 36-Item Short-Form Health Survey; SSAP = Subjective Symptoms Assessment Profile; Vo2 = oxygen consumption; VT1 = first ventilatory threshold; W = watts.

b Reported as mean (SD) unless otherwise indicated.

c Reported as mean (range).

Muscle strength

Only 3 studies examined muscle strength.27,29,34 Two studies examined changes in both upper and lower limb strength, whereas 1 study looked at differences in lower limb strength alone. Muscle strength was assessed using the 1-repetition maximum method for both upper and lower limb strength. Lower extremity muscle strength was assessed on the quadriceps muscle group. Upper extremity strength was measured using the chest press and/or the butterfly, pull down forward, and backward tests to assess different muscle groups, including the pectoralis major and minor, latissimus dorsi, serratus anterior, biceps brachii, deltoideus, triceps brachii, and rhomboideus. Among the studies that examined lower extremity muscle strength, 2 studies demonstrated a significant improvement in the intervention group, whereas the third study did not show statistically significant improvement (Suppl. Fig. 2). Pooled analysis did not demonstrate significant improvement (SMD = 0.05; 95% CI = −0.24 to 0.35). Upper extremity muscle strength significantly improved in the intervention group over the usual care group in both studies (mean change in strength from 7.8 to 13.2 kg versus from −1 to 5.7 kg in the comparison group). Supplementary Table 4 describes the details of muscle strength change across studies.

Muscle endurance

Only 1 study examined upper and lower extremity muscle endurance. The intervention group receiving both aerobic and resistance training demonstrated significant improvements in both upper and lower extremity muscle endurance (Suppl. Tab. 3).

Quality of Life

Due to heterogeneity in the type of quality-of-life outcome utilized and the methods of reporting the results in different studies, a meta-analysis could not be completed for all types of outcomes. Four studies compared the MLHFQ which was included in the meta-analysis (Fig. 3). Both comparison and intervention groups demonstrated an improvement in quality of life after intervention, as evidenced by a reduction in the total scores compared to baseline. A random-effects model was utilized to account for heterogeneity (I2 = 95%; P < .01). Although there was a greater change in MLHFQ from before the intervention to after the intervention on pooled analysis in the intervention group than in the comparison group, indicating better quality of life, the difference was not statistically significant between groups (SMD = −0.81; 95% CI = −2.28 to 0.66). Despite other quality-of-life outcomes included in other studies, we were unable to include those in the meta-analysis due to the high variability in the included instruments to measure quality of life across studies. Two studies31,32 used the 36-Item Short-Form Health Survey physical and mental components, and both noted greater improvements in scores with conventional on-site hospital-based outpatient cardiac rehabilitation. Two other studies30,31 used the depression and anxiety subscales of the Hospital Anxiety and Depression Scale and demonstrated inconsistent findings. Zwisler et al noted equal improvements in the anxiety subscale in both groups, whereas the depression subscale demonstrated no change in either group.31 Freyssin et al demonstrated improvements in both groups on both subscales, but the magnitude of improvements in the comparison group was smaller.30Supplementary Table 4 describes the details of quality-of-life scales across studies.

Figure 3.

Figure 3

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Meta-analysis of measures of quality of life across studies. SMD = standardized mean differences.

Exercise Capacity Using Peak Vo2

Seven studies included Vo2 to measure exercise capacity as an outcome to compare cardiac rehabilitation and usual care (Fig. 4). One study did not include mean and SD values of Vo2 and therefore was excluded from the meta-analysis (Suppl. Tab. 5).33 The mean change from before the intervention to after the intervention in the comparison and intervention groups for Vo2 was compared. Pooled results indicated no heterogeneity across studies (I2 = 25%; P < .25); therefore, a fixed-effects model was utilized. The results demonstrate a positive SMD indicating significant improvement in Vo2 with the intervention group (SMD = 0.23; 95% CI = 0.06 to 0.40).

Figure 4.

Figure 4

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Meta-analysis of oxygen consumption across studies. SMD = standardized mean differences.

Discussion

This systematic review and meta-analysis of 11 moderate to high-quality RCTs involving 1523 patients with heart failure provide strong evidence to support comprehensive, multicomponent exercise-based outpatient cardiac rehabilitation programs for improving oxygen consumption, and 6-minute walk distance compared to conventional care (with or without exercise) in other settings. We conducted these meta-analyses on studies that exclusively utilized comprehensive cardiac rehabilitation in the outpatient setting to examine the benefits in the clinical context.

Previous meta-analyses in patients with heart failure demonstrated benefits of cardiac rehabilitation on left ventricular ejection fraction, physical activity, oxygen consumption, and mortality.18,36,37 However, the results of previous meta-analyses provide a pooled effect from studies performed in a variety of settings (home-based, outpatient, hospital, and home)38,39; studies examining both cardiac rehabilitation and controlled exercise interventions outside of cardiac rehabilitation38–40; studies examining the effectiveness of specific interventions, such as hydrotherapy and aquatic therapy, on clinical outcomes in heart failure40; and studies published before 2019.38–40 These findings as presented provide substantial heterogeneity and limit the ability to exclusively examine the effectiveness of comprehensive outpatient cardiac rehabilitation programs on clinical outcomes. The findings of the present meta-analysis advance past work by adding recent RCTs and confirming the unique effectiveness of comprehensive cardiac rehabilitation on functional status and exercise capacity. We found a statistically significant positive effect of comprehensive cardiac rehabilitation on improvement in functional status as measured by the 6-minute walk distance (SMD = 0.30; 95% CI = 0.06 to 0.54) and exercise capacity (SMD = 0.23; 95% CI = 0.06 to 0.40). Moreover, the improvement in 6-minute walk distance in the intervention group exceeded the established a minimal clinically important difference of 30.1 m for this population, indicating evidence of clinically meaningful improvements as compared to the comparison group.41 However, comprehensive cardiac rehabilitation did not significantly improve muscle strength and quality of life beyond what was observed in the comparison groups, and the magnitude of the pooled differences was relatively inconsistent across studies.

The comparison groups used in this review were not conventional control groups. Since we focused on intervention combinations performed as part of comprehensive cardiac rehabilitation, groups that received exercise as part of usual care in other settings or outside of cardiac rehabilitation or those that received only a single exercise within a cardiac rehabilitation setting were considered as comparison groups. In this regard, many participants in the comparison groups received some form of exercise intervention. Despite our comparison groups’ participation in exercise training, we found statistically significant differences in improvement in exercise capacity and 6-minute walk distance in the intervention group as compared to the comparison groups. Thus, our findings suggest that the improvement in these outcomes was large enough to overcome the wash out effect that might have occurred from the comparison groups’ participation in exercise or physical activities.

In contrast to previous meta-analyses, we did not find statistically significant differences between groups on quality of life measured via MLHFQ. Both intervention and comparison groups demonstrated improvements in quality of life. Although the improvements in quality of life among participants in the intervention group were greater than the comparison groups, the differences in improvement were not statistically significant between groups. This is likely due to the heterogeneity of the sample and severity of disease, sample sizes, the outcomes measured, and the way these were measured. Also, given that the comparison groups in some of the studies actively participated in exercise,26,28 and that the number of studies included in the meta-analysis for MLHFQ were much lower than the number of studies for exercise capacity and 6-minute walk distance outcomes, it is possible that improvements in quality of life in the comparison groups washed out the improvements noted in the intervention groups. Also noteworthy is that the studies that demonstrated significant improvement in quality of life with MLHFQ following comprehensive cardiac rehabilitation had larger sample sizes as compared to the studies that did not show significant between-group differences. It is likely that the studies were underpowered to reach statistical significance between groups despite within group improvements after intervention. Larger trials assessing quality of life using standardized measures are needed.

Similar results were also noted in the muscle strength category. Although both groups demonstrated improvement in upper and lower extremity muscle strength across studies, the pooled differences in improvement (change scores) were not significant between groups. Similar to studies that assessed quality of life, all studies, with the exception of 1, included comparison groups that also engaged in formal exercise training. Despite this, the intervention group demonstrated greater improvement in muscle strength than the comparison group. It is likely that increasing the sample by including more studies with similar outcomes could translate to statistically significant between-group differences.

This study provides strong evidence to support comprehensive outpatient cardiac rehabilitation, which could significantly improve exercise capacity and functional mobility in patients with heart failure. Findings also demonstrate a tendency toward improvements in quality of life, muscle strength, and endurance. However, more randomized clinical trials are needed to examine quality of life, muscle strength, and endurance outcomes in this setting. Systematic reviews and meta-analyses are needed to look at the unique effectiveness of home-based cardiac rehabilitation, and a comparison between home and outpatient-based cardiac rehabilitation in this population.

This study was not without limitations. First, we only conducted a meta-analysis of studies that used the MLHFQ as the quality-of-life outcome due to the variability in outcome measures used for quality of life across studies and the way those were measured. Second, the sample in the included studies ranged widely (NYHA classes I–IV), which makes it difficult to make recommendations for a specific disease severity category. Third, studies comparing functional status measures such as muscle strength and endurance were too few to draw valid conclusions. Fourth, the sample sizes of the included studies were relatively small, limiting the generalizability of the findings. Finally, we do not have information on whether cardiac rehabilitation was initiated by nurse educators, nutrition specialists, exercise specialists, or physical therapists, which may play roles in the outcomes.

Conclusion

This systematic review and meta-analysis provide moderate to high evidence on the effectiveness of comprehensive outpatient cardiac rehabilitation on exercise capacity and functional status in individuals diagnosed with heart failure. Based on findings from this meta-analysis of RCTs, these results support the recommendation of comprehensive outpatient cardiac rehabilitation for patients with heart failure. Due to variations in methodological quality and heterogeneity of outcomes, more RCTs are needed to conclusively identify ideal dosing of exercise for optimal benefits in cardiac rehabilitation for this population.

Supplementary Material

2022-0543_R2_Supplementary_Material_TSR_pzad119
Click here for additional data file. (308.7KB, pdf)

Acknowledgments

The authors thank Dr Pamela Bosch (P.B.) for providing her clinical expertise and assisting with initial screening of articles. We also acknowledge the contributions of physical therapist student Breanne Alexa Bornscheuer for her help screening articles.

Contributor Information

Shweta Gore, Department of Physical Therapy, School of Health and Rehabilitation Sciences, MGH Institute of Health Professions, Boston, Massachusetts, USA.

Hargun Khanna, Department of Physical Therapy, School of Health and Rehabilitation Sciences, MGH Institute of Health Professions, Boston, Massachusetts, USA.

Amit Kumar, Department of Physical Therapy and Athletic Training, College of Health, University of Utah, Salt Lake City, Utah, USA.

Author Contributions

Shweta Gore (Conceptualization [equal], Formal analysis [lead], Funding acquisition [lead], Methodology [equal], Project administration [lead], Software [lead], Supervision [lead], Validation [equal], Visualization [equal], Writing—original draft [equal], Writing—review & editing [equal]), Hargun Khanna (Data curation [equal], Methodology [supporting], Validation [supporting], Writing—original draft [supporting], Writing—review & editing [supporting]), and Amit Kumar (Conceptualization [equal], Data curation [equal], Funding acquisition [equal], Investigation [equal], Methodology [equal], Visualization [equal], Writing—review & editing [equal]).

Funding

This research was supported by an NIH grant from the National Institutes on Aging (NIA) R15 REAP award: R15AG070730.

Systematic Review Registration

This study protocol was registered in PROSPERO (CRD42022318055).

Data Availability

Article links to all studies included in this Review are included in the manuscript.

Disclosures

The authors completed the ICMJE Form for Disclosure of Potential Conflicts of Interest and reported no conflicts of interest.

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Associated Data

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Supplementary Materials

2022-0543_R2_Supplementary_Material_TSR_pzad119
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Data Availability Statement

Article links to all studies included in this Review are included in the manuscript.

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