The Impact of Cardiac Rehabilitation on Psychosocial Factors, Functional Capacity, and Left Ventricular Function in Patients with Coronary Artery Disease: Systematic Review and Meta-Analysis

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Revised. Amendments from Version 1

This version includes the addition of ORCID identifiers for two authors and an update to the institutional affiliation of one author to ensure accurate author metadata. The manuscript also underwent language revision to improve clarity, readability, and grammatical accuracy. No changes were made to the study design, methodology, data analysis, results, interpretation of findings, or conclusions. These revisions are administrative and editorial in nature and do not affect the scientific content or findings of the article.

Abstract

Background

Cardiac rehabilitation is a multifaceted program implemented after adverse events. It aims at facilitating the return to normal life. This review aimed to examine the impact of cardiac rehabilitation on psychosocial risk factors, functional capacity, and left ventricular function.

Methods

The following databases: CINAHL, Scopus, PubMed, and Cochrane Library have been searched to retrieve the randomised controlled trials that investigate the effectiveness of cardiac rehabilitation versus usual care on anxiety, depression, peak oxygen consumption, six-minute walk distance, left ventricular ejection fraction, and left ventricular end-systolic and diastolic dimensions. Filters were set to retrieve trials published in the English Language between 2000 and 2024. Risk of bias was assessed using the Cochrane risk-of-bias tool (Rob2). Data were analysed meta-analytically.

Results

Twenty-two (22) trials were included, randomised 2283 participants. A significant improvement favouring intervention groups was observed in anxiety SMD = -0.3890 (95% CI: -0.5640 to -0.2140; p˂0.001), depression SMD = -0.4032 (95% CI: -0.7114 to -0.0950; p= 0.002), peak oxygen consumption MD = 1.2471 (95% CI: 0.3963 to 2.0979; p = 0.004), six-minute walk distance MD = 36.0290 (95% CI: 7.7497 to 64.3082; p = 0.013), and left ventricular ejection fraction MD = 3.0650 (95% CI: 1.1279 to 5.0022; p = 0.001), Although cardiac rehabilitation had no significant effect in decreasing left ventricular end-diastolic dimension MD = -0.0480 (95% CI: -0.2609 to 0.1648; p = 0.658) and left ventricular end-systolic and MD = -0.0670 (95% CI: -0.2829 to 0.1489; p = 0.543) a favourable trend toward intervention group was seen. Risk of bias was high in 1 study and unclear in 7 studies.

Conclusion

For patients with Coronary Artery Disease, cardiac rehabilitation demonstrated effectiveness in improving psychological symptoms such as anxiety and depression, functional capacity as measured by peak oxygen consumption and six-minute walk test, and left ventricular function.

Introduction

Cardiovascular disease (CVD) remains the main cause of morbidity and mortality internationally, contributing to a significant health burden worldwide. Nearly 19 million deaths were associated with CVD in 2020, representing an 18.7% growth from 2010, and over 500 million individuals are affected by CVD. Coronary artery disease (CAD) is the most frequently encountered CVD and is associated with a decline in quality of life. ^{1 , 2} Despite technological progression in CAD treatment, patients still experience subsequent cardiovascular events, ^{3 , 4} resulting in frequent readmissions, and escalating the individual and social burden of CAD. ⁵ Hence, presence of ongoing management after being diagnosed with CAD is vital.

Cardiac rehabilitation (CR) is a multifaceted program implemented after cardiac event. It aims to facilitate the return to normal life and improving exercise capacity. ⁶ Cardiac rehabilitation includes health education, behavioural counselling, lifestyle management and exercise training. ⁶ It is recommended to start the program early in-hospital (phase I) and then continue with (phase II and III) either in-home or centre-based program. ⁷

The presence of psychosocial risk factors such as anxiety and depression disturb the prognosis of CAD. ^{8 – 11} Studies have shown that depression and anxiety increase the risk of frequent cardiac events and cardiac and all-cause mortality in patients with CAD. ^{11 – 13} Conversely, psychosocial well-being has been described as a protective factor. ¹⁴ Psychosocial risk factors adversely affect cardiac outcomes, by contributing to unhealthy lifestyle and by diminishing the likelihood of successful modification of cardiac risk factors. ¹⁵ They are also associated with decreased adherence to medical treatment and rehabilitation. ^{15 – 17}

As a major clinical outcome of CR, functional capacity is a key an indicator in secondary prevention of CVD. ¹⁸ It refers to the capability of an individual to perform aerobic work. ¹⁹ The coordinated performance of cardiovascular, pulmonary, and musculoskeletal systems determines an individual’s functional capacity. ²⁰ Several studies have reported that the evaluation of functional capacity offers essential diagnostic and prognostic information about patients with CVD. ²¹ Therefore, it is important to assess the impact of CR on functional capacity. Functional capacity is frequently measured by exercise tests such as peak oxygen consumption (VO _2peak) and the 6-minute walk test (6-MWT). ^{22 , 23}

The left ventricle is a core component of the cardiovascular system. The primary function of the left ventricle is to suplly other organs with blood flow. Maintaining sufficient blood supply requires effective contractility of the left ventricle. Patients with CAD may experience cardiac remodelling: a process defined as a group of alterations within the heart that lead to changes in the size, shape and function. ²⁴ The progression of cardiac remodelling may lead to severe left ventriculare impairment and chronic heart failure. ²⁵ Therefore, evaluation of the impact of CR on left ventricular function is very important.

Cardiac rehabilitation research is a dynamic field, and the emergence of new evidence comparing CR with usual care requires the synthesis of recent findings, appraisal of the expanding literature, and consideration of potential sources of heterogeneity. The aim of this systematic review and meta-analysis was to examine the impact of CR on psychosocial outcomes, functional capacity, and left ventricular function, including anxiety and depression, 6-minute walk test (6-MWT), peak oxygen uptake (VO _2peak), left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), and left ventricular end-systolic dimension (LVESD).

Methods

Search strategy

The current systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. ²⁶ Two authors (ASH and PY) independently searched the following databases: PubMed, CINAHL, Scopus, Cochrane Library and EMBASE. Additionally, the references of included studies were manually searched to retrieve studies undetected in the primary search. Medical Subject Headings (MeSH) were used in the search process to retrieve the relevant studies. The filters were set to retrieve studies published in the English language between 2000 and 2024. The retrieved studies were checked primarily by titles for potential inclusion in this review, subsequently, those potentially included papers were checked by abstract and then full text for eligibility. Any conflict was resolved by discussion until consensus was reached, and the final decision about the included and excluded paper was made by the senior author (KLS).

Inclusion and exclusion criteria

This systematic review and meta-analysis included studies that met the following criteria: 1) randomized controlled trial; 2) examined the impact of CR on at least one outcome of interest; 3) involving patients with CAD aged ≥ 18 years; 4) the minimum follow-up duration of four weeks. studies that did not meet these criteria were excluded. In addition, studies with mixed populations (i.e., patients with CAD and patients with non-CAD) were excluded. The EndNote software (Endnote X9) was used to remove the duplicated articles, then a manual check was done.

Data extraction and analysis

A pre-set Microsoft Excel spreadsheet was prepared to record the extracted data. Two authors (ASH and PY) independently extracted the following data: first author’s name; year of publication; the location where the study was conducted; sample size and the number of participants in each group; percentage of each gender; intervention’s main components; duration of follow-up; populations’ diagnosis; the p-value for each comparison; and post-intervention means and standard deviations for each group.

The Population, Intervention, Comparator and Outcomes (PICO) framework was used to guide this review. The intended population encompassed patients with CAD, including those who were diagnosed with, myocardial infarction, and those who had undergone percutaneous intervention, or coronary artery bypass graft, The interventions considered were the home-based CR (HBCR) or centre-based CR (CBCR); The comparator group included patients receiving usual care or no cardiac rehabilitation, the outcomes of interest are: 1) psychosocial risk factors anxiety and depression; 2) functional capacity measured by VO _2peak and 6-MWT; and 3) left ventricular function measured by left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), and left ventricular end-systolic dimension (LVESD).

Data were analysed following the guidelines of the Cochrane Handbook for systematic reviews of interventions. ²⁷ Using Jamovi software (Jamovi 24.11). A random effect statistical model was applied. To estimate the effect of CR versus usual care, post-intervention between groups mean differences (MD) and standard deviations were used. Alternatively, standardised mean difference (SMD) was used in case the outcome was measured by different scales among the studies. Heterogeneity was tested using I ², whereby values of 25%, 50%, and 75% indicate low, moderate, and high heterogeneity, respectively. Hypothesis testing was performed at a two-tailed 0.05 level and a 95% CI. If I ² values showed high heterogeneity (I ² > 50%), sensitivity analysis was performed by using ‘leave-one-out approach, removing one study at a time and observing the impact on heterogeneity. Publication bias was assessed visually by a funnel plot and statistically by the Egger test. Subgroup analysis was performed based on the duration of follow-up (≥ 3 vs ˂ 3 months), and population average age (≥ 60 vs ˂ 60 years).

Risk of bias

Two authors (ASH and PY) independently assessed the risk of bias in the included studies. Version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2) was employed to assess the risk of bias in the included trials. ²⁸ RoB 2 is structured into a set of domains of bias: (1 bias arising from the randomisation process; (2 bias due to deviations from intended interventions; (3 bias due to missing outcome data; (4 bias in the measurement of the outcome; (5 bias in the selection of the reported result. For each domain, a set of questions (signalling questions) is designed to guide the user in extracting information related to the risk of bias. Judgment regarding the risk of bias arising from each domain is made by an algorithm, based on answers to the signalling questions. Judgment can be ‘Low’ or ‘High’ risk of bias, or ‘some concerns’. the final decision about the risk of bias Judgment was made by the senior author (KLS).

Certainty of evidence assessment

The quality of evidence across the outcomes was assessed using the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. ²⁹ GRADE has four levels of evidence: high, moderate, low, or very low. Based on GRADE guidelines RCTs are considered high-quality evidence, then they may be downgraded 1 or 2 levels based on the assessment of risk of bias, inconsistency, indirectness, imprecision, and publication bias for each outcome.

Results

Search results

The preliminary search in the databases identified 3,357 studies. Duplicated articles were removed using the EndNote software. The remaining articles were screened by titles for potential inclusion. The retrieved articles were checked by reading the abstracts. After excluding the articles that did not meet the inclusion criteria. 95 articles were eligible for full-text reading. The final number of trials included in this review was 22 studies. The details of the search process are illustrated in Figure 1.

Figure 1. PRISMA flow chart.

Characteristics of included studies

The present review included 22 RCTs conducted in 11 countries. Five studies were conducted in Iran, five in China, two in Portugal, two in Japan, and two in Denmark, while one study each was conducted in the USA, Brazil, Hong Kong, Turkey, Finland, and Indonesia. The included trials were published between 2003 and 2023. The studies randomised 2,283 participants, with 1,196 allocated to the intervention groups and 1,087 to the control group. Sample sizes ranged from 29 to 310 participants. The mean age of participants ranged from 40 to 85 years across studies. One study reported a high proportion of female participants (71.2%), whereas the remaining studies included mostly male participants with low female representation. Follow-up durations ranged from 4 weeks to 12 months. Table 1 illustrates the studies’ characteristics.

Table 1. Characteristics of included studies.

Authors Year country	Sample size		Age year	Follow-up duration	Population	Intervention main components	Outcomes	Between groups p value
	Exp	Cont
	Female (%)
(Sharif et al., 2012) Iran.	40	40	40-70	2- month	patients scheduled for CABG	Two sessions/week 2 hours each of education and training include : • Medication. • Diet. • Weight control. • Stress management. • Quitting smoking. • Light physical exercise • Relaxation.	Anxiety	0.079
	(70%)						Depression	0.014
(Snoek et al., 2021) Finland.	58	60	60-59	12- month	Patients with CAD	• Remote monitoring and coaching using a smartphone and Bluetooth-connected heart rate belt. • The device records training mode, training time and training intensity. • Participants were advised to exercise at least 30 min/day for 5 days/week. • Participants had insight into their training history through an individual webpage. • A standard operating procedure, composed with a psychologist, was used for the individual coaching. • They were contacted weekly by telephone for supportive guidance.	Anxiety	0.11
	NP						Depression	0.24
							Vo 2peak	0.74
(Xu et al., 2016) China	26	26	55.5-55.8	4-week	Patients with CAD	1-Inpatient phase for 1 week, • Casual limb movements while in bed and simple walk training. • Energy expenditure estimated at 2 to 4 (METs). • Intensity targeted 4 and 5 perceived exertion Borg (PEB) scale rating. • Reach 60% (HRmax). 2-Outpatient phase for 4 weeks • A 5-minute warm-up (stretching), 20-minute aerobic exercise (walking or jogging, gymnastics), and a 5-minute cool-down (stretching). • Brochure that included information about cardiac disease, risk factor management, the importance of exercise, dietary advice, psychological support, and compliance with medication. • Phone interview 1/week.	LVEF	0.315
	(15.4%)
(Abtahi et al., 2017) Iran,	25	25	53.6-53.76	8-week	Post-PCI patients	• Three sessions/week, 1hour Each. • A warm-up (10 minutes), and 40 minutes of aerobic exercise training,10 minutes cooling down and finished by relaxation. • 40-60% of HRmax. • 2- Educated about risk factors, stress reduction methods, smoking cessation, body weight control, psychological, and nutritional.	LVESD	0.004
	(42%0						LVEDD	>0.05
							LVEF	<0.001
(Yu et al., 2004) Hong Kong,	181	88	63.7-63.9	8-week	Patients after AMI or elective PCI	Three phases: • Phase 1: inpatient ambulating program lasted for 7 to 14 days. • Phase 2: twice-weekly outpatient exercise and education program lasting for 8 weeks, 1 hour of education class followed by 2 hours of exercise training. • Phase 3: home exercise program lasted 6 months consisted of daily walking exercise for at least 60 minutes after warm-up exercise.	LVESD	˂0.05
	(25%)						LVEDD	ns
							LVEF	ns
(Oliveira et al., 2014) Portugal.	39	44	54.6-58.6	8-week	Patients after AMI	• Three sessions/week 40-minute each (10 minutes of warm-up, 30 minutes of aerobic exercise on a cycle ergometer or treadmill). • 70%-85% of HRmax. • Regular appointments with a cardiologist. • medication optimisation.	Vo 2peak	0.024
	(16.4%)
(Noites et al., 2017) Portugal	16	16	62.5-59.5	8-week	Patients after AMI	• three sessions/week. 70-85 minutes each include warm-up and cool down. • 60-70 % of HRmax. • moderate-intensity workout.	Vo 2peak	0.02
	(21.9%)
(Zhao et al., 2022) China	30	29	60.95	12-week	Patients with CAD	• Six to seven sessions/week, 40–60 minute each. • Included upper and lower extremities, breathing, self-massage, and whole-body exercises. • Moderate-intensity	Vo 2peak	<0.05
	(71.2%)
(Kulcu et al., 2007) Turkey	23	21	85.3-60.4	8-week	Patients with CAD	• Three sessions/week, 1 hour each. • Treadmill walking with adjusted speed and inclination. • 60-70 % of HRmax. • Every training session began and ended with 5 min warm-up cool-down periods.	Vo 2peak	0.001
	(27.2 %)						Anxiety	0.034
							Depression	0.004
(Soleimannejad et al., 2014) Iran.	73	73	58-56.7	8-week	Patients with CAD	• Phase I: (Inpatient): Lasted 7-14 days, initiated after PCI. • Phase II (Outpatient Exercise and Education): Conducted three times weekly, lasting 2-3 months. each session comprised one hour of education followed by two hours of exercise training. • Electrocardiography (ECG) monitoring during exercise sessions. • Phase III (Community-based Home Exercise): Implemented between six and twelve months. • Phase IV (Long-term Follow-up): Extended until the end of the second post-PCI year. emphasised the importance of regular exercise and risk factor modification.	LVESD	0.070
	(31.5%)						LVEDD	0.571
							LVEF	0.006
(Cao et al., 2021) China	24	10	61.7	8-week	patients after PCI	• Three sessions/week, 30 minutes each. • Targeted intensity individually determined based on the HR recorded 1 minute before the threshold of anaerobic ventilation during CPET examination (70–80%) of HRmax. • 5 minutes warm-up, Gradual intensity increase over 20 minutes, 5 minutes cool down.	Vo 2peak	0.009
	(26.4%)
(Seki et al., 2003) Japan	20	18	69.3-70.1	6-month	Patients with CAD	• Physical exercise and educational components • Warm-Up Exercises (Approximately 20 Minutes) • Upright Aerobic and Dynamic Exercise (20–30 Minutes) • Cool-Down (Approximately 20 Minutes) • Dietary and Educational Program.	Vo 2peak	<0.05
	(0%)						Anxiety	<0.01
							Depression	NS
(Ma et al., 2020) China	150	150	63.1-62.8	12-month	Patients post- CABG	• CAD-related health education (Once a week (2 months), each lasting about 60 minutes, covering basic CAD knowledge and post-discharge rehabilitation management. • Exercise guidance and surveillance (once a month for 10 months), 60 to 90 min each time; (3) frequency: 3 to 5 times per week; (4) intensity: fairly light to somewhat hard (11–13 on Borg scale). • Risk factor control (once a month for 10 months). • Psychological nursing (once a month for 10 months).	Anxiety	<0.001
	(21.3%)						Depression	<0.001
(Basati et al., 2012) Iran	15	14	51.7-59	8-week	Patients Post-PCI	• Three session/week, 60-90 minutes each and included 10-20 minutes of warm-up followed by 20-40 minutes of aerobic exercise and a final 10-minute cool-down. In addition, there was a 20-minute relaxation at the end of each session. • 60-85% of HRmax. • (HR) achieved on the exercise test. • Psychological, nutritional, and smoking cessation consultations.	LVEDD	0.001
	(0%)						LVESD	NS
							LVEF	0.001
(Peixoto et al., 2015) Brazil	45	43	56.8-56	30-day	Patients Post-PCI	Stage I: Early Mobilization Post-AMI • Begins 12 hours after AMI, conducted twice daily during the inpatient phase. • Starts at 2 METs and progressively increases to 4 METs. • Educational Program covers information about cardiac diagnosis, sexual activity, exercise continuation, nutritional advice, and pharmacological regimen adherence. Stage II: Unsupervised Progressive Exercise • 4 times a week for 4 weeks following hospital discharge. • Endurance Training Period: • First week: Starts with a walking time of 20 minutes. • Second week: Increases to 25 minutes. • Third week: increases to 30-35 minutes. • Fourth week: Reaches 35-40 minutes. • Cool-Down Period (5 minutes).	6MWD	<0.001
	(29.5%)
(Ma et al., 2021) China	70	70	65.2/65.1	12-month	Patients post-CABG	• Health Education: once weekly focusing on topics such as post-CABG medicine management, risk factor management, and secondary prevention. • Rehabilitation Guidance: Includes aerobic, resistance, flexibility, and balance training guidance delivered weekly through video courses. • Exercise Supervision: Individualised exercise prescriptions based on pre-discharge evaluations • Psychological Care: twice weekly personal nurse-led counseling sessions via video call to address mental health and emotional support.	Anxiety	0.034
	(21%)						Depression	0.048
(Højskov et al., 2019) Denmark	152	158	65-65.1	4-week	Patients post-CABG	Physical Exercise Component • At admission: Included respiratory physiotherapy and aerobic training. • Post-hospital discharge (up to 4 weeks post-CABG): Involved continuous daily walking, muscle strengthening, and • Endurance exercises. Psycho-educational Component • Mindfulness practices were a key element, offered as a set of recorded meditation instructions.	Anxiety	0.2
	(14%)						Depression	0.04
(Dwiputra et al., 2023) Indonesia,	44	43	56.3-57.2	6-week	Patients post- CABG	Resistance Training: 2-3 sessions/week Aerobic Training: Participants walked as quickly as possible for 6 minutes on a 45-meter walkway, with allowances to slow down, stop, and rest as needed.	6mwt	0.033
	11%
(Nishitani-Yokoyama et al., 2018) Japan	18	14	58-59	8- month	Patients with CAD	• Warm-Up: Begins with stretching exercises to prepare muscles and joints. • Aerobic Exercise: Includes cycling, treadmill walking, and in-room track walking for about 20 minutes. • Intensity tailored to individual anaerobic threshold or Borg’s scale rating. • Cool Down: Follows aerobic exercise to gradually lower heart rate. • Schedule: Conducted once daily in the hospital. • Additional Components: • Dietary Recommendations: Follow American Heart Association's phase II diet. • Educational Program: Provided by physicians, nurses, and dietitians, covering CAD and risk factors.	Vo 2peak	NS
	(6%)
(Ghashghaei et al., 2012) Iran.	17	15	62-58.5	2-month	Patients post- CABG	• A combination of aerobic and resistance exercise training. • 24 supervised sessions, 90 minutes each, • intensity was set between 60-85% of maximum heart rate. • The program also offered nutritional and psychological consultations, along with risk factor management. • Center vs usual	6-MWD	<0.01
	(19%)						LVESD	0.02
(Oerkild et al., 2012) Denmark	19	21	76.5-77.3	12- month	Patients with CAD	• two visits from a physiotherapist over 6 weeks with a follow-up call for any questions. • 6 sessions/week.30-minute each, with warm-up and cool-down, done Exercises matched personal abilities. • moderate effort (Borg scale 11–13). • Shorter exercises for very disabled patients, done more times a day. • physician visits at the start, 3, 6, and 12 months, plus follow-up calls at 4 and 5 months for monitoring and motivation. • dietary advice and help to quit smoking if needed.	6-MWD	NS
	(43%)
(Golbus et al., 2023) USA	111/	109	59.5-59.7	6-month	Patients with CAD	• Two types: activity messages and exercise planning messages. • Activity messages encouraged low-level physical activity • Exercise planning messages encouraged participants to exercise the next day • Mobile Application Features: Allowed participants to engage in activity self-monitoring and goal-setting. • Smartwatch data shared with exercise physiologists via email and a web-based dashboard.	6-MWD	0.28
	(30%)

CAD: coronary artery disease; CAPG: coronary artery bypass graft; PCI: percutaneous intervention; LVEF: left ventricular ejection fraction,

LVEDD: left ventricular end-diastolic dimension, LVESD: left ventricular end-systolic dimension; NP: not provided; NS; not significant;

Vo _2peak: peak oxygen consumption; HRmax: maximum heart rate; PCI: percutaneous intervention; 6-MWD: six-minute walk distance.

Risk of bias in included studies

Of the 22 studies included in this review, 1 study (4.5%) was assessed as having a high risk of bias related to the randomization process. Because the participants were allocated based on the initial assessment rather than being randomly assigned.. (7 studies) (32%) were assessed as having unclear risk of bias since they did not provide information about allocation concealment. The remaining 14 studies (63%) explicitly reported the allocation and randomization methods such as using a sealed opaque envelope, coin flipping, computer-generated random numbers and block randomisation. There was no evidence indicating deviation from the intended intervention, therefore, all studies were assessed as having a low risk of bias regarding this domain. regarding missing outcome data, 1 study (4.5%) showed high risk of bias due to a substantial amount of missing data, 4 studies (18%) had an unclear risk of bias, and the remaining 17 studies (77%) reported handling missing data based on intention-to-treat (ITT) analysis. For measurement of the outcome domain, 12 studies (55%) did not provide sufficient information whether the data was analysed blindly or not, resulting in unclear risk of bias. On the other hand, a low risk of bias was observed in the remaining 10 studies (45%), either by reporting blind assessors or by showing a robust methodology. All studies showed low risk regarding reporting bias. Figures 2 and 3 summarise the outcomes of risk bias assessment.

Figure 2. Risk of bias summary of included studies.

Figure 3. Risk of bias graph.

Certainty of evidence

The GRADE framework was used to evaluate the quality of the evidence in the included studies. Of the seven outcomes investigated in this review, five outcomes had moderate quality evidence (anxiety, depression, VO _2peak, 6-MWT, and LVEF), and two had low-quality of evidence LVEDD and LVESD. Table 2 details the assessment of certainty of evidence.

Table 2. Certainty of evidence.

Outcome	No. studies	No. participants		Risk of bias	Inconsistency	Indirectness	Imprecision	Publication bias	Certainty
		CR	UC
Anxiety	8	1068		Not serious	Not serious	Not serious	Not serious	undetected	⨁⨁⨁◯ Moderate
		532	532
Depression	8	1068		serious	Not serious	Not serious	Not serious	undetected	⨁⨁⨁◯ Moderate
		532	534
VO 2 peak	8	440		Not serious	Not serious	Not serious	Not serious	undetected	⨁⨁◯◯ Low
		228	212
6-MWD	5	404		Not serious	Not serious	Not serious	serious	undetected	⨁⨁⨁◯ Moderate
		202	202
LVEF	6	578		serious	Not serious	Not serious	Not serious	undetected	⨁⨁⨁◯ Moderate
		337	2241
LVEDD	4	494		Not serious	Not serious	Not serious	Not serious	undetected	⨁⨁⨁◯ Moderate
		294	294
LVESD	4	494		serious	Not serious	Not serious	serious	undetected	⨁⨁◯◯ Low
		294	200

CR: cardiac rehabilitation, LVEF: left ventricular ejection fraction, LVEDD: left ventricular end-diastolic dimension, LVESD: left ventricular end-systolic dimension, peak oxygen consumption, 6-MWD: six-minute walk distance, UC: usual care.

Meta-analysis of included studies

Psychosocial risk factors

Anxiety: Eight studies evaluated the effect of CR on anxiety levels. The meta-analysis showed a statistically significant reduction in anxiety in intervention groups compared with control SMD = -0.3890 (95% CI: -0.5640 to -0.2140). (z = -4.3577, p < 0.0001). Moderate heterogeneity was observed across studies, I ² = 41.62%, p = 0.0672. No indication of publication bias was observed (see Figure 4).

Figure 4. The forest plot of the effect of CR vs usual care on Anxiety.

Depression: Eight studies examined the effect of CR on depression. The meta-analysis revealed a statistically significant reduction in depression among the intervention groups compared to the control groups. SMD = -0.4032 (95% CI: -0.7114 to -0.0950). (z = -2.5638, p = 0.0018). However, high heterogeneity was observed I ² = 81.1861%, p = 0.0034. employing the sensitivity test by removing the study by Sharif et al. (2012) ³³ and the study by Kulcu et al. (2007) ³² revealed statistically significant result without a significant amount of heterogeneity. SMD = -0.2663 (95% CI: -0.3948 to -0.1378), (z = -4.0626, p < 0.0001). I ² = 0.0000%, p = 0.4598. No indication of publication bias was observed (see Figure 5).

Figure 5. The forest plot of the effect of CR vs usual care on Depression.

Functional capacity

Peak VO _2peak : Eight studies investigated the impact of CR on VO ₂ peak. The meta-analysis showed a statistically significant improvement in VO ₂ peak among participants in the intervention groups compared to those in the control groups. MD = 1.2471 (95% CI: 0.3963 to 2.0979). (z = 2.8728, p = 0.0041). There was no evidence of significant heterogeneity across studies I ² = 0.0000%. p = 0.5604. No indication of publication bias was observed (see Figure 6).

Figure 6. The forest plot of the effect of CR vs usual care on VO ₂ peak.

6-MWT: Five studies investigated the effect of CR vs usual care on 6-MWT. The pooled effect showed a statistically significant increase in 6-MWT among participants in intervention groups compared to those in control groups. MD = 54.7948 (95% CI: 15.6115 to 93.9782). (z = 2.1630, p = 0.0305). However, the true outcomes appear to be heterogeneous, I ² = 73.3622%, p = 0.0234. employing the sensitivity test by removing the study by Oerkild et al. (2012) ³⁶ and the study by Ghashghaei et al. (2012) ³⁵ revealed a statistically significant result MD = 36.0290 (95% CI: 7.7497 to 64.3082). (z = 2.4971, p = 0.0125) with moderate amount of heterogeneity, I ² = 45.3613%, p = 0.1670. No indication of publication bias was observed (see Figure 7).

Figure 7. The forest plot of the effect of CR vs usual care on 6-MWT.

Left ventricular function

LVEF: Six studies examined the effect of CR vs usual care on LVEF. When compared to the control, participants in intervention groups demonstrated a statistically significant increase in LVEF. MD = 3.0650 (95% CI: 1.1279 to 5.0022). (z = 3.1011, p = 0.0019) with a moderate heterogeneity, I ² = 39.10%, p = 0.0196. No indication of publication bias was observed (see Figure 8).

Figure 8. The forest plot of the effect of CR vs usual care on LVEF.

LVEDD: Four studies evaluated the impact of CRP vs usual care on LVEDD. Meta-analysis demonstrated a non-statistically significant reduction in LVEDD in intervention groups compared to control, = -0.0480 (95% CI: -0.2609 to 0.1648). (z = -0.4422, p = 0.6583). No heterogeneity was observed I ² = 0.0000%, p = 0.6501. No indication of publication bias was observed (see Figure 9).

Figure 9. The forest plot of the effect of CR vs usual care on LVEDD.

LVESD: Five studies assessed the impact of CRP vs usual care on LVESD. Meta-analysis revealed that the intervention groups exhibited a non-statistically significant decrease in LVESD compared to control groups. MD = -0.0670 (95% CI: -0.2829 to 0.1489). (z = -0.6086, p = 0.5428). All studies appeared homogeneous I ² = 0.0000%, p = 0.6005. No indication of publication bias was observed (see Figure 10).

Figure 10. The forest plot of the effect of CR vs usual care on LVESD.

Discussion

The main findings for this systematic review and meta-analysis were that CR improved psychosocial risk factors, functional capacity, and left ventricular function, as indicated by the statistically significant improvement in (anxiety, depression, VO _2peak, 6-MWT, and LVEF) in the intervention groups as compared to the control groups, and the favourable trend toward the intervention groups in LVEDD and LVESD. There was no significant amount of heterogeneity among all outcomes, except for depression, 6-MWT, and LVEF. However, the heterogeneity could be handled by sensitivity analysis.

Constant feelings of fear and worry about social and physical aspects of life influence the patient’s mental health. ⁵¹ Anxiety and depression are common psychological disorders after cardiovascular events such as acute myocardial infarction and revascularization. ^{51 , 52} Studies documented that the prevalence of anxiety and depression in patients diagnosed with CAD is very high compared to the general population. ^{53 , 54} A recent meta-analysis aimed to estimate the prevalence of anxiety and depression in cardiac patients reported that the prevalence of anxiety was 32.9% (95% CI: 21.9-46.6%), while depression was noted at 31.3% (95% CI: 21.9-46.6%). ⁵⁵

Those cardiac patients who are anxious and depressed are more susceptible to major adverse cardiac events and death. ^{56 – 58} This necessitates the need for early assessment and treatment of anxiety and depressive symptoms. The findings of this review emphasize the role of CR in alleviating anxiety and depression. By training the patients to adhere to a healthy lifestyle, CR aims to enhance patients’ satisfaction and return to normal life. Multidisciplinary CR that includes physical training, psychological support, and health education appeared to be highly effective and have shown significant benefits in reducing anxiety and depression levels. The result of this review was in line with previous works. For instance, Yohannes and colleagues concluded that CR had a positive impact on particular psychological disorders, such as depression and anxiety and this impact was maintained at short and long follow-up. ⁵⁹ Escobar and colleagues also observed improvement in anxiety and depressive symptoms in patients undergoing CR. ⁶⁰

Functional capacity is a key outcome of CR, considered a key element in CAD secondary prevention. ⁶¹ Functional capacity adversely affected by CAD results in a sedentary lifestyle. ^{62 , 63} The inverse correlation between functional capacity and mortality rate has been reported in many studies. In a study conducted by Laukkanen and colleagues aimed to evaluate the relationship between functional capacity and cardiac and all-cause mortality rate, functional capacity appeared as a strong predictor of mortality beyond traditional risk factors. ⁶⁴

Functional capacity is frequently assessed using VO _2peak and 6-MWT. ⁶⁵ VO _2peak is a vital physiological indicator determining an individual’s upper capability for oxygen utilization during strenuous physical exertion, ⁶⁶ as this metric reflects cardiovascular fitness and aerobic endurance it plays a crucial role in shaping exercise prescription and assessing the efficiency of therapeutic interventions such as CR. ⁶⁷ Additionally, the 6-MWT provides a practical and valuable evaluation of functional capacity. serves as a fundamental marker of cardiovascular fitness and aerobic endurance. ^{65 , 68}

The present review demonstrated a statistical significant improvement in functional capacity in CR groups compared to the control groups. While the heterogeneity in the VO _2peak outcome was low, it was high in the 6-MWT outcome, after employing the sensitivity test by removing the studies by Oerkild et al. (2012) ³⁶ and Ghashghaei et al. (2012) ³⁵ the result remained significant, with moderate heterogeneity. The relatively smaller sample sizes of these two studies compared to other studies in this outcome may contribute to the heterogeneous result observed. These significant results highlight the effectiveness of CR in enhancing patients’ functional capacity and overall health. These findings are supported by the findings of a recent scientific review, where the authors observed improvement in functional capacity after CR. ^{69 , 70}

Despite advances in contemporary treatment aimed at restoring coronary blood flow, ischemic myocardial injury leads to left ventricular remodelling; a transformative process that involves changes in the left ventricle’s dimensions, shape, and function. ²⁵ Therefore, there is a need for treatment that enhances the left ventricular function without adversely affecting the ventricular remodelling.

The findings of the present review demonstrated that CR significantly improved the left ventricular function. as evidenced by the significant increase in LVEF and the reduction in LVEDD and LVESV in the intervention groups as compared with the control groups. Although the reduction in LVEDD and LVESD between the intervention and the control groups was not statistically significant, a favourable trend was observed in the participants in intervention groups without heterogeneity. These results emphasise that CR did not adversely affect the structure, shape, and function of the heart. These findings are consistence with the findings of previous studies which concluded that CR has favourable effects on LV function and remodelling in patients with CAD. ^{71 – 73}

Some limitations in this review should be mentioned. Firstly, the variation of CR in terms of onset, duration, intensity and frequency among the included studies may influenced the outcomes differently, CR with higher does may produce better improvement. Secondly, the small sample size in some included studies diminished the statistical power and increased the heterogeneity in particular investigated outcomes. Thirdly, some studies lacked sufficient information to allow for judgment on the risk of bias, especially information about blinding of the data assessors. Finally, the limited number of available trials that met the inclusion criteria especially those that investigated the impact of CR on 6-MWT, LVEDD and LVESD. Future studies are recommended to explore the impact of CR on other physical, psychological, and cardiac outcomes, such studies may comprehensively clarify the beneficiary effect of CR and underscore the areas of improvement.

Conclusion

For patients with CAD, including patients after PCI or CABG, CR effectively improved psychosocial risk factors such as anxiety and depression, functional capacity as measured by VO _2peak and 6-MWT, and left ventricular ejection fraction. The findings underscore CR as a method that enhances patients’ overall health.

Data availability

Underlying data

“All data underlying the results are available as part of the article and no additional source data are required.”

Software and code

The Endnote reference manager available from: https://endnote.com/downloads/ alternative free access reference manager available from: https://www.mendeley.com/download-reference-manager/windows

Meta-analysis statistical spreadsheet available from: https://www.jamovi.org/download.html

Risk of bias assessment available from: https://sites.google.com/site/riskofbiastool/welcome/rob-2-0-tool/current-version-of-rob-2?authuser=0

Reporting guidelines

Zenodo: PRISMA Checklist for Article “The Impact of Cardiac Rehabilitation on Psychosocial Factors, Functional Capacity, and Left Ventricular Function in Patients with Coronary Artery Disease: Systematic Review and Meta-Analysis”. https://doi.org/10.5281/zenodo.11186070

Data are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).

Zenodo: PRISMA flow chart for Article “The Impact of Cardiac Rehabilitation on Psychosocial Factors, Functional Capacity, and Left Ventricular Function in Patients with Coronary Artery Disease: Systematic Review and Meta-Analysis”. https://doi.org/10.5281/zenodo.11186649

Data are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).

Funding Statement

The author(s) declared that no grants were involved in supporting this work.