Posted: May 1st, 2025

PICOT Question: Systematic Reviews or Meta-Analyses of RCTs

Prospective Clinical Research Report
Effectiveness of early cardiac
rehabilitation in patients
with heart valve surgery: a
randomized, controlled trial
Journal of International Medical Research
50(7) 1–13
! The Author(s) 2022
Article reuse guidelines:
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DOI: 10.1177/03000605211044320
journals.sagepub.com/home/imr
Wei Xue , Zhang Xinlan and Zheng Xiaoyan
Abstract
Objective: Complications of heart valve surgery lead to physical inactivity and produce harmful
effects. This study aimed to investigate the role of a cardiac rehabilitation program and its longterm effect in patients after heart valve surgery.
Methods: We performed a single-blind, randomized, controlled trial. Patients with heart valve
surgery were randomly assigned to receive early cardiac rehabilitation (intervention group,
44 patients) or the usual care (control group, 43 patients). The intervention group performed
sitting, standing, and walking exercises, followed by endurance training. The control group
received usual care and did not engage in any physical activity. Physical function was assessed
by the Short Physical Performance Battery (SPPB) and other measurement tools.
Results: The intervention group showed a significant beneficial effect regarding physical capacity
as shown by the SPPB and the 6-minute walking test at hospital discharge, and a better long-term
effect was achieved at 6 months compared with the control group. An improvement in physical
function (e.g., the SPPB) after hospital discharge predicted follow-up mortality (odds
ratio ¼ 0.416, 95% confidence interval: 0.218–0.792).
Conclusion: Early cardiac rehabilitation appears to be an effective approach to improve the
physical function and survival of patients with heart valve surgery.
Keywords
Coronary artery disease, heart valve surgery, early cardiac rehabilitation, physical function,
mental health, short physical performance battery, exercise
Date received: 5 January 2021; accepted: 17 August 2021
Department of Cardiovascular Surgery, The First
Affiliated Hospital of Anhui Medical University, Hefei,
Anhui, China
Corresponding author:
Zheng Xiaoyan, Department of Cardiovascular Surgery,
The First Affiliated Hospital of Anhui Medical University,
120 Wanshui Road, High-tech Zone, Hefei City, Anhui
Province, 230000, China.
Email: 3530175086@qq.com
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attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
2
The trial was retrospectively registered in
the ISCTRN database (reference number:
ISRCTN54158701).
Introduction
Valvular heart disease is a major and growing public health issue accompanied by
population aging and a lengthy life expectancy in developing countries. Heart valve
surgery is a well-established procedure
worldwide with excellent cardiovascular
benefits, quality of life, and mortality
rates.1 However, patients who have heart
valve surgery often experience complications in the postoperative period because
of the complexity of the procedure, including low cardiac output syndrome, postoperative bleeding, infection, and difficulty in
glycemic control.2,3
Complications in the postoperative
period of heart valve treatment increase
sedation and bed rest,4 leading to an
extended period of physical inactivity and
muscle weakness.5 The harmful effects of
physical inactivity involve reduced muscle
protein synthesis, increased proteolysis,
and loss of muscle strength and lean
mass.6–8 These issues prevent patients
from fully returning to a normal functional
ability8 and increasing the risk of readmission and mortality.9,10
The importance of adequate physical
activity has been stressed by clinical guidelines.11 Physical activity and exercisebased cardiac rehabilitation are thought to
increase cardiorespiratory fitness and
reduce long-term cardiac mortality and
short-term hospitalization in patients with
coronary heart disease.12–14 Additionally,
physical exercise is associated with reduced
respiratory complications, decreased loss of
muscle strength, and a decline in hospital
readmission rates in patients with coronary
heart disease.15–17 Therefore, exercise-based
cardiac rehabilitation is recommended after
Journal of International Medical Research
heart valve surgery to increase physical
capacity and improve clinical outcomes.
Maintaining adequate physical activity
for patients who have heart valve surgical
treatment may be challenging and causes
safety issues outside the hospital.
Therefore, exercise-based cardiac rehabilitation should be considered in these
patients. Recently, early cardiac rehabilitation was applied to patients with cardiac
surgery in the in-hospital setting,18 and it
decreased the duration of the hospital stay
and medical costs after cardiac surgery.19,20
However, the role of early cardiac rehabilitation on physical and psychological functions and its long-term effects on patients
who have heart valve surgery have not
been fully determined.
This study aimed to investigate the role
of early cardiac rehabilitation in physical
and psychological function and its longterm effects in patients with heart valve surgery. Early cardiac rehabilitation was
performed in the hospital setting on the
day after the operation.
Methods
Participants
The was a prospective study that was performed in a hospital setting. The sample
size was calculated by the difference between
two independent means (two groups) using
G*Power software (version 3.1.9.7; HeinrichHeine-University, Düsseldorf, Germany),21
using the following parameters: alpha ¼
0.05, power (1b) ¼ 0.80, and effect
size ¼ 0.7. The sample size was determined
to be 37 patients or more in each group.
Considering a possible dropout of 10%,
the final sample size was determined to be
40 patients or more in each group. Ninetyseven consecutive patients who had heart
valve surgery performed were enrolled in
the study between January 2018 and
December 2019 (Figure 1). The inclusion
Xinlan et al.
3
Figure 1. Flowchart showing patient selection for participation in early cardia rehabilitation.
criteria were elective left-sided or rightsided heart valve surgery, including aortic,
mitral, tricuspid, and pulmonary valve
replacement, >18 years old, and being
able to understand and complete measurements and provide informed written
consent. One experienced physician performed the assessment for eligibility. The
exclusion criteria were ischemic heart disease before surgery, diseases in the musculoskeletal system, comorbidity complicating
physical activity, and an expectation to not
4
cooperate in the trial instructions. Patients
who had persistent or paroxysmal atrial
fibrillation diagnosed by Holter electrocardiography preoperatively were excluded
from this study. Patients who underwent
an emergency surgical treatment or transcatheter aortic valve implantation were
also excluded. The study was approved by
the Medical Ethics Committee of Anhui
Medical University (Hefei City, China;
January 4, 2018; approval number:
AHMULS20180465) and complied with
the Declaration of Helsinki. The trial was
retrospectively registered in the ISCTRN
database (ISRCTN54158701, http://www.
isrctn.com/).
Randomization
The early cardiac rehabilitation program
was conducted in a randomized, controlled
trial (RCT), which followed the CONSORT
statement (http://www.consort-statement.
org/). Patients were grouped by simple
random sampling. The randomization program was created using a computer and
performed by an investigator who was not
involved in the treatment and recruitment
of patients. The allocation of patients was
screened, and allocations were placed in
numbered, sealed, opaque envelopes. On
the first day of treatment after surgery,
the envelope that was allocated to the
patient was unfolded by the physical therapist. Patients were randomly assigned to
two groups of those who received cardiac
rehabilitation (intervention group) or
those who received the usual care (control
group). Before surgery (baseline), at hospital discharge, and after 6 months of followup, the physical capacity and psychological
status were measured. Blinding of the participants and clinicians is usually inconceivable in a rehabilitation trial. Nonetheless,
outcome assessment, data management,
and statistical analyses were performed
with blinding to the allocation groups.
Journal of International Medical Research
Intervention and controls
Implementation of this study followed the
StaRI statement of the Equator Network
guideline
(https://www.equator-network.
org/). The intervention group underwent
the cardiac rehabilitation program from
the day following surgery in accordance
with a clinical guideline for rehabilitation
in patients with cardiovascular disease.22
This rehabilitation exercise program comprised lower and upper extremity exercise
in bed, sitting on the edge of the bed, standing at the bedside, and walking around the
bed and for 100 m in the ward. The exercise
included four sessions lasting for 4 days,
three times a day, with approximately 30
minutes each time. After the rehabilitation
exercise, patients continued with gait practice for up to 500 m and carried out endurance training by using a stationary bike in
the rehabilitation center of the hospital. The
training session took place three times a day
with approximately 30 minutes each time
until they were discharged from the hospital. The intensity of physical activity was
limited by clinical conditions and activity
tolerance, and monitored and assisted by
physical therapists. The control group did
not participate in any rehabilitation program and only received routine clinical
care during the duration of the hospital
stay.22
Data collection
The investigators assessed all patients on
the day before surgery (baseline assessment), the day of hospital discharge, and
6 months after hospital discharge.
Primary measurement: physical function. The
Short Physical Performance Battery
(SPPB) was used to evaluate physical function.23 The SPPB is a useful and wellestablished tool for assessing the physical
ability of elderly people,.24 The SPPB
Xinlan et al.
consists of a timed 4-minute walking test, a
five-repetition sit-to-stand test, and a set of
standing balance.23 Each measurement was
assigned a score ranging from 0 to 4. The
total scores (0–12) were used to obtain an
overall measurement of physical function.
The SPPB is advantageous and has been
widely used in the clinical setting.25,26
Secondary measurement: mental health. The
mental health of patients was measured
with a mental component summary
(MCS) from the 12-item Short-Form
Health Survey,27 as recommended by a previous study.28
Six-minute walking test and other physical and
mental measurements. We performed the
6-minute walking test (6MWT), which
involved measurement of the 6-minute
walking distance and is a submaximal functional test indicative of performing daily
activities.29 The safety and feasibility of
this test have led to its use in cardiovascular
rehabilitation.30 The physical component
summary (PCS) from the 12-item ShortForm Health Survey and the Hospital
Anxiety and Depression Scale were also
included as self-reported measurements.
Outcome measurements: readmission and
mortality. After 6 months of hospital discharge, all-cause readmission and mortality
as outcome measurements were collected
from the clinical records and follow-up
investigation by the research team.
Statistical analysis. The intention-to-treat
analysis was recommended in the RCT.31
For outcomes of patients who withdrew
from the trial, an intention-to-treat analysis
was performed using the last value (e.g., at
the time point of hospital discharge)
obtained for each of the outcome measures.
Finally, normality was examined by the
Kolmogorov–Smirnov test. Data are
expressed as mean with standard deviation
5
for continuous variables (e.g., SPPB, PCS,
MCS, and 6MWT) and as the frequency
and percentage for categorical variables
(e.g., sex, type of valve, readmission, and
mortality). Group comparisons of categorical variables were carried out with the chisquare test. Comparisons of continuous
variables between the two groups were performed using the independent sample t-test
and repeated analysis of variance. Age, sex,
the length of hospital stay, and types of surgery were selected as confounding factors.
Differences with a two-sided p value
of 0.50,
which indicated a moderate clinical effect
and a long-term effect.
Similarly, physical outcomes, including
the PCS score and 6MWT distance,
showed a significant improvement in the
intervention group at hospital discharge
and at 6 months of follow-up compared
with those at baseline (Table 2). In addition, the intervention group showed a
shorter length of stay in the hospital compared with that in the control group
(t ¼ 8.30, p < 0.001; Table 3). However, the
Hospital Anxiety and Depression Scale and
MCS scores were not significantly different
between the two groups at different time
points (Table 2).
Effect of variables on outcomes
In regression analysis, age, sex, the type
of surgery, and physical functional
10.18 1.28
0.001
51.30 8.84
0.299
50.16 6.47
0.292
360.36 60.26
0.000
5.05 1.29
0.761
4.86 1.25
0.927
8.86 1.52
0.684
40.66 5.64
0.417
46.45 7.04
0.329
311.52 54.98
0.326
5.23 1.16
0.335
4.77 1.61
0.827
10.11 1.70
0.023
51.16 8.70
0.001
51.75 8.05
0.110
415.50 65.68
0.004
5.16 1.75
0.512
4.70 1.13
0.961
After
6 months
(n ¼ 40)
8.74 1.83
–
40.63 5.32
–
47.58 7.16
–
309.58 57.44
–
4.91 1.23
–
4.93 1.55
–
Baseline
(n ¼ 43)
Control group
9.09 1.38
–
45.91 7.18
–
48.79 7.19
–
316.56 61.14
–
5.00 1.16
–
4.86 1.11
–
Hospital
discharge
(n ¼ 43)
8.95 1.70
–
45.56 7.38
–
48.14 8.47
–
367.77 54.69
–
5.12 1.61
–
4.60 1.28
–
After
6 months
(n ¼ 34)
0.002
0.002
0.283
1 repeated measure over
time were analyzed using a generalized estimating equations model. When findings were significant, we applied
Bonferroni’s post hoc test. Analyses of outcomes such as
the 6MWD were corrected for age, while maximal inspiratory pressure (MIP) and maximal expiratory pressure were
corrected for both age and sex. The significance level was
set at P .05). Table 1 also provides
pre-operative and post-operative data for the study sample.
Mean length of intensive care unit (ICU) stay was longer
in the control group than in the other 3 groups. No such
difference was observed for overall length of hospital stay,
which was similar across all 4 groups (Table 1).
Table 2 presents the primary and secondary outcomes
of interest by group. Analysis of the mean values for the
6MWD shows that the greatest impairment in functional capacity from baseline in the immediate post-operative
period was seen in G3 and G4 as compared with G1 and
G2. On analysis of this variable in the late post-operative
period (30 d after hospital discharge), patients in G4 (control) were found to have experienced the least amount of
recovery. However, despite a lower functional capacity than
patients in other groups, within-group comparison showed
that control-group participants were able to achieve 6MWD
values similar to their pre-operative baseline. In turn, all other groups experienced a significant improvement in functional capacity from baseline, as measured by the 6MWT. The
progression of 6MWD in the 4 study groups at the 3 time
points of assessment is illustrated in Figure 2.
Table 2 also shows lung capacity outcome measures.
All behaved similarly across the groups throughout the
follow-up period, with no significant between-group differences for any measure. However, all groups exhibited a significant decline from baseline in lung capacity
www.jcrpjournal.com
measures in the immediate post-operative period. In the
late post-operative period (day 30 after hospital discharge),
only group 3 failed to show significant recovery in relation
to the immediate post-operative period (day 6 post-CABG).
Like pulmonary function measures, respiratory muscle
function parameters did not differ across groups. On analysis of MIP, only group 2 did not exhibit any significant
decline in performance in the immediate post-operative period. However, 30 d after hospital discharge, values in all
groups were similar to baseline levels. Regarding maximal
expiratory pressure, all groups exhibited significant loss of
expiratory muscle function in the immediate post-operative
period, but all had returned to baseline levels in the late
post-operative period.
Table 3 shows the main measurements from the CPET.
Notably, both G1 and G2 exhibited significantly higher peak
oxygen uptake (V̇o2) values than G3 and G4.
DISCUSSION
The main finding of this randomized controlled trial is that
groups that received protocols combining active physical
exercise and early ambulation experienced a more effective
recovery of functional capacity, both before hospital discharge and at 30 d after discharge. When implemented as
part of a structured ICR program, such rehabilitation strategies can serve as the cornerstone for the resumption of the
activities of daily living by post-CABG patients.
For many years, protocols used in clinical studies of
inpatient rehabilitation after cardiac surgery were based
predominantly on respiratory therapy techniques.9,14,24 Evidence shows that the combination of active upper limb or
lower limb exercise and early ambulation can provide benefits beyond prevention of thromboembolism or of range
of motion limitation.25 Early mobilization seems to be important to prevent post-operative complications, improve
functional capacity, and reduce length of hospital stays in
patients after cardiac surgery.26
In 2008, Hirschhorn et al11 conducted a randomized
controlled trial evaluating the effects of intervention on
Inpatient CR After Coronary Artery Bypass Graft Surgery    E21
Copyright © 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Table 1
Patient Characteristics (Pre-operative, Intraoperative, and Post-operative) in All Groupsa
Anthropometric data
Age, yr
BMI, kg/m2
Male
Risk factors
  Sedentary lifestyle
  Tobacco smoking
  Diabetes
  Hypertension
Pre-operative data
Creatinine, mg/dL
Angina class
  I
  II
  III
NYHA class
  Class 1
  Class 2
  Class 3
ASA class
  II
  III
  IV
Intraoperative data
Operative time, min
Ischemic time, min
On-pump time, min
Number of grafts
Post-operative data
IMV time, hr
Length of ICU stay, d
Length of hospital stay, d
Atrial fibrillation
Group 1 (n = 10)
Group 2 (n = 10)
Group 3 (n = 10)
Group 4 (n = 10)
58 ± 5
28 ± 2.9
9 (90)
56 ± 7
26 ± 3.8
7 (70)
59 ± 8
28 ± 3.7
6 (60)
61 ± 5
28 (4.2)
7 (70)
7 (70)
8 (80)
3 (30)
8 (80)
8 (80)
9 (90)
7 (70)
8 (80)
7 (70)
7 (70)
6 (60)
9 (90)
9 (90)
7 (70)
3 (30)
7 (70)
0.98 ± 0.19
0.99 ± 0.25
1.1 ± 0.4
0.95 ± 0.34
2 (20)
4 (40)
4 (40)
0 (0)
9 (90)
1 (10)
1 (10)
6 (60)
3 (30)
3 (30)
4 (40)
3 (30)
2 (20)
4 (40)
4 (40)
1 (10)
7 (70)
2 (20)
1 (10)
7 (70)
2 (20)
0 (0)
5 (50)
5 (50)
1 (10)
8 (80)
1 (10)
3 (30)
5 (50)
2 (20)
3 (30)
6 (60)
1 (10)
3 (30)
4 (40)
3 (30)
180 ± 33
39 ± 13
56 ± 17
3 ± 0.9
158 ± 27
33 ± 10
50 ± 14
3 ± 0.9
167 ± 42
40 ± 17
60 ± 24
3 ± 0.8
174 ± 51
44 ± 16
67 ± 24
3 ± 0.5
8 ± 3.3
3 ± 0.5
7 ± 0.7
2 (20)
9 ± 5.9
3 ± 0.3
6 ± 0.8
1 (10)
11 ± 5.9
3 ± 0.5
7 ± 0.6
2 (20)
11 ± 3.9
4 ± 0.9b
8±3
3 (30)
Abbreviations: ASA, American Association of Anesthesiologists; BMI, body mass index; ICU, intensive care unit; IMV, intermittent mandatory ventilation; NYHA, New York Heart Association.
a
Data reported as mean ± standard deviation or number (%).
b
P < .05 compared with the other groups.
functional capacity. In this experiment, the authors assessed moderate-intensity exercise programs, combined or
not with respiratory exercises, and found improvements in
functional capacity as measured by 6MWD at discharge.
However, at 30 d after discharge, there was no significant
difference between groups. This finding differs from that of
the present study at 30 d post-discharge, in which patients
who received conventional CPT alone performed poorly as
compared with the other groups that received active exercise and early ambulation. It is noteworthy that Oliveira
et al27 demonstrated that the type of surgery, cardiopulmonary bypass time, functional independence measure, and
body mass index were determinants of 6MWD at hospital discharge in patients undergoing cardiac surgery. As
all groups evaluated by us were homogeneous in terms of
clinical and surgical variables, we consider that the impact
observed in the intervention groups is attributable to the
protocols performed.
Two other randomized controlled trials13,28 that also
employed ICR protocols of progressive walking plus active exercise, with usual care as a comparator, validate
our findings. In these studies, patients exhibited improvement in functional capacity both before discharge and on
day 30 after discharge. Stein et al13 found that 30 d after
discharge, V̇o2 peak was higher in the intervention group
(CPT with EPAP plus active upper and lower limb exercise
plus ambulation) than in the control group (no physical
therapy). In this study, the authors postulated that physiological adaptations induced by exercise might relieve
pain in the saphenous vein donor limb and thus facilitate
improved performance on functional tests.13 Furthermore,
the superior performance of such rehabilitation protocols
may also be attributed to optimization of oxygen transport secondary to increased ventilation and improved ventilation/perfusion ratio. In this context, ambulation would
serve as a gravitational stimulus capable of restoring the
normal distribution of extravascular fluid, thus mitigating
the effects of immobility.29 It is entirely plausible that a
combination of such effects would have a positive impact
on functional capacity.
Impaired lung function is a frequent occurrence after
CABG surgery and, throughout the present study, outcome
measures of lung capacity and respiratory muscle function
did not differ across groups. All groups derived benefit
from the physical therapy protocols administered during
the intervention, including the control group, which also
E22    Journal of Cardiopulmonary Rehabilitation and Prevention 2019;39:E19-E25
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Copyright © 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Table 2
Measures of Functional Capacity (6MWD) and Lung Capacity for Patients in All Groupsa
6MWD, m
Pre-operative baseline
PO6
PD30
FVC, % predicted
Pre-operative baseline
PO6
PD30
FEV1, % predicted
Pre-operative baseline
PO6
PD30
MIP, cm H2O
Pre-operative baseline
PO6
PD30
MEP, cm H2O
Pre-operative baseline
PO6
PD30
Group 1
Group 2
Group 3
Group 4
398 (21)A
365 (23)A,ce
531 (23)B,de
419 (20)A
401 (20)A,c
531 (16)B,e
384 (22)A
275 (23)B,d
471 (14)C,cd
423 (17)A
291 (22)B,de
433 (14)A,c
90.4 (3.7)A
65.8 (3.6)B
82.6 (4.0)C
94.8 (3.3)A
67.6 (2.6)B
83.5 (2.7)C
96.8 (5.0)A
73.2 (5.2)B
82.6 (4.5)B
100.4 (3.6)A
61.8 (5.6)B
85.3 (4.6)C
91.3 (2.9)A
67.0 (3.1)B
82.1 (4.4)C
94.7 (3.2)A
65.0 (2.6)B
80.8 (3.2)C
93.5 (5.1)A
68.9 (5.0)B
75.9 (4.1)B
97.7 (3.7)A
59.3 (5.9)B
80.7 (4.5)C
91.7 (11.2)A
62.8 (8.6)B
87.5 (8.6)A
88.8 (8.9)AB
68.2 (11.1)A
92.4 (10.8)B
89.5 (8.5)A
68.0 (6.7)B
85.3 (9.3)A
87.1 (4.4)A
65.7 (7.3)B
76.0 (5.9)AB
124.9 (14.0)A
89.2 (10.7)B
121.8 (11.1)A
105.2 (12.8)A
83.6 (14.4)B
113.5 (9.5)A
123.0 (13.9)A
100.1 (13.2)B
115.3 (10.6)AB
114.4 (11.3)A
92.3 (12.2)B
98.8 (12.6)AB
P Value (G)b
P Value (T)b
P Value (G  T)b