EURO PEAN

SO CIETY O F
Review CARDIOLOGY ®

European Journal of Preventive

Cardiology

Cardiac rehabilitation programme after 2017, Vol. 24(7) 688–697

! The European Society of
Cardiology 2017
transcatheter aortic valve implantation Reprints and permissions:
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versus surgical aortic valve replacement: DOI: 10.1177/2047487316686442
journals.sagepub.com/home/ejpc
Systematic review and meta-analysis

Gustavo S Ribeiro1, Rosangela D Melo1, Luı́s F Deresz1,2,

Pedro Dal Lago1,3, Mauro RN Pontes4,5 and Marlus Karsten1,6

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Abstract
Background: Aortic stenosis is a valvular heart disease characterised by fixed obstruction of the left ventricular
outflow. It can be managed by surgical aortic valve replacement (sAVR) or transcatheter aortic valve implantation
(TAVI). This review aimed to describe the evidence supporting a cardiac rehabilitation programme on functional capacity
and quality of life in aortic stenosis patients after sAVR or TAVI.
Methods: The search was conducted on multiple databases from January to March 2016. All studies were eligible that
evaluated the effects of a post-interventional cardiac rehabilitation programme in aortic stenosis patients. The meth-
odological quality was assessed using the PEDro scale. Meta-analysis was performed separately by procedure and
between procedures. The walked distance during the six-minute walk test (6MWD) and Barthel index were evaluated.
The analysis was conducted in Review Manager.
Results: Five studies were included (292 TAVI and 570 sAVR patients). The meta-analysis showed that a cardiac
rehabilitation programme was associated with a significant improvement in 6MWD (0.69 (0.47, 0.91); P < 0.001) and
Barthel index (0.80 (0.29, 1.30); P ¼ 0.002) after TAVI and 6MWD (0.79 (0.43, 1.15); P < 0.001) and Barthel index (0.93
(0.67, 1.18); P < 0.001) after sAVR. In addition, the meta-analysis showed that the cardiac rehabilitation programme
promoted a similar gain in 6MWD (4.28% (12.73, 21.29); P ¼ 0.62) and Barthel index (1.52 points (4.81, 1.76);
P ¼ 0.36) after sAVR or TAVI.
Conclusions: The cardiac rehabilitation programme improved the functional capacity and quality of life in aortic stenosis
patients. Patients who underwent TAVI benefitted with a cardiac rehabilitation programme similar to sAVR patients.

Keywords
Aortic valve stenosis, transcatheter aortic valve implantation, surgical aortic valve replacement, exercise, cardiac
rehabilitation
Received 13 October 2016; accepted 6 December 2016

1
Programa de Pós-graduação em Ciências da Reabilitação, Universidade
Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil
2
Departamento de Educação Fı́sica, Universidade Federal de Juiz de Fora
Introduction (UFJF), Brazil
3
Aortic stenosis (AS) is the most common acquired Departamento de Fisioterapia, UFCSPA, Brazil
4
Departamento de Farmacociências, UFCSPA, Brazil
valvular heart disease in the industrialised countries 5
Unidade de Pesquisa, Hospital São Francisco, Brazil
and affects more than 4% of North American and 6
Departamento de Fisioterapia, Universidade do Estado de Santa
European individuals older than 75 years.1,2 Catarina (UDESC), Brazil
Moreover, AS has been associated with higher morbid-
ity and mortality rates than other diseases involving Corresponding author:
cardiac valves.3 The mean survival in the symptomatic Marlus Karsten, Centro de Ciências da Saúde e do Esporte, Universidade
do Estado de Santa Catarina, Rua Pascoal Simone 358, 88080-350,
phase is 2–3 years.4 The main symptoms related to this Florianópolis, SC, Brazil.
disease are chest pain, weakness, syncope or dyspnoea Email: marlus.karsten@udesc.br
during and/or after performing basic activities of daily Twitter: @marluskarsten
Ribeiro et al. 689

living, decreasing functional independence and quality following electronic databases: PubMed, EMBASE,
of life.5 Surgical aortic valve replacement (sAVR) is the SCOPUS, Web of Knowledge, PEDro, Cochrane
procedure of choice for patients with symptomatic AS. Library and LILACS/BIREME. Relevant studies
However, a significant proportion of these patients has were identified using the following MeSH terms:
a high level of frailty, which increases the risk of com- aortic valve stenosis, transcatheter aortic valve implant-
plications and perioperative mortality. For these ation, aortic valve replacement, exercise, cardiac
patients, transcatheter aortic valve implantation rehabilitation, oxygen uptake and electric stimulation
(TAVI) has robust therapeutic potential.6 therapy. Bibliographies of the included studies and of
The PARTNER trial was the first large randomised the identified related papers were searched manually.
study that compared sAVR to TAVI in high-risk The search was limited to clinical trials with humans
patients (PARTNER cohort A) and showed that the over 18 years old and was not restricted by language.
death rates in both groups were similar (35% vs. The full search strategy can be reviewed in

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34%; P ¼ 0.31).7 In a second study, the authors evalu- Supplementary Appendix 1.
ated patients who were deemed ineligible for surgery
based on the prohibitive surgical risk (PARTNER
cohort B) and randomly assigned them for TAVI or
Eligibility criteria
medical treatment. The patients in the TAVI group All eligible studies evaluating the effects of CRP in AS
exhibited a significantly lower mortality rate at 3 patients after TAVI or sAVR were considered. There
years when compared to medical treatment (54% vs. was no limitation concerning sample size or study
81%; P < 0.001).8 In addition, it has been observed design, and the eligibility criteria did not enforce com-
that death in the medium and long term in the patients parisons with a control group. Studies published
who underwent TAVI was predominantly from non- between January 2000 and March 2016 were included,
cardiac causes.9 and no trial was excluded based on the presence of
A cardiac rehabilitation programme (CRP) may pro- distinct comorbidities at baseline. A priori, editorials
mote a positive impact in relevant clinical outcomes and reviews were deemed ineligible.
and is strongly recommended for patients after cardiac
surgery, especially in the elderly because of the high
Study selection
prevalence of comorbidities and frailty.9 Various stu-
dies that used different CRP intervention strategies The results of each search were exported to EndNote
investigating the safety and effects of CRP in patients X7 (Thomson Reuters, USA) and two reviewers (GSR
undergoing sAVR or TAVI have recently been pub- and RDM) assessed the title and abstract independ-
lished.10–14 However, available evidence on the efficacy ently. The full texts of all potentially eligible papers
and safety of a CRP after AS correction is very limited. were downloaded to determine their inclusion or exclu-
Therefore, the main purpose of this systematic review sion in accordance with the pre-established criteria.
and meta-analysis was to summarise the evidence on Disagreements were resolved by discussion with the
the impact of a CRP on functional capacity, exercise third assessor (LFD). If any disagreement remained,
tolerance and health-related quality of life in AS the senior researcher (MK) made the final decision.
patients after intervention either by sAVR or TAVI. The k coefficient was used to measure the level of agree-
ment between the reviewers taking into account the clas-
sification proposed by Landis and Koch.16 The authors
Methods provided a narrative synthesis of the included studies
containing the type of intervention, population charac-
Study design teristics and outcomes achieved.
A systematic review of studies comparing the effects of
a CRP in individuals with corrected AS undergoing
Data extraction and quality assessment
TAVI or sAVR was performed. This review followed
the recommendations of the preferred reporting items The data were extracted independently (GSR and
for systematic reviews and meta-analyses (PRISMA) RDM). We sought to extract information on: (a) coun-
statement.15 This project was previously registered on try of origin; (b) sample size; (c) baseline characteristics,
PROSPERO (CRD42015025038). including mean age, gender, body mass index, New
York Heart Association class, left ventricular ejection
fraction and EuroSCORE; (d) CRP characteristics
Data sources and search strategy
(modality of exercise, times per week, intensity and dur-
We conducted a systematic review, including papers ation); and (e) outcomes, featuring measures of func-
published from January 2000 to March 2016, with the tional capacity (e.g. oxygen uptake and/or workload)
690 European Journal of Preventive Cardiology 24(7)

and exercise tolerance (e.g. walked distance and exer- plotted the effect estimate by the inverse of its standard
cise time). Measures of secondary outcomes were also error. The symmetry of such ‘funnel plots’ was assessed
extracted – variables indicating effects on functional both visually and formally with Egger’s test to detect
independence (e.g. Barthel index (BI)) and functional possible publication bias. Review Manager version 5.3
independence measure (FIM)) and health-related qual- (Cochrane Collaboration, DNK) was employed for the
ity of life (e.g. hospital anxiety and depression scale statistical analyses and to produce both the funnel and
(HADS) or the EuroQoL visual analogue scale). forest plots.
Finally, we also collected reported data on all-cause
and cardiovascular mortality as well as safety out-
comes. After extraction, the data were summarised in Results
a previously standardised worksheet of Excel for
Search and selection
Windows 2010 (Microsoft Corporation, USA).

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The methodological quality of studies was assessed The systematic search retrieved 1364 references from all
by MRNP and PD using the PEDro scale. Briefly, on sources. Of these, 100 studies were from PubMed, 401
this scale, the reviewers indicated the presence or from EMBASE, 622 from SCOPUS databases, 155
absence of 11 quality measures. Considering that criter- from Web of Science, three from PEDro, 53 from the
ion 1 was not utilised to calculate the score, the sum of Cochrane Library’s basis, 30 from the LILACS/
the others may have led to a maximum of 10 points. BIREME databases and four from additional papers.
Trials with a score greater than or equal to 6 points After the exclusion of duplicates and initial screening
were classified as ‘high-quality trials’, while those with (reading title and abstracts), 19 potentially relevant stu-
a score equal to or lower than 5 points were graded as dies were identified. According to the study criteria, five
‘poor quality’.17 clinical trials were selected for qualitative analysis, all
of them being published in English. These five studies
had sufficient information for quantitative analysis
Statistical analysis (meta-analysis). Figure 1 shows the summary of the
The meta-analysis included the studies in which the search and selection process.
description of walked distance in the six-minute walk
test (6MWD) before and after a CRP were available in
Study characteristics
order to evaluate the effect size of a CRP after AS cor-
rection, and this was done separately for both TAVI The characteristics of the included studies are presented
and sAVR. Another meta-analysis comprised studies in in Table 1. All participants (TAVI 292, sAVR 570) were
which description of the BI before and after a CRP was selected consecutively in a non-probabilistic conveni-
available. For both analyses, we utilised the standar- ence sample and were allocated to a CRP. In general,
dised mean difference (SMD) before and after a CRP studies showed that patients undergoing TAVI were
(so-called standardised mean improvement) as the older, predominantly women and with a EuroSCORE
treatment effect estimate, with a 95% confidence inter- that was quite poor. Interestingly, European groups in
val (CI), using both fixed-effects and random-effects partnership with regional hospitals developed all
models. A SMD higher than 0.5 was considered a mod- selected studies. The greatest number of publications
erate, clinically relevant effect size.18 A SMD higher was from Italy,11,13,14 followed by Switzerland10 and
than 0.8 was determined to be a large, clinically rele- Germany.12
vant effect size.18
Afterwards, were performed a meta-analysis of the
studies comparing the magnitude of the effect of a post-
Cardiac rehabilitation programme
operative CRP in TAVI versus sAVR patients, both in The CRPs were performed mostly during the early
terms of the 6MWD and BI to establish whether a CRP phase following the procedure (26.9  18.7 days after
was more effective after surgical or transcatheter AS valve repair) and within a relatively short period
intervention. In this analysis, we assessed the crude, (2.75  0.45 weeks). In four studies, the CRP length
non-standardised difference between groups as the was 3 weeks,10,12–14 while one trial reported a shorter
treatment-effect estimate, with 95% CI, using a fixed length (2 weeks).11 Training frequency ranged from
or random-effects models based on the heterogeneity four to six times per week. In certain studies, the train-
of the studies. ing programme was carried out at up to two13 or
Statistical I2 was calculated to assess the heterogen- three10 sessions per day. Two studies did not address
eity of the studies included. An I2 score above or near the intensity prescription,12,14 while three studies
50% was considered indicative of heterogeneity. In reported the use of the BORG scale to control exercise
order to test for publication bias, for each trial, we intensity.10,11,13 Although there was no difference
Ribeiro et al. 691

Identification
Records identified through Additional records identified
database searching through other sources
(n = 1364) (n = 4)

Records duplicates removed

(n = 273)
Screening

Records screened 1076 records were

(n = 1095) excluded

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Eligibility

19 full-text articles 14 Full-text articles were excluded

assesed for eligibility
• Letter to the editor (n = 1)

• Not AS patients (n = 2)

• CRP not described (n = 4)

5 studies included in
qualitative synthesis • Case reports (n = 3)
Included

• Rehabilitation pre valve repair (n = 2)

• Update studies (n = 2)
4 studies included in
quantitative synthesis

Figure 1. Flowchart of the selection of trials included in this systematic review.

AS: aortic stenosis; CRP: cardiac rehabilitation programme.

between the cardiac rehabilitation protocols in the regardless of the procedure (sAVR or TAVI) and the
sAVR and TAVI groups (within studies), the employed treatment of choice (type, frequency and intensity). In
interventions differed among studies. Generally, they two studies,10,12 all patients were able to complete the
included exercises for endurance training (cycle or entire CRP, and there was no report of dropouts,
treadmill),10–14 resistance training10–12,14 and/or adverse events or major complications. In one
inspiratory muscle training.10,11,13 The characteristics study,11 there was a very low (1.1%) rate of acute
of each study are summarised in Table 2. non-fatal complications that required transference to
the surgical centre (one TAVI patient and one sAVR
patient). In another study,13 in spite of the fact that
Quality assessment TAVI patients were older and more functionally
The agreement level of the reviewers was 0.88 (95% CI impaired than sAVR patients, the CRP was safe for
0.76–0.99). The PEDro scale oscillated from 3 to 5 both groups with no report of adverse events related
points (see Supplementary data). Thus, the methodo- to the CRP; however, TAVI patients, when compared
logical quality of those studies in general was poor with sAVR patients, tolerated a lower workload, had a
(4.0  0.7 points).16 The trials included in the meta-ana- worse BI score and were frailer at discharge.
lysis were scored at three,13 four10,12 and five points.11 Subsequently, at the mid-term follow-up, the patients
A study investigating only TAVI patients had a score of from the TAVI group presented higher mortality com-
four points.14 Overall, no study described a random pared to the sAVR group (19% vs. 6%; P < 0.05). In
allocation process beyond the blinding of subjects, ther- one study evaluating the effects of CRP exclusively in
apists and assessors. The methodological qualities of patients undergoing TAVI,14 these patients were very
each study are shown in Supplementary Appendix 2. frail, dependent and functionally impaired, with a high
risk of clinical complications. In fact, one-third of the
patients evolved with clinical complications; only three
Safety of a CRP in AS patients
patients (5%) required transference to an acute care
The data indicated that a CRP was a safe and effective facility. Generally, no patient died during the cardiac
form of treatment for patients undergoing valve repair, rehabilitation period. These data suggest that
692 European Journal of Preventive Cardiology 24(7)

12  9 25  14 <0.001
P value
in patients with AS, those submitted to TAVI were

–
older and sicker than those submitted to sAVR, but
for both groups, the postoperative rehabilitation pro-

22  13
TAVI

–
EuroSCORE

grammes were safe.

sAVR: surgical aortic valve replacement; TAVI: transcatheter aortic valve implantation; BMI: body mass index; NYHA: New York Heart Association; LVEF: left ventricular ejection fraction.
P value sAVR

–
Effect of CRP on exercise tolerance and functional

–
independence after TAVI
57  8 56  11 0.55

57  9 0.38
–

–
The data for the 6MWD were available for all five
trials, which reported data for 286 patients before a
TAVI

CRP and 291 patients after a CRP (Figure 2(a)). The

–
–

–
LVEF (%)

mean walked distance before a CRP was 186  86 m,

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56  8
P value sAVR

increasing to 257  111 m following a CRP. In the

–

pooled analysis, CRP after TAVI was associated with

–

a significant 6MWD standardised mean improvement

1.9  0.8 2.2  0.8 0.003
2.7  0.8 2.9  0.8 0.22

3.0  0.2 2.9  0.3 0.40

(0.69 (0.47, 0.91); P < 0.001), suggesting a moderate,

clinically relevant effect size.18 There was no evidence
1.8  0.4

for significant heterogeneity between studies (I2 ¼ 40%;

–
TAVI
NYHA classes

P ¼ 0.16).
The data for the BI scoring were available for three
P value sAVR

trials, which reported data for 190 patients before a

–

CRP and 195 patients after a CRP (Figure 2(b)).

The mean BI score before a CRP was 77  19, increas-
27.6  6.1 28.2  5.4 0.66

26.0  3.8 24.7  3.7 0.14

58% <0.001 27.2  4.7 26.1  4.4 0.06

–

ing to 90  14 after a CRP. In the pooled analysis, a

CRP subsequent to TAVI was associated with a signifi-
25.2  4.5

cant BI standardised mean improvement (0.80 (0.29,

–
TAVI

1.30); P ¼ 0.002), indicative of a large, clinically rele-

vant effect size.18 We did detect a significant heterogen-
BMI (kg/m2)

eity across studies with this comparison (I2 ¼ 83%;

–

–
P value sAVR TAVI P value sAVR

P ¼ 0.002). However, we felt that all three studies

pointed in the same direction, showing a significant
0.78

0.10

0.07

standardised mean improvement in BI scoring after a

Table 1. Characteristics of studies included in the methodological analysis.

CRP in patients submitted to TAVI. In addition, a

sensitivity analysis using a fixed-effects model demon-
62%

68%

75%

53%
female (%)

strated very similar results that also featured a

Gender

BI standardised mean improvement (0.74 (0.53, 0.95);

0.001 59%

50%

66%

68  11 80  6 <0.001 34%

P < 0.001).
0.06

Effect of CRP on exercise tolerance and functional

78  6 82  5

81  3 83  4

82  4 86  5

83  5

independence after sAVR

TAVI
Age (years)

The data for the 6MWD were available for four trials,
which included post-sAVR patients; they reported data
sAVR TAVI sAVR

for 570 patients before a CRP and 570 patients after a

CRP (Figure 3(a)). The mean walked distance before
34

64

58

76

60

a CRP was 228  94 m, rising to 315  122 m after a

size (n)
Sample

CRP. In the pooled analysis, a CRP after sAVR was

366
78

74

52

associated with a significant 6MWD standardised mean

Switzerland

improvement (0.93 (0.81, 1.05); P < 0.001). There was

Germany
Country

evidence for significant heterogeneity between studies

Italy

Tarro-Genta Italy

Italy

(I2 ¼ 84%; P < 0.001), leading us to perform a

random-effects model meta-analysis. This analysis indi-
cated a significant 6MWD standardised mean improve-
Fauchère

Zanettini
(2014)

(2014)

(2015)

(2015)

(2014)
Russo
(year)

Völler

ment (0.79 (0.43, 1.15); P < 0.001), a large, clinically

Study

relevant effect size.18

Ribeiro et al. 693

Table 2. Characteristics of cardiac rehabilitation programme and main findings.

Main
Study (year) Modality Frequency Intensity findings

Fauchère (2014) Gymnastic Daily: 2–3/day Low/medium sAVR
6MWD (82.8  65.1 m);

FIM (12.2  10.9)
Aerobic exercise Weekly: 6/week BORG scale TAVI
6MWD (84.2  68.7 m);

FIM (9.9  6.1)
Respiratory workout Length: 3 weeks
Russo (2014) 30 min of IMT followed Daily: 1/day Low/medium sAVR
6MWD (72.3  57.3 m);
cycling on the morning
Barthel index (10.6  13.2)
30 min callisthenic exercise Weekly: 6/week 70% HRM predict TAVI
6MWD (60.4  46.4 m);

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in the afternoon
Barthel index (9.3  12.3)
Length: 2 weeks BORG scale
Tarro-Genta 30 min of cycling or treadmill Daily: 2/day Low/medium sAVR
6MWD (98  95 m);
(2015) starting at minimum
Barthel index (20  16)
workload
30 min of respiratory training Length: 3 weeks BORG scale (14) TAVI
6MWD (94  86 m);

Barthel index (18  15)
Völler (2015) Gymnastics in groups or Daily: 1/day Not described sAVR
6MWD (136.9  135.4 m);
single
ExCap (18.5  30.8 Watts);

HADS (–1.2  3.6)
Cycle and outdoor walking Weekly: 6/week TAVI
6MWD (73.8  89.9 m);

ExCap (10.6  30.3 Watts)
Resistance training Length: 3 weeks
Zanettini (2014) Ambulatory training Daily: 1/day Not described TAVI
6MWD (65  92 m);

Barthel index (11.0  15.5);

EQ-VAS (21.0  12.5)
Bed and sitting exercises Weekly: 6/week
Cycle ergometer/treadmill Length: 3 weeks
Calisthenics exercises
sAVR: surgical aortic valve replacement; 6MWD: six-minute walk distance; FIM: functional independence measure; TAVI: transcatheter aortic valve
implantation; IMT: inspiratory muscle training; HRM: maximal heart rate; ExCap: maximal exercise capacity; HADS: hospital anxiety and depression
scale; EQ-VAS: EuroQoL visual analogue scale.

The data for the BI were available for two trials, improvement with respect to the HADS.12 One study
which reported data for 132 patients before a CRP did not demonstrate any changes in HADS after the
and 132 patients after a CRP (Figure 3(b)). The mean CRP in both groups10 (Table 2).
BI score before a CRP was 80  21, increasing to 95  9 The data for studies comparing the effect of a CRP
after a CRP. In the pooled analysis, CRP after sAVR in TAVI versus sAVR patients for the 6MWD were
was associated with a significant BI standardised mean available for four studies. They altogether reported
improvement (0.93 (0.67, 1.18); P < 0.001), a large, clin- data for 570 sAVR patients and 232 TAVI patients
ically relevant effect size.18 There was no evidence for (Figure 4(a)). The mean additional improvement in
heterogeneity across studies within this comparison 6MWD after a CRP in sAVR patients was 42  37%
(I2 ¼ 0%; P ¼ 0.72). (97  88 m) and 50  45% (78  73 m) in TAVI
patients, without difference between procedures in the
Comparison of effects of CRP in TAVI versus pooled analysis (4.28% (12.73, 21.29); P ¼ 0.62).
There was evidence for high heterogeneity among stu-
sAVR patients dies (I2 ¼ 81%; P ¼ 0.001).
Both groups exhibited improved exercise tolerance Despite its greater diagnostic precision, the cardio-
(6MWD),10–12,14 functional independence (BI11 and pulmonary exercise test was used in only one study,
FIM10 and maximal exercise capacity (workload)12 after performing valve repair procedures.11 Although
after a CRP, but only the sAVR group showed it was not possible to evaluate the cardiovascular,
694 European Journal of Preventive Cardiology 24(7)

(a) After CRP Before CRP Std. Mean Difference Std. Mean Difference
Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
Fauchère et al. 2014 232 133 34 147 102 34 14.3% 0.71 [0.22, 1.20]
Russo et al. 2014 273 108 64 241 95 64 22.2% 0.31 [–0.04, 0.66]
Tarro-Genta et al. 2015 168 131 58 74 58 58 19.9% 0.92 [0.54, 1.31]
Völler et al. 2015 336 86 76 262 90 76 23.5% 0.84 [0.50, 1.17]
Zanettini et al. 2014 275 97 59 210 87 54 20.1% 0.70 [0.32, 1.08]

Total (95% CI) 291 286 100.0% 0.69 [0.47, 0.91]

Heterogeneity: Tau2 = 0.02; Chi2 = 6.66, df=4 (P= 0.16); I2 = 40%
–2 –1 0 1 2
Test for overall effect: Z= 6.16 (P < 0.00001)
6MWD worsening 6MWD improvement

(b)
After CRP Before CRP Std. Mean Difference Std. Mean Difference

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Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
Russo et al. 2014 90 17 78 81 24 78 34.9% 0.43 [0.11, 0.75]
Tarro-Genta et al. 2015 84 15 58 66 12 58 32.2% 1.32 [0.91, 1.72]
Zanettini et al. 2014 95 10 59 84 21 54 32.9% 0.67 [0.29, 1.05]

Total (95% CI) 195 190 100.0% 0.80 [0.29, 1.30]

2 2 2
Heterogeneity: Tau = 0.17; Chi = 11.63, df=2 (P= 0.003); I = 83%
–2 –1 0 1 2
Test for overall effect: Z= 3.07 (P = 0.002)
BI worsening BI improvement

Figure 2. Forest plot of the standardised mean improvement on (a) six-minute walked distance and (b) Barthel index in post-TAVI
patients after a CRP.
TAVI: transcatheter aortic valve implantation; CRP: cardiac rehabilitation programme; SD: standard deviation; CI: confidence interval.

(a)
After CRP Before CRP Std. Mean Difference Std. Mean Difference
Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
Fauchère et al. 2014 283 117 78 201 96 78 24.5% 0.76 [0.44, 1.09]
Russo et al. 2014 294 101 74 260 98 74 24.5% 0.34 [0.02, 0.66]
Tarro-Genta et al. 2015 249 132 52 151 80 52 22.1% 0.89 [0.49, 1.30]
Völler et al. 2015 437 140 366 301 102 366 28.9% 1.11 [0.95, 1.26]

Total (95% CI) 570 570 100.0% 0.79 [0.43, 1.15]

2 2 2
Heterogeneity: Tau = 0.11; Chi = 18.84, df=3 (P= 0.0003); I = 84%
–2 –1 0 1 2
Test for overall effect: Z= 4.29 (P < 0.0001)
6MWD worsening 6MWD improvement

(b) After CRP Before CRP Std. Mean Difference Std. Mean Difference
Study or Subgroup Mean SD Total Mean SD Total Weight IV, Fixed, 95% CI IV, Fixed, 95% CI
Russo et al. 2014 98 4 80 88 14 80 60.2% 0.97 [0.64, 1.29]
Tarro-Genta et al. 2015 92 14 52 72 29 52 39.8% 0.87 [0.47, 1.27]

Total (95% CI) 132 132 100.0% 0.93 [0.67, 1.18]

2 2
Heterogeneity: Chi = 0.13, df=1 (P= 0.72); I = 0%
–2 –1 0 1 2
Test for overall effect: Z= 7.16 (P < 0.00001)
BI worsening BI improvement

Figure 3. Forest plot of the standardised mean improvement on (a) six-minute walked distance and (b) Barthel index in post-sAVR
patients after a CRP.
sAVR: surgical aortic valve replacement; CRP: cardiac rehabilitation programme; SD: standard deviation; CI: confidence interval.

ventilatory and metabolic responses to CRP, in patients mean additional improvement in BI scoring after a
that completed the test, exercise capacity at the end of CRP in sAVR patients was 15.3  14.6 points, while
the CRP was similar between groups. Besides that, in the TAVI patients this enhancement was
there was direct correlation between 6MWD and peak 13.7  13.6 points. In the pooled analysis, there was
oxygen consumption, both assessed after CRP. no significant difference between the improvement in
The data for studies comparing the effect of CRP in BI scoring for TAVI versus sAVR patients (1.52
TAVI versus sAVR patients on the BI were available points (4.81, 1.76); P ¼ 0.36). Also, there was no evi-
for two studies that reported data for 132 sAVR dence for heterogeneity across studies via this compari-
patients and 136 TAVI patients (Figure 4(b)). The son (I2 ¼ 0%; P ¼ 0.85).
Ribeiro et al. 695

(a)
After TAVI After sAVR Mean Difference Mean Difference
Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
Fauchère et al. 2014 56 47 34 41 32 78 23.5% 15.00 [–2.32, 32.32]
Russo et al. 2014 25 19 64 28 22 74 29.6% –3.00 [–9.84, 3.84]
Tarro-Genta et al. 2015 90 82 58 53 52 52 18.3% 37.00 [11.60, 62.40]
Völler et al. 2015 28 34 76 46 45 366 28.6% –18.00 [–26.93, –9.07]

Total (95% CI) 232 570 100.0% 4.28 [–12.73, 21.29]

2 2 2
Heterogeneity: Tau = 242.62; Chi = 24.09, df=3 (P<0.0001); I = 88%
Test for overall effect: Z= 0.49 (P = 0.62) –100 –50 0 50 100
Favours sAVR Favours TAVI

(b) After TAVI After sAVR Mean Difference Mean Difference

Study or Subgroup Mean SD Total Mean SD Total Weight IV, Fixed, 95% CI IV, Fixed, 95% CI

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Russo et al. 2014 9.3 12.3 78 10.6 13.2 80 68.1% –1.30 [–5.28, 2.68]
Tarro-Genta et al. 2015 18 15 58 20 16 52 31.9% –2.00 [–7.81, 3.81]

Total (95% CI) 136 132 100.0% –1.52 [–4.81, 1.76]

Heterogeneity: Chi2 = 0.04, df=1 (P = 0.85); I2 = 0%
–20 –10 0 10 20
Test for overall effect: Z= 0.91 (P = 0.36)
Favours sAVR Favours TAVI

Figure 4. Forest plot of the mean difference on (a) six-minute walked distance, in relative values (%), and (b) Barthel index, in points,
post-CRP in TAVI versus sAVR patients.
CRP: cardiac rehabilitation programme; TAVI: transcatheter aortic valve implantation; sAVR: surgical aortic valve replacement; SD:
standard deviation; CI: confidence interval.

Discussion Effect of CRP on exercise tolerance

To our knowledge, this is the first systematic review Our data showed a similar gain in exercise tolerance
investigating CRP effects in patients with severe AS after the sAVR or TAVI procedure, assessed by the
repaired by either sAVR or TAVI. In both groups, a 6MWD. In all trials, both groups exhibited a significant
CRP increased exercise tolerance, functional independ- increase in walked distance without a difference between
ence, health-related quality of life and maximal exercise groups, even considering the higher age, risk scores and
capacity. In addition, the meta-analysis results showed cardiac comorbidities present in the TAVI group. One
that patients undergoing sAVR or TAVI had similar study found that TAVI patients walked 15.9% less than
benefits in exercise tolerance and functional independ- the sAVR group after propensity score adjustment
ence. It was not possible to assess objectively the pooled (P ¼ 0.004).12 The authors attributed this finding to the
effect estimates for other variables based on the diver- short time that patients stayed in the CRP (sAVR
sity of the outcomes and assessment tools used in the 20.6  3.9 days vs. TAVI 19.2  4.6 days; P ¼ 0.013).
clinical trials. Although there was no study that showed the minimum
clinically important difference (MCID) for the 6MWD
in AS patients who underwent the valve repair proced-
CRP protocols ure, both groups had an average increase that was three
The CRP consisted of activities aimed at improving times greater than the MCID observed in CAD patients
aerobic capacity (walking or cycling) and peripheral who participated in a CRP by 8 weeks after percutan-
or respiratory muscle resistance. The routine was eous transluminal coronary angioplasty or coronary
engaged in daily for 2 or 3 weeks under supervision stenting.19 Moreover, Völler et al.12 reported similar
of physiotherapists. The authors did not report the improvements in exercise tolerance (26.7% to sAVR,
details of the callisthenic and respiratory workouts, hin- P < 0.001; 19.8% to TAVI, P ¼ 0.01) as assessed by a
dering their reproduction in clinical practice and/or in cycle exercise test. As in other studies,11,13 this work
other research. The greatest contribution was from showed the safety and efficacy of an early and intensive
Russo et al.,11 who described that the aerobic training CRP during the in-hospital phase in elderly patients with
started with 10-minute sessions and increased 5 minutes AS undergoing TAVI or sAVR.12
per session up to 30 minutes. The intensity did not
exceeded 70% of the predicted maximal heart rate, Effect of CRP on functional independence
monitored by a digital telemetry system. In another
and health-related quality of life
two trials, the prescription and control of intensity
were by the Borg scale of rating of perceived exertion Similar to exercise tolerance, all patients demonstrated
(up to level 14).10,13 gains in autonomy and mobility as gauged by the BI.
696 European Journal of Preventive Cardiology 24(7)

In applying this scale, it is possible to assess physical

Conclusion
and cognitive disability by a score that ranges between In conclusion, in patients with AS corrected by sAVR
0 and 100 points, where high scores indicate a greater or TAVI, an early CRP improves the exercise tolerance,
grade of independence. The same authors did not functional independence, health-related quality of life
observe any changes in anxiety and depression levels, and maximal exercise capacity. In addition, patients
by way of the HADS, after a CRP in both groups. undergoing sAVR or TAVI had similar benefits in exer-
However, Völler et al.12 did note a reduction in anxiety cise tolerance and functional independence. However,
and depression with the same scale, emphasising its future studies need to improve their quality of report-
subjectivity. In addition, Zanettini et al.14 provided ing, particularly in terms of risk of bias, characteristics
evidence for improvement in the EuroQoL visual ana- of the CRP protocol and control group.
logue scale, representing a variable of health-related
quality of life (54  14 to 75  11, P < 0.001).

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Author contribution
GSR, RDM and MK contributed to the conception and
Limitations design of this study. LFD contributed to the design of this
study. GSR and RDM contributed to the acquisition of the
Few studies were found that addressed this issue, all data. GSR, LFD, PD, MRNP and MK contributed to the
conducted in Europe perhaps because of the greater analysis and interpretation of the data. GSR, LFD, MRNP
life span of the local population,20 particularly in the and MK drafted and critically revised the manuscript. RDM
countries where the studies were conducted. The poor and PD revised the manuscript. All authors gave final
methodological quality observed in studies such as this approval and agree to be accountable for all aspects of the
is usually attributed to experimental design, namely work ensuring integrity and accuracy.
offering treatment to all patients, which prevented the
blinding and randomisation of the sample. In addition, Declaration of conflicting interests
the scale adopted in this study (PEDro scale) was devel- The author(s) declared no potential conflicts of interest with
oped to rate the methodological quality of randomised respect to the research, authorship, and/or publication of this
controlled trials, which differ from our sample, being a article.
primary limitation of our review. Furthermore, two of
the five papers selected had their methodological evalu- Funding
ation compromised for being published as a ‘Letter to
The author(s) disclosed receipt of the following financial sup-
the Editor’, or a short communication and conference port for the research, authorship, and/or publication of this
paper. In addition, one researcher did not make use of a article: Brazilian National Council for Improvement of
sAVR group to compare the effect of CRP. However, Higher Education (CAPES) master degree scholarships.
as a consequence of the few studies published in this
area, they were determined as worthwhile to include in
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