784345

research-article2018
CRE0010.1177/0269215518784345Clinical RehabilitationGomes Neto et al.

CLINICAL
Original Article REHABILITATION

Clinical Rehabilitation

The impact of high-intensity 1­–11

© The Author(s) 2018
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DOI: 10.1177/0269215518784345
https://doi.org/10.1177/0269215518784345

exercise capacity and inspiratory journals.sagepub.com/home/cre

muscle strength in heart failure

with reduced ejection fraction: a
systematic review and meta-analysis

Mansueto Gomes Neto1,2,3 , Filipe Ferrari4,5,

Lucas Helal4,6, Antônio Alberto Lopes2,7,
Vitor Oliveira Carvalho3,8 and Ricardo Stein4,5,9

Abstract
Objective: Inspiratory muscle training (IMT) improves prognostic clinical variables in patients with heart
failure. However, the optimal intensity for increasing those outcomes remains unclear. Thus, we aimed
to determine whether high-intensity inspiratory muscle training (HIIMT) improves exercise capacity and
respiratory muscle strength in patients with heart failure with reduced ejection fraction (HFrEF).
Methods: We searched for randomized controlled clinical trials at MEDLINE, the Cochrane Central
Register of Controlled Trials, the Physiotherapy Evidence Database, SciELO and CINAHL from the
earliest date available to May 2018. Primary studies on HIIMT against low-intensity IMT or sham-IMT that
evaluated exercise capacity and inspiratory muscle strength were included. Two independent reviewers
evaluated the eligibility of studies retrieved from the databases. Disagreements were resolved by discussion
or by a third reviewer. Weighted mean difference (WMD), standardized mean difference (SMD) and 95%
confidence interval (CI) were estimated by random effect models.
Results: Five studies met the eligibility criteria (138 patients). HIIMT improved VO2peak (WMD
2.65 mL kg−1 min−1; 95% CI: 2.2 to 3.1 mL kg−1 min−1), walking tests (SMD 1.71; 95% CI: 0.83 to 2.59) and maximal
inspiratory pressure (WMD 16.63 cmH2O; 95% CI: 10.34 to 22.91 cmH2O). The estimate for potential risks
of adverse events was not performed because of the low prevalence of reports in primary studies.

1Physical 7Diagnostic Support and Internal Medicine Department,

Therapy Department, Universidade Federal da Bahia
(UFBA), Salvador, Brazil School of Medicine, Universidade Federal da Bahia (UFBA),
2Graduate Program in Medicine and Health, Universidade Salvador, Brazil
8Physical Therapy Department, Federal University of Sergipe
Federal da Bahia (UFBA), Salvador, Brazil
3Physiotherapy Research Group, Universidade Federal da (UFS), Aracaju, Brazil
9School of Medicine, HCPA/UFRGS, Porto Alegre, Brazil
Bahia (UFBA), Salvador, Brazil
4Graduate Program in Cardiology and Cardiovascular
Corresponding author:
Sciences, Hospital de Clínicas de Porto Alegre (HCPA),
Mansueto Gomes Neto, Physical Therapy Department,
Federal University of Rio Grande do Sul, Porto Alegre, Brazil
5Exercise Cardiology Research Group (CardioEx), HCPA/
Universidade Federal da Bahia (UFBA), Instituto de Ciências
da Saúde. Av. Reitor Miguel Calmon s/n—Vale do Canela,
UFRGS, Porto Alegre, Brazil
6Exercise Pathophysiology Laboratory (LaFiEx), HCPA/
Salvador 40.110-100, BA, Brazil.
Email: mansueto.neto@ufba.br
UFRGS, Porto Alegre, Brazil
2 Clinical Rehabilitation 00(0)
Conclusion: HIIMT seems to be a useful strategy for improving exercise capacity and inspiratory muscle
strength in HFrEF patients.
Keywords
Heart failure, high-intensity training, respiratory weakness
Received: 6 January 2018; accepted: 20 May 2018
Introduction
Heart failure with reduced ejection fraction
(HFrEF) is clinically characterized by exercise
intolerance, muscle weakness/deconditioning and
poor quality of life.1–3 The peripheral and respira-
tory muscles in HFrEF patients are impaired,
resulting in reduced inspiratory and expiratory
function.4–6 Inspiratory muscle training (IMT) is an
attractive intervention for HFrEF patients and can
improve exercise capacity and inspiratory muscle
function.7,8 Different IMT strategies have been
used and it is not clear which IMT intensity is the
most efficient. In a study by Kawauchi et al.,9 low-
intensity inspiratory and peripheral resistance mus-
cle training improved inspiratory and peripheral
muscle strength and walking distance.
Moderate-intensity resistance training has also
been associated with improved expiratory muscle
strength and New York Heart Association func-
tional class in patients with heart failure. However,
Chiappa et al.10 reported improved lung function in
HFrEF patients who underwent a high-intensity
inspiratory muscle training (HIIMT) protocol.
Almost a decade ago, Laoutaris et al.11 compared
HIIMT with low-IMT (15% of maximal inspira-
tory pressure) in a sample of 23 patients with
chronic heart failure. Improved maximal inspira-
tory pressure was observed in patients who received
either treatment type, although greater benefits
were observed in the HIIMT group. More recently,
two small studies also suggested that high-intensity
workloads may be beneficial for patients with heart
failure.12,13
To the best of our knowledge, there is no sys-
tematic review with meta-analysis that has evalu-
ated the impact of HIIMT in this setting.
Considering the gap in this area of knowledge, we
performed a comprehensive systematic review of
the literature and quantitative summary effect
estimation by meta-analysis of controlled clinical
trials with HFrEF patients to compare the efficacy
of HIIMT vs low-intensity IMT (or sham-IMT) on
exercise capacity and respiratory muscle strength
in this complex syndrome.
Methods
The systematic review was planned and conducted
in accordance with Cochrane Collaboration recom-
mendations and reported in accordance with the
Preferred Reporting Items for Systematic Reviews
and Meta-Analyses (PRISMA) guidelines.14
Data sources and search strategies
Potential studies were identified by searching the
following sources: MEDLINE, the Cochrane
Central Register of Controlled Trials (CENTRAL),
the Physiotherapy Evidence Database (PEDro), the
Scientific Electronic Library Online (SciELO) and
the LILACS database up to May 2018 without lan-
guage or publication status restrictions. We also
performed handsearches of relevant literature, and
gray literature was consulted in Google Scholar.
The search strategies were based on three groups of
keywords: study design, participant/problem and
interventions. The study design group of keywords
included the terms randomized controlled trials,
clinical trials and controlled trials; the participant/
problem group of keywords included the terms
heart failure, dilated cardiomyopathy and systolic
heart failure and the intervention group of key-
words included the terms exercise, IMT, respira-
tory exercise, breathing exercises and physical
training. The optimally sensitive filter developed
by Higgins and Green15 was used to exclude non-
controlled clinical trials in PubMed/MEDLINE.
Gomes Neto et al.
The full search strategy can be found in Electronic
Supplementary File 1 for independent replication.
Study selection
Studies were eligible for this systematic review if
they met the following criteria: (1) included adult
patients (aged ⩾18 years) with HFrEF (<40%); (2)
a randomized controlled clinical trial design and (3)
controlled by low-intensity IMT or sham-IMT. No
restriction was made in terms of gender, the dura-
tion of exercise intervention, publication status or
language. HIIMT was defined as IMT involving at
least 60% of respiratory muscle strength or being
estimated or described as such by the authors. The
main outcomes of interest were exercise capacity
(evaluated only by VO2peak and distance walked in
the 6-minute walk test or 12-minute walk test) and
maximal inspiratory pressure.
Assessment of study eligibility
The list of titles and abstracts from each data source
were independently evaluated by two authors
(M.G.N. and F.F.) to identify potential studies for
the systematic review. If at least one of the authors
considered a reference eligible, the full text was
obtained for complete assessment. The full texts of
the selected articles were independently assessed by
three reviewers (M.G.N., F.F. and L.H.) to identify
those meeting the criteria for inclusion or exclusion.
Disagreements were discussed by the authors, and a
final decision was reached by consensus.
We checked each selected article’s reference list
to identify other potentially eligible studies. The
authors of ongoing studies were contacted by email
for information about the work in progress and any
unpublished data that could be synthesized by our
work. Studies in which we were unable to provide
qualitative or quantitative evidence meeting our
eligibility criteria, after contacting authors, were
excluded thereafter.
Data extraction
Two authors (M.G.N. and F.F.) independently
extracted the data from the published reports using
standard data extraction forms adapted from the
Cochrane Collaboration15 model that considered (1)
3
aspects of the study population, such as sex and mean
age; (2) aspects of the intervention performed (sam-
ple size, IMT type, exercise type, the presence of
supervision and the frequency and duration of each
session); (3) follow-up; (4) follow-up losses; (5) out-
come measures and (6) results. Disagreements were
resolved by consensus or by discussion with a third
investigator (L.H.). Any further information required
from the original authors was requested by email.
Risk of bias in the primary studies
The risk of bias in the studies included in this sys-
tematic review and meta-analysis was scored using
the 11-item PEDro scale,16 which is based on the
9-item Delphi List developed by Verhagen et al.17
One item on the PEDro scale (eligibility criteria) is
related to external validity and is generally not
used to calculate the method score, leaving a score
range of 0–10.18 The entire process was conducted
independently by two researchers, and disagree-
ments were resolved by discussion.
Certainty in the evidence and strength of
recommendations
We assessed the certainty of evidence and the
strength of recommendations for the outcomes
exercise capacity and improved inspiratory muscle
strength after HIIMT of our meta-analysis using
the Grading of Recommendations, Assessment,
Development and Evaluation (GRADE) system’s
GRADEpro software, the results of which are pre-
sented in the Summary of Findings Table.19
The assessment involved five items: risk of bias,
imprecision, inconsistency, indirectness and publi-
cation bias. The evidence for each item was classi-
fied as follows: none (no reduction in points),
serious (reduction of 1 point) and very serious
(reduction of 2 points), being scored according to
the interference biases detected in these items. The
quality of evidence was interpreted as high quality,
moderate quality, low quality or very low quality.19
Statistical analysis
Pooled-effect estimates were obtained by comparing
the least square mean percentage change from
4 Clinical Rehabilitation 00(0)

Figure 1. Eligibility and data-synthesis PRISMA flow diagram.

baseline until the end of the study for each group and
were expressed as the weighted mean difference
(WMD) between groups. Standardized mean differ-
ences (SMDs) were only used to estimate effect size
for exercise capacity, since some studies presented
data for the 12-minute walk test and not for 6-min-
ute walk test. All meta-analyses were performed
using the random-effects model, despite any
observed heterogeneity. Only one comparison was
made: HIIMT group vs control group. An α value of
0.05 was chosen as the threshold for significance.
Heterogeneity of the treatment effect was assessed
using Cochrane’s Q and the I2 test, in which values
greater than 50% were considered indicative of het-
erogeneity.20 Due to the low number of included
studies, no asymmetry statistics were included. All
analyses were conducted using Review Manager
version 5.3 (Cochrane Collaboration).21
Results
Description of selected studies
The initial search identified 475 records, of which
12 were considered potentially eligible and
retrieved for full-text eligibility assessment. Five
articles11,22–25 met the eligibility criteria and were
included for data extraction. Seven studies did not
meet the eligibility criteria and were excluded.
Figure 1 shows the PRISMA flow diagram of
Gomes Neto et al.
studies in this review. The reference list of excluded
studies after full-text checking can be found in
Electronic Supplementary File 2.
Study characteristics
The number of participants in the analyzed studies
ranged from 20 to 38, with a mean of 27 patients,
resulting in a total of 138 subjects. The samples of the
selected studies largely consisted of middle-aged and
elderly individuals, whose mean age ranged from 54.9
to 69.3 years. All studies included individuals of both
genders, but there was a general predominance of men
(118 men vs 18 women—85% vs 15%). All reviewed
studies included patients with systolic chronic heart
failure, with a mean ejection fraction ranging from
23.8% to 28.8% in four of the five studies. In Marco
et al.,24 the ejection fraction was 36.9%. Regarding
New York Heart Association functional class, 61.5%
of the patients were in class I or II, while the remaining
38.5% were in class III or IV. Because in Weiner
et al.25 the functional class of the patients was pre-
sented as the mean value (2.35), a combinatory calcu-
lation was necessary to standardize the results.
Maximal inspiratory pressure was expressed in
cmH2O, ranging from 46.5 to 84.2 cmH2O in the
five studies.11,22–25 All studies described exclusion
criteria. The reported exclusion criteria were pul-
monary disease, chronic obstructive pulmonary
disease, cognitive problems, acute/chronic infec-
tions, rheumatoid disease, cancer and inflamma-
tory diseases. Treatment with anti-inflammatory
drugs, current smoking and the absence of general
and/or respiratory muscle training in the previous
three months were also exclusion criteria. A com-
prehensive qualitative evaluation of primary data
can be found in Table 1 (i.e. sample size, drop-outs,
mean age, intervention and assessed outcomes). A
complimentary table with potential sources of bias
(i.e. disclosures, trial register, funding) and meta-
data (e.g. digital object identifier number—DOI)
can be found in Electronic Supplementary File 3.
Characteristics of intervention programs
The duration of intervention programs ranged from 4
to 12 weeks. HIIMT was applied for 4 weeks in Marco
et al.,24 10 weeks in Laoutaris et al.11,21,22 and 12 weeks
5
in Weiner et al.25 The training intensity ranged from
15% (control group) to 60% (intervention group) in
three studies.22,23,25 Marco et al.24 used 100% of 10
maximal repetitions. Sustained maximum inspiratory
pressure was performed in only one study23 and ranged
from 15% (control group) to 60% (intervention group)
of sustained maximal inspiratory pressure. The studies
included in this review used standardized and vali-
dated outcome measures to assess the benefits of IMT:
maximal inspiratory pressure and exercise capacity
(VO2peak and 6-minute walk test or 12-minute walk
test). The included studies’ exercise intervention char-
acteristics are provided in Table 2.
PEDro scale results
After assessing methodological aspects and risk of
bias with the PEDro scale tool, we found that all of
the studies included a control group and two used
random allocation. All studies described adequate
follow-up and presented baseline comparability,
between-group comparisons, point estimates and
variability. Therapists and assessors were blinded
in two of the five studies (40%), patients were
blinded in one of the studies (20%) and intention-
to-treat analysis was reported for one study (20%).
None of the studies reported allocation conceal-
ment. The total PEDro scores are presented in
Table 1.
Exercise capacity
Three studies assessed VO2peak as an out-
come.11,22,23 The meta-analyses showed (Figure 2)
a pooled effect of 2.65 mL kg−1 min−1 (95% confi-
dence interval (CI): 2.2 to 3.1 mL kg−1 min−1) in
VO2peak for the HIIMT group vs the control group.
Three studies assessed the walking test as an
outcome—two used the 6-minute walk test22,23 and
one used the 12-minute walk test.26 The meta-anal-
ysis comparing the HIIMT group with a control
group showed (Figure 3) a pooled standardized
mean effect on exercise capacity of 1.71 (95% CI:
0.83 to 2.59, P = 0.0001).
Inspiratory muscle strength
Five studies assessed maximal inspiratory pressure
as an outcome.11,22–25 One study, Marco et al.,24
6 Clinical Rehabilitation 00(0)

Table 1. Comprehensive qualitative evidence synthesis for HIIMT on exercise capacity and respiratory muscle
strength.

Study Sample Drop- Mean LVEF NYHA Interventions Outcomes Adverse Key Findings PEDro
size outs (%) age (y) (%) events
Laoutaris 35 NR 58.6 24.4 NYHA (II/ HIIMT vs VO2peak, NR Higher 5
et al.22 III) low-IMT 6MWT, VO2peak,
MIP 6MWT and MIP
in the HIIMT
group than the
control group
(P < 0.005)
Laoutaris 38 NR 56.6 27.4 NYHA (II/ HIIMT vs VO2peak, NR Higher 6
et al.23 III) low-IMT 6MWT, VO2peak,
MIP 6MWT and MIP
in the HIIMT
group than the
control group
(P < 0.001)
Laoutaris 23 NR 54.9 28.8 NYHA (II/ HIIMT vs VO2peak, NR Higher 6
et al.11 III) low-IMT MIP VO2peak and
MIP in the
HIIMT group
than control
group (P < 0.01)
Marco 22 0 69.3 36.9 NYHA (II/ HIIMT vs MIP None Higher MIP 8
et al.24 III) sham-IMT in the HIIMT
group than the
control group
(P < 0.0001)
Weiner 20 NR 65 23.8 NYHA (II/ HIIMT vs VO2peak, NR Higher 6MWT 5
et al.25 III) sham-IMT 12MWT, and MIP in
MIP the HIIMT
group than the
control group
(P < 0.001). No
statistically
significant
change in mean
VO2peak in
either group

HIIMT, high-intensity inspiratory muscle training; IMT, inspiratory muscle training; LVEF, left ventricular ejection fraction; MIP,
maximal inspiratory pressure; 6MWT, 6 minute walk test; 12MWT, 12 minute walk test; NYHA, New York Heart Association; NR,
not reported.

described maximal inspiratory pressure as % pred.24 GRADE assessments

To standardize the scales, this was converted to
cmH2O. The meta-analysis showed (Figure 4) an
improvement in maximal inspiratory pressure of
16.63 cmH2O (95% CI: 10.34 to 22.91 cmH2O) in
the HIIMT group compared to controls.
The quality of evidence according to the GRADE
system is presented in Table 3. The quality of evi-
dence for the outcomes VO2peak and inspiratory
muscle strength were determined to be low. The
Gomes Neto et al. 7

Table 2. Characteristics of the interventions included in this review.

Study Intensity Volume Frequency (times Time Length Supervision

per week) (minute) (week)
Laoutaris 60% MIP Six inspiratory efforts at each level 3 NR 10 Yes
et al.22 with rest intervals until fatigue
Laoutaris 60% MIP Six inspiratory efforts at each level 3 NR 10 Yes
et al.23 with rest intervals until fatigue
Laoutaris 60% MIP Six inspiratory efforts at each level 3 NR 10 Yes
et al.11 with rest intervals until fatigue
Marco 100% of Five sets of 10 repetitions at a rate 7 (twice a day) NR 4 Yes (once a
et al.24 10 MR of 15–20 breaths/minute week)
Weiner 60% MIP NR 6 30 12 Yes
et al.25

MIP, maximal inspiratory pressure; MR, maximal repetitions; NR, not reported.

Figure 2. High-intensity inspiratory muscle training vs controls for VO2peak outcome.

Figure 3. High-intensity inspiratory muscle training vs controls for walk capacity outcome.

Figure 4. High-intensity inspiratory muscle training vs controls for maximal inspiratory pressure outcome.
 8
Table 3. Summary of findings on evidence strength by the GRADE tool.

High-intensity inspiratory muscle training compared to controls in HFrEF

Patient or population: HFrEF

Setting: Rehabilitation
Intervention: High-intensity inspiratory muscle training
Comparison: Control

Outcomes
Exercise capacity assessed
with walking tests.
Follow-up: mean 10–
12 weeks
Inspiratory muscle strength
assessed with maximal
inspiratory pressure.
Follow-up: mean 4–12 weeks
VO2peak assessed with
cardiopulmonary exercise
test.
Follow-up: mean 10 weeks
Anticipated absolute effects (95% CI)
Risk Risk* HIIMT
control
The mean exercise capacity
in the intervention group
was 86.22 m higher (36.22
higher to 136.23 higher)
The mean inspiratory
muscle strength in the
intervention group was
16.77 cmH2O higher to
22.85 cmH2O higher
The mean peak VO2 in the
intervention group was
2.65 mL−1 kg−1 min−1 higher
(2.19 higher to 3.11 higher)
Relative effect Participants GRADE Comments
(95% CI) (studies) rate
− 93 (3 RCTs) VERY Exercise capacity was assessed
LOW using two different methods.
Higher walking test scores indicate
improvement. WMD of 86.22 m is
considered clinically relevant
− 134 (5 RCTs) LOW Higher inspiratory pressure scores
indicate improvement. WMD
of 16.77 cmH2O is considered
clinically relevant
− 96 (3 RCTs) LOW Higher VO2peak scores indicate
improvement. WMD of 2.65 is
considered clinically relevant

CI, confidence interval; HFrEF, heart failure with reduced ejection fraction; HIIMT, high-intensity inspiratory muscle training; MD, mean difference; WMD, weighted mean difference.
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its
95% CI).
GRADE: Working Group grades of evidence.
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is
substantially different.
Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
Explanations:
(a) Only one study randomized.
(b) Studies without allocation concealment, random allocation and/or sample size calculation.
(c) 12 = 97%.
Clinical Rehabilitation 00(0)

(d) Meta-analysis with statistical significance in heterogeneity test and high I2.
Gomes Neto et al.
certainty of evidence and strength of recommenda-
tion for all outcomes was rated as very low.
Adverse events
As shown in Table 1, the risk of adverse events was
not systematically reported in the studies selected
for the present review. Only one study reported an
absence of adverse effects during HIIMT.23 The
other studies provided no data on adverse
events.11,22,23,25
Discussion
According to our results, HIIMT was associated
with improved exercise capacity and inspiratory
muscle strength compared to sham- or low-inten-
sity IMT. The observed improvement in outcomes
due to HIIMT is likely due to progressive overload,
that is, the great demand placed on the body.26
Despite apparent controversies, recommendations
for rehabilitation favor higher intensity over low-
intensity training. There is almost a consensus that
higher intensity training will result in improve-
ments in both patient-centered and physiological
outcomes.27
The data indicate that training period, intensity
and rest between sets play important roles in
improving respiratory muscle strength,28,29 which
supports the implementation of resistance exercise
training programs both for healthy individuals and
patients with chronic diseases. Significant improve-
ment in exercise capacity was observed for patients
with systolic heart failure allocated in the interven-
tion group compared to controls. Evidence sug-
gests that relatively low increase in exercise
capacity result in major health benefits. For exam-
ple, for each increment of 1-MET in exercise
capacity, there may be reductions of up to 25% in
mortality.30
Studies of patients with heart failure have pro-
vided evidence supporting the role of VO2peak as a
strong prognostic factor of mortality.31,32 VO2peak
is also a useful indicator of the optimal timing for
cardiac transplantation in HFrEF patients.33 One of
the largest trials with an exercise protocol in heart
failure patients found that each increase of 6% in
9
VO2peak corresponds to a 5% decrease in mortal-
ity risks or hospitalization for all causes.34 In abso-
lute terms, this systematic review found a
significant difference of 2.65 mL kg−1 min−1 in
VO2peak. Stevenson et al.35 showed that an
increase of only 2 mL kg−1 min−1 in VO2peak was
accompanied by stable clinical status without con-
gestion in 31 of 38 patients who were on the heart
transplant waiting list. Due to this strong improve-
ment in clinical status, it is possible that these
patients could be safely removed from the waiting
list. Taken together, these results support greater
emphasis on HIIMT to improve outcomes in
patients with systolic heart failure. Unlike the pre-
sent meta-analysis, a recent systematic review by
Plentz et al.13 found no association between IMT
and improved VO2peak in HFrEF patients.
However, HIIMT was the tested intervention in
only one-third of the studies included in this
meta-analysis.
Our study rationale implies that the relevance of
HIIMT for cardiac rehabilitation programs has to
do with the potential relationship between respira-
tory muscle dysfunction and survival,6 as well as
between quality of life and exercise tolerance.5 Our
findings revealed a substantial improvement in
inspiratory muscle strength in patients who under-
went HIIMT compared to controls, which supports
the idea that IMT protocols of at least 60% of max-
imal inspiratory pressure can be viewed as useful
for this purpose.
There was variation in some parameters of the
study protocols included in the present review. The
duration of observations varied from 4 to 12 weeks
and the HIIMT protocols included exercises at a
frequency of three to seven times per week,
although session duration was not reported in most
of the studies. Furthermore, the limited number of
studies did not allow a sensitivity analysis or meta-
regression to assess the possibility of HIIMT dose–
response effects.
Of the five studies included in the present
review, three are trials from the same research
group.11,22,23 It would be important and useful if
other groups conducted similar research to ensure
that the methods and findings also apply outside a
rehabilitation center.
10
The present systematic review calls attention to
the need for randomized studies to assess the risk
of possible adverse effects of HIIMT in addition to
its potential benefits. As previously mentioned,
only one study described an absence of adverse
effects during the intervention period,24 while the
other four provided no information on adverse
effects.11,22,23,25
This systematic review assessed the quality of
evidence of primary studies according to the
GRADE system, which ranked four of them as low-
to-moderate quality11,22,23,25 and only one as high
quality.24 Thus, we were unable to perform sensitiv-
ity analyses stratified by methodological quality.
Likewise, some gender-based inferences should be
restricted to males, since only 15% of study partici-
pants were females.5,11,22,23 Finally, readers should
interpret our results in light of the small number of
included studies, although this ultimately reflects
the body of evidence about HIIMT and relevant
outcomes for HFrEF patients. New large-scale ran-
domized controlled trials are needed to confirm the
findings of this systematic review.
Clinical Messages
•• The evidence from a small number of tri-
als with only 138 patients in total sug-
gests that high-intensity inspiratory
muscle training in patients with heart
failure improves cardiac functions, with-
out major adverse events.
•• Further larger studies in different centers
are needed before this treatment is used
routinely.
Declaration of Conflicting Interests
Ricardo Stein receives research productivity funding by the
CNPq foundation. Lucas Helal receives PhD funding sup-
port by the CAPES foundation. The other authors declare
that they have no competing interests (financial, political,
personal, religious, ideological, academic, intellectual or
any other) to declare in relation to this manuscript.
Funding
This study was supported in part by the Fundo de
Incentivo à Pesquisa e Eventos from Hospital de Clínicas
de Porto Alegre (FIPE/HCPA).
Clinical Rehabilitation 00(0)
ORCID iD
Mansueto Gomes Neto https://orcid.org/orcid.org/
0000-0002-0717-9694
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