855183

research-article2019
CNU0010.1177/1474515119855183European Journal of Cardiovascular NursingPalau et al.

Original Article

European Journal of Cardiovascular Nursing

Home-based inspiratory muscle training

2019, Vol. 18(7) 621­–627
© The European Society of Cardiology 2019
Article reuse guidelines:
for management of older patients with sagepub.com/journals-permissions
DOI: 10.1177/1474515119855183
https://doi.org/10.1177/1474515119855183

heart failure with preserved ejection journals.sagepub.com/home/cnu

fraction: does baseline inspiratory

muscle pressure matter?

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Patricia Palau1, Eloy Domínguez1, José María Ramón2,
Laura López3, Antonio Ernesto Briatore1, J Pablo Tormo1,
Bruno Ventura1, Francisco J Chorro2,4 and Julio Núñez2,4

Abstract
Background: Heart failure with preserved ejection fraction is a clinical syndrome characterised by reduced exercise
capacity. Some evidence has shown that a simple and home-based programme of inspiratory muscle training offers
promising results in terms of aerobic capacity improvement in patients with heart failure with preserved ejection fraction.
This study aimed to investigate whether the baseline inspiratory muscle function predicts the changes in aerobic capacity
(measured as peak oxygen uptake; peak VO2) after a 12-week home-based programme of inspiratory muscle training in
patients with heart failure with preserved ejection fraction.
Methods: A total of 45 stable symptomatic patients with heart failure with preserved ejection fraction and New York
Heart Association II–III received a 12-week home-based programme of inspiratory muscle training between June 2015
and December 2016. They underwent cardiopulmonary exercise testing and measurements of maximum inspiratory
pressure pre and post-inspiratory muscle training. Maximum inspiratory pressure and peak VO2 were registered in
both visits. Multivariate linear regression analysis was used to assess the association between changes in peak VO2 (Δ-
peakVO2) and baseline predicted maximum inspiratory pressure (pp-MIP).
Results: The median (interquartile range) age was 73 (68–77) years, 47% were women and 35.6% displayed New
York Heart Association III. The mean peak VO2 at baseline and Δ-peakVO2 post-training were 10.4±2.8 ml/min/kg and
+2.2±1.3 ml/min/kg (+21.3%), respectively. The median (interquartile range) of pp-MIP and Δ-MIP were 71% (64–92)
and 39.2 (26.7–80.4) cmH2O, respectively. After a multivariate analysis, baseline pp-MIP was not associated with Δ-
peakVO2 (β coefficient 0.005, 95% confidence interval −0.009–0.019, P=0.452).
Conclusions: In symptomatic and deconditioned older patients with heart failure with preserved ejection fraction,
a home-based inspiratory muscle training programme improves aerobic capacity regardless of the baseline maximum
inspiratory pressure.

Keywords
Heart failure with preserved ejection fraction, inspiratory muscle function, aerobic capacity

Date received: 23 February 2019; accepted: 15 May 2019

1Servicio The first two authors contributed equally.

de Cardiología. Hospital General Universitario de Castellón.
Universitat Jaume I, Spain Corresponding author:
2Servicio de Cardiología, Hospital Clínico Universitario, INCLIVA.
Patricia Palau, Cardiology Department, Hospital General Universitario
Universitat de València. Spain de Castellón, Universitat Jaume I, Avda. Benicasim, s/n, Castellón
3Departamento de Fisioterapia, Universitat de València, Spain
12004, Spain.
4Servicio de Cardiología, Hospital Clínico Universitario, CIBERCV,
Email: palaup@uji.es
Spain
622
Introduction
Heart failure (HF) with preserved left ventricular ejection
fraction (HFpEF) constitutes the most prevalent form of
HF in the aging population.1 To date, the most representa-
tive pharmacological trials in patients with HFpEF have
failed to demonstrate a substantial prognostic benefit,2–4
which may explain why the associated morbidity and
mortality of this syndrome remains excessively high.5–7
The principal clinical features of patients with HFpEF are
exertional dyspnoea and reduced aerobic capacity, which
limits patients’ activities of daily living and quality of life
(QoL).5,8
Inspiratory muscle weakness (IMW) occurs in 30–50%
of patients with HF with reduced ejection fraction (HFrEF)
and has been proposed as a potential mechanism explain-
ing reduced aerobic capacity.9–11 For this reason, recent
recommendations of exercise training in HF advocate a
routine screening for IMW before tailoring exercise train-
ing in HFrEF patients.11,12
Regarding patients with HFpEF, current evidence about
IMW is scarce and conflicting with results in patients with
HFrEF. In fact, a recent study conducted by our group did
not find an association between IMW and aerobic capacity
measured by peak oxygen consumption (peak VO2) in a
group of 74 patients with HFpEF.13 Along the same line, a
small randomised clinical trial showed that a simple, low-
intensity and home-based programme of inspiratory mus-
cle training (IMT) improved significantly aerobic capacity
and QoL in patients with HFpEF with low aerobic capacity
and non-IMW.14
The present study aimed to investigate whether baseline
inspiratory muscle function predicts the changes in aerobic
capacity (measured as peak oxygen uptake; peak VO2)
after a 12-week home-based programme of IMT in patients
with HFpEF.
Methods
Study design and patients
This was a prospective study that included 45 consecu-
tive stable patients with the diagnosis of HFpEF accord-
ing to the criteria of the European Society of Cardiology15
and New York Heart Association (NYHA) functional
class II–III/IV who received a 12-week home-based
programme of IMT between June 2015 and December
2016. Patients were referred from the HF outpatient
clinic of the Hospital Clínico Universitario de Valencia
(Spain). All of them met the following inclusion crite-
ria: (a) previous history of symptomatic chronic HF
NYHA functional class ⩾II); (b) normal left ventricular
ejection fraction (ejection fraction >0.50 by Simpson
method and end-diastolic diameter <60 mm); (c)
structural heart disease (left ventricular hypertrophy/
left atrial enlargement) and/or diastolic dysfunction
European Journal of Cardiovascular Nursing 18(7)
estimated by two-dimensional (2D) echocardiography;
(d) previous admission for acute HF; and (e) clinical
stability, without hospital admissions in the past 3
months.
Patients were excluded if they could not perform a valid
baseline exercise test or presented with any medical condi-
tion such as: significant primary moderate to severe valvu-
lar disease; acute coronary syndrome or cardiac surgery
within the previous 3 months; signs of ischaemia during
cardiopulmonary exercise testing (CPET); and any other
comorbidity with an expectancy of life less than one year.
The study was conducted in a single tertiary referral
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hospital in Spain. All patients provided signed informed
consent before participation. The protocol was approved
by the research ethics committee of our centre in accord-
ance with the principles of the Declaration of Helsinki and
national regulations.
Training intervention
Patients were instructed to train at home twice daily, for 20
minutes each session (alternating short training periods
with free breathing periods) and during 12 weeks, using a
threshold inspiratory muscle trainer (Threshold IMT;
Respironics Inc.) which provides consistent and manually
adjustable pressure (from 9 to 41 cmH2O) for inspiratory
muscle strength training. All of the patients were previ-
ously instructed to learn how to breathe using the dia-
phragm (diaphragmatic breathing technique) in different
positions (lying, sitting and standing) by a physiotherapist.
After learning the diaphragmatic technique, all of them
were educated to maintain diaphragmatic breathing during
the training periods. Furthermore, the patients were edu-
cated in how to fill in a patient diary card (training sessions
per day and time of each session). The subjects started
breathing at a resistance equal to 25–30% of their maximal
inspiratory pressure (MIP) for one week. The physiothera-
pist examined the patients at 7−10-day intervals by check-
ing the diary card and measuring their MIP each time. The
resistance was modified by the physiotherapist each visit
according to the 25–30% of their MIP measured. The diary
card and breathing technique was carefully checked each
visit by the physiotherapist for adequate adherence and
compliance.
Procedures
Procedures of the study included: echocardiography,
inspiratory muscle function test and CPET, successively.
The examination tests were performed the same day.
Cardiopulmonary exercise testing. Maximal functional
capacity was evaluated with an incremental and symptom-
limited cardiopulmonary exercise test (CORTEX Meta-
max 3B) on a bicycle ergometer, beginning with a workload
Palau et al.
of 10W and increasing stepwise at 10W increments every
one minute. During exercise, patients were continuously
monitored with 12-lead electrocardiogram and blood pres-
sure measurements every 2 minutes. Gas exchange data
and cardiopulmonary variables were averaged every 10
seconds. Peak VO2 was considered the highest value of
VO2 during exercise. Δ-peakVO2 was defined as the dif-
ference between peak VO2 at baseline and after 12-week
training. The peak respiratory exchange ratio was evalu-
ated as a measure of subject effort. The ventilatory effi-
ciency slope (VE/VCO2 slope) was determined by
measuring the slope across the entire course of exercise.16
Each subject will undergo two examinations (at baseline
and 12 weeks) by two trained cardiologists.
Echocardiography. Doppler echocardiogram examinations
will be performed under resting conditions using 2D echo-
cardiography (iE33; Philips). All parameters, including tis-
sue Doppler parameters will be measured according to
current guidelines of the European Society of Echocardi-
ography17 by two trained cardiologists.
Inspiratory muscle strength test. MIP was obtained using a
hand-held respiratory mouth pressure meter (electronic
manometer-ELKA, PM15). With a nose clip on, patients
were instructed to breathe through a mouthpiece only dur-
ing inspiration. The MIP values were obtained in a stand-
ing position by inspiration from the residual volume and
were repeated within a one minute interval until three tech-
nically satisfactory and reproducible measurements were
obtained (variation of −10%). The MIP was calculated by
using the mean of three reproducible measurements and
expressed as a percentage of the normal predicted value of
MIP (pp-MIP).18 IMW was defined as MIP less than 70%
of normal predicted values.19 Δ-MIP was defined as the
difference between MIP at baseline and after 12 weeks
training. Each subject will undergo 10−12 MIP measure-
ments (at baseline and during each visit) by a trained
physiotherapist.
Study outcomes
The primary outcome was to evaluate whether baseline
predicted MIP (pp-MIP) predicts the changes in peak VO2
from baseline to 12 weeks (Δ-peakVO2) in patients with
HFpEF undergoing home-based inspiratory muscle
training.
Statistical analysis
Continuous variables are presented as mean (± standard
deviation; SD) or median (interquartile range; IQR), as
appropriate. Categorical variables are depicted as percent-
ages. The correlation between Δ-peakVO2 and pp-MIP
was evaluated with a Spearman test. A multivariable linear
623
regression analysis was performed to identify whether the
exposure (pp-MIP) was independently associated with Δ-
peakVO2. Reduced multivariate models were achieved
through a stepwise backward selection procedure with
simultaneous transformation of continuous variables using
fractional polynomials.20 All variables listed in Table 1
were tested in multivariate analysis. Final multivariate
models included the following set of covariates: history of
chronic obstructive pulmonary disease (COPD), dyslipi-
demia, history of ischaemic heart disease and Δ-MIP. The
final multivariable models accounted for 35% of the vari-
ability in peak VO2 (R-squared 0.352%) of the variability
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in peak VO2. A two-sided P value less than 0.05 was con-
sidered to be statistically significant. All analyses were
performed using Stata 15.
Results
Baseline patient characteristics
The median (IQR) age of the overall cohort was 73 (68–
77) years, 47% were women, 35.6% displayed NYHA III
and the median (IQR) of N-terminal pro brain natriuretic
peptide was 922 pg/ml (297–2016). The mean (SD) for
peak VO2 and pp-peak VO2 were 10.4±2.8 ml/min/kg and
58.2±12.4%, respectively. The median (IQR) for MIP and
pp-MIP was 61.3 cmH2O (51.3–72.5) and 71.1% (63.9–
92.1), respectively. IMW was observed in 18 (40%)
patients. The baseline characteristics of patients with IMW
and without IMW are summarised in Table 1. There were
no significant differences in comorbidity, echocardio-
graphic and functional capacity across IMW status. Only
the percentage of women and heart rate were lower in
those with IMW.
Changes in MIP and aerobic capacity
After IMT, median (IQR) MIP significantly improved
(61.3 cmH2O (51.3–72.5) vs. 97 cmH2O (82.1−150),
P<0.001). Compared with baseline, mean±SD peak VO2
increased significantly at 12 weeks (10.4±2.8 ml/min/kg
vs. 12.6±3.2 ml/min/kg, P<0.001 (∆ = +2.2 (0.9–3.4 ml/
min/kg; P<0.001)). Besides, a significant improvement in
ventilatory efficiency and in respiratory exchange ratio
during exercise was observed.
Association between changes in aerobic
capacity and baseline MIP
In univariate analysis, Δ-peakVO2 was not correlated with
pp-MIP (r=0.028, P=0.855) and Δ-MIP was also not cor-
related with Δ-peakVO2 (r=0.108, P=0.479). In a multi-
variate regression model, baseline pp-MIP was not
associated with Δ-peakVO2 (β coefficient 0.005, 95% con-
fidence interval (CI) −0.009–0.019, P=0.452) as is shown
624 European Journal of Cardiovascular Nursing 18(7)

Table 1. Baseline characteristics of patients.

Variables Overall Without IMW With IMW P

(n=45) (n=27) (n=18) value
Demographic and medical history
Age, years 73 (68–77) 72 (66–76) 76 (68–80) 0.23
Female, n (%) 21(47) 16 (59) 5 (28) 0.04
BSA, m2 1.9±0.2 1.9±0.2 1.9±0.2 0.58
Prior AHF hospitalisation, n (%) 45 (100) 27(100) 18 (100) 1
Hypertension, n (%) 41 (91) 26 (96) 15 (83) 0.14
Dyslipidemia, n (%) 38 (84) 24 (89) 14 (78) 0.32
Diabetes mellitus, n (%) 24 (53.3) 16 (59.3) 8 (44.4) 0.33

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Ischemic heart disease, n (%) 19 (33) 9 (33.3) 10 (55.6) 0.14
History of COPD, n (%) 2 (4.4) 1 (3.7) 1 (5.6) 0.77
Baseline NYHA class III/IV, n (%) 16 (35.6) 10 (37) 6 (33.3) 0.90
Vital signs
Heart rate, bpm 70±13.8 74±14 64±10 0.02
Systolic blood pressure, mmHg 126±15 122±12 131±17 0.10
Laboratory
Haemoglobin, g/dl 12.9±1.6 13±1.5 12.8±1.7 0.54
Serum creatinine, mg/dl 1.4±0.7 1.2±0.4 1.6±0.8 0.12
Glomerular filtration rate, ml/min/m2a 49.1±19.1 49±15.5 49.2±17 0.9
NT-proBNP, pg/ml 922 (297–2016) 638 (222−1626) 1589 (325–2899) 0.15
Echocardiography
LVEF, % 67.8±10.3 68.6±11.2 66±9 0.69
LAVI, ml/m2 36.3±9.7 34.3±9.5 39.3±9.3 0.09
E/e′ ratio 17 (12–23) 17 (11.2–21.7) 19.5(12.3–26.5) 0.33
PASP,b mmHg 44.8±9.1 47±10 42.1±7.3 0.13
Exercise performance and maximal inspiratory pressure
Peak VO2, mL/min/kg 10.4±2.8 10.5 ±2.9 10.3±2.7 0.94
RER 1.06±0.1 1.07±0.1 1.03±0.09 0.25
VE/VCO2 slope 36.1±7.9 35±8 37.8±8 0.11
MIP, cmH2O 61.3 (51.3–72.5) 72 (55.7–92) 51 (38.6–66.6) <0.01
pp-MIP, % 71.1 (63.3–92.1) 90.6 (76.9−109) 56.1 (49.4–66) <0.01

Continuous and categorical variables are presented as mean (standard deviation), median (interquartile range) or percentages, as appropriate.
AHF: acute heart failure; BSA: body surface area; COPD: chronic obstructive pulmonary disease; E: early mitral inflow velocity; e′: early mitral valve
tissue inflow velocity; eGFR: estimated glomerular filtration rate; HF: heart failure; IMW: inspiratory muscle weakness; LAVI: left atrial volume index;
LVEF: left ventricular ejection fraction; MIP: maximal inspiratory mouth pressure; NT-proBNP: N-terminal pro brain natriuretic peptide; NYHA:
New York Heart Association; PASP: pulmonary artery systolic pressure; peakVO2: peak exercise pulmonary oxygen uptake; pp-MIP: percentage of
predicted maximal inspiratory mouth pressure; RER: respiratory exchange ratio; VE/VCO2 slope: relationship between minute ventilation and the
rate of CO2 elimination.
aEstimated GFR (eGFR) using the modification of diet in renal disease formula.
bData available in 32 patients.

in Figure 1. Likewise, IMW and Δ-MIP were not related to Discussion

Δ-peakVO2 (β coefficient −0.325, 95% CI −1.060–0.411,
P=0.377 and −0.001, 95% CI −0.007–0.004, P=0.621).
Covariates included in the final model were: history of
COPD (β coefficient −1.16, 95% CI 2.87–0.60), dyslipi-
demia (β coefficient −0.80, 95% CI −1.75–0.20) and his-
tory of ischaemic heart disease (β coefficient 1.49, 95% CI
0.67–2.32). In a sensitivity analysis (including in the mul-
tivariate model age, gender, NYHA class, COPD, dyslipi-
demia and history of ischaemic heart disease), pp-MIP
remained not associated with Δ-peakVO2 (β coefficient
0.005, 95% CI −0.010–0.020, P=0.529).
The most significant novel finding of this study is that in a
subset of older and deconditioned patients with HFpEF, a
12-week home-based IMT programme improved signifi-
cantly aerobic capacity, and the baseline inspiratory mus-
cle strength was not associated with this improvement.
These results suggest that a home-based programme of
IMT is a useful physical therapy in this population and
reveal the futility of IMW routine screening for selecting
patients with HFpEF who benefit from IMT.
Based on previous trials, a current exercise training con-
sensus document in patients with HF suggests that IMT can
Palau et al.
Figure 1. Relationship between baseline inspiratory muscle
function and changes in exercise capacity at 12 weeks after
inspiratory muscle training.
Δ-peakVO2: changes in peak oxygen uptake before and after 12 weeks
inspiratory muscle training; pp-MIP: percentage of predicted maximal
inspiratory pressure at baseline.
improve aerobic capacity and QoL, particularly in those
who present with IMW.12 Nevertheless, it is important to
highlight that this recommendation is based on scarce and
small studies. In addition, most of the evidence comes from
patients with HFrEF with heterogeneous findings.10
The present findings are in line with results found in
healthy individuals,21 older healthy women,22 COPD,23
pulmonary artery hypertension24 and asthmatic patients25
in whom IMT resulted in an improvement in exercise per-
formance regardless of baseline MIP.
In patients with HFpEF, recent evidence has shown that
a simple and home-based programme of IMT offers prom-
ising results in terms of aerobic capacity and QoL improve-
ment in elderly and deconditioned patients.14,26
We postulate there are some reasons that could explain
why baseline inspiratory muscle strength was not associ-
ated with the improvement in aerobic capacity after IMT
in patients with HFpEF. On the basis of the heterogeneous
pathophysiology of HFpEF, the role of other extracardiac
conditions for explaining exercise intolerance has gained
special importance in this syndrome.27 In this sense, sev-
eral studies have shown the crucial contribution of
impaired pulmonary function,28 activation of the central
and peripheral chemoreflex pathway29 and altered endothe-
lial function30 in the pathophysiology of HFpEF. IMT has
already shown improvement in: (a) neurovascular control
in patients with HF;31 (b) autonomic control in healthy
older women;22 (c) blood flow to resting and exercising
limbs in HF patients;32 (d) oxidative stress biomarkers of
endothelium in haemodialysis patients;31 (e) respiratory
muscle performance in pulmonary diseases;23–25 and (f)
ventilatory efficiency during exercise.14,31 Therefore, we
believe that IMT in patients with HFpEF may exert its
625
effect on pulmonary function through an improvement in
ventilatory efficiency and decreasing stress on respiratory
muscles during exercise secondary to augmented chem-
oreflex activity. Moreover, IMT could improve peripheral
blood flow by reducing sympathetic vasoconstrictor activ-
ity and improving endothelium function.23,32,33
Furthermore, in line with these results, a previous study
conducted for our group did not find an association
between exercise intolerance and baseline inspiratory
muscle function in patients with HFpEF.13 In addition, it is
important to discuss how other theoretical important base-
line predictors of aerobic capacity (for instance, age, gen-
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der and NYHA) were not associated with functional
improvement in this study. Along this line, we should be
cautioned interpreting these findings because this is a
highly selected population (elderly, comorbid and with
advanced NYHA class) in which these characteristics did
not largely differ among enrolled patients. The negative
association between COPD and improvement in peak VO2
could be explained by several factors such as a worse base-
line risk profile or greater baseline functional impair-
ment.34 Likewise, the positive association between
functional improvement and ischaemic heart disease could
be explained by an improvement in muscle strength, as has
been found for resistance training.35 For dyslipidemia, the
explanation for this negative association remains more
speculative, but we postulate the negative effect of statin
treatment on muscular function may play a role.36
Thus further studies should focus on defining the
exact mechanisms by which IMT improves aerobic
capacity in patients with HFpEF, but meanwhile a home-
based programme of IMT offers an alternative to conven-
tional exercise training that improves aerobic capacity in
deconditioned patients regardless of baseline inspiratory
muscle function.
Limitations
Our study has several limitations that deserve to be men-
tioned. First, as a single centre observational study, the
generalisability of our results to other populations may be
limited. Second, as a non-supervised training, we cannot
certainly evaluate the duration of training sessions. Third,
we do not evaluate the level of physical activity of each
patients during the training period. Finally, these findings
cannot be directly extrapolated to patients with milder
forms of the disease.
Conclusion
In symptomatic and deconditioned elderly patients with
HFpEF, IMT offers an alternative to conventional cardiac
rehabilitation programmes that improves maximal func-
tional capacity regardless of baseline MIP. Further studies
are warranted to confirm these results.
626
Implications for practice
•• Heart failure with preserved ejection fraction
prevalence increases with age and the clinical
hallmarks of this symdrome are dyspnea and
reduced aerobic capacity.
•• These patients are less likely to receive referral to
a conventional cardiac rehabilitation programme.
•• Home-based inspiratory muscle training is a
simple and harmless intervention that improved
aerobic capacity regardless of baseline maximal
inspiratory pressure.
Declaration of conflicting interests
The authors have no other funding, financial relationships, or
conflicts of interest to disclose.
Funding
This work was supported in part by grants from: Sociedad
Española de Cardiología: Investigación Clínica en Cardiología,
grant SEC 2015, CIBER CV 16/11/00420, 16/11/00403, FEDER
and PIE15/00013.
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