Inspiratory muscle training improves six-minute walk distance in adults with pulmonary arterial hypertension

Dr Rachael CordinaDepartment of Cardiology, Royal Prince Alfred Hospital University of SydneyMurdoch Children’s Research InstituteAustralia

Hypothesis and Aims

• Aims: To investigate the efficacy of inspiratory muscle training (IMT) on exercise capacity parameters in adults with pulmonary arterial hypertension

• Hypothesis: IMT will increase inspiratory muscle strength and improve exercise capacity

Outcome Measures

• Primary outcome exercise capacity parameters

• Peak oxygen uptake (VO2)

• Functional exercise capacity (six-minute walk distance)

• Secondary outcome measures

• Cardiac function

• Pulmonary function testing parameters

• Quality of life

• NT-proBNP

Methods: Recruitment and Randomization

• Participants were recruited at Royal Prince Alfred, St George and Macquarie University Hospital, Sydney Australia

• Randomized (sex stratified) into a ‘routine care’ control group or intervention group

• Inclusion criteria;

• Diagnosed group I or chronic thromboembolic pulmonary hypertension by RHC

• WHO FC II/III

• Aged 18 years and over

Randomized (n = 12)

Allocated to inspiratory muscle

training group (n = 6)

Allocated to control group of

‘routine care’ (n = 6)

Methods

▪ The intervention group participated in 8 weeks of inspiratory muscle training

▪ The control group continued with ‘routine care’

▪ At baseline and follow-up, participants underwent detailed assessment of;

▪ PImax (inspiratory muscle strength)

▪ PEmax (expiratory muscle strength)

▪ Peak oxygen uptake

▪ Functional exercise capacity (six-minute walk test)

▪ Pulmonary function testing

▪ Quality of life assessment (Minnesota Living with Heart Failure Questionnaire)

Inspiratory Muscle Training (IMT)

▪ Two cycles of 30 breaths at 30-40% of PImax on an electronic

IMT device (KHP2)

▪ Five days a week (one supervised session) for eight weeks

▪ PImax was reassessed every week using the KH2 device and

training intensity was adjusted accordingly

Results: Patient Characteristics

All PAH patients Control IMT

Sex (males/females) 2/10 1/5 1/5

Age (years) 60 ± 14 66 ± 10 55 ± 17

Height (m) 1.64 ± 0.11 1.65 ± 0.10 1.64 ± 0.13

Weight (kg) 68.2 ± 17.8 76.1 ± 20.5 60.3 ± 11.5

BMI (kg/m2) 25.1 ± 5.5 27.7 ± 5.7 22.6 ± 4.2

6MWD (m) 522.4 ± 115.6 549.5 ± 61.5 495.3 ± 154.4

WHO FC (II/III) 11/1 6/0 5/1

Right heart catheterization

mPAP (mmHg) 38.1 ± 10.2 38.3 ± 9.0 37.8 ± 12.1

PAWP (mmHg) 9.0 ± 2.4 10.4 ± 1.5 7.8 ± 2.5

PVR (Wood units) 6.7 ± 3.0 5.0 ± 1.7 7.5 ± 3.3

PAH Type (Group I/CTEPH) 11/1 5/1 5/1

Results: Respiratory Muscle Strength

• At baseline 58% of the cohort had inspiratory muscle weakness

(<80 cmH2O)

• Both the control and IMT groups improved their inspiratory muscle

strength (PImax)

• Control: +10.3 cmH2O

• IMT: +30.8 cmH2O

• Between group difference was +20.5 cmH2O, 95% CI 3.9 to 37.1,

p = 0.02

• There was no change in expiratory muscle strength (PEmax)

between groups at follow up, p = 0.5

Baseline Follow-up Baseline Follow-up

0

20

40

60

80

100

120

140

160

The Effect of IMT on Maximal Static Inspiratory Strength

PIm

ax c

mH

2O

IMT

Control

Primary Outcome 1: Functional Exercise Capacity (6MWD)

• No differences between groups at baseline, p = 0.4

• Control group: 549.5 m

• IMT group: 495.3 m

• After eight weeks of IMT, 6MWD increased by 24.5 m and

fell by 12 m in the control group

• Between-group difference of change was 36.5 m, 95% CI

3.5 to 69.5, p = 0.03

Primary Outcome 2: Peak Oxygen Uptake

• No significant between-group difference at follow up, p = 0.7

• Post hoc paired t-test:

• IMT +1.9 mL/kg/min, p = 0.03

• Control +1.5 mL/kg/min, p = 0.22

Baseline Follow-up Baseline Follow-up

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5

10

15

20

25

30

The Effect of IMT on Peak Oxygen Uptake

Peak V

O2 m

L/k

g/m

in

Control

IMT

Results: Pulmonary Function

Control IMT

n Baseline ∆ n Baseline ∆ Between-group difference (95% CI) p value

Spirometry

FVC (% pred) 6 91.0 -0.4 6 91.3 0.0 0.4 (-6.3 to 7.2) 0.89

FEV1 (% pred) 6 86.3 -0.4 6 87.1 -2.6 -2.2 (-7.3 to 2.9) 0.35

FEV1/FVC (% pred) 6 94.3 0.1 6 95.4 -2.3 -2.4 (-9.5 to 4.6) 0.46

Lung Volumes

FRC (% pred) 6 84.6 -0.7 6 93.9 -4.5 -3.8 (-17.3 to 9.7) 0.54

TLC (% pred) 6 90.9 -1.0 6 88.9 -2.2 -1.2 (-6.5 to 4.1) 0.62

RV (% pred) 6 87.3 -1.8 6 81.3 -5.5 -3.7 (-22.1 to 14.8) 0.67

RV/TLC (% pred) 6 91.9 -0.5 6 88.8 -3.8 -3.3 (-20.0 to 13.3) 0.67

ERV 6 0.62 0.02 6 1.13 -0.01 -0.03 (-0.24 to 0.19) 0.81

Diffusion

DLCO (% pred) 6 67.3 0.3 6 54.4 1.7 1.5 (-4.3 to 7.2) 0.59

∆ Difference after 8 weeks (follow-up – baseline), ‡Between-group difference of the mean change.

Results: Cardiac Function

• No significant change in neurohormonal activation (NT-proBNP) following IMT, p = 0.8

• There was also no changes in stroke volume at follow-up

Control IMT

n Baseline ∆ n Baseline ∆ Between-group difference (95% CI) p value‡

Baseline SV (mL) 4 62.8 1.2 6 70.0 -3.4 -4.6 (-14.8 to 5.6) 0.33

Baseline SVI (mL/m2) 4 32.7 0.9 6 43.0 -2.1 -3.0 (-8.7 to 2.7) 0.26

Peak SV (mL) 4 82.7 9.0 6 84.7 1.6 -7.4 (-17.5 to 2.7) 0.13

Peak SVI (mL/m2) 4 43.3 4.9 6 51.5 1.2 -3.7 (-9.7 to 2.2) 0.18

∆ Difference after 8 weeks (follow-up – baseline), ‡Between-group difference of the mean change.

Conclusions

• IMT improves inspiratory muscle strength and functional exercise capacity

• The effects of IMT on peak oxygen uptake remain uncertain

• IMT may be a beneficial adjunct therapy, especially in patients who are severely

debilitated or are unable to attend cardiac/pulmonary rehabilitation

Acknowledgments

• Mr Derek Tran

• Dr Phillip Munoz, Dr Edmund Lau, Dr Jennifer Alison, A/Prof Martin Brown, Dr Yizhong Zheng, Sr Patricia Corkery, Dr Keith Wong, Dr Steven Lindstrom, Prof David Celermajer, Prof Glen Davis