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Programas de rehabilitación con ejercicios para la hipertensión pulmonar

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References

References to studies included in this review

Chan 2013 {published data only}

Chan L, Chin LM, Kennedy M, Woolstenhulme JG, Nathan SD, Weinstein AA, et al. Benefits of intensive treadmill exercise training on cardiorespiratory function and quality of life in patients with pulmonary hypertension. Chest 2013;143(2):333‐43. [DOI: 10.1378/chest.12‐0993]CENTRAL
Chan L, Kennedy M, Woolstenhulme J, Connors G, Nathan S, Weir N, et al. Improved six‐minute walk distance and cardiorespiratory fitness in patients with pulmonary arterial hypertension following an intensive exercise program. Chest 2011;140(4):854A. CENTRAL
Weinstein AA, Chin LMK, Keyser RE, Kennedy M, Nathan SD, Woolstenhulme JG, et al. Effect of aerobic exercise training on fatigue and physical activity in patients with pulmonary arterial hypertension. Respiratory Medicine 2013;107(5):778‐84. [DOI: http://dx.doi.org/10.1016/j.rmed.2013.02.006]CENTRAL

Ehlken 2016 {published data only}

Ehlken N, Lichtblau M, Klose H, Weidenhammer J, Fischer C, Nechwatal R, et al. Exercise training improves peak oxygen consumption and haemodynamics in patients with severe pulmonary arterial hypertension and inoperable chronic thrombo‐embolic pulmonary hypertension: a prospective, randomized, controlled trial. European Heart Journal 2015;37(1):35‐44. CENTRAL

Ganderton 2013 {published data only}

Ganderton L, Gain K, Fowler R, Lunt D, Winship P, Bostock S, et al. Effects of exercise training on exercise capacity and quality of life in pulmonary arterial hypertension. Respirology 2013;18(Suppl 2):74 (P146). CENTRAL
Ganderton L, Jenkins S, Gain K, Fowler R, Winship P, Lunt D, et al. Short term effects of exercise training on exercise capacity and quality of life in patients with pulmonary arterial hypertension: protocol for a randomised controlled trial. BMC Pulmonary Medicine 2011;11:25. [DOI: 10.1186/1471‐2466‐11‐25]CENTRAL

Ley 2013 {published data only}

Ley S, Fink C, Risse F, Ehlken N, Fischer C, Ley‐Zaporozhan J, et al. Magnetic resonance imaging to assess the effect of exercise training on pulmonary perfusion and blood flow in patients with pulmonary hypertension. European Radiology 2013;23(2):324‐31. [DOI: http://dx.doi.org/10.1007/s00330‐012‐2606‐z]CENTRAL

Mereles 2006 {published data only}

Ehlken N, Mereles D, Kreuscher S, Ghofrani S, Hoeper MM, Halank M, et al. Exercise and respiratory training to improve exercise capacity and quality of life in patients with severe chronic pulmonary hypertension. European Respiratory Journal 2006;28(Suppl 50):372s (2220). CENTRAL
Mereles D, Ehlken N, Kreuscher S, Ghofrani S, Hoeper MM, Halank M, et al. Exercise and respiratory training improve exercise capacity and quality of life in patients with severe chronic pulmonary hypertension. Circulation 2006;114(14):1482‐9. [DOI: 10.1161/CIRCULATIONAHA.106.618397]CENTRAL

Wilkinson 2007 {published data only}

Wilkinson A, Elliot CA, Condliffe R, Mawson S, Armstrong IJ, Billings C, et al. A randomised‐controlled trial of a physiotherapist‐led rehabilitation programme in patients with pulmonary hypertension. European Respiratory Society 18th Annual Congress; 2008 Oct 3‐7; Berlin. 2008:P1004. CENTRAL
Wilkinson A, Elliot CA, Mawson S, Armstrong I, Billings C, Kiely DG. A randomised controlled trial to investigate the effects of a physiotherapist‐led rehabilitation programme on exercise capacity and quality of life measures in patients with pulmonary hypertension. Thorax 2007;62(Suppl iii):A16. CENTRAL

References to studies excluded from this review

Babu 2013 {published data only}

Babu AS, Padmakumar R, Maiya AG. A review of ongoing trials in exercise based rehabilitation for pulmonary arterial hypertension. Indian Journal of Medical Research 2013;137(5):900‐6. CENTRAL

Babu 2014 {published data only}

Babu AS, Padmakumar R, Maiya AG. Effects of the pulmonary hypertension manual (PulHMan) on awareness of exercise among patients with pulmonary hypertension. World Congress of Cardiology Scientific Sessions; 2014 May 4‐7; Melbourne. 2014:e311. CENTRAL

Barbosa 2011 {published data only}

Barbosa PB, Ferreira EMV, Arakaki JSO, Takara LS, Moura J, Nascimento RB, et al. Kinetics of skeletal muscle O2 delivery and utilization at the onset of heavy‐intensity exercise in pulmonary arterial hypertension. European Journal of Applied Physiology 2011;111(8):1851‐61. [DOI: 10.1007/s00421‐010‐1799‐6]CENTRAL

Becker Grunig 2013 {published data only}

Becker‐Gruenig T, Ehlken N, Gorenflo M, Hager A, Halank M, Lichtblau M, et al. Efficacy of exercise training in pulmonary arterial hypertension associated with congenital heart disease. ESC Congress; 2012 25‐28 Aug; Munich 2012;33 suppl 1(264):P1676. CENTRAL
Becker‐Grunig T, Klose H, Ehlken N, Lichtblau M, Nagel C, Fischer C, et al. Efficacy of exercise training in pulmonary arterial hypertension associated with congenital heart disease. International Journal of Cardiology 2013;168(1):375‐81. CENTRAL

Bernheim 2007 {published data only}

Bernheim AM, Kiencke S, Fischler M, Dorschner L, Debrunner J, Mairbäurl H, et al. Acute changes in pulmonary artery pressures due to exercise and exposure to high altitude do not cause left ventricular diastolic dysfunction. Chest 2007;132(2):380‐7. [DOI: 10.1378/chest.07‐0297]CENTRAL

Ehlken 2014 {published data only}

Ehlken N, Verduyn C, Tiede H, Staehler G, Karger G, Nechwatal R, et al. Economic evaluation of exercise training in patients with pulmonary hypertension. Lung 2014;192(3):359‐66. [DOI: http://dx.doi.org/10.1007/s00408‐014‐9558‐9]CENTRAL

Fox 2011 {published data only}

Fox BD, Kassirer M, Weiss I, Raviv Y, Peled N, Shitrit D, et al. Ambulatory rehabilitation improves exercise capacity in patients with pulmonary hypertension. Journal of Cardiac Failure 2011;17(3):196‐200. CENTRAL

Grunig 2011 {published data only}

Grunig E, Ehlken N, Ghofrani A, Staehler G, Meyer FJ, Juenger J, et al. Effect of exercise and respiratory training on clinical progression and survival in patients with severe chronic pulmonary hypertension. Respiration 2011;81(5):394‐401. CENTRAL

Grunig 2012 {published data only}

Grunig E, Maier F, Ehlken N, Fischer C, Lichtblau M, Blank N, et al. Exercise training in pulmonary arterial hypertension associated with connective tissue diseases. Arthritis Research and Therapy 2012;14(3):R148. CENTRAL
Maier F, Gruenig E, Ehlken N, Fischer C, Lichtblau M, Blank N, et al. Exercise training in pulmonary arterial hypertension associated with connective tissue diseases. ESC Congress; 2012 25‐29 August; Munich. 2012, issue var.pagings:515. CENTRAL

Kabitz 2014 {published data only}

Kabitz HJ, Bremer HC, Schwoerer A, Sonntag F, Walterspacher S, Walker DJ, et al. The combination of exercise and respiratory training improves respiratory muscle function in pulmonary hypertension. Lung 2014;192(2):321‐8. CENTRAL

Kolesnikova 2011a {published data only}

Kolesnikova E, Arutyunov G, Rylova A, Rylova N. Respiratory muscle trainings started in acute period of complicated myocardial infarction in patients with pulmonary hypertension. Circulation 2011;124(21):suppl 1. CENTRAL

Kolesnikova 2011b {published data only}

Kolesnikova EA, Arutyunov GP, Rylova NV, Rylova AK. Rehabilitation of patients with severe heart failure and pulmonary hypertension. EuroPRevent; 2011 April 14‐16; Geneva. 2011, issue var.pagings:S2. CENTRAL

Marvisi 2013 {published data only}

Marvisi M, Herth FJF, Ley S, Poletti V, Chavannes NH, Spruit MA, et al. Selected clinical highlights from the 2012 ERS congress in Vienna. European Respiratory Journal 2013;41(5):1219‐27. CENTRAL

Nagel 2012 {published data only}

Nagel C, Prange F, Guth S, Herb J, Ehlken N, Fischer C, et al. Exercise training improves exercise capacity and quality of life in patients with inoperable or residual chronic thromboembolic pulmonary hypertension. PloS one 2012;7(7):e41603. CENTRAL
Prange F, Guth S, Ehlken N, Reichenberger F, Halank M, Kabitz HJ, et al. Exercise training improved exercise capacity and quality of life in patients with inoperable or residual chronic thromboembolic pulmonary hypertension. ESC Congress; 2012 25‐29 August; Munich. 2012:416. CENTRAL

Robalo Cordeiro 2011 {published data only}

Robalo Cordeiro C, Singh S, Herth FJ, Ley S, Chavannes NH, Clini E, et al. Selected clinical highlights from the 2010 ERS Congress in Barcelona. European Respiratory Journal 2011;38(1):209‐17. CENTRAL

Additional references

Babu 2016a

Babu AS, Padmakumar R, Maiya AG, Mohapatra AK, Kamath RL. Effects of exercise training on exercise capacity in pulmonary arterial hypertension: a systematic review of clinical trials. Heart, Lung and Circulation 2016;25(4):333‐41.

Babu 2016b

Babu AS, Arena R, Myers J, Padmakumar R, Maiya AG, Cahalin LP, et al. Exercise intolerance in pulmonary hypertension: mechanism, evaluation and clinical implications. Expert Review of Respiratory Medicine September 2016;10(9):979‐90.

Benza 2010

Benza RL, Miller DP, Gomberg‐Maitland M, Frantz RP, Foreman AJ, Coffey CS, et al. Predicting survival in pulmonary arterial hypertension: insights from the registry to evaluate early and long‐term pulmonary arterial hypertension disease management (REVEAL). Circulation 2010;122(2):164‐72.

Buys 2015

Buys R, Avila A, Cornelissen VA. Exercise training improves physical fitness in patients with pulmonary arterial hypertension: a systematic review and meta‐analysis of controlled trials. BMC Pulmonary Medicine 2015;15:40.

Casserly 2009

Casserly B, Klinger JR. Brain natriuretic peptide in pulmonary arterial hypertension: biomarker and potential therapeutic agent. Drug Design, Development and Therapy 2009;3:269‐87.

Coggan 1992

Coggan AR, Spina RJ, King DS, Rogers MA, Brown M, Nemeth PM, et al. Skeletal muscle adaptations to endurance training in 60‐ to 70‐yr‐old men and women. Journal of Applied Physiology 1992;72(5):1780‐6.

Covidence 2016 [Computer program]

Veritas Health Innovation. Covidence systematic review software. Melbourne, Australia: Veritas Health Innovation, Accessed 2016.

D'Alonzo 1991

D'Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, et al. Survival in patients with primary pulmonary hypertension: Results from a national prospective registry. Annals of Internal Medicine 1991;115(5):343‐9.

de Man 2009

de Man FS, Handoko ML, Groepenhoff H, van't Hul AJ, Abbink J, Koppers RJ, et al. Effects of exercise training in patients with idiopathic pulmonary arterial hypertension. European Respiratory Journal 2009;34(3):669‐75.

Deeks 2011

Deeks JJ, Higgins JPT, Altman DG (editors). Chapter 9: Analysing data and undertaking meta‐analyses. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.handbook.cochrane.org.

Downs and Black 1998

Downs SH, Black N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non‐randomised studies of health care interventions. Journal of Epidemiology and Community Health 1998;52:377‐84.

Ennion 1995

Ennion S, Sant'ana Pereira J, Sargeant AJ, Young A, Goldspink G. Characterization of human skeletal muscle fibres according to the myosin heavy chains they express. Journal of Muscle Research and Cell Motility 1995;16(1):35‐43.

Fowler 2012

Fowler RM, Gain KR, Gabbay E. Exercise intolerance in pulmonary arterial hypertension. Pulmonary Medicine 2012;Article ID 359204:10. [DOI: 10.1155/2012/359204]

Frost 2013

Frost AE, Badesch DB, Miller DP, Benza RL, Meltzer LA, McGoon MD. Evaluation of the predictive value of a clinical worsening definition using 2‐year outcomes in patients with pulmonary arterial hypertension: a REVEAL Registry analysis. Chest 2013;144(5):1521‐9.

Galie 2009

Galie N, Hoeper MM, Humbert M, Torbicki A, Vachiery JL, Barbera JA, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension. European Respiratory Journal 2009;34(6):1219‐63.

Galie 2013

Galie N, Corris PA, Frost A, Girgis RE, Granton J, Jing ZC, et al. Updated treatment algorithm of pulmonary arterial hypertension. Journal of the American College of Cardiology 2013;62(25 Suppl):60‐72.

Galie 2015

Galiè N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The joint task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). European Respiratory Journal 2015;46(4):903‐75.

Gollnick 1973

Gollnick PD, Armstrong RB, Saltin B, Saubert CW, Sembrowich WL, Shepherd RE. Effect of training on enzyme activity and fiber composition of human skeletal muscle. Journal of Applied Physiology 1973;34(1):107‐11.

GRADEpro GDT 2015 [Computer program]

GRADE Working Group, McMaster University. GRADEpro GDT. Version accessed 23 September 2016. Hamilton, Ontario: GRADE Working Group, McMaster University, 2014.

Higgins 2003

Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. BMJ 2003;327:557‐60.

Higgins 2011a

Higgins JPT, Altman DG, Sterne JAC (editors). Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.handbook.cochrane.org.

Hoeper 2013

Hoeper MM, Bogaard HJ, Condliffe R, Frantz R, Khanna D, Kurzyna M, et al. Definitions and diagnosis of pulmonary hypertension. Journal of the American College of Cardiology 2013;62(25 Suppl):D42‐50.

Holland 2014

Holland AE, Spruit MA, Troosters T, Puhan MA, Pepin V, Saey D, et al. An official European Respiratory Society/American Thoracic Society technical standard: field walking tests in chronic respiratory disease. European Respiratory Journal 2014;44(6):1428‐46.

Mainguy 2010a

Mainguy V, Maltais F, Saey D, Gagnon P, Martel S, Simon M, et al. Peripheral muscle dysfunction in idiopathic pulmonary arterial hypertension. Thorax 2010;65(2):113‐7.

Mainguy 2010b

Mainguy V, Maltais F, Saey D, Gagnon P, Martel S, Simon M, et al. Effects of a rehabilitation program on skeletal muscle function in idiopathic pulmonary arterial hypertension. Journal of Cardiopulmonary Rehabilitation 2010;30(5):319‐23.

Martinez‐Quintana 2010

Martinez‐Quintana E, Miranda‐Calderin G, Ugarte‐Lopetegui A, Rodriguez‐Gonzalez F. Rehabilitation program in adult congenital heart disease patients with pulmonary hypertension. Congenital Heart Disease 2010;5(1):44‐50.

Mathai 2012

Mathai SC, Puhan MA, Lam D, Wise RA. The minimal important difference in the6‐minute walk test for patients with pulmonary arterial hypertension. American Journal of Respiratory and Critical Care Medicine September 2012;185(5):428‐33.

McGoon 2013

McGoon MD, Benza RL, Escribano‐Subias P, Jiang X, Miller DP, Peacock AJ, et al. Pulmonary arterial hypertension: epidemiology and registries. Journal of the American College of Cardiology 2013;62(25 Suppl):51‐9.

Morris 2015

Morris NR, Seale H, Harris J, Hall K, Hopkins P, Kermeen F. Serious adverse events during a 6‐min walk test in patients with pulmonary hypertension. European Respiratory Journal 2015;45(4):1179‐82.

NYHA 1994

Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels. 9. Boston, Mass: Little, Brown & Co, 1994:253‐255.

Ogawa 1992

Ogawa T, Spina RJ, Martin WH, Kohrt WM, Schechtman KB, Holloszy JO, et al. Effects of aging, sex, and physical training on cardiovascular responses to exercise. Circulation 1992;86(2):494‐503.

Panagiotou 2015

Panagiotou M, Peacock AJ, Johnson MK. Respiratory and limb muscle dysfunction in pulmonary arterial hypertension: a role for exercise training?. Pulmonary Circulation 2015;5(3):424‐34.

Pandey 2015

Pandey A, Khunger M, Garg S, Kumbhani DJ, Chin KM, Berry JD. Efficacy and safety of exercise training in chronic pulmonary hypertension: systematic review and meta‐analysis. Circulation Heart Failure 2015;8(6):1032‐43.

Piepoli 2014

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Pluim 2000

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Provencher 2006

Provencher S, Chemla D, Herve P, Sitbon O, Humbert M, Simonneau G. Heart rate responses during the 6‐minute walk test in pulmonary arterial hypertension. European Respiratory Journal 2006;27(1):114‐20.

Provencher 2008

Provencher S, Herve P, Sitbon O, Humbert M, Simonneau G, Chemla D. Changes in exercise haemodynamics during treatment in pulmonary arterial hypertension. European Respiratory Journal 2008;32(2):393‐8.

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Simonneau 2013

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Characteristics of studies

Characteristics of included studies [ordered by study ID]

Jump to:

Chan 2013

Methods

Study design: RCT

Study grouping: Parallel group

Participants

Baseline characteristics

Exercise training

  • Number enrolled: 10

  • Gender (male/female): 0/10

  • Age (years): 53 (13)

  • Body Mass Index: 30.2 (7)

  • Haemodynamics: mPAP (mmHG, RHC): 40.3 (13.8)

  • Haemodynamics: PVR (Wood Units, RHC): 508 (293)

  • Height (cm):

  • Weight (kg):

  • Medications (mono/dual/triple): 5/1/4

  • NYHA, WHO Functional Class (I/II/III/IV): 1/4/4/1

Control

  • Number enrolled: 13

  • Gender (male/female): 0/13

  • Age (years): 55.5 (8.5)

  • Body Mass Index: 31.8 (7.4)

  • Haemodynamics: mPAP (mmHG, RHC): 43.8 (14.2)

  • Haemodynamics: PVR (Wood Units, RHC): 583 (409)

  • Height (cm):

  • Weight (kg):

  • Medications (mono/dual/triple): 2/5/5 (one had no therapy)

  • NYHA, WHO Functional Class (I/II/III/IV): 0/208/5/0

Included criteria: Quote "Patients with World Health Organization (WHO) group 1 PH were recruited from local outpatient clinics and enrolled between September 2009 and October 2011. Men and women were eligible if they were between 21 and 82 years of age, had PH diagnosed by a resting mean pulmonary arterial pressure ≥ 25 mm Hg as measured by right‐sided heart catheterization, were on stable PH therapies for at least 3 months, were sedentary, and had no pulmonary rehabilitation for 6 months prior to enrolment".

Excluded criteria: Quote "To avoid “ceiling” or “floor” effects, patients were excluded if they were classified ed as WHO and New York Heart Association (NYHA) functional class I and could walk 400 m during a 6MWT, or classified as functional class IV and could not walk 50 m during a 6MWT. Additional exclusion criteria included FEV1 /FVC ratio ≤ 65%; history of ischaemic heart disease; ejection fraction < 40%; documented pulmonary capillary wedge pressure ≥ 18 mm Hg; significant hepatic, renal, or mitochondrial dysfunctions; severe psychiatric disease; use of medications that may limit exercise capacity or ability to adapt to exercise training; antiretroviral therapies; illicit drugs; tobacco use; or pregnancy".

Pretreatment: Control group had worse lung function

Interventions

Intervention characteristics

Exercise training

  • Setting: outpatient programme

  • Components: exercise training and education

  • Training dose (frequency number/week): 2‐3 times/week (24‐30 sessions in total, 10‐week programme). Mean number of sessions 28 ± 2

  • Training dose (duration ‐ min): 30‐45 min

  • Training dose (intensity): quote: "A target exercise intensity of 70% to 80% of each patient’s heart rate (HR) reserve obtained from the baseline CPET was used to guide each exercise session. Target HR range was calculated ....in accordance with the method of Karvonen."

  • Training dose (mode): treadmill walking

  • Education (total hours): 10, "The education sessions consisted of weekly 1‐hour lectures on anatomy and physiology, lung disease processes, medication use, oxygen therapy, sleep disorders, preventing infection, airway clearance, interpreting pulmonary function tests, energy conservation, panic control, relaxation techniques, breathing retraining, community resources, advance directives, social well being, nutrition, and benefits of exercise."

Control

  • Education only

Outcomes

6MWD

VO2peak

Anaerobic threshold
HRQoL (SF‐36): Physical functioning

HRQoL (SF‐36): Role physical

HRQoL (SF36): Bodily pain

HRQoL (SF‐36): General health

HRQoL (SF‐36): Vitality

HRQoL (SF‐36): Social function

HRQoL (SF‐36): Role emotional

HRQoL (SF‐36): Mental health

HRQoL: Physical summary score (SF‐36)

HRQoL: Mental summary score (SF‐36)

HRQol (CAMPHOR): Symptoms

HRQol (CAMPHOR): Activities

HRQol (CAMPHOR): QoL

NYHA Class

Identification

This work was supported by the US National Institutes of Health (Intramural Funds 1 Z01 CL060068‐05 CC)

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "Patients who enrolled in the protocol were sequentially assigned subject numbers that randomly corresponded to a group receiving concurrent patient education plus aerobic exercise training (EXE) or to a group that received only the patient education portion of the regimen (EDU)."

Allocation concealment (selection bias)

Unclear risk

Not specified. Quote " Following the baseline evaluations, patients were informed of the group to which they were randomly assigned"

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Quote: "Study personnel were blind to the randomization of patients during all baseline evaluations."

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote: "Investigators administering the CPET, 6MWT, and questionnaires were blind to randomization at baseline."

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Quote: "criterion (Fig. 1). All 29 of these patients performed base‐ line testing. Based on their test responses, two of these patients were required to obtain additional medical clearance prior to beginning the intervention. One patient declined further participation while the other patient was cleared for participation and subsequently assigned a new subject number upon re‐entry into the protocol. This patient was originally assigned a subject number corresponding to EXE, but at re‐entry the randomization procedure resulted re‐assignment to EDU. As such, 28 patients in total participated in either the EXE or EDU groups (Fig. 1). Of the 14 patients allocated to the EXE group, two patients withdrew due to changes in medication and one withdrew due to low attendance at the exercise sessions. One patient in the EDU group was withdrawn from the study due to medication changes."

Selective reporting (reporting bias)

High risk

Comment: Trial protocol at clinicaltrials.gov states that they were also going to collect IPAQ, stages of exercise change, exercise self efficacy, profile of mood states and near infrared spectroscopy

Other bias

Low risk

Ehlken 2016

Methods

Study design: RCT

Study grouping: Parallel group

Participants

Baseline characteristics

Exercise

  • Number enrolled: 46

  • Gender (male/female): 20/26

  • Type of PH: CTEPH n = 11, PAH n = 35

  • Haemodynamics: PASP (mmHG, Echo):

  • Haemodynamics: CI (L/min/m2, Echo):

  • Haemodynamics: mPAP (mmHG, RHC): 41 (11.7)

  • Haemodynamics: PVR (Dyne.s/cm5, RHC): 540 (267)

  • Age: 55(15)

  • Height (cm): 170 (9)

  • Weight (kg): 75( 18)

  • Medications (single/double/triple): 13/20/6

  • NYHA, WHO Functional Class (I/II/III/IV): 0/8/36/0

  • B‐type natriuretic peptide (pg/mL): 1163+2520

Control

  • Number enrolled: 41

  • Gender (male/female): 20/21

  • Type of PH: CTEPH n = 15, PAH n = 26

  • Haemodynamics: PASP (mmHG, Echo):

  • Haemodynamics: CI (L/min/m2, Echo):

  • Haemodynamics: mPAP (mmHG, RHC): 37.6(11.8)

  • Haemodynamics: PVR (Dyne.s/cm5, RHC): 512(338)

  • Age: 57(15)

  • Height (cm):171 (8)

  • Weight (kg): 79 (18)

  • Medications (single/double/triple): 14/22/4

  • NYHA, WHO Functional Class (I/II/III/IV): 0/6/30/4

  • B‐type natriuretic peptide (pg/mL): 1114+1386

Included criteria: participants with PAH and inoperable or persistent CTEPH and chronic right heart failure who were stable on disease‐targeted medication for at least 2 months prior to inclusion were randomly assigned to a control and a training group. Medication remained unchanged during the study period.

Excluded criteria: not specified

Pretreatment: Nil evident

Interventions

Intervention characteristics

Exercise

  • Setting: 3 weeks inpatient training, followed by 12 weeks unsupervised outpatient training at home

  • Components: exercise training, mental training, psychological support

  • Training ose frequency: inpatient, walking and cycling 7 d/week, resistance exercises and respiratory training 5 d/week. Outpatient, cycling 5 x/week, walk twice a week, respiratory training and resistance ex second daily.

  • Intervention (mode): interval bicycle ergometer training, walking, respiratory training, resistance training

  • Training dose: duration: 10‐25 min cycle ergometer, 60 min walking, 30 min resistance training, 30 min respiratory training

  • Training dose: intensity: cycle ergometer: 60%‐80% of HR on CPET. HR maintained < 120 bpm, oxygen saturation > 85%

Control

  • Continued usual lifestyle

Outcomes

6MWD

VO2peak

Wpeak (peak power)

Morbidity ‐ adverse events

Disease Progression

Precluded from Training

HRQoL (SF‐36): Physical functioning

HRQoL (SF‐36): Role physical

HRQoL (SF36): Bodily pain

HRQoL (SF‐36): General health

HRQoL (SF‐36): Vitality

HRQoL (SF‐36): Social function

HRQoL (SF‐36): Role emotional

HRQoL (SF‐36): Mental health

Discontinued training

Haemodynamics ‐ mPAP (mmHg), PVR (Dynes), cardiac output (L/min)

B‐type natriuretic peptide

Identification

Sponsorship Source: funding to pay the open access publication charges for this article was provided by Centre for Pulmonary Hypertension, Thorax clinic at the University of Heidelberg, Germany

Comments Author's contact details Nicola Ehlken University Hospital Heidelberg, [email protected]‐heidelberg.de Amalienstrasse 5, Heidelberg D‐69126, Germany

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Does not specify methods of randomisation

Allocation concealment (selection bias)

Unclear risk

Does not specify whether allocation was concealed

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Not possible to blind participants to intervention

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Quote: "Assessment of 6MWD, SF‐36 and other efficacy parameter were performed by investigators who were blinded to the clinical data"

Not clear whether assessors were blinded to group allocation, especially for primary outcome

Incomplete outcome data (attrition bias)
All outcomes

High risk

Differential attrition ‐ 17% lost to follow‐up in exercise group, none lost to follow‐up in control group

Selective reporting (reporting bias)

High risk

Not all outcomes specified in the trial protocol are reported

Other bias

High risk

CONSORT diagram does not report how many people were assessed to arrive at the 95 participants enrolled

Ganderton 2013

Methods

Study design: RCT

Study grouping: Parallel group

Participants

Baseline characteristics

Exercise

  • Number enrolled: 5

  • Gender (male/female): 0/5

  • Age (years): 51 (40–53)

  • Body Mass Index: 26 (23–41)

  • Haemodynamics: mPAP (mmHG, RHC): 23 (19‐29)

  • Haemodynamics: PVR (Dynes, RHC):

  • FVC (% predicted): 98 (92–102)

  • NYHA WHO Functional Class (I/II/III/IV): 0/3/2/0

  • Medications (single/double/triple): 3/2

  • Median sessions 31 of 26

Control

  • Number enrolled: 5

  • Gender (male/female): 1/4

  • Age (years): 53 (42–57)

  • Body Mass Index: 28 (26–31)

  • Haemodynamics: mPAP (mmHG, RHC): 49 (20‐65)

  • Haemodynamics: PVR (Dynes, RHC):

  • FVC (% predicted): 78 (72–110)

  • NYHA Functional Class (I/II/III/IV): 0/3/2/0

  • Medications (single/double/triple): 3/2

Included criteria: participants were included in the study if they had a confirmed diagnosis of idiopathic PAH, familial PAH or PAH associated with connective tissue disorders, based on elevated pulmonary artery pressures (> 25 mmHg at rest or > 30 mmHg during exercise) measured by right heart catheterisation; were medically stable and had been on PAH‐specific pharmaceutical therapy for 3 months prior to enrolment into the study; were in WHO functional class II or III; and were willing to complete the 12‐week supervised and 12‐week home exercise training programmes.

Excluded criteria: participants were excluded if they had:

  • resting hypoxaemia requiring supplemental oxygen therapy;

  • significant musculoskeletal disease, claudication pain, neurological or cognitive impairment, psychiatric/psychological or mood disorders that may have affected their ability to undertake exercise testing or training;

  • a history of moderate or severe chronic lung disease;

  • cardiac disease associated with cardiac failure, poorly controlled angina, unstable cardiac rhythm;

  • participated in a supervised exercise training programme within the last 12 months

Pretreatment: nil

Interventions

Intervention characteristics

Exercise

  • Setting: outpatient

  • Components: exercise only

  • Training dose (frequency number per week): 3 times per week, 12 weeks

  • Training dose (duration ‐ min): 60 min class

  • Training dose (intensity): 12 weeks. "Intensity for the lower limb endurance exercises will be prescribed with the aim of achieving 60‐70% HR max (based on age predicted maximum,220‐age [37]), while maintaining SpO2 ≥ 92% and symptom intensity (Borg CR10 dyspnoea < 4 and RPE < 4). Exercise intensity will be progressed, based on the individual’s response to training to maintain HR within the target HR range."

  • Training dose (mode): lower limb endurance training (walking and cycling). Lower limb functional strength training (step ups and sit to stands) and endurance training of the upper limbs

  • Education (total hours): 0

Control

  • Training dose (frequency number per week): nil

  • Training dose (duration ‐ min): nil

  • Training dose (intensity): nil

  • Training dose (mode): nil

  • Education (total hours): 0

Outcomes

6MWD

VO2peak

Wpeak

Anaerobic threshold

HRQoL (SF‐36): Physical functioning

HRQoL (Sf‐36): Role physical

HRQoL (SF36): Bodily pain

HRQoL (SF‐36): General health

HRQoL (SF‐36): Vitality

HRQoL (SF‐36): Social function

HRQoL (SF‐36): Role emotional

HRQoL (SF‐36): Mental health

HRQol (CAMPHOR): Symptoms

HRQol (CAMPHOR): Activities

HRQol (CAMPHOR): QoL

Morbidity

Disease progression

Symptoms precluding training

Discontinued training

NYHA class

HRQoL: Physical summary score (SF‐36)

HRQoL: Mental summary score (SF‐36)

Assessed at baseline, 12 weeks (post intervention) and 24 weeks (follow‐up)

Identification

Sponsorship source: Advanced Lung Disease Unit at Royal Perth Hospital and the Lung Institute of Western Australia

Country: Australia

Setting: Outpatient, hospital

Comments:

Author's name: Louise Ganderton

Institution: Curtin University

Email: [email protected]

Address: School of Physiotherapy, Faculty of Health Sciences, The University of Sydney

Notes

Protocol paper published: Ganderton 2011

Thesis available: http://espace.library.curtin.edu.au:80/R?func=dbin‐jump‐full&local_base=gen01‐era02&object_id=198083

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

From thesis: "Permuted block randomisation with block sizes of four was used to generate a randomisation chart. Fourteen blocks were created in total using a web‐based research randomiser."

Allocation concealment (selection bias)

Unclear risk

Not specified

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Not possible to blind participants to intervention

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

From thesis: "The primary investigator (LG) carried out all assessments at baseline, 12 weeks and 24 weeks and was blinded to the participants group allocation...The physiotherapists responsible for conducting the exercise training sessions were not involved in any of the formal assessments"

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Data available on all recruited participants for ITT. However planned to enrol 34 and only recruited 10

Selective reporting (reporting bias)

Low risk

All outcomes reported

Other bias

Low risk

Ley 2013

Methods

Study design: RCT

Study grouping: Parallel group

Participants

Baseline characteristics

Exercise

  • Number enrolled: 10

  • Gender (male/female): 2/8

  • Age (years): 47 (8)

  • Type of PH: Group 1 PH n = 9, CTEPH n = 1

  • Haemodynamics: mPAP (mmHG, RHC):

  • Haemodynamics: PVR (Wood Units, RHC):

  • Height (cm): 168 (12)

  • Weight (kg): 69 (11)

  • Medications (mono/dual/triple): 2/6/2

  • NYHA, WHO Functional Class (I/II/III/IV): 0/3/7/0

Control

  • Number enrolled: 10

  • Gender (male/female): 4/6

  • Age (years): 54 (14)

  • Type of PH: Group 1 PH n = 7, CTEPH n = 3

  • Haemodynamics: mPAP (mmHG, RHC):

  • Haemodynamics: PVR (Wood Units, RHC):

  • Height (cm): 165 (5)

  • Weight (kg): 76 (17)

  • Medications (mono/dual/triple): 3/6/1

  • NYHA, WHO Functional Class (I/II/III/IV): 0/1/9/0

Included criteria: adults (≥ 18 years) with confirmed PAH and CTEPH who underwent complete clinical work‐up including RHC. All participants were stable under optimised medical therapy (such as endothelin antagonists, iloprost, sildenafil, calcium channel blockers, anticoagulants, diuretics and supplemental oxygen) for at least 3 months before entering the study. Additional inclusion criteria were WHO functional class II to III

Excluded criteria: no recent syncope, and no skeletal or muscle abnormalities prohibiting participation in an exercise training programme

Pretreatment: nil

Interventions

Intervention characteristics

Exercise

  • Setting: inpatient

  • Components: "specialized respiratory and exercise training programme"

  • Training dose: frequency: cycle ergometry and walking daily, resistance training 5 x/week, 3 weeks

  • Training dose: duration: 10‐25 min/day cycle ergo, 60 mins walking/day, 30 mins respiratory training, light weights (500‐1000 g)

  • Training dose: intensity: commence at 60%‐80% of HR on CPET, progress as per individual tolerability and improvement

  • Intervention (mode): respiratory and exercise training programme as per Mereles 2006 ‐ interval training on cycle ergometer, walking, resistance training, respiratory training (PLB, body perception, yoga, respiratory muscle training)

Control

  • "Patients in the control group received a programme without specific exercise training."

Outcomes

Morbidity ‐ adverse events

Disease progression

Precluded from training

6MWD

Identification

Sponsorship source: this work was supported by the German National Research Agency (DFG): “Image‐based V/Q analysis” (FOR 474‐2)

Country: Germany

Setting: inpatient rehabilitation

Comments:

Author's name: Sebastian Ley

Institution: University Hospital Heidelberg

Email: [email protected]

Address: Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Im Neuenheimer Feld 430,69120 Heidelberg, Germany

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "patients were randomly assigned to either a training or a control group using a permuted block randomization procedure."

Allocation concealment (selection bias)

Unclear risk

The method of allocation was not specified.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Unabel to blind participants or personnel due to the to intervention

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote: "Assessment of 6MWD and MR examination were performed by investigators who were blinded to the clinical data and group assignment of the patients. Evaluation of the MR data was done blinded to the clinical setting and in random order."

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All randomised patients were analysed

Selective reporting (reporting bias)

Low risk

Unclear whether trial was registered but reporting does not appear selective

Other bias

Low risk

Mereles 2006

Methods

Study design: RCT

Study grouping: Parallel group

Participants

Baseline characteristics

Exercise

  • Number enrolled: 15

  • Gender (male/female): 5/10

  • Age (years): 47 (12)

  • Type of PH: PAH n = 13, CTEPH n = 2

  • Haemodynamics: PASP (mmHG, Echo): 61 (18)

  • Haemodynamics: CI (L/min/m2, Echo):

  • Haemodynamics: mPAP (mmHG, RHC): 49.5 (17.6)

  • Haemodynamics: PVR (Dyne.s/cm5, RHC): 968.7 (444.1)

  • Height (cm): 171 (11)

  • Weight (kg): 75 (13)

  • Medications (single/double/triple): 6/5/4

  • NYHA, WHO Functional Class (I/II/III/IV): 0/2/12/1

Control

  • Number enrolled: 15

  • Gender (male/female): 5/10

  • Age (years) 53 (14)

  • Type of PH: PAH n = 11, CTEPH n = 4

  • Haemodynamics: PASP (mmHG, Echo): 61 (18)

  • Haemodynamics: CI (L/min/m2, Echo):

  • Haemodynamics: mPAP (mmHG, RHC): 49.6 (12.3)

  • Haemodynamics: PVR (Dyne.s/cm5, RHC): 901.8 (358.0)

  • Height (cm): 166 (5)

  • Weight (kg): 78 (18)

  • Medications (single/double/triple): 7/5/3

  • NYHA, WHO Functional Class (I/II/III/IV): 0/4/10/1

Included criteria: people with severe chronic PH who were stable and compensated under optimised medical therapy (such as endothelin antagonists, iloprost, sildenafil, calcium channel blockers, anti‐coagulants, diuretics, and supplemental oxygen) for at least 3 months before entering the study were invited to participate. Additional inclusion criteria were age 18‐75 years, WHO functional class II to IV.

Excluded criteria: no recent syncope, and no skeletal or muscle abnormalities prohibiting participation in an exercise programme

Pretreatment: Nil evident

Interventions

Intervention characteristics

Exercise

  • Setting: 3 weeks inpatient followed by 12 weeks outpatient, unsupervised training

  • Components: exercise training (see below), mental training to improve perception of physical abilities and limits to keep physical exercise safe even in demanding situations, dumbbell training of single muscle groups with low weights (500‐1000 g) and 30 min of respiratory training, including stretching, breathing techniques such as pursed lip breathing, body perception, yoga, and strengthening of respiratory muscles

  • Training dose: frequency: inpatient: walking and cycling 7 d/week, resistance ex and respiratory training 5 d/week. Outpatient: cycling 5 x/week, walk twice a week, respiratory training and resistance ex second daily

  • Intervention (mode): interval bicycle ergometer training, walking, respiratory training, resistance training

  • Training dose: duration: 10‐25 min cycle ergometer, 60 min walking, 30 min resistance training, 30 min respiratory training

  • Training dose: intensity: cycle ergometer; 60%‐80% of HR on CPET. HR maintained < 120 bpm, oxygen saturation > 85%

Control

  • Intervention (mode): "Patients in the control group received a common rehabilitation program based on healthy nutrition, physical therapy such as massages, inhalation, counselling, and muscular relaxation without exercise and respiratory training but were allowed to perform daily activity as usual. All patients were advised to avoid heavy exercise"

  • Training dose: duration: 0 (I) 0 (O)

  • Training dose: intensity: 0 (I) 0 (O)

  • 10 of 15 participants entered the exercise training arm at the end of the study

Outcomes

6MWD

VO2peak

Wpeak

Morbidity ‐ adverse events

Disease progression

Precluded from training

Anaerobic threshold

HRQoL (SF‐36): Physical functioning

HRQoL (SF‐36): Role physical

HRQoL (SF36): Bodily pain

HRQoL (SF‐36): General health

HRQoL (SF‐36): Vitality

HRQoL (SF‐36): Social function

HRQoL (SF‐36): Role emotional

HRQoL (SF‐36): Mental health

HRQoL:Physical Summary score (SF36)

HRQoL:Mental Summary score (SF36)

HRQol (CAMPHOR): QoL

NYHA Class

Discontinued training

Identification

Sponsorship source: this study was funded by a grant from the German Pulmonary Hypertension Group, Pulmonale Hypertonie e.V., Rheinstetten, Germany.

Country: Germany

Setting: inpatient rehabilitation

Comments:

Author's name: Derliz Mereles

Institution: University Hospital Heidelberg

Email: [email protected]‐heidelberg.de

Address: Department of Cardiology and Pneumology, University Hospital Heidelberg, INF 410, D‐69120 Heidelberg

Notes

Adverse Outcomes
Authors report that all participants tolerated training and had no adverse events during training and no progression of the disease as defined by progression of symptoms, PH or right heart failure. Two participants perceived a short episode of dizziness without fainting immediately after bicycle ergometer training. In 1 participant, oxygen saturation dropped from 88% to 74% during exercise, although the training was performed with an oxygen mask.
Continuous Outcomes
6MWD is reported as a change from baseline at the post‐inpatient and post‐outpatient time points

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Comment: participants were randomly assigned to either a primary training group or a sedentary control group using a permuted block randomization procedure

Allocation concealment (selection bias)

Unclear risk

Comment: there is no comment regarding allocation concealment

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Comment: unable to blind participants and personnel due to nature of intervention

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote: "The completed questionnaire at baseline was compared with the results after 15 weeks by investigators who were blinded to the patients’ clinical data and group assignment. To avoid bias as far as possible in this study, all measurements and/or offline readings were performed by investigators who were blinded to patient data and group assignment."

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No dropouts reported

Selective reporting (reporting bias)

Low risk

The protocol was not registered or published however the outcome reporting is comprehensive.

Other bias

High risk

Comment: No CONSORT diagram so not possible to tell how many people were assessed in order to recruit the sample.

Wilkinson 2007

Methods

Study design: RCT

Study grouping: Parallel group

Participants

Baseline characteristics

Exercise

  • Number enrolled: 18

  • Age: unclear

  • Type PH: unclear

Control

  • Number enrolled: 18

  • Age: unclear

  • Type of PH: unclear

Included criteria: "Clinically stable PH patients in a single centre"

Excluded criteria: unclear

Interventions

Intervention characteristics

Exercise

  • Setting: outpatient, 3 months, 1 supervised session followed by unsupervised home training, telephone follow‐up

  • "Best practice treatment plus a physiotherapist‐led rehabilitation programme (rehabilitation group). Patients in the rehabilitation group attended a single one to one class with a physiotherapist and received a prescribed set of exercises tailored to their needs. They also received telephone support during the 3 month period and were encouraged to continue with their regular exercise regime."

Control

  • "Best practice treatment"

Outcomes

Incremental shuttle walk test

Endurance shuttle walk test

Assessed at baseline and 3 months

Identification

Sponsorship source:

Country:

Setting:

Comments:

Author's name: Anna Wilkinson

Institution: Royal Hallamshire Hospital

Email:

Address:

Notes

Reported as two abstracts

In the Thorax abstract it does not specify the number in each group, only that 40 were randomised. ERS abstract says 18 in each group. Neither specifies age by allocated group

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Abstract only, does not specify how sequence was generated

Allocation concealment (selection bias)

Unclear risk

Abstract only, does not specify

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Not possible to blind participants to intervention

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote: "Blind assessment was undertaken pre intervention and following 3 months"

Incomplete outcome data (attrition bias)
All outcomes

High risk

Dropouts unclear. 2007 abstract specifies 40 participants and 2008 abstract specifies 36 participants.

Selective reporting (reporting bias)

High risk

Abstract only, not all outcomes reported

Other bias

High risk

Abstract only

bpm: beats per minute; CAMPHOR: Cambridge Pulmonary Hypertension Outcome Review; CI: Cardiac Index; CPET: cardiopulmonary exercise test; CTEPH: chronic thromboembolitic pulmonary hypertension; Dual: patients on two pharmacotherapies; FEV1: forced expired volume in one second; FVC: forced vital capacity; HR: heart rate; HRQoL: health‐related quality of life; ITT: intention‐to‐treat; Mono: patients on single pharmacotherapy; mPAP: mean pulmonary artery pressure; NYHA: New York Heart Association; PAH: Pulmonary Artery Hypertension; PASP: Pulmonary Artery Systolic Pressure; PH: Pulmonary Hypertension, PLB: pursed lip breathing; PVR: pulmonary vascular resistance; RCT: randomised controlled trial; SF‐36: Short‐form 36; 6MWD: six minute walk distance; SPO2: oxygen saturation; Triple: patients on 3 pharmacotherapies; QoL: quality of life; VO2peak: peak oxygen uptake; Wpeak: peak power

Characteristics of excluded studies [ordered by study ID]

Jump to:

Study

Reason for exclusion

Babu 2013

Review paper

Babu 2014

Not an RCT

Barbosa 2011

No exercise training

Becker Grunig 2013

Not an RCT

Bernheim 2007

Wrong patient population

Ehlken 2014

Not an RCT

Fox 2011

Not an RCT

Grunig 2011

Not an RCT

Grunig 2012

Not an RCT

Kabitz 2014

Not an RCT

Kolesnikova 2011a

Wrong intervention

Kolesnikova 2011b

Wrong intervention

Marvisi 2013

No exercise training

Nagel 2012

Not an RCT

Robalo Cordeiro 2011

No exercise training

RCT: randomised controlled trial

Data and analyses

Open in table viewer
Comparison 1. Exercise vs control

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Exercise capacity: 6MWD Show forest plot

5

165

Mean Difference (IV, Random, 95% CI)

60.12 [30.17, 90.07]

Analysis 1.1

Comparison 1 Exercise vs control, Outcome 1 Exercise capacity: 6MWD.

Comparison 1 Exercise vs control, Outcome 1 Exercise capacity: 6MWD.

2 Exercise capacity: VO2peak Show forest plot

4

145

Mean Difference (IV, Random, 95% CI)

2.41 [1.38, 3.44]

Analysis 1.2

Comparison 1 Exercise vs control, Outcome 2 Exercise capacity: VO2peak.

Comparison 1 Exercise vs control, Outcome 2 Exercise capacity: VO2peak.

3 Exercise capacity: Peak power Show forest plot

4

145

Mean Difference (IV, Random, 95% CI)

16.44 [10.90, 21.99]

Analysis 1.3

Comparison 1 Exercise vs control, Outcome 3 Exercise capacity: Peak power.

Comparison 1 Exercise vs control, Outcome 3 Exercise capacity: Peak power.

4 Exercisecapacity: Anaerobic threshold Show forest plot

3

66

Std. Mean Difference (IV, Random, 95% CI)

1.05 [0.53, 1.58]

Analysis 1.4

Comparison 1 Exercise vs control, Outcome 4 Exercisecapacity: Anaerobic threshold.

Comparison 1 Exercise vs control, Outcome 4 Exercisecapacity: Anaerobic threshold.

5 HRQoL SF36: Physical component score Show forest plot

2

33

Mean Difference (IV, Random, 95% CI)

4.63 [0.80, 8.47]

Analysis 1.5

Comparison 1 Exercise vs control, Outcome 5 HRQoL SF36: Physical component score.

Comparison 1 Exercise vs control, Outcome 5 HRQoL SF36: Physical component score.

6 HRQoL SF36: Mental component score Show forest plot

2

33

Mean Difference (IV, Random, 95% CI)

4.17 [0.01, 8.34]

Analysis 1.6

Comparison 1 Exercise vs control, Outcome 6 HRQoL SF36: Mental component score.

Comparison 1 Exercise vs control, Outcome 6 HRQoL SF36: Mental component score.

7 Adverse events Show forest plot

5

165

Risk Difference (M‐H, Random, 95% CI)

0.00 [‐0.04, 0.04]

Analysis 1.7

Comparison 1 Exercise vs control, Outcome 7 Adverse events.

Comparison 1 Exercise vs control, Outcome 7 Adverse events.

8 HRQoL SF36: Physical function Show forest plot

4

118

Mean Difference (IV, Random, 95% CI)

6.13 [‐3.73, 16.00]

Analysis 1.8

Comparison 1 Exercise vs control, Outcome 8 HRQoL SF36: Physical function.

Comparison 1 Exercise vs control, Outcome 8 HRQoL SF36: Physical function.

9 HRQoL SF36: Role physical Show forest plot

4

116

Mean Difference (IV, Random, 95% CI)

21.81 [14.40, 29.23]

Analysis 1.9

Comparison 1 Exercise vs control, Outcome 9 HRQoL SF36: Role physical.

Comparison 1 Exercise vs control, Outcome 9 HRQoL SF36: Role physical.

10 HRQoL SF36: Bodily pain Show forest plot

3

88

Mean Difference (IV, Random, 95% CI)

5.64 [‐3.09, 14.36]

Analysis 1.10

Comparison 1 Exercise vs control, Outcome 10 HRQoL SF36: Bodily pain.

Comparison 1 Exercise vs control, Outcome 10 HRQoL SF36: Bodily pain.

11 HRQoL SF36: General health Show forest plot

3

84

Mean Difference (IV, Random, 95% CI)

5.76 [‐0.80, 12.32]

Analysis 1.11

Comparison 1 Exercise vs control, Outcome 11 HRQoL SF36: General health.

Comparison 1 Exercise vs control, Outcome 11 HRQoL SF36: General health.

12 HRQoL SF36: Mental health Show forest plot

3

87

Mean Difference (IV, Random, 95% CI)

6.21 [‐1.85, 14.27]

Analysis 1.12

Comparison 1 Exercise vs control, Outcome 12 HRQoL SF36: Mental health.

Comparison 1 Exercise vs control, Outcome 12 HRQoL SF36: Mental health.

13 HRQoL SF36: Role emotional Show forest plot

3

87

Mean Difference (IV, Random, 95% CI)

2.79 [‐7.43, 13.01]

Analysis 1.13

Comparison 1 Exercise vs control, Outcome 13 HRQoL SF36: Role emotional.

Comparison 1 Exercise vs control, Outcome 13 HRQoL SF36: Role emotional.

14 HRQol SF36: Vitality Show forest plot

4

115

Mean Difference (IV, Random, 95% CI)

13.47 [7.55, 19.40]

Analysis 1.14

Comparison 1 Exercise vs control, Outcome 14 HRQol SF36: Vitality.

Comparison 1 Exercise vs control, Outcome 14 HRQol SF36: Vitality.

15 HRQoL SF36: Social function Show forest plot

4

118

Mean Difference (IV, Random, 95% CI)

14.01 [9.82, 18.21]

Analysis 1.15

Comparison 1 Exercise vs control, Outcome 15 HRQoL SF36: Social function.

Comparison 1 Exercise vs control, Outcome 15 HRQoL SF36: Social function.

16 HRQoL: CAMPHOR activities Show forest plot

2

33

Mean Difference (IV, Random, 95% CI)

‐1.33 [‐3.56, 0.90]

Analysis 1.16

Comparison 1 Exercise vs control, Outcome 16 HRQoL: CAMPHOR activities.

Comparison 1 Exercise vs control, Outcome 16 HRQoL: CAMPHOR activities.

17 HRQoL: CAMPHOR symptoms Show forest plot

2

36

Mean Difference (IV, Random, 95% CI)

‐3.08 [‐7.78, 1.62]

Analysis 1.17

Comparison 1 Exercise vs control, Outcome 17 HRQoL: CAMPHOR symptoms.

Comparison 1 Exercise vs control, Outcome 17 HRQoL: CAMPHOR symptoms.

18 HRQoL: CAMPHOR QoL Show forest plot

2

36

Mean Difference (IV, Random, 95% CI)

‐5.42 [‐8.03, ‐2.81]

Analysis 1.18

Comparison 1 Exercise vs control, Outcome 18 HRQoL: CAMPHOR QoL.

Comparison 1 Exercise vs control, Outcome 18 HRQoL: CAMPHOR QoL.

19 Cardiopulmonary haemodynamics Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Subtotals only

Analysis 1.19

Comparison 1 Exercise vs control, Outcome 19 Cardiopulmonary haemodynamics.

Comparison 1 Exercise vs control, Outcome 19 Cardiopulmonary haemodynamics.

20 Functional class Show forest plot

2

40

Mean Difference (IV, Random, 95% CI)

‐0.60 [‐0.85, ‐0.35]

Analysis 1.20

Comparison 1 Exercise vs control, Outcome 20 Functional class.

Comparison 1 Exercise vs control, Outcome 20 Functional class.

21 B‐type natriuretic peptide Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Subtotals only

Analysis 1.21

Comparison 1 Exercise vs control, Outcome 21 B‐type natriuretic peptide.

Comparison 1 Exercise vs control, Outcome 21 B‐type natriuretic peptide.

22 Exercise capacity: 6MWD, sensitivity analysis Show forest plot

4

86

Mean Difference (IV, Random, 95% CI)

67.91 [27.12, 108.69]

Analysis 1.22

Comparison 1 Exercise vs control, Outcome 22 Exercise capacity: 6MWD, sensitivity analysis.

Comparison 1 Exercise vs control, Outcome 22 Exercise capacity: 6MWD, sensitivity analysis.

23 Exercise capacity: VO2peak, sensitivity analysis Show forest plot

3

66

Mean Difference (IV, Random, 95% CI)

1.94 [0.86, 3.01]

Analysis 1.23

Comparison 1 Exercise vs control, Outcome 23 Exercise capacity: VO2peak, sensitivity analysis.

Comparison 1 Exercise vs control, Outcome 23 Exercise capacity: VO2peak, sensitivity analysis.

24 Exercise capacity: Peak power, sensitivity analysis Show forest plot

3

66

Mean Difference (IV, Random, 95% CI)

15.27 [8.57, 21.97]

Analysis 1.24

Comparison 1 Exercise vs control, Outcome 24 Exercise capacity: Peak power, sensitivity analysis.

Comparison 1 Exercise vs control, Outcome 24 Exercise capacity: Peak power, sensitivity analysis.

25 Exercise capacity 6MWD, PAH subgroup only Show forest plot

2

36

Mean Difference (IV, Random, 95% CI)

33.84 [0.95, 66.73]

Analysis 1.25

Comparison 1 Exercise vs control, Outcome 25 Exercise capacity 6MWD, PAH subgroup only.

Comparison 1 Exercise vs control, Outcome 25 Exercise capacity 6MWD, PAH subgroup only.

26 Exercise capacity: VO2peak, PAH subgroup only Show forest plot

2

36

Mean Difference (IV, Random, 95% CI)

1.28 [‐0.19, 2.75]

Analysis 1.26

Comparison 1 Exercise vs control, Outcome 26 Exercise capacity: VO2peak, PAH subgroup only.

Comparison 1 Exercise vs control, Outcome 26 Exercise capacity: VO2peak, PAH subgroup only.

27 Exercise capacity: Peak power, PAH subgroup only Show forest plot

2

36

Mean Difference (IV, Random, 95% CI)

14.24 [5.78, 22.70]

Analysis 1.27

Comparison 1 Exercise vs control, Outcome 27 Exercise capacity: Peak power, PAH subgroup only.

Comparison 1 Exercise vs control, Outcome 27 Exercise capacity: Peak power, PAH subgroup only.

28 Exercise capacity: Anaerobic threshold, PAH subgroup only Show forest plot

2

36

Mean Difference (IV, Random, 95% CI)

41.31 [‐52.05, 134.67]

Analysis 1.28

Comparison 1 Exercise vs control, Outcome 28 Exercise capacity: Anaerobic threshold, PAH subgroup only.

Comparison 1 Exercise vs control, Outcome 28 Exercise capacity: Anaerobic threshold, PAH subgroup only.

29 Exercise capacity: 6MWD, subgroup analysis for setting of rehabilitation Show forest plot

5

Mean Difference (IV, Random, 95% CI)

Subtotals only

Analysis 1.29

Comparison 1 Exercise vs control, Outcome 29 Exercise capacity: 6MWD, subgroup analysis for setting of rehabilitation.

Comparison 1 Exercise vs control, Outcome 29 Exercise capacity: 6MWD, subgroup analysis for setting of rehabilitation.

29.1 Inpatient exercise training

3

129

Mean Difference (IV, Random, 95% CI)

72.79 [28.09, 117.49]

29.2 Outpatient exercise training

2

36

Mean Difference (IV, Random, 95% CI)

33.84 [0.95, 66.73]

Study flow diagram
Figures and Tables -
Figure 1

Study flow diagram

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
Figures and Tables -
Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies

Risk of bias summary: review authors' judgements about each risk of bias item for each included study
Figures and Tables -
Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study

Forest plot of comparison: 1 Exercise vs control, outcome: 1.1 Exercise capacity: 6MWD
Figures and Tables -
Figure 4

Forest plot of comparison: 1 Exercise vs control, outcome: 1.1 Exercise capacity: 6MWD

Comparison 1 Exercise vs control, Outcome 1 Exercise capacity: 6MWD.
Figures and Tables -
Analysis 1.1

Comparison 1 Exercise vs control, Outcome 1 Exercise capacity: 6MWD.

Comparison 1 Exercise vs control, Outcome 2 Exercise capacity: VO2peak.
Figures and Tables -
Analysis 1.2

Comparison 1 Exercise vs control, Outcome 2 Exercise capacity: VO2peak.

Comparison 1 Exercise vs control, Outcome 3 Exercise capacity: Peak power.
Figures and Tables -
Analysis 1.3

Comparison 1 Exercise vs control, Outcome 3 Exercise capacity: Peak power.

Comparison 1 Exercise vs control, Outcome 4 Exercisecapacity: Anaerobic threshold.
Figures and Tables -
Analysis 1.4

Comparison 1 Exercise vs control, Outcome 4 Exercisecapacity: Anaerobic threshold.

Comparison 1 Exercise vs control, Outcome 5 HRQoL SF36: Physical component score.
Figures and Tables -
Analysis 1.5

Comparison 1 Exercise vs control, Outcome 5 HRQoL SF36: Physical component score.

Comparison 1 Exercise vs control, Outcome 6 HRQoL SF36: Mental component score.
Figures and Tables -
Analysis 1.6

Comparison 1 Exercise vs control, Outcome 6 HRQoL SF36: Mental component score.

Comparison 1 Exercise vs control, Outcome 7 Adverse events.
Figures and Tables -
Analysis 1.7

Comparison 1 Exercise vs control, Outcome 7 Adverse events.

Comparison 1 Exercise vs control, Outcome 8 HRQoL SF36: Physical function.
Figures and Tables -
Analysis 1.8

Comparison 1 Exercise vs control, Outcome 8 HRQoL SF36: Physical function.

Comparison 1 Exercise vs control, Outcome 9 HRQoL SF36: Role physical.
Figures and Tables -
Analysis 1.9

Comparison 1 Exercise vs control, Outcome 9 HRQoL SF36: Role physical.

Comparison 1 Exercise vs control, Outcome 10 HRQoL SF36: Bodily pain.
Figures and Tables -
Analysis 1.10

Comparison 1 Exercise vs control, Outcome 10 HRQoL SF36: Bodily pain.

Comparison 1 Exercise vs control, Outcome 11 HRQoL SF36: General health.
Figures and Tables -
Analysis 1.11

Comparison 1 Exercise vs control, Outcome 11 HRQoL SF36: General health.

Comparison 1 Exercise vs control, Outcome 12 HRQoL SF36: Mental health.
Figures and Tables -
Analysis 1.12

Comparison 1 Exercise vs control, Outcome 12 HRQoL SF36: Mental health.

Comparison 1 Exercise vs control, Outcome 13 HRQoL SF36: Role emotional.
Figures and Tables -
Analysis 1.13

Comparison 1 Exercise vs control, Outcome 13 HRQoL SF36: Role emotional.

Comparison 1 Exercise vs control, Outcome 14 HRQol SF36: Vitality.
Figures and Tables -
Analysis 1.14

Comparison 1 Exercise vs control, Outcome 14 HRQol SF36: Vitality.

Comparison 1 Exercise vs control, Outcome 15 HRQoL SF36: Social function.
Figures and Tables -
Analysis 1.15

Comparison 1 Exercise vs control, Outcome 15 HRQoL SF36: Social function.

Comparison 1 Exercise vs control, Outcome 16 HRQoL: CAMPHOR activities.
Figures and Tables -
Analysis 1.16

Comparison 1 Exercise vs control, Outcome 16 HRQoL: CAMPHOR activities.

Comparison 1 Exercise vs control, Outcome 17 HRQoL: CAMPHOR symptoms.
Figures and Tables -
Analysis 1.17

Comparison 1 Exercise vs control, Outcome 17 HRQoL: CAMPHOR symptoms.

Comparison 1 Exercise vs control, Outcome 18 HRQoL: CAMPHOR QoL.
Figures and Tables -
Analysis 1.18

Comparison 1 Exercise vs control, Outcome 18 HRQoL: CAMPHOR QoL.

Comparison 1 Exercise vs control, Outcome 19 Cardiopulmonary haemodynamics.
Figures and Tables -
Analysis 1.19

Comparison 1 Exercise vs control, Outcome 19 Cardiopulmonary haemodynamics.

Comparison 1 Exercise vs control, Outcome 20 Functional class.
Figures and Tables -
Analysis 1.20

Comparison 1 Exercise vs control, Outcome 20 Functional class.

Comparison 1 Exercise vs control, Outcome 21 B‐type natriuretic peptide.
Figures and Tables -
Analysis 1.21

Comparison 1 Exercise vs control, Outcome 21 B‐type natriuretic peptide.

Comparison 1 Exercise vs control, Outcome 22 Exercise capacity: 6MWD, sensitivity analysis.
Figures and Tables -
Analysis 1.22

Comparison 1 Exercise vs control, Outcome 22 Exercise capacity: 6MWD, sensitivity analysis.

Comparison 1 Exercise vs control, Outcome 23 Exercise capacity: VO2peak, sensitivity analysis.
Figures and Tables -
Analysis 1.23

Comparison 1 Exercise vs control, Outcome 23 Exercise capacity: VO2peak, sensitivity analysis.

Comparison 1 Exercise vs control, Outcome 24 Exercise capacity: Peak power, sensitivity analysis.
Figures and Tables -
Analysis 1.24

Comparison 1 Exercise vs control, Outcome 24 Exercise capacity: Peak power, sensitivity analysis.

Comparison 1 Exercise vs control, Outcome 25 Exercise capacity 6MWD, PAH subgroup only.
Figures and Tables -
Analysis 1.25

Comparison 1 Exercise vs control, Outcome 25 Exercise capacity 6MWD, PAH subgroup only.

Comparison 1 Exercise vs control, Outcome 26 Exercise capacity: VO2peak, PAH subgroup only.
Figures and Tables -
Analysis 1.26

Comparison 1 Exercise vs control, Outcome 26 Exercise capacity: VO2peak, PAH subgroup only.

Comparison 1 Exercise vs control, Outcome 27 Exercise capacity: Peak power, PAH subgroup only.
Figures and Tables -
Analysis 1.27

Comparison 1 Exercise vs control, Outcome 27 Exercise capacity: Peak power, PAH subgroup only.

Comparison 1 Exercise vs control, Outcome 28 Exercise capacity: Anaerobic threshold, PAH subgroup only.
Figures and Tables -
Analysis 1.28

Comparison 1 Exercise vs control, Outcome 28 Exercise capacity: Anaerobic threshold, PAH subgroup only.

Comparison 1 Exercise vs control, Outcome 29 Exercise capacity: 6MWD, subgroup analysis for setting of rehabilitation.
Figures and Tables -
Analysis 1.29

Comparison 1 Exercise vs control, Outcome 29 Exercise capacity: 6MWD, subgroup analysis for setting of rehabilitation.

Summary of findings for the main comparison. Exercise compared to control for pulmonary hypertension

Exercise compared to control for pulmonary hypertension

Patient or population: people with pulmonary hypertension
Settings: inpatient or outpatient rehabilitation, or both
Intervention: exercise training
Comparison: control: people that had usual care and did not undertake exercise training programme

Outcomes

Illustrative comparative effects* (95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Response on control

Treatment effect

Control

Exercise

Change in functional exercise capacity (6MWD)
Distance, metres
Follow‐up median 12 weeks

Median change = 5 m

The mean exercise capacity 6MWD in the intervention groups was 60.12 higher
(30.17 to 90.07 higher)

165
(5 studies)

⊕⊕⊝⊝
low1,2

Subgroup PAH: (2 studies, n = 36), mean 6MWD for intervention group was 33.84 m higher (0.95 to 66.73 higher); these studies used outpatient exercise rehabilitation whilst other studies contributing to meta‐analysis had an inpatient training component

Minimal important difference was 30 metres

Exercise capacity: VO2peak

Oxygen uptake, ml/kg/min
Follow‐up median 13.5 weeks

Median change = ‐0.25 ml/kg/min

The mean VO2peak in the intervention groups was 2.41 ml/kg/min higher
(1.38 to 3.44 higher)

145
(4 studies)

⊕⊕⊝⊝
low1,2

Subgroup PAH (2 studies, n = 36), the mean VO2peak in the intervention groups was 1.28 ml/kg/min higher (‐0.19 to 2.75 higher); these two studies used outpatient exercise rehabilitation whilst other studies contributing to meta‐analysis had an inpatient training component

Exercise capacity: peak power

watts
Follow‐up median 13.5 weeks

Median change = 1 watt

The mean exercise capacity: peak power in the intervention groups was 16.44 W higher
(10.90 to 21.99 higher)

145
(4 studies)

⊕⊕⊝⊝
low1,2

Subgroup PAH (2 studies, n = 36), the mean peak power in the intervention groups was 14.24 watts higher (5.78 to 22.70 higher); these two studies used outpatient exercise rehabilitation whilst other studies contributing to meta‐analysis had an inpatient training component

HRQoL SF‐36: PCS

units

Follow‐up median 11 weeks

Median change = ‐0.49 units

The mean HRQoL SF‐36: PCS in the intervention groups was 4.63 higher (0.80 to 8.47 higher)

33
(2 studies)

⊕⊕⊝⊝
low2,3

Both studies were only PAH

HRQoL SF‐36: MCS

units

Follow‐up median 11 weeks

Median change = ‐0.31 units

The mean HRQoL SF‐36: MCS in the intervention groups was 4.17 higher (0.01 to 8.34 higher)

33
(2 studies)

⊕⊕⊝⊝
low2,3

Both studies were only PAH

*The basis for the response on control is the median control group response across studies

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Two studies did not report random sequence generation, no studies reported allocation concealment
2 Indirectness: 2 studies did not report number of people assessed to achieve sample size; trial participants may represent a highly selected subgroup of people with PH

3 Imprecision (2 small studies of 33 participants) and neither reported allocation concealment

Figures and Tables -
Summary of findings for the main comparison. Exercise compared to control for pulmonary hypertension
Comparison 1. Exercise vs control

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Exercise capacity: 6MWD Show forest plot

5

165

Mean Difference (IV, Random, 95% CI)

60.12 [30.17, 90.07]

2 Exercise capacity: VO2peak Show forest plot

4

145

Mean Difference (IV, Random, 95% CI)

2.41 [1.38, 3.44]

3 Exercise capacity: Peak power Show forest plot

4

145

Mean Difference (IV, Random, 95% CI)

16.44 [10.90, 21.99]

4 Exercisecapacity: Anaerobic threshold Show forest plot

3

66

Std. Mean Difference (IV, Random, 95% CI)

1.05 [0.53, 1.58]

5 HRQoL SF36: Physical component score Show forest plot

2

33

Mean Difference (IV, Random, 95% CI)

4.63 [0.80, 8.47]

6 HRQoL SF36: Mental component score Show forest plot

2

33

Mean Difference (IV, Random, 95% CI)

4.17 [0.01, 8.34]

7 Adverse events Show forest plot

5

165

Risk Difference (M‐H, Random, 95% CI)

0.00 [‐0.04, 0.04]

8 HRQoL SF36: Physical function Show forest plot

4

118

Mean Difference (IV, Random, 95% CI)

6.13 [‐3.73, 16.00]

9 HRQoL SF36: Role physical Show forest plot

4

116

Mean Difference (IV, Random, 95% CI)

21.81 [14.40, 29.23]

10 HRQoL SF36: Bodily pain Show forest plot

3

88

Mean Difference (IV, Random, 95% CI)

5.64 [‐3.09, 14.36]

11 HRQoL SF36: General health Show forest plot

3

84

Mean Difference (IV, Random, 95% CI)

5.76 [‐0.80, 12.32]

12 HRQoL SF36: Mental health Show forest plot

3

87

Mean Difference (IV, Random, 95% CI)

6.21 [‐1.85, 14.27]

13 HRQoL SF36: Role emotional Show forest plot

3

87

Mean Difference (IV, Random, 95% CI)

2.79 [‐7.43, 13.01]

14 HRQol SF36: Vitality Show forest plot

4

115

Mean Difference (IV, Random, 95% CI)

13.47 [7.55, 19.40]

15 HRQoL SF36: Social function Show forest plot

4

118

Mean Difference (IV, Random, 95% CI)

14.01 [9.82, 18.21]

16 HRQoL: CAMPHOR activities Show forest plot

2

33

Mean Difference (IV, Random, 95% CI)

‐1.33 [‐3.56, 0.90]

17 HRQoL: CAMPHOR symptoms Show forest plot

2

36

Mean Difference (IV, Random, 95% CI)

‐3.08 [‐7.78, 1.62]

18 HRQoL: CAMPHOR QoL Show forest plot

2

36

Mean Difference (IV, Random, 95% CI)

‐5.42 [‐8.03, ‐2.81]

19 Cardiopulmonary haemodynamics Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Subtotals only

20 Functional class Show forest plot

2

40

Mean Difference (IV, Random, 95% CI)

‐0.60 [‐0.85, ‐0.35]

21 B‐type natriuretic peptide Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Subtotals only

22 Exercise capacity: 6MWD, sensitivity analysis Show forest plot

4

86

Mean Difference (IV, Random, 95% CI)

67.91 [27.12, 108.69]

23 Exercise capacity: VO2peak, sensitivity analysis Show forest plot

3

66

Mean Difference (IV, Random, 95% CI)

1.94 [0.86, 3.01]

24 Exercise capacity: Peak power, sensitivity analysis Show forest plot

3

66

Mean Difference (IV, Random, 95% CI)

15.27 [8.57, 21.97]

25 Exercise capacity 6MWD, PAH subgroup only Show forest plot

2

36

Mean Difference (IV, Random, 95% CI)

33.84 [0.95, 66.73]

26 Exercise capacity: VO2peak, PAH subgroup only Show forest plot

2

36

Mean Difference (IV, Random, 95% CI)

1.28 [‐0.19, 2.75]

27 Exercise capacity: Peak power, PAH subgroup only Show forest plot

2

36

Mean Difference (IV, Random, 95% CI)

14.24 [5.78, 22.70]

28 Exercise capacity: Anaerobic threshold, PAH subgroup only Show forest plot

2

36

Mean Difference (IV, Random, 95% CI)

41.31 [‐52.05, 134.67]

29 Exercise capacity: 6MWD, subgroup analysis for setting of rehabilitation Show forest plot

5

Mean Difference (IV, Random, 95% CI)

Subtotals only

29.1 Inpatient exercise training

3

129

Mean Difference (IV, Random, 95% CI)

72.79 [28.09, 117.49]

29.2 Outpatient exercise training

2

36

Mean Difference (IV, Random, 95% CI)

33.84 [0.95, 66.73]

Figures and Tables -
Comparison 1. Exercise vs control