Skip to main content

Advertisement

SpringerLink
Log in

Rationale and Design of a Randomized Controlled Trial Evaluating Whole Muscle Exercise Training Effects in Outpatients with Pulmonary Arterial Hypertension (WHOLEi+12)

  • ORIGINAL ARTICLE
  • Published:
Cardiovascular Drugs and Therapy Aims and scope Submit manuscript

Abstract

Background and Aims

Physical exercise is an important component in the management of pulmonary artery hypertension (PAH). The aim of this randomized controlled trial (RCT) is to determine the effects of an 8-week intervention combining muscle resistance, aerobic and inspiratory pressure load exercises in PAH outpatients.

Methods

The RCT will be conducted from September 2015 to September 2016 following the recommendations of the Consolidated Standards of Reported Trials (CONSORT), with a total sample size of n ≥ 48 (≥24 participants/group). We will determine the effects of the intervention on: (i) skeletal-muscle power and mass (primary end points); and (ii) NT-proBNP, cardiopulmonary exercise testing variables (VO2peak, ventilatory equivalent for CO2 at the anaerobic threshold (VE/VCO2 at the AT), end-tidal pressure of CO2 at the anaerobic threshold (PETCO2 at the AT), 6-min walking distance (6MWD), maximal inspiratory pressure (PImax), health-related quality of life (HRQoL), objectively-assessed spontaneous levels of physical activity, and safety (secondary end points).

Conclusions and Perspectives

This trial will provide insight into biological mechanisms of the disease and indicate the potential benefits of exercise in PAH outpatients, particularly on muscle power.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Waxman AB, Zamanian RT. Pulmonary arterial hypertension: new insights into the optimal role of current and emerging prostacyclin therapies. Am J Cardiol. 2013;111:1A–6.

    Article  CAS  PubMed  Google Scholar 

  2. Humbert M, Morrell NW, Archer SL, et al. Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol. 2004;43:13S–24.

    Article  CAS  PubMed  Google Scholar 

  3. McLaughlin VV, Archer SL, Badesch DB, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: developed in collaboration with the American College of Chest Physicians, American Thoracic Society, Inc., and the Pulmonary Hypertension Association. Circulation. 2009;119:2250–94.

    Article  PubMed  Google Scholar 

  4. Humbert M, Sitbon O, Yaici A, et al. Survival in incident and prevalent cohorts of patients with pulmonary arterial hypertension. Eur Respir J. 2010;36:549–55.

    Article  CAS  PubMed  Google Scholar 

  5. Escribano-Subias P, Blanco I, Lopez-Meseguer M, et al. Survival in pulmonary hypertension in Spain: insights from the Spanish registry. Eur Respir J. 2012;40:596–603.

    Article  PubMed  Google Scholar 

  6. British Cardiac Society G, Medical Practice C, approved by the British Thoracic S, the British Society of R. Recommendations on the management of pulmonary hypertension in clinical practice. Heart 2001;86 Suppl 1:I1-13

  7. Fox BD, Kassirer M, Weiss I, et al. Ambulatory rehabilitation improves exercise capacity in patients with pulmonary hypertension. J Card Fail. 2011;17:196–200.

    Article  PubMed  Google Scholar 

  8. Grunig E, Ehlken N, Ghofrani A, et al. Effect of exercise and respiratory training on clinical progression and survival in patients with severe chronic pulmonary hypertension. Respiration. 2011;81:394–401.

    Article  PubMed  Google Scholar 

  9. Grunig E, Lichtblau M, Ehlken N, et al. Safety and efficacy of exercise training in various forms of pulmonary hypertension. Eur Respir J. 2012;40:84–92.

    Article  PubMed  Google Scholar 

  10. Grunig E, Maier F, Ehlken N, et al. Exercise training in pulmonary arterial hypertension associated with connective tissue diseases. Arthritis Res Ther. 2012;14:R148.

    Article  PubMed Central  PubMed  Google Scholar 

  11. Mereles D, Ehlken N, Kreuscher S, et al. Exercise and respiratory training improve exercise capacity and quality of life in patients with severe chronic pulmonary hypertension. Circulation. 2006;114:1482–9.

    Article  PubMed  Google Scholar 

  12. Dimopoulos S, Tzanis G, Manetos C, et al. Peripheral muscle microcirculatory alterations in patients with pulmonary arterial hypertension: a pilot study. Respir Care. 2013;58:2134–41.

    Article  PubMed  Google Scholar 

  13. Tolle J, Waxman A, Systrom D. Impaired systemic oxygen extraction at maximum exercise in pulmonary hypertension. Med Sci Sports Exerc. 2008;40:3–8.

    Article  CAS  PubMed  Google Scholar 

  14. Meyer FJ, Lossnitzer D, Kristen AV, et al. Respiratory muscle dysfunction in idiopathic pulmonary arterial hypertension. Eur Respir J. 2005;25:125–30.

    Article  CAS  PubMed  Google Scholar 

  15. Bauer R, Dehnert C, Schoene P, et al. Skeletal muscle dysfunction in patients with idiopathic pulmonary arterial hypertension. Respir Med. 2007;101:2366–9.

    Article  PubMed  Google Scholar 

  16. Marra AM, Arcopinto M, Bossone E, et al. Pulmonary arterial hypertension-related myopathy: an overview of current data and future perspectives. Nutr Metab Cardiovasc Dis. 2015;25:131–9.

    Article  CAS  PubMed  Google Scholar 

  17. Nagel C, Prange F, Guth S, et al. Exercise training improves exercise capacity and quality of life in patients with inoperable or residual chronic thromboembolic pulmonary hypertension. PLoS ONE [Electron Resour]. 2012;7:e41603.

    Article  CAS  Google Scholar 

  18. Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med. 2004;351:1425–36.

    Article  CAS  PubMed  Google Scholar 

  19. Humbert M, Nunes H, Sitbon O, et al. Risk factors for pulmonary arterial hypertension. Clin Chest Med. 2001;22:459–75.

    Article  CAS  PubMed  Google Scholar 

  20. 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 Pulm Med. 2015;15:40.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Martinez-Quintana E, Miranda-Calderin G, Ugarte-Lopetegui A, Rodriguez-Gonzalez F. Rehabilitation program in adult congenital heart disease patients with pulmonary hypertension. Congenit Heart Dis. 2010;5:44–50.

    Article  PubMed  Google Scholar 

  22. Ley S, Fink C, Risse F, et al. Magnetic resonance imaging to assess the effect of exercise training on pulmonary perfusion and blood flow in patients with pulmonary hypertension. Eur Radiol. 2012;23:324–31.

    Article  PubMed  Google Scholar 

  23. Chan L, Chin LM, Kennedy M, et al. Benefits of intensive treadmill exercise training on cardiorespiratory function and quality of life in patients with pulmonary hypertension. Chest. 2012;143:333–43.

    Article  PubMed Central  Google Scholar 

  24. Ehlken N, Verduyn C, Tiede H, et al. Economic evaluation of exercise training in patients with pulmonary hypertension. Lung. 2014;192:359–66.

    Article  PubMed  Google Scholar 

  25. Wensel R, Opitz CF, Anker SD, et al. Assessment of survival in patients with primary pulmonary hypertension: importance of cardiopulmonary exercise testing. Circulation. 2002;106:319–24.

    Article  PubMed  Google Scholar 

  26. Oudiz RJ, Midde R, Hovenesyan A, et al. Usefulness of right-to-left shunting and poor exercise gas exchange for predicting prognosis in patients with pulmonary arterial hypertension. Am J Cardiol. 2010;105:1186–91.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Quezada-Loaiza CA, Flox-Camacho A, Santos-Lozano A, et al. Predictive value of NT-proBNP combined with exercise capacity variables in pulmonary artery disease: Insights from a Spanish cohort. Int J Cardiol. 2015;186:32–4.

    Article  PubMed  Google Scholar 

  28. Moher D, Hopewell S, Schulz KF, et al. CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. Int J Surg. 2012;10:28–55.

    Article  PubMed  Google Scholar 

  29. Robertson RJ, Goss FL, Rutkowski J, et al. Concurrent validation of the OMNI perceived exertion scale for resistance exercise. Med Sci Sports Exerc. 2003;35:333–41.

    Article  PubMed  Google Scholar 

  30. Borg GA. Psychophysical bases of perceived exertion. Med Sci Sports Exerc. 1982;14:377–81.

    CAS  PubMed  Google Scholar 

  31. Ferreira JBPR, Stein C, Casali KR, Arena R, Lago PD. Inspiratory muscle training reduces blood pressure and sympathetic activity in hypertensive patients: a randomized controlled tria. Int J Cardiol. 2013;166:61–7.

    Article  PubMed  Google Scholar 

  32. Mello PR, Guerra GM, Borile S, et al. Inspiratory muscle training reduces sympathetic nervous activity and improves inspiratory muscle weakness and quality of life in patients with chronic heart failure: a clinical trial. J Cardiopulm Rehabil Prev. 2012;32:255–61.

    Article  PubMed  Google Scholar 

  33. Gonzalez-Badillo JJ, Sanchez-Medina L. Movement velocity as a measure of loading intensity in resistance training. Int J Sports Med. 2010;31:347–52.

    Article  CAS  PubMed  Google Scholar 

  34. Sanchez-Medina L, Perez CE, Gonzalez-Badillo JJ. Importance of the propulsive phase in strength assessment. Int J Sports Med. 2010;31:123–9.

    Article  CAS  PubMed  Google Scholar 

  35. Santalla A, Munguia-Izquierdo D, Brea-Alejo L, et al. Feasibility of resistance training in adult McArdle patients: clinical outcomes and muscle strength and mass benefits. Front Aging Neurosci. 2015;6:334.

    Google Scholar 

  36. Jones SE, Kon SS, Canavan JL, et al. The five-repetition sit-to-stand test as a functional outcome measure in COPD. Thorax. 2013;68:1015–20.

    Article  PubMed  Google Scholar 

  37. Calbet JA, Moysi JS, Dorado C, Rodriguez LP. Bone mineral content and density in professional tennis players. Calcif Tissue Int. 1998;62:491–6.

    Article  CAS  PubMed  Google Scholar 

  38. Lucia A, Hoyos J, Perez M, Chicharro JL. Heart rate and performance parameters in elite cyclists: a longitudinal study. Med Sci Sports Exerc. 2000;32:1777–82.

    Article  CAS  PubMed  Google Scholar 

  39. Guyatt GH, Pugsley SO, Sullivan MJ, et al. Effect of encouragement on walking test performance. Thorax. 1984;39:818–22.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Standardization of spirometry--1987 update. Official statement of American Thoracic Society. Respir Care 1987;32:1039–1060

  41. Nici L, Donner C, Wouters E, et al. American thoracic society/European respiratory society statement on pulmonary rehabilitation. Am J Respir Crit Care Med. 2006;173:1390–413.

    Article  PubMed  Google Scholar 

  42. Ware Jr JE, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992;30:473–83.

    Article  PubMed  Google Scholar 

  43. Alonso J, Regidor E, Barrio G, et al. Population reference values of the Spanish version of the health questionnaire SF-36. Med Clin (Barc). 1998;111:410–6.

    CAS  Google Scholar 

  44. Vilagut G, Valderas JM, Ferrer M, et al. Interpretation of SF-36 and SF-12 questionnaires in Spain: physical and mental components. Med Clin (Barc). 2008;130:726–35.

    Article  Google Scholar 

  45. Ruiz-Casado A, Verdugo AS, Solano MJ, et al. Objectively assessed physical activity levels in Spanish cancer survivors. Oncol Nurs Forum. 2014;41:E12–20.

    Article  PubMed  Google Scholar 

  46. Santos-Lozano A, Marin PJ, Torres-Luque G, et al. Technical variability of the GT3X accelerometer. Med Eng Phys. 2012;34:787–90.

    Article  PubMed  Google Scholar 

  47. Freedson PS, Melanson E, Sirard J. Calibration of the computer science and applications, Inc. accelerometer. Med Sci Sports Exerc. 1998;30:777–81.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We acknowledge to Powerbreathe Spain, Biocorp Europa, Andoain, Basque Country, Spain for the kind donation of devices for inspiratory muscle training. Research by A.L. is funded by Fondo de Investigaciones Sanitarias (grant #PS12/00194) and Fondos FEDER.

Author information

Author notes

    Authors and Affiliations

    1. Research Institute Hospital 12 de Octubre (‘i + 12’), Edificio actividades ambulatorias, 6ª planta. Avda. de Córdoba s/n, 28041, Madrid, Spain

      Fabian Sanchis-Gomar, Laura González-Saiz, Carmen Fiuza-Luces, Alfredo Santalla, Alejandro Santos-Lozano, Helios Pareja-Galeano & Alejandro Lucia

    2. Department of Rehabilitation, Hospital Universitario 12 de Octubre, Avda. de Córdoba s/n, 28041 Madrid, Spain

      Paz Sanz-Ayan

    3. Cardiology Department, Hospital Universitario 12 de Octubre, Avda. de Córdoba s/n, 28041 Madrid, Spain

      Carlos A. Quezada-Loaiza, Angela Flox-Camacho & Pilar Escribano-Subías

    4. Department of Sports and Computer Science, Section of Physical Education and Sports, Universidad Pablo de Olavide, ES-41013 Seville, Spain

      Alfredo Santalla & Diego Munguía-Izquierdo

    5. Department of Health Sciences, European University Miguel de Cervantes, C/Padre Julio Chevalier, 47012, Valladolid, Spain

      Alejandro Santos-Lozano

    6. European University, C/Tajo S/N, Urbanización El Bosque, 28670 Villaviciosa de Odón, Madrid, Spain

      Helios Pareja-Galeano & Alejandro Lucia

    7. Growth, Exercise, Nutrition and Development (GENUD) Toledo Research Group, Universidad de Castilla-La Mancha, Avda Carlos III s/n, 45071 Toledo, Spain

      Ignacio Ara

    Authors
    1. Fabian Sanchis-Gomar
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Laura González-Saiz
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Paz Sanz-Ayan
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Carmen Fiuza-Luces
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Carlos A. Quezada-Loaiza
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Angela Flox-Camacho
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Alfredo Santalla
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Diego Munguía-Izquierdo
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Alejandro Santos-Lozano
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Helios Pareja-Galeano
      View author publications

      You can also search for this author in PubMed Google Scholar

    11. Ignacio Ara
      View author publications

      You can also search for this author in PubMed Google Scholar

    12. Pilar Escribano-Subías
      View author publications

      You can also search for this author in PubMed Google Scholar

    13. Alejandro Lucia
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Fabian Sanchis-Gomar.

    Ethics declarations

    Conflict of Interest

    The authors declare they have no financial competing interests.

    Additional information

    Fabian Sanchis-Gomar and Laura González-Saiz contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Sanchis-Gomar, F., González-Saiz, L., Sanz-Ayan, P. et al. Rationale and Design of a Randomized Controlled Trial Evaluating Whole Muscle Exercise Training Effects in Outpatients with Pulmonary Arterial Hypertension (WHOLEi+12). Cardiovasc Drugs Ther 29, 543–550 (2015). https://doi.org/10.1007/s10557-015-6623-4

    Download citation

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s10557-015-6623-4

    Keywords

    Search

    Navigation