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Skeletal muscle exercise training in pulmonary arterial hypertension
International Journal of Cardiology 246 (2017) 59–60
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Editorial
Skeletal muscle exercise training in pulmonary arterial hypertension BP Madden ⁎, EJ Shaw Department of Cardiothoracic Medicine, St Georges Hospital, Blackshaw Road, London SW17 0QT, United Kingdom
a r t i c l e
i n f o
Article history: Received 2 March 2017 Accepted 6 March 2017
Pulmonary hypertension is a condition defined by a mean pulmonary artery pressure of greater than 25 mmHg at rest and can occur as a consequence of diverse aetiologies [1]. Recent classifications have divided the causes of pulmonary hypertension into five groups. Group 1 diseases are associated with the development of the unique histopathological entity known as plexogenic pulmonary arteriopathy [1] and comprise idiopathic, heritable, drug, toxin induced, connective tissue diseases, congenital heart diseases, portal hypertension, human immunodeficiency virus infection, schistosomiasis pulmonary veno-occlusive disease and/or pulmonary capillary haemangiomatosis. Typically the greatest increase in pulmonary vascular resistance is seen among these diseases and the tendency towards vasoconstriction and vascular remodelling justifies the use of pulmonary vasoactive compounds including phosphodiesterase type 5 inhibitors (e.g. sildenafil) and agents which antagonise vascular remodelling (endothelin receptor antagonists) in these patients [1]. The group 1 disorders are those conditions which gave rise to pulmonary arterial hypertension (PAH). Chronic thromboembolic pulmonary hypertension (CTEPH) is placed in group 4. Selective patients with this condition may benefit from surgical intervention (pulmonary thromboendarterectomy) or advanced pulmonary vasodilator therapy [1]. The use of targeted therapy for pulmonary hypertension in patients in the other classifications e.g. pulmonary hypertension associated with cardiac (group 2), pulmonary (group 3) and miscellaneous (group 5) diseases is not well defined. Exercise capacity is limited in patients with PAH for a number of reasons, which include cardiovascular compromise in the presence of an increasing pulmonary vascular resistance, potential other consequences of the underlying disease process driving the PAH (e.g. HIV, connective tissue disease, hepatic impairment as a consequence of cirrhosis), deconditioning and perhaps a generalised myopathy [1–4]. DOI of original article: http://dx.doi.org/10.1016/j.ijcard.2016.12.026. ⁎ Corresponding author. E-mail address: [email protected] (B.P. Madden).
http://dx.doi.org/10.1016/j.ijcard.2017.03.017 0167-5273/© 2017 Elsevier B.V. All rights reserved.
There has been a reluctance in the past in considering exercise programmes in patients with PAH because of concern of poor patient tolerance or indeed of developing a pulmonary hypertension crisis, exacerbating right heart function and potentially leading to serious complications such as arrhythmias, a precipitous fall in cardiac output or even death. A variety of recent studies have addressed exercise training in patients with PAH and suggest that this leads to an important benefit with improvement in six minute walk test or in VO2 peak [5,6]. Furthermore such training seems to be safe and well tolerated [7]. In the present study [8] the authors performed a randomised controlled trial to assess the effects of an eight week intervention combining muscle resistance, aerobic and inspiratory pressure load exercises on upper and lower body muscle power and in some other functional variables in patients with PAH and CTEPH. Patients had similar haemodynamic results and the authors concluded that such exercise intervention was safe in these patients and produced improvement in muscle power. There was a trend towards an improvement in six minute walk test although this did not reach statistical significance. Changes in mean NT-proBNP values during the eight week period did not significantly differ between the two groups. Improvement was also noted in VO2 peak, 5-STS test and PI MAX. Unfortunately there were no prospective measurements of haemodynamics. In total 19 patients in the exercise group and 16 patients in the control group were studied. This study is interesting and addresses an important aspect of the care of patients with PAH and CTEPH. It is hoped that this will act as a platform for the development of further work in this area. For example it would be important to know how patient selection in these groups should take place and how the exercise programme should relate to proximity to diagnosis and commencement of specific targeted therapy. It would be helpful to know how functional class will influence suitability and tolerability of the exercise regime. It would also be important to titrate exercise regimes to patient capabilities with regard to their functional class status. Prospective information on the potential impact of exercise training on pulmonary vascular resistance would be helpful as would further information on quality of life. Many patients with PAH have other comorbidities e.g. arthritis, which may limit their ability to engage in this type of exercise regime. It would be useful to consider other potential avenues to explore in these patients. If patients are engaging in exercise classes would it be worth keeping similar groups with regard to functional class in the same session?
60
Editorial
Bearing in mind that the diseases, which lead to the development of PAH (group 1) are diverse, it would be worth studying specific subgroups within this group to identify optimal patient selection and to assess what patients may benefit more from this intervention. Patient numbers for group 1 and those with CTEPH in the present study are small and therefore it is difficult to extrapolate further from this work. Nevertheless exercise training in patients with PAH is important and warrants further attention. It is hoped that this study and others will stimulate ongoing work in this area, so that outstanding questions can be addressed and patient selection pathways defined to determine who would best benefit from this intervention and when it should be commenced. Conflict of interest The authors report no relationships that could be construed as a conflict of interest.
References [1] B. Madden, Treatment of Pulmonary Hypertension, Springer International Publishing Switzerland, 2015. [2] A.B. Waxman, R.T. Zamanian, Pulmonary arterial hypertension: new insights into the optimal role of current and emerging prostacyclin therapies, Am. J. Cardiol. 111 (2013) 1A–16A (quiz 17A-19A). [3] L.A. Matura, A. McDonough, D.L. Carroll, Cluster analysis of symptoms in pulmonary arterial hypertension: a pilot study, Eur. J. Cardiovasc. Nurs. 11 (2012) 51–61. [4] V. Mainguy, F. Maltais, D. Saey, et al., Peripheral muscle dysfunction in idiopathic pulmonary arterial hypertension, Thorax 65 (2010) 113–117. [5] R. Buys, A. Avila, V.A. Cornelissen, Exercise training improves physical fitness in patients with pulmonary arterial hypertension: a systematic review and metaanalysis of controlled trails, BMC Pulm. Med. 15 (2015) 40. [6] A. Pandey, S. Garg, M. Khunger, et al., Efficacy and safety of exercise training in chronic pulmonary hypertension: systematic review and meta-analysis, Circ. Heart Fail. 8 (2015) 1032–1043. [7] E. Grunig, M. Lichtblau, N. Ehlken, et al., Safety and efficacy of exercise training in various forms of pulmonary hypertension, Eur. Respir. J. 40 (2012) 84–92. [8] Benefits of skeletal-muscle exercise training in pulmonary arterial hypertension: the WHOLEi+12 trail: Int. J. Cardiol.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Editorial
Skeletal muscle exercise training in pulmonary arterial hypertension BP Madden ⁎, EJ Shaw Department of Cardiothoracic Medicine, St Georges Hospital, Blackshaw Road, London SW17 0QT, United Kingdom
a r t i c l e
i n f o
Article history: Received 2 March 2017 Accepted 6 March 2017
Pulmonary hypertension is a condition defined by a mean pulmonary artery pressure of greater than 25 mmHg at rest and can occur as a consequence of diverse aetiologies [1]. Recent classifications have divided the causes of pulmonary hypertension into five groups. Group 1 diseases are associated with the development of the unique histopathological entity known as plexogenic pulmonary arteriopathy [1] and comprise idiopathic, heritable, drug, toxin induced, connective tissue diseases, congenital heart diseases, portal hypertension, human immunodeficiency virus infection, schistosomiasis pulmonary veno-occlusive disease and/or pulmonary capillary haemangiomatosis. Typically the greatest increase in pulmonary vascular resistance is seen among these diseases and the tendency towards vasoconstriction and vascular remodelling justifies the use of pulmonary vasoactive compounds including phosphodiesterase type 5 inhibitors (e.g. sildenafil) and agents which antagonise vascular remodelling (endothelin receptor antagonists) in these patients [1]. The group 1 disorders are those conditions which gave rise to pulmonary arterial hypertension (PAH). Chronic thromboembolic pulmonary hypertension (CTEPH) is placed in group 4. Selective patients with this condition may benefit from surgical intervention (pulmonary thromboendarterectomy) or advanced pulmonary vasodilator therapy [1]. The use of targeted therapy for pulmonary hypertension in patients in the other classifications e.g. pulmonary hypertension associated with cardiac (group 2), pulmonary (group 3) and miscellaneous (group 5) diseases is not well defined. Exercise capacity is limited in patients with PAH for a number of reasons, which include cardiovascular compromise in the presence of an increasing pulmonary vascular resistance, potential other consequences of the underlying disease process driving the PAH (e.g. HIV, connective tissue disease, hepatic impairment as a consequence of cirrhosis), deconditioning and perhaps a generalised myopathy [1–4]. DOI of original article: http://dx.doi.org/10.1016/j.ijcard.2016.12.026. ⁎ Corresponding author. E-mail address: [email protected] (B.P. Madden).
http://dx.doi.org/10.1016/j.ijcard.2017.03.017 0167-5273/© 2017 Elsevier B.V. All rights reserved.
There has been a reluctance in the past in considering exercise programmes in patients with PAH because of concern of poor patient tolerance or indeed of developing a pulmonary hypertension crisis, exacerbating right heart function and potentially leading to serious complications such as arrhythmias, a precipitous fall in cardiac output or even death. A variety of recent studies have addressed exercise training in patients with PAH and suggest that this leads to an important benefit with improvement in six minute walk test or in VO2 peak [5,6]. Furthermore such training seems to be safe and well tolerated [7]. In the present study [8] the authors performed a randomised controlled trial to assess the effects of an eight week intervention combining muscle resistance, aerobic and inspiratory pressure load exercises on upper and lower body muscle power and in some other functional variables in patients with PAH and CTEPH. Patients had similar haemodynamic results and the authors concluded that such exercise intervention was safe in these patients and produced improvement in muscle power. There was a trend towards an improvement in six minute walk test although this did not reach statistical significance. Changes in mean NT-proBNP values during the eight week period did not significantly differ between the two groups. Improvement was also noted in VO2 peak, 5-STS test and PI MAX. Unfortunately there were no prospective measurements of haemodynamics. In total 19 patients in the exercise group and 16 patients in the control group were studied. This study is interesting and addresses an important aspect of the care of patients with PAH and CTEPH. It is hoped that this will act as a platform for the development of further work in this area. For example it would be important to know how patient selection in these groups should take place and how the exercise programme should relate to proximity to diagnosis and commencement of specific targeted therapy. It would be helpful to know how functional class will influence suitability and tolerability of the exercise regime. It would also be important to titrate exercise regimes to patient capabilities with regard to their functional class status. Prospective information on the potential impact of exercise training on pulmonary vascular resistance would be helpful as would further information on quality of life. Many patients with PAH have other comorbidities e.g. arthritis, which may limit their ability to engage in this type of exercise regime. It would be useful to consider other potential avenues to explore in these patients. If patients are engaging in exercise classes would it be worth keeping similar groups with regard to functional class in the same session?
60
Editorial
Bearing in mind that the diseases, which lead to the development of PAH (group 1) are diverse, it would be worth studying specific subgroups within this group to identify optimal patient selection and to assess what patients may benefit more from this intervention. Patient numbers for group 1 and those with CTEPH in the present study are small and therefore it is difficult to extrapolate further from this work. Nevertheless exercise training in patients with PAH is important and warrants further attention. It is hoped that this study and others will stimulate ongoing work in this area, so that outstanding questions can be addressed and patient selection pathways defined to determine who would best benefit from this intervention and when it should be commenced. Conflict of interest The authors report no relationships that could be construed as a conflict of interest.
References [1] B. Madden, Treatment of Pulmonary Hypertension, Springer International Publishing Switzerland, 2015. [2] A.B. Waxman, R.T. Zamanian, Pulmonary arterial hypertension: new insights into the optimal role of current and emerging prostacyclin therapies, Am. J. Cardiol. 111 (2013) 1A–16A (quiz 17A-19A). [3] L.A. Matura, A. McDonough, D.L. Carroll, Cluster analysis of symptoms in pulmonary arterial hypertension: a pilot study, Eur. J. Cardiovasc. Nurs. 11 (2012) 51–61. [4] V. Mainguy, F. Maltais, D. Saey, et al., Peripheral muscle dysfunction in idiopathic pulmonary arterial hypertension, Thorax 65 (2010) 113–117. [5] R. Buys, A. Avila, V.A. Cornelissen, Exercise training improves physical fitness in patients with pulmonary arterial hypertension: a systematic review and metaanalysis of controlled trails, BMC Pulm. Med. 15 (2015) 40. [6] A. Pandey, S. Garg, M. Khunger, et al., Efficacy and safety of exercise training in chronic pulmonary hypertension: systematic review and meta-analysis, Circ. Heart Fail. 8 (2015) 1032–1043. [7] E. Grunig, M. Lichtblau, N. Ehlken, et al., Safety and efficacy of exercise training in various forms of pulmonary hypertension, Eur. Respir. J. 40 (2012) 84–92. [8] Benefits of skeletal-muscle exercise training in pulmonary arterial hypertension: the WHOLEi+12 trail: Int. J. Cardiol.