The Effects of Exercise Training in Patients With Persistent Dyspnea Following Pulmonary Embolism

Abstract

BackgroundPersistent dyspnea, functional limitations, and reduced quality of life (QoL) are common following pulmonary embolism (PE). Rehabilitation is a potential treatment option, but the scientific evidence is limited.Research QuestionDoes an exercise-based rehabilitation program improve exercise capacity in PE survivors with persistent dyspnea?Study Design and MethodsThis randomized controlled trial was conducted at two hospitals. Patients with persistent dyspnea following PE diagnosed 6 to 72 months earlier, without cardiopulmonary comorbidities, were randomized 1:1 to either the rehabilitation or the control group. The rehabilitation program consisted of two weekly sessions of physical exercise for 8 weeks and one educational session. The control group received usual care. The primary end point was the difference in Incremental Shuttle Walk Test between groups at follow-up. Secondary end points included differences in the Endurance Shuttle Walk Test (ESWT), QoL (European Quality of Life-5 Dimensions and Pulmonary Embolism-QoL questionnaires) and dyspnea (Shortness of Breath questionnaire).ResultsA total of 211 subjects were included: 108 (51%) were randomized to the rehabilitation group and 103 (49%) to the control group. At follow-up, participants allocated to the rehabilitation group performed better on the ESWT compared with the control group (mean difference, 53.0 m; 95% CI, 17.7 to 88.3; P = .0035). The rehabilitation group reported better scores on the Pulmonary Embolism-QoL questionnaire (mean difference, –4%; 95% CI, –0.09 to 0.00; P = .041) at follow-up, but there were no differences in generic QoL, dyspnea scores, or the ESWT. No adverse events occurred during the intervention.InterpretationIn patients with persistent dyspnea following PE, those who underwent rehabilitation had better exercise capacity at follow-up than those who received usual care. Rehabilitation should be considered in patients with persistent dyspnea following PE. Further research is needed, however, to assess the optimal patient selection, timing, mode, and duration of rehabilitation.Clinical Trial RegistrationClinicalTrials.gov; No.: NCT03405480; URL: www.clinicaltrials.gov Persistent dyspnea, functional limitations, and reduced quality of life (QoL) are common following pulmonary embolism (PE). Rehabilitation is a potential treatment option, but the scientific evidence is limited. Does an exercise-based rehabilitation program improve exercise capacity in PE survivors with persistent dyspnea? This randomized controlled trial was conducted at two hospitals. Patients with persistent dyspnea following PE diagnosed 6 to 72 months earlier, without cardiopulmonary comorbidities, were randomized 1:1 to either the rehabilitation or the control group. The rehabilitation program consisted of two weekly sessions of physical exercise for 8 weeks and one educational session. The control group received usual care. The primary end point was the difference in Incremental Shuttle Walk Test between groups at follow-up. Secondary end points included differences in the Endurance Shuttle Walk Test (ESWT), QoL (European Quality of Life-5 Dimensions and Pulmonary Embolism-QoL questionnaires) and dyspnea (Shortness of Breath questionnaire). A total of 211 subjects were included: 108 (51%) were randomized to the rehabilitation group and 103 (49%) to the control group. At follow-up, participants allocated to the rehabilitation group performed better on the ESWT compared with the control group (mean difference, 53.0 m; 95% CI, 17.7 to 88.3; P = .0035). The rehabilitation group reported better scores on the Pulmonary Embolism-QoL questionnaire (mean difference, –4%; 95% CI, –0.09 to 0.00; P = .041) at follow-up, but there were no differences in generic QoL, dyspnea scores, or the ESWT. No adverse events occurred during the intervention. In patients with persistent dyspnea following PE, those who underwent rehabilitation had better exercise capacity at follow-up than those who received usual care. Rehabilitation should be considered in patients with persistent dyspnea following PE. Further research is needed, however, to assess the optimal patient selection, timing, mode, and duration of rehabilitation. ClinicalTrials.gov; No.: NCT03405480; URL: www.clinicaltrials.gov Take-home PointsStudy Question: Does an exercise-based rehabilitation program improve exercise capacity, symptoms, and QoL in subjects who experience persistent dyspnea following PE?Results: Subjects who underwent the rehabilitation program exhibited better exercise capacity and reported improved disease-specific QoL compared with those who received usual care, although generic QoL and dyspnea scores revealed no difference.Interpretation: Rehabilitation following PE is promising and should be considered in patients with persistent dyspnea following PE. Study Question: Does an exercise-based rehabilitation program improve exercise capacity, symptoms, and QoL in subjects who experience persistent dyspnea following PE? Results: Subjects who underwent the rehabilitation program exhibited better exercise capacity and reported improved disease-specific QoL compared with those who received usual care, although generic QoL and dyspnea scores revealed no difference. Interpretation: Rehabilitation following PE is promising and should be considered in patients with persistent dyspnea following PE. Persistent dyspnea, functional limitations, and reduced quality of life (QoL) are common following pulmonary embolism (PE), with studies suggesting a prevalence of 30% to 50%.1Kahn S.R. Hirsch A.M. Akaberi A. et al.Functional and exercise limitations after a first episode of pulmonary embolism: results of the ELOPE Prospective Cohort Study.Chest. 2017; 151: 1058-1068Abstract Full Text Full Text PDF PubMed Scopus (141) Google Scholar, 2Albaghdadi M.S. Dudzinski D.M. Giordano N. et al.Cardiopulmonary exercise testing in patients following massive and submassive pulmonary embolism.J Am Heart Assoc. 2018; 7e006841Crossref PubMed Scopus (38) Google Scholar, 3Klok F.A. van der Hulle T. den Exter P.L. Lankeit M. Huisman M.V. Konstantinides S. The post-PE syndrome: a new concept for chronic complications of pulmonary embolism.Blood Rev. 2014; 28: 221-226Crossref PubMed Scopus (233) Google Scholar, 4Klok F.A. van Kralingen K.W. van Dijk A.P. et al.Quality of life in long-term survivors of acute pulmonary embolism.Chest. 2010; 138: 1432-1440Abstract Full Text Full Text PDF PubMed Scopus (121) Google Scholar The underlying mechanisms of post-PE impairment, apart from those with chronic thromboembolic pulmonary hypertension (CTEPH), are unclear and probably multifactorial. Several studies suggest that deconditioning and psychological factors are important contributors to post-PE impairment.1Kahn S.R. Hirsch A.M. Akaberi A. et al.Functional and exercise limitations after a first episode of pulmonary embolism: results of the ELOPE Prospective Cohort Study.Chest. 2017; 151: 1058-1068Abstract Full Text Full Text PDF PubMed Scopus (141) Google Scholar,2Albaghdadi M.S. Dudzinski D.M. Giordano N. et al.Cardiopulmonary exercise testing in patients following massive and submassive pulmonary embolism.J Am Heart Assoc. 2018; 7e006841Crossref PubMed Scopus (38) Google Scholar Current guidelines for the management of PE make little comment regarding this patient group, and optimal management is unknown.5Konstantinides S.V. Meyer G. Becattini C. et al.2019 ESC guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS): the Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC).Eur Heart J. 2020; 41: 543-603Crossref PubMed Scopus (1625) Google Scholar,6Ortel T.L. Neumann I. Ageno W. et al.American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism.Blood Adv. 2020; 4: 4693-4738Crossref PubMed Scopus (377) Google Scholar Rehabilitation for patients with COPD or cardiac diseases is safe and well documented in improving patients’ symptoms, exercise capacity, and QoL.7Spruit M.A. Singh S.J. Garvey C. et al.An official American Thoracic Society/European Respiratory Society statement: key concepts and advances in pulmonary rehabilitation.Am J Respir Crit Care Med. 2013; 188: e13-e64Crossref PubMed Scopus (2277) Google Scholar Because deconditioning has been proposed to be a major factor in post-PE impairment, exercise-based rehabilitation stands out as a potential treatment option.1Kahn S.R. Hirsch A.M. Akaberi A. et al.Functional and exercise limitations after a first episode of pulmonary embolism: results of the ELOPE Prospective Cohort Study.Chest. 2017; 151: 1058-1068Abstract Full Text Full Text PDF PubMed Scopus (141) Google Scholar,2Albaghdadi M.S. Dudzinski D.M. Giordano N. et al.Cardiopulmonary exercise testing in patients following massive and submassive pulmonary embolism.J Am Heart Assoc. 2018; 7e006841Crossref PubMed Scopus (38) Google Scholar However, evidence regarding the benefits of rehabilitation in a post-PE setting is limited, and larger, randomized trials are lacking.8Ghram A. Jenab Y. Soori R. et al.High-intensity interval training in patients with pulmonary embolism: a randomized controlled trial.Med Sci Sports Exerc. 2021; 53: 2037-2044Crossref PubMed Scopus (5) Google Scholar, 9Lakoski S.G. Savage P.D. Berkman A.M. et al.The safety and efficacy of early-initiation exercise training after acute venous thromboembolism: a randomized clinical trial.J Thromb Haemost. 2015; 13: 1238-1244Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar, 10Rolving N. Brocki B.C. Bloch-Nielsen J.R. et al.Effect of a physiotherapist-guided home-based exercise intervention on physical capacity and patient-reported outcomes among patients with acute pulmonary embolism: a randomized clinical trial.JAMA Netw 2020; PubMed Scopus Google Scholar, M. S. et of exercise after acute pulmonary 2020; PubMed Scopus Google Scholar, S. F.A. et pulmonary rehabilitation in patients with after pulmonary embolism.J Med. 2020; PubMed Scopus Google Scholar, G. S. et and safety of a pulmonary rehabilitation program in post-PE 2021; Full Text Full Text PDF PubMed Scopus Google Scholar The of the was to the of an exercise-based rehabilitation program on exercise capacity, dyspnea, and QoL in patients with persistent dyspnea following PE. This randomized controlled trial was conducted at and in S. et rehabilitation to improve physical capacity, dyspnea, and quality of life following pulmonary embolism for a randomized controlled 2021; PubMed Scopus Google Scholar The for and in the and participants The is with Scholar patients from the in and of and at of and M. et al.The venous thrombosis in and Thromb Full Text Full Text PDF Scopus Google Scholar PE than diagnosed with pulmonary 6 to 72 months to to and persistent dyspnea to dyspnea with or at the of PE The clinical diagnosis of pulmonary an Med. 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Becattini C. et al.2019 ESC guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS): the Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC).Eur Heart J. 2020; 41: 543-603Crossref PubMed Scopus (1625) Google Scholar,6Ortel T.L. Neumann I. Ageno W. et al.American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism.Blood Adv. 2020; 4: 4693-4738Crossref PubMed Scopus (377) Google Scholar At participants a questionnaire on physical and those who were to of group The primary end point was the difference in Incremental Shuttle Walk Test between the groups at follow-up. The is a to assess exercise capacity, participants between two apart in a a S.J. 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The rehabilitation group reported better disease-specific QoL than the control group at follow-up, as the although this difference was QoL, dyspnea scores, and the ESWT revealed no difference between the groups at follow-up. the of this is randomized trial to the of rehabilitation following PE, a on exercise capacity and QoL in subjects with persistent Several studies reported promising results of rehabilitation following A. Jenab Y. Soori R. et al.High-intensity interval training in patients with pulmonary embolism: a randomized controlled trial.Med Sci Sports Exerc. 2021; 53: 2037-2044Crossref PubMed Scopus (5) Google Scholar, 9Lakoski S.G. Savage P.D. Berkman A.M. et al.The safety and efficacy of early-initiation exercise training after acute venous thromboembolism: a randomized clinical trial.J Thromb Haemost. 2015; 13: 1238-1244Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar, 10Rolving N. Brocki B.C. Bloch-Nielsen J.R. et al.Effect of a physiotherapist-guided home-based exercise intervention on physical capacity and patient-reported outcomes among patients with acute pulmonary embolism: a randomized clinical trial.JAMA Netw 2020; PubMed Scopus Google Scholar, M. S. et of exercise after acute pulmonary 2020; PubMed Scopus Google Scholar, S. F.A. et pulmonary rehabilitation in patients with after pulmonary embolism.J Med. 2020; PubMed Scopus Google Scholar, G. S. et and safety of a pulmonary rehabilitation program in post-PE 2021; Full Text Full Text PDF PubMed Scopus Google Scholar However, of studies been or included a control group, and there is regarding mode, and duration of intervention. The to the evidence of the benefits of rehabilitation following PE. The difference of in was than the in a be a group of is studies group differences of to as and is well the Singh S.J. R. 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Berkman A.M. et al.The safety and efficacy of early-initiation exercise training after acute venous thromboembolism: a randomized clinical trial.J Thromb Haemost. 2015; 13: 1238-1244Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar, 10Rolving N. Brocki B.C. Bloch-Nielsen J.R. et al.Effect of a physiotherapist-guided home-based exercise intervention on physical capacity and patient-reported outcomes among patients with acute pulmonary embolism: a randomized clinical trial.JAMA Netw 2020; PubMed Scopus Google Scholar, M. S. et of exercise after acute pulmonary 2020; PubMed Scopus Google Scholar or the of dyspnea has been S. F.A. et pulmonary rehabilitation in patients with after pulmonary embolism.J Med. 2020; PubMed Scopus Google Scholar However, a reported in training scores, and following weeks of rehabilitation in patients with to dyspnea after PE, as at G. S. et and safety of a pulmonary rehabilitation program in post-PE 2021; Full Text Full Text PDF PubMed Scopus Google Scholar capacity and following PE improve during the first to 6 months after S.R. Akaberi A. et al.Quality of dyspnea, and functional exercise capacity following a first episode of pulmonary embolism: results of the ELOPE J Med. 2017; Full Text Full Text PDF PubMed Scopus Google Scholar In the included subjects 6 months following the acute PE, as considered that 6 months be and with the potential of rehabilitation. participants underwent with a at This the participants the safety of physical exercise and to improved at follow-up for is an important in rehabilitation in and studies suggest that this a following life of from acute pulmonary embolism A 2021; Full Text Full Text PDF PubMed Scopus Google Scholar In the there were no adverse events during to the on the safety of the physical exercise following A. Jenab Y. Soori R. et al.High-intensity interval training in patients with pulmonary embolism: a randomized controlled trial.Med Sci Sports Exerc. 2021; 53: 2037-2044Crossref PubMed Scopus (5) Google Scholar, 9Lakoski S.G. Savage P.D. Berkman A.M. et al.The safety and efficacy of early-initiation exercise training after acute venous thromboembolism: a randomized clinical trial.J Thromb Haemost. 2015; 13: 1238-1244Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar, 10Rolving N. Brocki B.C. Bloch-Nielsen J.R. et al.Effect of a physiotherapist-guided home-based exercise intervention on physical capacity and patient-reported outcomes among patients with acute pulmonary embolism: a randomized clinical trial.JAMA Netw 2020; PubMed Scopus Google Scholar, M. S. et of exercise after acute pulmonary 2020; PubMed Scopus Google Scholar, S. F.A. et pulmonary rehabilitation in patients with after pulmonary embolism.J Med. 2020; PubMed Scopus Google Scholar, G. 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