Exercise training in pulmonary arterial hypertension associated with connective tissue diseases

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Abstract

Introduction

The objective of this prospective study was to assess short- and long-term efficacy of exercise training (ET) as add-on to medical therapy in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-APAH).

Methods

Patients with invasively confirmed CTD-APAH received ET in-hospital for 3 weeks and continued at home for 12 weeks. Efficacy parameters have been evaluated at baseline and after 15 weeks by blinded-observers. Survival rate has been evaluated in a follow-up period of 2.9 ± 1.9 years.

Results

Twenty-one consecutive patients were included and assessed at baseline, and after 3 weeks, 14 after 15 weeks. Patients significantly improved the mean distance walked in 6 minutes compared to baseline by 67 ± 52 meters after 3 weeks (p < 0.001) and by 71 ± 35 meters after 15 weeks (p = 0.003), scores of quality of life (p < 0.05), heart rate at rest, peak oxygen consumption, oxygen saturation and maximal workload. Systolic pulmonary artery pressure and diastolic systemic blood pressure improved significantly after 3 weeks of ET. The 1- and 2-year overall-survival rates were 100%, the 3-year survival 73%. In one patient lung transplantation was performed 6 months after ET.

Conclusion

ET as add-on to medical therapy is highly effective in patients with CTD-APAH to improve work capacity, quality of life and further prognostic relevant parameters and possibly improves the 1-, 2- and 3-year survival rate. Further randomized controlled studies are needed to confirm these results.

Trial registration

ClinicalTrials.gov: NCT00491309.

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Most cited references 15

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Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2.

Nazzareno Galiè, Horst Olschewski, Ronald Oudiz … (2008)

Ambrisentan is a propanoic acid-based, A-selective endothelin receptor antagonist for the once-daily treatment of pulmonary arterial hypertension. Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy Study 1 and 2 (ARIES-1 and ARIES-2) were concurrent, double-blind, placebo-controlled studies that randomized 202 and 192 patients with pulmonary arterial hypertension, respectively, to placebo or ambrisentan (ARIES-1, 5 or 10 mg; ARIES-2, 2.5 or 5 mg) orally once daily for 12 weeks. The primary end point for each study was change in 6-minute walk distance from baseline to week 12. Clinical worsening, World Health Organization functional class, Short Form-36 Health Survey score, Borg dyspnea score, and B-type natriuretic peptide plasma concentrations also were assessed. In addition, a long-term extension study was performed. The 6-minute walk distance increased in all ambrisentan groups; mean placebo-corrected treatment effects were 31 m (P=0.008) and 51 m (P 3 times the upper limit of normal. In 280 patients completing 48 weeks of treatment with ambrisentan monotherapy, the improvement from baseline in 6-minute walk at 48 weeks was 39 m. Ambrisentan improves exercise capacity in patients with pulmonary arterial hypertension. Improvements were observed for several secondary end points in each of the studies, although statistical significance was more variable. Ambrisentan is well tolerated and is associated with a low risk of aminotransferase abnormalities.

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Effect of encouragement on walking test performance.

Helen Jones, Cindy L Berman, E Fallen … (1984)

Walking tests, frequently used to document effects of treatment on exercise capacity, have never been standardised. We studied the effects of encouragement on walking test performance in a randomised study that controlled for the nature of the underlying disease, time of day, and order effects. We randomised 43 patients with chronic airflow limitation or chronic heart failure or both to receive or not receive encouragement as they performed serial two and six minute walks every fortnight for 10 weeks. Simple encouragement improved performance (p less than 0.02 for the six minute walk), and the magnitude of the effect was similar to that reported for patients in studies purporting to show beneficial effects of therapeutic manoeuvres. Age and test repetition also affected performance. These results demonstrate the need for careful standardisation of the performance of walking tests, and suggest caution in interpreting studies in which standardisation is not a major feature of the study design.

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Effect of exercise and respiratory training on clinical progression and survival in patients with severe chronic pulmonary hypertension.

Jana Juenger, Hans Klose, Gerd Staehler … (2010)

Even though specific agents for the treatment of patients with pulmonary hypertension (PH) are available, in PH patients, physical capacity and quality of life (QoL) are often restricted and survival is reduced. This study prospectively investigated the long-term effects of respiratory and exercise training in patients with severe chronic PH regarding safety, time to clinical worsening and survival. Fifty-eight consecutive patients with severe PH on stable disease-targeted medication received exercise and respiratory training in hospital for 3 weeks and continued at home. They were prospectively followed for 24 ± 12 months. Primary endpoints were time to clinical worsening and survival. Adverse events and changes in the 6-min walking test, QoL, WHO functional class and gas exchange were secondary endpoints and were evaluated at baseline and at weeks 3 and 15. All patients tolerated the exercise training well without severe adverse events. In week 15, 6-min walking test results were significantly improved compared to baseline (by 84 ± 49 m, p < 0.001), as well as QoL scores, WHO functional class (from 2.9 ± 0.5 to 2.6 ± 0.6, p < 0.01), peak oxygen consumption (from 12.5 ± 3.0 to 14.6 ± 3.9 ml/min/kg, p < 0.001), heart rate at rest (from 75 ± 12 to 61 ± 18 beats/min, p < 0.001) and maximal workload (from 65 ± 21 to 80 ± 25 W, p < 0.001). Survival at 1 and 2 years was 100 and 95%, respectively. Fifteen events occurred during the follow-up. This study indicates that exercise and respiratory training as add-on to medical treatment may improve exercise capacity and QoL, and that they have a good long-term safety in the described setting. Copyright © 2011 S. Karger AG, Basel.

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Author and article information

Journal

Journal ID (nlm-ta): Arthritis Res Ther

Journal ID (iso-abbrev): Arthritis Res. Ther

Title: Arthritis Research & Therapy

Publisher: BioMed Central

ISSN (Print): 1478-6354

ISSN (Electronic): 1478-6362

Publication date (Print): 2012

Publication date (Electronic): 18 June 2012

Volume: 14

Issue: 3

Page: R148

Affiliations

[1 ]Centre for Pulmonary Hypertension at Thoraxclinic Heidelberg, Thoraxclinic at the University Hospital Heidelberg, Amalienstraße 5, Heidelberg, 69126, Germany

[2 ]Department of Human Genetics, University of Heidelberg, Im Neuenheimer Feld 366, Heidelberg, 69120, Germany

[3 ]Department of Rheumatology, University of Heidelberg, Im Neuenheimer Feld 410, Heidelberg, 69120, Gemany

[4 ]Department of Rheumatology, ACURA Centre for Rheumatic Diseases, Rotenbachtalstraße 5, Baden-Baden, 76530, Germany

[5 ]Department of Internal Medicine, Medical Clinic III, Grafenstraße 9, Darmstadt, 64283, Germany

[6 ]Centre for Pulmonary Hypertension, Clinic Löwenstein, Geißhölzle 62, Löwenstein, 74245, Germany

[7 ]Department of Pneumology, University Hospital Gießen, Klinikstraße 33, Giessen, 35392, Germany

[8 ]Department of Pneumology, University Hospital Dresden, Fetscherstraße 74, Dresden, 01307, Germany

[9 ]Department of Pneumology, University Hospital Leipzig, Liebigstraße 20, Leipzig, 04103, Germany

[10 ]Department of Neurology, University Hospital Heidelberg, Im Neuenheimer Feld 400, Heidelberg, 69126, Germany

Article

Publisher ID: ar3883

DOI: 10.1186/ar3883

PMC ID: 3446533

PubMed ID: 22709477

SO-VID: b48c0324-0896-4fb0-a9fb-1219ace7ef5c

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 14 February 2012

Date revision received : 30 April 2012

Date accepted : 18 June 2012

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Exercise training in pulmonary arterial hypertension associated with connective tissue diseases

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Abstract

Introduction

Methods

Results

Conclusion

Trial registration

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Orthopedics

Most cited references 15

Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2.

Effect of encouragement on walking test performance.

Effect of exercise and respiratory training on clinical progression and survival in patients with severe chronic pulmonary hypertension.

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Cited by 35

Most referenced authors 755