Exercise testing and non-invasive haemodynamics in the assessment and monitoring of pulmonary hypertension: novel submaximal and peak exercise variables

Thomson, Stephen D. (2017) Exercise testing and non-invasive haemodynamics in the assessment and monitoring of pulmonary hypertension: novel submaximal and peak exercise variables. MD thesis, University of Glasgow.

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Abstract

Pulmonary hypertension is a disease characterised by progressive pulmonary vascular remodelling and obliteration with consequent development of right heart failure and ultimately death. First described many decades ago with a median survival of less than 3 years and no available treatments, the development of disease specific pulmonary vasodilator therapy has led to only modest improvements in survival and it remains an almost universally fatal disease. One of the key symptoms of pulmonary hypertension is exercise intolerance, primarily a consequence of the underlying right ventricular failure and an inability to augment stroke volume on exercise. The gold standard diagnostic test is right heart catheterisation but this is unattractive as a tool for ongoing monitoring as it is invasive and not without risk, albeit that risk is small. As a result most monitoring of disease progression and of treatment response is carried out using surrogate markers, often exercise based such as the 6 minute walk test. Increasing attention is focused on the role of exercise both in that monitoring of patients and also in helping to understand better the pathophysiology. The work presented in this thesis therefore aimed to explore novel exercise derived variables and noninvasive haemodynamic measurement as tools to improve our understanding of the disease limitation, to enhance our monitoring of treatment response and to give additional prognostic information. In Chapter 3 the role of peripheral muscle oxygen extraction and exercise limitation was explored by performing right heart catheterisation on exercise with measurement of mixed venous oxygen saturation. This demonstrated that patients with pulmonary hypertension demonstrate no evidence of impaired oxygen extraction and that they appear to extract at least as much oxygen on exercise as healthy individuals have been shown to in other studies. This indicates that impairment of oxygen extraction is not a cause of exercise limitation in pulmonary hypertension. 3 Chapter 4 describes a series of studies evaluating the potential role of the oxygen uptake efficiency slope in pulmonary hypertension. This variable derived from the oxygen consumption and ventilation across an incremental cardiopulmonary exercise test has demonstrated promise as a potential submaximal measure of exercise performance and predictor of survival in left heart failure. The studies conducted demonstrated that this variable is a measure of peak exercise performance in pulmonary hypertension, that it can be measure on submaximal levels of exercise and that it predicts survival in patients with Group 1 and Group 4 disease. The studies described in Chapter 5 investigated the rates of recovery of heart rate and oxygen consumption after exercise and found that both could predict survival. In particular the rate of recovery of heart rate after exercise was demonstrated to be a strong predictor of survival on multivariate analysis, thus providing a further method of assessing prognosis with exercise. Finally the ability of noninvasive measures of stroke volume to predict outcome was explored in the studies detailed in Chapter 6. The underlying haemodynamic abnormalities are not assessed when surrogate measures such as exercise testing are employed in patient follow up. Standard practice is to review patients 3 to 4 months after any change in treatment and to assess them using these surrogate measures. Acute haemodynamic changes are able to be detected invasively immediately after administration of pulmonary vasodilator therapy. This study therefore investigated the ability of two noninvasive methods of measuring stroke volume, inert gas rebreathing and cardiac MRI, to detect treatment response after only 2 weeks and assess how this related to functional improvement at the standard 4 months. The study found that haemodynamic changes were able to be detected at 2 weeks and these appeared to relate to changes in 6 minute walk distance at the same time point but did not appear to relate to 6 minute walk distance at 4 months. This study however did not reach its recruitment target and therefore further work is needed in this area.

Item Type: Thesis (MD)
Qualification Level: Doctoral
Keywords: pulmonary hypertension, exercise physiology, exercise test, cardiopulmonary exercise test, noninvasive haemodynamic measurement, inert gas rebreathing, treatment response, oxygen extraction, oxygen uptake efficiency slope.
Subjects: R Medicine > R Medicine (General)
R Medicine > RC Internal medicine
Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Funder's Name: UNSPECIFIED
Supervisor's Name: Johnson, Dr. Martin K. and Berry, Professor Colin
Date of Award: 2017
Depositing User: Dr Stephen D Thomson
Unique ID: glathesis:2017-8918
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 27 Mar 2018 13:29
Last Modified: 24 Apr 2018 08:21
URI: http://theses.gla.ac.uk/id/eprint/8918

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