Integration of advanced echocardiographic metrics and biomarkers to the fields of heart failure and exercise physiology in the era of precision medicine
AuthorMoneghetti, Kegan James
AffiliationMedicine (St Vincent's)
Document TypePhD thesis
Access StatusThis item is embargoed and will be available on 2021-03-15.
© 2018 Dr. Kegan James Moneghetti
Exercise testing is widely used for risk stratification of ischaemic heart disease, however, its application in other cardiovascular conditions, specifically heart failure and other disease states is less defined. Heart failure is a leading cause of mortality and morbidity. Despite advances in medical therapy, its prevalence is expected to increase. Recent developments in cardiac echocardiography, exercise testing and reducing costs of biomarker assays provides the opportunity to improve identification and prognostication of the heart failure syndrome. These principles may also prove useful in the discrimination of other disease states, in which a diagnostic biomarker is lacking. The principle aim of this thesis was to identify novel echocardiographic and non-invasive cardiopulmonary parameters during exercise that provide incremental prognostic value to established risk markers in heart failure. An exploratory sub aim was to investigate the ability of a personalised exercise test to discriminated disease states outside the cardiovascular system. Cohorts of heart failure patients undergoing assessment with echocardiography and cardiopulmonary exercise testing were selected to assess the incremental value of novel parameters. Recently, deformation imaging, also known as strain and quantitative measures of the right heart have shown prognostic value in patients with heart failure. These measures have rarely been analysed with cardiopulmonary exercise testing, therefore, their prognostic value in outcome models and contemporary risk scores were assessed. Dynamic changes in selected parameters were evaluated with regard to risk stratification potential. Finally, as biomarker assays are becoming increasingly used to identify the heart failure syndrome, their contribution to discrimination of disease and risk modeling when performed in conjunction with an exercise test was evaluated. In summary the main findings of this thesis were: 1. Echocardiographic contractile reserve and cardiopulmonary exercise testing parameters provide complementary information, therefore, in combination provide an opportunity to improve prognostication in heart failure. 2. Right heart metrics specifically, right atrial volume and exercise performance add value to previously validated heart failure risk scores in dilated cardiomyopathy. 3. The combination of exercise performance, left ventricular strain and left atrial volume presents a simple model for predicting heart failure outcomes in hypertrophic cardiomyopathy. 4. Percent predicted values of maximal oxygen consumption derived from the Fitness Registry and the Importance of Exercise National Database (FRIEND) registry equation appear to accurately predict heart failure outcomes. 5. Cytokine profiling post exercise appears to have greater discriminatory power than at rest when used to identify patients with myalgic encephalomyelitis / chronic fatigue syndrome; Echocardiographic parameters, have limited value. 6. The integration of cardiac biomarkers, cytokine profiling, exercise performance and cardiac imaging in a personalised exercise test is achievable and has the potential to improve risk profiling. In conclusion, this thesis demonstrated the opportunity to further refine risk stratification in heart failure using novel images techniques, specifically deformation imaging, right heart metrics and exercise performance. The use of serum samples post a bout of exercise may provide an opportunity to further refine diagnostics in the field. Future studies should address biological variability of serum biomarkers and investigate their value when integrated with established markers of risk.
Keywordsechocardiography; exercise testing; biomarkers; heart failure; cytokines; cardiomyopathy
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