Exercise therapy and cardiac, autonomic and systemic function in patients with chronic heart failure Melissa Jane Pearson Bachelor of Exercise & Sports Science (Clinical Exercise Physiology) (Honours, Class 1) A thesis submitted in fulfilment for the degree of Doctor of Philosophy School of Science and Technology University of New England, NSW Australia June 2018 i Declaration I declare that this work has not been and is not being submitted for any other degree to this or any other University. To the best of my knowledge it does not contain any materials previously published or written by another person except where due reference is made in the text; and all substantive contributions by others to the work presented, including jointly authored publications is clearly acknowledged. 20th June 2018 Signed Date ii Acknowledgments To my Principal Supervisor Professor Neil Smart, I would like to acknowledge and express my sincere thanks for your guidance, advice, support, knowledge and patience. Reflecting back to the start of the journey I really wasn’t sure what to expect, however, I can honestly say that I am extremely grateful for the opportunity and experience. It did not go the original way it was planned, but that’s life and all part of the journey. I am taking a lot more away from this journey then I expected. I would also like to thank Associate Professor Gudrun Dieberg for your support, advice and friendship over the years. Most importantly, I would like to acknowledge my husband Warwick. Words cannot fully express how I feel. It was not in our plan for me to undertake such a commitment, but when the opportunity arose you were encouraging and supportive as you always are. There have been ups and down (probably a nice way of putting it), but your unconditional love, encouragement and support have kept me going. You are the most patient person I have ever known. Thank you for reading all the papers, even though they are way outside your field of research. Yes you deserve a PhD as well (oh wait you already have one). Finally, while he cannot read, Bucky kept me company while sitting at the computer all those hours and helped me keep my sanity. Financial Support This body of work was supported by an Australian Postgraduate Award Scholarship (APA) funded by the Australian Federal Government. iii Thesis Format This thesis is presented as a thesis by publication. The listed publications have been inserted into the thesis as chapters. Each of the following has been accepted and published in peer reviewed journals, in press or submitted for peer-review. Pearson, M. J., & Smart, N. A. (2017). Effect of exercise training on endothelial function in heart failure patients: a systematic review meta-analysis. International Journal of Cardiology, 231, 234-243, https://doi.org/10.1016/j.ijcard.2016.12.145 Pearson, M. J., & Smart, N. A. (2017). Aerobic training Intensity for Improved Endothelial Function in Heart Failure Patients: A Systematic Review and Meta-Analysis. Cardiology Research and Practice, 2017. Article ID 2450202, https://doi.org/10.1155/2017/2450202 Pearson, M. J., & Smart, N. A. (2018). Exercise therapy and autonomic function in heart failure patients: a systematic review and meta-analysis. Heart Failure Reviews, 23(1), 91-108. https://doi.org/10.1007/s10741-017-9662-z Pearson, M. J., Mungovan, S. F., & Smart, N. A. (2018). Effect of aerobic and resistance training on inflammatory markers in heart failure patients: systematic review and meta-analysis. Heart Failure Reviews, 23(2), 209-223. https://doi.org/10.1007/s10741-018-9677-0 Pearson, M. J., King, N., & Smart, N. A. (2018). Effect of exercise therapy on established and emerging circulating biomarkers in heart failure patients: A systematic review and meta-analysis. Open Heart. ARTICLE IN PRESS http://dx.doi.org/10.1136/openhrt-2018-000819. iv Pearson, M. J., Mungovan, S. F., & Smart, N. A. (2017). Effect of exercise on diastolic function in heart failure patients: a systematic review and meta-analysis. Heart Failure Reviews, 22(2), 229-242. https://doi.org/10.1007/s10741-017-9600-0 Pearson, M. J., & Smart, N. A. (2018). Reported methods for handling missing change standard deviations in meta-analyses of exercise therapy interventions in patients with heart failure: a systematic review. Submitted to PLOS ONE 25th May 2018 Under review v Please be advised that this is a thesis by publication. The published chapters have been retained in this version of the thesis, under Exception 200AB of the Copyright Act 1968 (http://www.austlii.edu.au/au/legis/cth/consol_act/ca1968133/s200ab.html) Publications arising from thesis: Chapter 3: Pearson, M., & Smart, N. (2017). Effect of exercise training on endothelial function in heart failure patients: A systematic review meta-analysis. International Journal Of Cardiology, 231, 234-243. doi: 10.1016/j.ijcard.2016.12.145 Chapter 4: Pearson, M., & Smart, N. (2017). Aerobic Training Intensity for Improved Endothelial Function in Heart Failure Patients: A Systematic Review and Meta-Analysis. Cardiology Research And Practice, 2017, 1-10. doi: 10.1155/2017/2450202 Chapter 5: Pearson, M., & Smart, N. (2017). Exercise therapy and autonomic function in heart failure patients: a systematic review and meta-analysis. Heart Failure Reviews, 23(1), 91-108. doi: 10.1007/s10741-017-9662-z Chapter 6: Pearson, M., Mungovan, S., & Smart, N. (2018). Effect of aerobic and resistance training on inflammatory markers in heart failure patients: systematic review and meta-analysis. Heart Failure Reviews, 23(2), 209-223. doi: 10.1007/s10741-018- 9677-0 Chapter 7: Pearson, M., King, N., & Smart, N. (2018). Effect of exercise therapy on established and emerging circulating biomarkers in patients with heart failure: a systematic review and meta-analysis. Open Heart, 5(2), e000819. doi: 10.1136/openhrt-2018- 000819 Chapter 8: Pearson, M., Mungovan, S., & Smart, N. (2017). Effect of exercise on diastolic function in heart failure patients: a systematic review and meta-analysis. Heart Failure Reviews, 22(2), 229-242. doi: 10.1007/s10741-017-9600-0 Chapter 9: Pearson, M., & Smart, N. (2018). Reported methods for handling missing change standard deviations in meta-analyses of exercise therapy interventions in patients with heart failure: A systematic review. PLOS ONE, 13(10), e0205952. doi: 10.1371/journal.pone.0205952 Downloaded from [email protected], the institutional research repository of the University of New England at Armidale, NSW Australia. Table of Contents DECLARATION .................................................................................................................. II ACKNOWLEDGMENTS ...................................................................................................... III FINANCIAL SUPPORT ....................................................................................................... III THESIS FORMAT .............................................................................................................. IV LIST OF FIGURES .............................................................................................................. IX LIST OF TABLES ................................................................................................................ IX ABBREVIATIONS ............................................................................................................... X ABSTRACT ........................................................................................................................ 1 1 CHAPTER 1 INTRODUCTION - THESIS OVERVIEW ........................................................ 3 2 CHAPTER 2 - LITERATURE REVIEW ............................................................................ 12 2.1 Introduction ......................................................................................................... 12 2.1.1 Epidemiology and Burden of Heart Failure ........................................................... 12 2.1.2 Definition, Diagnosis and Classification ................................................................. 13 2.1.3 Aetiology and Pathophysiology ............................................................................. 15 2.1.4 Heart Failure Management ................................................................................... 19 2.2 Exercise Training and Heart Failure ....................................................................... 20 2.2.1 History .................................................................................................................... 20 2.2.2 Exercise Rehabilitation Practices and Guidelines .................................................. 23 2.3 Evidenced-based Medicine in Healthcare Interventions – Systematic Reviews and Meta-analyses ................................................................................................................ 24 2.4 Evidence Map of Systematic Reviews and Meta-analyses – Effects and/or benefits of exercise training/therapy interventions in heart failure patients ................................. 26 2.5 Summary ............................................................................................................. 41 2.6 References ........................................................................................................... 42 vi 3 CHAPTER 3 - PEER REVIEWED PUBLICATION: EFFECT OF EXERCISE TRAINING ON ENDOTHELIAL FUNCTION IN HEART FAILURE PATIENTS: A SYSTEMATIC REVIEW META- ANALYSIS ......................................................................................................................