The Use of Activity Monitoring and Machine Learning for the Functional Classification of Heart Failure by Jonathan-F. Benjamin Jason Jérémy Baril A thesis submitted in conformity with the requirements for the degree of Master of Health Science, Clinical Engineering Institute of Biomaterials and Biomedical Engineering University of Toronto CC BY 4.0 by Jonathan-F. Benjamin Jason Jérémy Baril, unless otherwise prohibited The Use of Activity Monitoring and Machine Learning for the Functional Classification of Heart Failure Jonathan-F. Benjamin Jason Jérémy Baril Master of Health Science, Clinical Engineering Institute of Biomaterials and Biomedical Engineering University of Toronto 2018 Abstract Background: Assessing the functional status of a heart failure patient is a highly subjective task. Objective: This thesis aimed to find an accessible, objective means of assessing the New York Heart Association (NYHA) functional classification (FC) of a patient by leveraging modern machine learning techniques. M ethods: We first identified relevant quantitative data and upgraded Medly, a remote patient monitoring system (RPMS), to support data collection. We then proceeded to build six different machine learning classifiers including hidden Markov model, Generalized Linear Model (GLM), random forest and neural network based classifiers. Results: The best overall classifier was found to be a boosted GLM, which achieved a classification performance (Cohen’s Kappa statistic 휅=0.73, balanced accuracy=85%) comparable to human level performance (휅=0.75). Conclusions: Although the investigated classifiers are not ready for implementation into a real RPMS, they show promise for making the evaluation of NYHA FC more universally consistent and reliable. ii dédié à Papa, sans ton encouragement cette thèse n'aurait jamais existée iii Acknowledgments Ah! The acknowledgements. As painful and lonely as it may be to compose a thesis, the acknowledgements section is by far the easiest and most pleasant section to write. It is both heart- warming and humbling to be reminded of how much, and how many others, have sacrificed to breathe life into this work - truly without the help of these people this project would still be a mere figment of an idea in someone’s mind. If you’ve contributed to this work, whether directly or indirectly know that, even if I’ve somehow forgotten to include your name here I am eternally grateful for your help and contribution to this work. Firstly, I need to acknowledge our patients: it is probably only those of us who do health research who truly understand how much these projects life and die by the pure self-less generosity of patients. Thank you for trusting us with your health and your data. I can only hope this work will somehow contribute to ultimately making the need for your generosity obsolete. Second, my committee: Drs. Joe Cafazzo, Cedric Manlhiot, Heather Ross, and Babak Taati. Your contributions to this project can only be understated – in fact my biggest regret in this project is not having taken greater advantage of your experience and wisdom. Your guidance, correction, teaching, encouragement and advice was invaluable to having gotten this project anywhere. Thanks also go to Dr. Rob Nolan for taking time to serve as the external examiner for this thesis. I am also hugely indebted to Simon Bromberg, Raghad Abdulmajeed and Dr. Yasbanoo Moayedi, not only for your foundational work on which I was able build my work but also for leaving behind a treasure trove of data that was indispensable for getting this project started. Special thanks to Edgar Crowdy, Steven Fan, Bridgette Mueller, Mohammad Peikari, Emily Somerset, and Kabir Sakhrani at the Cardiovascular Data Management Centre for your advice and tips with regards to the analytics but also your incredible help with much of the last-minute data collection, analytics, processing and people-power that went into the ‘research’ part of this project. Heartfelt thanks also go to Jason Hearn, not only for contributions to this work as part of the aforementioned group, but also your puns, listening ear and friendship journeying through the adventure of doing an MHSc at the Centre these last 2 years. If only all graduate students were so fortunate. Enormous thanks to Iqra Ashfaq, Alana Tibbles, Patrick Ware, Dr. Emily Seto, and Mary O’Sullivan. Goodness knows how many times I interrupted your work for this project. Thank you so much for your iv patience and for being so willing to share your time, your resources, and expertise around all things Medly (as well as for rooting for me all along the way). Additional thanks go to: Stephanie Wilson, Diane De Sousa and especially Larissa Maderia for all the hard work you put in so we could get Fitbit integrated into Medly. Damon Pfaff, Owen Thijssen and Mike Lovas for your design advice and allowing me to leech off your expertise. James Agnew and Vlad Voloshyn for your technical help. Melanie Yeung and Akib Uddin, not only for your operational and project management help on the Fitbit integration (and for the internship) but also for your timely encouragement and advice for getting through this degree. Aarti Mathur and Alison Bison for your always joyous help with various admin and purchasing issues. Similarly, Jess Fifield, but who also deserves additional accolades for her eternal patience in filtering my incessant requests, and for arranging, rearranging and further rearranging Dr. Cafazzo’s calendar and always managing to find an available slot for Jason or for myself to meet with Dr. Cafazzo when necessary. Thanks also to Anna Yuan for managing to wrangle the schedules of 5 incredibly busy university professors so I could defend on time. Quynh Pham, for your mentorship and encouragement, and for your unwavering enthusiasm at the Centre; for always always [sic] finding time to thoughtfully answer my questions, whether on REB applications, thesis writing, EPR or the myriad other elements of the research student life. Plinio Morita, for your help and suggestions regarding some of the analytics in this project. Shivani Goyal, especially for your help and advice regarding my OGS/CGS-M proposal. And speaking of: Many thanks are owned to The Ted Rogers Centre for Heart Research and Peter Munk Cardiac Centre, (hSITE) Health Support through Information Technology Enhancements, (NSERC) the Natural Sciences and Engineering Research Council, (CIHR) the Canadian Institutes for Health Research, the Government of Ontario, and the University of Toronto for funding various parts of this project at various times. v And of course, thank you to everyone else at Healthcare Human Factors and at eHealth Innovation who at various times pitched in, shared their expertise, provided advice or encouraging word or even just expressed interest in the work. Thank you also to Wayne, Chris and Anjum for extending the opportunity to learn, work and travel with the human factors team as part of my internships. Thanks to Rhonda Marley, our wonderful Clin. Eng. coordinator for alleviating, as you could, a lot of the burdensome administrative workload involved in a graduate degree. Thank you to BESA, the IBBME community and especially the Clin. Eng. students who were part of our program. It was a true pleasure. We made it. And lastly, on a personal note, none of this work would have been possible without friends and family who supported and encouraged me over these last 2 years - words cannot express how grateful I am for you. Merci Maman, Papa, Alisson, Benjamin; Ruth and Alvis (my home away from home); Kyle F, Thomas, Esteban (when I needed a nice invigorating round of PUBG or GTA); Vanessa, Rebecca, Theresa, Duela, Sara & Matthew, Matt & Moni, Rachel & Justin, Melanie, Kyle N, Shawn, Valerie, Jamie, and Courtney (all of whom graciously let me go to the big TO but would probably rather I have stayed with them in Winnipeg). Special thanks in particular though have to go to: Paul White, who had the dubious honor of reviewing the first draft of this thesis; Cameron MacGregor, who brought this program to my attention and joined me on the adventure; Knox Church (and my home church in particular; Sam, Chris, Hendrick, Stephen, Andrew, Bella, Roydon, Sarah, Lori, Thomas, Emily, Deborah, Larissa, Katie, Jackie, Danielle, and so many others), for your open arms and being my much-needed community in this new city; to Tanisha Strachan, for keeping me sane these past few months, even though no one warned you that dating a grad student is often too much akin to dating a hermit and of course; and Jesus, because ultimately this was all for you. Thank you all for your love, for your encouragement, and for your patience. Now on to the main event… vi Table of Contents Acknowledgments ......................................................................................................................................... iv Table of Contents ........................................................................................................................................ vii List of Tables ................................................................................................................................................ xi List of Figures ............................................................................................................................................. xiii List of Abbreviations .................................................................................................................................. xvi - Introduction ...............................................................................................................................