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Avtaar Singh, Sanjeet Singh (2020) Creating a Multivariable Model To Avtaar Singh, Sanjeet Singh (2020) Creating a multivariable model to predict primary graft dysfunction after heart transplantation in the United Kingdom using the 2014 International Society of Heart and Lung Transplantation consensus definition. PhD thesis. https://theses.gla.ac.uk/79063/ Copyright and moral rights for this work are retained by the author A copy can be downloaded for personal non-commercial research or study, without prior permission or charge This work cannot be reproduced or quoted extensively from without first obtaining permission in writing from the author The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the author When referring to this work, full bibliographic details including the author, title, awarding institution and date of the thesis must be given Enlighten: Theses https://theses.gla.ac.uk/ [email protected] Creating a Multivariable Model to Predict Primary Graft Dysfunction after Heart Transplantation in the United Kingdom using the 2014 International Society of Heart and Lung Transplantation Consensus Definition A Thesis submitted to The University of Glasgow for the degree of DOCTOR OF PHILOSOPHY Student GUID: Sanjeet Singh Avtaar Singh Creating a Multivariable Model to Predict PGD after Heart Transplantation in the United Kingdom 2 Abstract Heart failure places a global strain on healthcare provision. It has an increasing incidence and represents the endpoint of a variety of cardiovascular diseases. The preceding decades have carved out a clear management algorithm for the use of pharmacotherapies (neurohormonal antagonists), device-based therapies (Implantable Cardioverting Defibrillator (ICD) and Cardiac Resynchronisation Therapy (CRT)) and mechanical therapies including left ventricular assist devices and heart transplantation. While heart transplantation remains the gold standard for the suitable few, the advancement of healthcare systems and improved working conditions and safety regulations have changed the demographics of the typical organ donor which traditionally were young brainstem death donors (DBD) with minimal other comorbidities. Nevertheless, transplantation confers a substantial survival benefit for selected patients with advanced heart failure, achieving a 1-year survival rate of ≥80%. The primary cause for early mortality in recipients remains primary graft dysfunction (PGD). The incidence of PGD throughout the UK and the world are variable due to the lack of a standardised definition until 2014. My research explored the true incidence of PGD throughout the UK using data collected from each of the 6 transplant centres alongside the National Health Service Blood and Transplant database. I then looked at risk factors for PGD which culminated in the largest PGD study recorded at the time of writing. I also looked into the role of mechanical circulatory support to bridge patients in cardiogenic shock post-myocardial infarction in Scotland. I finally developed 2 scoring systems, 1 for Primary Graft Dysfunction (PREDICTA) and 1 using the modified Delphi Method of a consensus agreement (GTS) to factor in elements of frailty which had been garnering increasing interest at conferences I had attended. Creating a Multivariable Model to Predict PGD after Heart Transplantation in the United Kingdom 3 Table of Contents Abstract ...................................................................................... 2 List of Tables ................................................................................ 6 List of Figures ............................................................................... 7 Acknowledgement .......................................................................... 9 Author’s Declaration ...................................................................... 11 Presentations and Publications .......................................................... 13 Presentations ............................................................................... 13 Published Abstracts ....................................................................... 16 Full Publications ........................................................................... 17 Submitted for Publication .............................. Error! Bookmark not defined. Definitions/Abbreviations ................................................................ 18 1 Introduction ........................................................................... 20 1.1 Thesis overview .................................................................. 20 1.2 Core Methodology ............................................................... 22 1.3 Organ transplantation and ancient history .................................. 24 1.4 The pre-transplant era .......................................................... 25 1.5 Pre-immunosuppression era .................................................... 27 1.6 Early Immunosuppression ....................................................... 28 1.7 History of Cardiac Surgery and Transplantation ............................ 29 1.8 Early Issues with Heart Transplantation ...................................... 34 1.9 Immunosuppression in Heart Transplantation ............................... 36 1.10 Current status of heart transplantation ................................... 42 1.11 Primary Diagnostic Indications for Transplant ............................ 45 1.12 Primary Graft Dysfunction after Heart Transplantation ................. 46 2 The process of heart transplantation .............................................. 74 2.1 The role of NHSBT in organ donation ......................................... 75 2.2 Patient Listing for Transplantation ........................................... 77 2.3 Donation after Brain Stem Death (DBD) ...................................... 80 2.4 Donation after Circulatory Death (DCD) ...................................... 98 2.5 The Implantation ............................................................... 104 2.6 The Recipient Cardiectomy ................................................... 106 2.7 Implantation ..................................................................... 107 2.8 Organ Shortage.................................................................. 112 3 ISHLT Primary Graft Dysfunction incidence, risk factors and outcome: a UK National Study ............................................................................ 119 3.1 Abstract .......................................................................... 120 Creating a Multivariable Model to Predict PGD after Heart Transplantation in the United Kingdom 4 3.2 Background ...................................................................... 122 3.3 Methods .......................................................................... 123 3.4 Statistical Analysis .............................................................. 123 3.5 Results ........................................................................... 124 3.6 Discussion ........................................................................ 131 3.7 Limitations ....................................................................... 138 3.8 Conclusion ....................................................................... 139 4 PREDICTA -A model to predict Primary Graft Dysfunction after adult heart transplantation in the United Kingdom ............................................... 140 4.1 Abstract .......................................................................... 141 4.2 Introduction ..................................................................... 143 4.3 Methods .......................................................................... 144 4.4 Results ........................................................................... 146 4.5 Discussion ........................................................................ 157 4.6 Limitation ........................................................................ 160 4.7 Conclusion ....................................................................... 160 5 The Glasgow Experience of extended myocardial protection: A novel method of implantation to reduce primary graft dysfunction after heart transplantation 162 5.1 Abstract .......................................................................... 163 5.2 Introduction ..................................................................... 165 5.3 Objectives ....................................................................... 165 5.4 Method ........................................................................... 166 5.5 Results ........................................................................... 171 5.6 Discussion ........................................................................ 176 5.7 Limitations ....................................................................... 179 5.8 Conclusion ....................................................................... 180 6 Mechanical circulatory support for refractory cardiogenic shock post-acute myocardial infarction – A decade of lessons .......................................... 181 6.1 Abstract .......................................................................... 182 6.2 Introduction ..................................................................... 184 6.3 Methodology ..................................................................... 185 6.4 Results ........................................................................... 185 6.5 Discussion .......................................................................
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