Medicine (Northern Health) - Theses

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    Peri-Operative Myocardial Injury and Type 2 Myocardial Infarction
    Rafiudeen, Rifly ( 2023-04)
    This thesis explores the major themes of Peri-Operative Myocardial Infarction and Injury (PMI), and Type 2 Myocardial Infarction (T2MI), both entities where understanding of pathophysiological mechanisms and clinical presentation and management are not completely understood and continuing to evolve (1, 2). PMI could be either T2MI, Type 1 Myocardial Infarction (T1MI), or Myocardial Injury, where T1MI refers to an acute plaque rupture and thrombus formation. T2MI on the other hand refers to an oxygen supply-demand mismatch to the myocardium, precipitated by a variety of potential factors, with or without underlying stable coronary plaque (3). Both PMI and T2MI are commonly encountered in a hospital in-patient setting, following non-cardiac surgery and precipitant other medical conditions respectively (4-6). Pivotal to the diagnosis of both is the measurement of cardiac troponin, and the other major thread to this body of work is the impact that the relatively new high-sensitivity troponin assays have had to the landscape of these conditions clinically, and to our understanding of them pathophysiologically (7). There are currently no proven, specific interventions that reduce cardiovascular risk in patients undergoing non-cardiac surgery (8, 9). The incidence of PMI is substantial, in the order of 30% for all non-cardiac surgery (10-12). In this setting, there is a great need for specific interventions that can reduce this incidence in patients at risk - this is the basis for the world-first, prospective, double-blind randomised multicentre placebo-controlled trial that is part of this thesis, which investigates a first-in-class drug Ivabradine in preventing PMI in an elderly population undergoing orthopaedic surgery for acute fracture. T2MI accounts for the majority of troponin elevations in a hospital population, and has similar if not worse prognosis to T1MI (13-15). However, the diagnosis, investigation, and management of T2MI at the bedside in any given patient is not always clear. Determining the likely pathophysiological process based on clinical information alone in some cases may be difficult, and there is a thought that the newer high-sensitivity troponin assays may exacerbate this. The broad aims of this body of work are: 1. To better understand the pathophysiological mechanisms of PMI and T2MI, in particular the role of increased heart rate 2. To investigate an intervention with Ivabradine started pre-operatively to reduce the risk of PMI, in a setting where there are currently no proven therapies. 3. To evaluate determinants and risk factors for PMI and T2MI in specific clinical contexts, and investigate long-term outcomes after PMI. 4. To explore the effect of the new high sensitivity troponin assay on all of the above, in particular the clinical diagnosis and landscape of both PMI and T2MI. We achieved the above aims through the following methods: 1. A world-first, prospective, double-blind, randomised, multicentre placebo-controlled trial investigating a novel use of the first-in-class drug Ivabradine. 2. A world-first prospective case series using intra-coronary Optical Coherence Tomography (OCT) imaging in an inpatient T2MI population. 3. A large-scale retrospective analysis of an entire tertiary hospital’s experience in the transition to the new high sensitivity troponin assay from a standard assay, focused on all T2MI relative to all T1MI. REFERENCES 1. Mauermann E, Puelacher C, Lurati Buse G. Myocardial injury after noncardiac surgery: an underappreciated problem and current challenges. Current opinion in anaesthesiology. 2016;29(3):403-12. 2. Helwani MA, Amin A, Lavigne P, Rao S, Oesterreich S, Samaha E, et al. Etiology of Acute Coronary Syndrome after Noncardiac Surgery. Anesthesiology. 2018. 3. Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, et al. Fourth Universal Definition of Myocardial Infarction (2018). Circulation. 2018;138(20):e618-e51. 4. Liem VGB, Hoeks SE, Grune F, Mol K, Wesdorp F, Stolker RJ, et al. Prognostic value of postoperative high-sensitivity troponin T in patients with different stages of kidney disease undergoing noncardiac surgery. British journal of anaesthesia. 2018;120(1):84-93. 5. Puelacher C, Lurati Buse G, Seeberger D, Sazgary L, Marbot S, Lampart A, et al. Perioperative Myocardial Injury After Noncardiac Surgery: Incidence, Mortality, and Characterization. Circulation. 2017. 6. Collinson P, Lindahl B. Type 2 myocardial infarction: the chimaera of cardiology? Heart (British Cardiac Society). 2015;101(21):1697-703. 7. Chong CP, van Gaal WJ, Savige J, Lim WK. Cardiac injury and troponin testing after orthopaedic surgery. Injury. 2011;42(9):855-63. 8. Hoshijima H, Denawa Y, Mihara T, Takeuchi R, Kuratani N, Mieda T, et al. Efficacy of prophylactic doses of intravenous nitroglycerin in preventing myocardial ischemia under general anesthesia: A systematic review and meta-analysis with trial sequential analysis. Journal of clinical anesthesia. 2017;40:16-22. 9. Devereaux PJ, Duceppe E, Guyatt G, Tandon V, Rodseth R, Biccard BM, et al. Dabigatran in patients with myocardial injury after non-cardiac surgery (MANAGE): an international, randomised, placebo-controlled trial. Lancet (London, England). 2018;391(10137):2325-34. 10. Ollila A, Vikatmaa L, Virolainen J, Vikatmaa P, Leppaniemi A, Alback A, et al. Perioperative Myocardial Infarction in Non-Cardiac Surgery Patients: A Prospective Observational Study. Scandinavian journal of surgery : SJS : official organ for the Finnish Surgical Society and the Scandinavian Surgical Society. 2017;106(2):180-6. 11. Toda H, Nakamura K, Nakagawa K, Watanabe A, Miyoshi T, Nishii N, et al. Diastolic Dysfunction Is a Risk of Perioperative Myocardial Injury Assessed by High-Sensitivity Cardiac Troponin T in Elderly Patients Undergoing Non-Cardiac Surgery. Circulation journal : official journal of the Japanese Circulation Society. 2018;82(3):775-82. 12. Bass AR, Szymonifka JD, Rondina MT, Bogardus M, Scott MG, Woller SC, et al. Postoperative Myocardial Injury and Inflammation Is Not Blunted by a Trial of Atorvastatin in Orthopedic Surgery Patients. HSS journal : the musculoskeletal journal of Hospital for Special Surgery. 2018;14(1):67-76. 13. Chapman AR, Adamson PD, Mills NL. Assessment and classification of patients with myocardial injury and infarction in clinical practice. Heart (British Cardiac Society). 2017;103(1):10-8. 14. Smilowitz NR, Naoulou B, Sedlis SP. Diagnosis and management of type II myocardial infarction: increased demand for a limited supply of evidence. Current atherosclerosis reports. 2015;17(2):478. 15. Sandoval Y, Smith SW, Thordsen SE, Apple FS. Supply/demand type 2 myocardial infarction: should we be paying more attention? Journal of the American College of Cardiology. 2014;63(20):2079-87.