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Title: Novel applications of cardiac troponin in cardiovascular medicine
Author: Shah, Anoop
ISNI:       0000 0004 7232 0425
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2016
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Cardiac troponins are released into the circulation following myocardial injury with measurement of serum troponin concentration integral to the diagnosis of myocardial infarction. The next generation of high-sensitivity cardiac troponin assays have enhanced precision at very low concentrations and for the first time permit troponin concentrations to be reliably quantified outwith acute coronary syndromes. My aim was to evaluate the impact of more sensitive troponin assays on the diagnosis of myocardial infarction and to determine the potential for novel applications in stable cardiovascular diseases. In 2,929 consecutive hospitalised patients with myocardial injury I assessed the impact of implementing a contemporary sensitive troponin assay and a lower diagnostic threshold, on the incidence, management and outcome of patients with primary (type 1) and secondary (type 2) causes of myocardial infarction. Lowering the threshold improved outcomes in patients with type 1 myocardial infarction, but disproportionately increased the diagnosis of type 2 myocardial infarction, and identified a group of patients who remained at high-risk of death over the next 12 months. In 1,126 consecutive patients with suspected acute coronary syndrome I evaluated the impact of a high-sensitivity cardiac troponin I assay and sex-specific diagnostic thresholds on the diagnosis of myocardial infarction. Whilst having little effect in men, the use of sex-specific diagnostic thresholds would double the diagnosis of myocardial infarction in women, identifying those at increased risk of recurrent events. In a second cohort of 4,870 patients, I evaluated the optimal threshold to rule out myocardial infarction. The negative predictive value for myocardial infarction or cardiac death at 30 days was evaluated for a range of troponin concentrations. Troponin concentrations < 5 ng/L on presentation identified half of all patients with suspected acute myocardial infarction as low risk. Implementation of this assay and approach would markedly reduce hospital admissions and improve the diagnosis of myocardial infarction, particularly in women. High-sensitivity cardiac troponin assays may help us to manage patients with chronic cardiovascular diseases, such as aortic stenosis or stable angina pectoris. In patients with aortic stenosis, cardiac troponin was associated with an advanced hypertrophic response on electrocardiography and the presence of myocardial fibrosis on cardiac magnetic resonance imaging. Furthermore, cardiac troponin concentrations were a strong independent predictor of cardiovascular death or aortic valve replacement. In patients with stable angina, cardiac troponin was associated with transient ST-segment depression on ambulatory monitoring, suggesting that troponin concentrations may be modified by silent myocardial ischaemia. My findings suggest that high-sensitivity troponin assays have major potential to improve the assessment, treatment and outcome of patients with suspected acute coronary syndrome. The potential for cardiac troponins to improve risk stratification and monitoring of disease progression in patients with chronic cardiovascular disease now needs to be evaluated in prospective cohort studies.
Supervisor: Mills, Nick ; Newby, David Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: troponin ; myocardial infarction