Computed tomography coronary angiography and positron emission tomography in acute coronary syndrome

Abstract

BACKGROUND: Acute coronary syndrome, including myocardial infarction and unstable angina, is the most serious manifestation of coronary atherosclerosis and remains the leading contributor to morbidity and mortality worldwide. In order to reduce disease burden and improve patient outcomes, current diagnostic and prognostic assessment based on electrocardiogram testing, cardiac troponin testing, clinical decision aids or risk scores, and angiographic stenosis severity require improvement. One potential approach is to incorporate existing and novel imaging techniques into clinical pathways, thereby enhancing disease detection and refining risk stratification. Computed tomography coronary angiography can identify and characterise morphologically milder but clinically important coronary atherosclerosis. However, its clinical utility has not yet been widely examined in intermediate-risk patients with suspected acute coronary syndrome. Whilst computed tomography coronary angiography provides anatomical and structural assessment of coronary arteries, it is unable to differentiate the underlying activity and biology of coronary atherosclerotic plaques. One emerging tool that can detect and measure such (patho)physiology is coronary positron emission tomography. As uptake of 18F-sodium fluoride representing active microcalcification triggered by inflammation colocalises with high-risk coronary atherosclerotic plaques, coronary 18F-sodium fluoride positron emission tomography can quantify coronary atherosclerotic plaque activity and identify patients with a heightened propensity to major adverse cardiac events.

The objective of this thesis was to evaluate the potential diagnostic and prognostic benefit of computed tomography coronary angiography and coronary 18F-sodium fluoride positron emission tomography in suspected or confirmed acute coronary syndrome by addressing the following questions: (a) Can computed tomography coronary angiography provide incremental diagnostic and prognostic value? (b) Are the clinical implications of early computed tomography coronary angiography independent of cardiac troponin concentrations? (c) Does early computed tomography coronary angiography facilitate targeting of preventative treatment? (d) Can coronary 18F-sodium fluoride positron emission tomography identify coronary arteries at risk for subsequent coronary atherothrombotic events?

METHODS AND RESULTS: In study one, the performance of three clinical decision aids and computed tomography coronary angiography, alone and then in combination, for the index hospital diagnosis of acute coronary syndrome and the use of coronary revascularisation within the first 30 days was compared in 699 intermediate-risk patients with suspected acute coronary syndrome. Computed tomography coronary angiography had the higher C-statistics both for the index hospital diagnosis of acute coronary syndrome (0.80; 95% confidence interval, 0.77 to 0.83) and for 30-day coronary revascularisation (0.80; 95% confidence interval, 0.77 to 0.83). In general, the addition of computed tomography coronary angiography to clinical decision aids improved the performance of clinical decision aids for diagnosis of acute coronary syndrome and prediction of early clinical events—coronary revascularisation and death or subsequent type 1 or 4b myocardial infarction.

In study two, the clinical impact of computed tomography coronary angiography on cardiovascular testing and clinical outcomes were compared between 1004 patients with and 744 patients without cardiac troponin elevation at presentation. The rates of non-invasive ischaemia investigations were consistently reduced with early computed tomography coronary angiography in those with an elevated (adjusted hazard ratio, 0.74; 95% confidence interval, 0.55 to 0.98) and a normal (adjusted hazard ratio, 0.59; 95% confidence interval, 0.44 to 0.80) cardiac troponin concentration, and the rates of invasive coronary angiography were also consistently lower with early computed tomography coronary angiography than with standard of care only amongst those with (adjusted hazard ratio, 0.82; 95% confidence interval, 0.71 to 0.95) and without (adjusted hazard ratio, 0.82; 95% confidence interval, 0.65 to 1.04) cardiac troponin elevation. Overall, presentation cardiac troponin levels had no demonstrable associations between the lack of effect of early computed tomography coronary angiography on coronary revascularisation or on death or subsequent type 1 or 4b myocardial infarction.

In study three, prescription of aspirin, P2Y12 receptor antagonist, statin, renin–angiotensin system blocker, and beta-blocker therapies from randomisation to hospital discharge were compared within and then between 874 and 869 patients randomised to early computed tomography coronary angiography and standard of care only respectively. Prescription of P2Y12 receptor antagonist (between-group difference, 4.6%; 95% confidence interval, 0.3 to 8.9), dual antiplatelet (between-group difference, 4.5%; 95% confidence interval, 0.2 to 8.7), and statin (between-group difference, 4.3%; 95% confidence interval, 0.2 to 8.5) therapies increased more with early computed tomography coronary angiography than with standard of care. Overall, early computed tomography coronary angiography facilitated targeted individualisation of these therapies based on the extent of coronary artery disease.

In study four, 2094 analysable vessels from 691 patients with recent myocardial infarction and multivessel coronary artery disease were identified. Vessels with increased coronary atherosclerotic plaque activity, compared with those without increased coronary atherosclerotic plaque activity, had the higher rate of myocardial infarction (4% versus 2%). Furthermore, patients with multivessel increase in coronary atherosclerotic plaque activity were at higher risk for cardiac death or myocardial infarction (adjusted hazard ratio, 2.43; 95% confidence interval, 1.37 to 4.30) as well as first (adjusted hazard ratio, 2.19; 95% confidence interval, 1.18 to 4.06) and total (adjusted hazard ratio, 2.50; 95% confidence interval, 1.42 to 4.39) myocardial infarctions.

CONCLUSION: Computed tomography coronary angiography and coronary 18F-sodium fluoride positron emission tomography offer valuable insights into the pathogenesis of acute coronary syndrome. Computed tomography coronary angiography improved the diagnostic and prognostic performance of clinical decision aids, reduced non-invasive and invasive cardiovascular testing regardless of cardiac troponin elevation, and enhanced individualisation of preventative treatment in intermediate-risk patients with suspected acute coronary syndrome. Coronary 18F-sodium fluoride positron emission tomography improved risk stratification and provided a potential approach to determining those who may benefit from more intensive therapeutic treatment for high-risk patients with confirmed acute coronary syndrome. Taken together, these four studies provide the mechanistic understanding of how imaging techniques can clarify clinical diagnoses earlier, elaborate risk prediction further, and refine treatment selection better, thereby potentially improving clinical outcomes, in patients with acute coronary syndrome.