BACKGROUND:
Coronary artery disease is the commonest cause of death worldwide and
clinicians have struggled to limit the associated inexorable tide of morbidity
and mortality over the past few decades. Most often patients only become
aware that they have coronary artery disease when they are admitted to
hospital with chest pain. Computed tomography coronary angiography has
revolutionised our ability to detect even mild coronary artery disease,
improving the prognosis of those with symptoms of stable angina. However,
its effectiveness is somewhat limited by physician reliance on the singular
factor of the severity of coronary artery stenosis. The ability to characterise
and to quantify the extent of coronary artery disease can incrementally improve
the prognostic capability of coronary computed tomography angiography in
patients with stable angina. However, we have yet to determine whether
quantifying plaque is of benefit in the more unstable populations of patients
who present to the Emergency Department with acute chest pain. Such
patients may or may not have suffered a myocardial infarction. Moreover, in
those who have myocardial infarction, this may or may not be due to plaque
rupture. Computed tomography and quantitative plaque analysis could provide
a novel avenue to assist both in the diagnosis and risk stratification of this
patient population.
Given this background, there are several questions that we put forward. These
include: 1) Can plaque be accurately and reproducibly quantified in patients
with a high burden of coronary artery disease? 2) Is there value in quantifying
plaque in patients who have had myocardial infarction excluded? 3) In those
with myocardial infarction, can quantitative plaque analysis assist in the
differentiation between type 1 and type 2 myocardial infarction? 4) Does
quantification of plaque burden predict recurrent events and mortality in
patients who present with acute chest pain to the Emergency Department?
METHODS AND RESULTS:
In study one, twenty patients with known multivessel disease underwent
repeated computed tomography coronary angiography 2 weeks apart.
Coronary artery segments were analysed using semi-automated software by
two trained observers to determine intraobserver, interobserver and interscan
reproducibility. Overall, 149 coronary arterial segments were analysed. There
was excellent intraobserver, interobserver and interscan agreement for all
plaque volume measurements. There were no substantial interscan
differences for measures of plaque burden. Whilst low-attenuation plaque
volume had relatively wider 95% limits of agreement, this reflected the lower
absolute volumes of low-attenuation plaque in this cohort of patients with
advanced coronary disease.
In study two, quantitative plaque analysis was performed on CT coronary
angiograms of 242 patients recruited in a single-centre cross-sectional
observational study. Patients with acute chest pain who had had myocardial
infarction excluded were dichotomised by plasma high-sensitivity cardiac
troponin I concentration into low (<5 ng/L, n=81) and intermediate (≥5 ng/L,
n=161) risk groups. There was a higher burden of plaque in the intermediate
risk group compared to the low risk group. Moreover, low-attenuation plaque
burden was associated with intermediate-risk plasma troponin concentrations
after adjustment for clinically relevant characteristics suggesting plaque
instability may contribute to the underlying cardiovascular risk of these
patients.
In study three, a post-hoc analysis of two prospective clinical studies of
patients with acute chest pain was conducted. Patients were classified as type
1 myocardial infarction, type 2 myocardial infarction or chest pain without
infarction. The diagnosis of type 2 myocardial infarction was adjudicated by an
expert panel due to the inherent difficulties in making this diagnosis.
Quantitative plaque analysis was conducted in 155 patients with type 1
myocardial infarction, 36 patients with type 2 myocardial infarction and 136
patients with chest pain without infarction. We showed that patients with type
1 myocardial infarction had a significantly greater burden of total, non-calcified
and low-attenuation plaque compared to those with type 2 myocardial
infarction. Low-attenuation plaque was an independent predictor of type 1
myocardial infarction and had better discrimination than non-calcified plaque
and even severity of coronary artery stenosis. This suggests that quantitative
plaque analysis holds potential to help differentiate between these diagnoses
thereby assisting in guiding patient management.
In study four, quantitative plaque analysis was conducted on 404 patients who
presented to the Emergency Department with suspected acute coronary
syndrome. Patients underwent early coronary CT angiography and were
followed up for 12 months. We assessed the association between plaque
burden and the primary endpoint of 1-year all cause death or non-fatal
myocardial infarction and compared this to traditional markers of risk including
the GRACE score and the presence of obstructive coronary disease. Following
the index admission, 25 patients went on to have an event. Events were
associated with larger burdens of all plaque subtypes. Total, non-calcified and
low-attenuation plaque were the strongest predictors of future events, and
these associations were independent of GRACE score and presence of
obstructive coronary disease. Plaque burden therefore was a major predictor
of 1-year death or recurrent myocardial infarction in patients who present to
hospital with suspected acute coronary syndrome.
CONCLUSION:
We have demonstrated that quantitative plaque analysis is a reliable tool and
gives precise results even in patients with a large burden of coronary
atherosclerosis. This technique can be applied to all patients who attend the
hospital and are suspected of having acute coronary syndrome. When troponin
concentrations do not reach the threshold to diagnose myocardial infarction
according to the Universal Definition, quantifying the low-attenuation plaque
burden of those with an intermediate concentration of troponin is a powerful
risk stratification tool that may assist in the decision to pursue more intensive
preventative medical therapy. When myocardial infarction is diagnosed but
clinicians are not sure if this is due to plaque rupture or a supply and demand
mismatch, the burden of low-attenuation plaque can assist in decision making
and help guide downstream medical investigation and management. Finally,
in all the above situations, the burden of plaque and low-attenuation plaque in
particular can identify those patients at highest risk of recurrent cardiovascular
events, further risk stratifying patients in the short to medium term. Taken
together, these four studies provide major impetus for future prospective
clinical trials that could base treatment decisions on the burden of high-risk
low-attenuation plaque
