Assessing coronary plaques: non-invasive and intracoronary imaging and haemodynamic measurements

Atherosclerotic plaque is the hidden culprit of angina and infarction. Commonly, we assume that a coronary plaque that causes ischaemia and/or angina is clinically relevant, although we have learned that even non-obstructive plaques can cause acute coronary syndromes. The assessment of haemodynamically relevant plaques is challenging. The so-called gold standard, i.e. coronary angiography, only provides an estimate of the significance of luminal narrowing as it provides only a two-dimensional pictures of the lumen and, unless it is analysed quantitatively, also involves a lot of subjectivity. Intracoronary imaging with intravascular ultrasound (IVUS) and optical coherence tomography (OCT), although invasive, has a big advantage in that it can provide both a quantitative and three-dimensional assessment of the entire coronary tree, as outlined in the Consensus Document entitled ‘Clinical use of intracoronary imaging. Part 1: Guidance and optimization of coronary interventions. An expert consensus document of the European Association of Percutaneous Cardiovascular Interventions.’ authored by Lorenz Räber and colleagues from the European Society of Cardiology Scientific Document Group. Intracoronary imaging can be used to guide percutaneous coronary interventions (PCIs), particularly in patients with complex anatomy. Specifically, prior to PCI, IVUS or OCT can be used for optimizing stent sizing (stent length and diameter) and planning the procedural strategy. Postimplantation, the consensus group recommends key parameters that characterize an optimal PCI result, and provides cut-offs to guide corrective measures and optimize the stenting result. Moreover, routine performance of intracoronary imaging in patients with stent failure (restenosis or stent thrombosis) is recommended, although further research is required. Molecular imaging goes a step further and uses molecules involved in the atherosclerotic process to visualize vulnerable plaques that require particular attention. In their article ‘Myeloperoxidase is a potential molecular imaging and therapeutic target for the identification and stabilization of high-risk atherosclerotic plaque’, Roland Stocker and colleagues from the Victor Chang Cardiac Research Institute in Darlinghurst, North South Wales, Australia used the inflammatory enzyme myeloperoxidase (MPO), which is abundantly expressed in ruptured atherosclerotic plaques. They employed the tandem stenosis model of plaque instability in apolipoprotein E gene knockout (ApoE) mice. To test the role of MPO, they used MpoApoE double knockout mice and the 2-thioxanthine MPO inhibitor AZM198. MPO activity was twofold greater in plaque with unstable compared with stable phenotype. Genetic deletion of MPO significantly increased fibrous cap thickness, and decreased plaque fibrin and haemosiderin content in plaque of the unstable phenotype. AZM198 inhibited MPO activity and increased fibrous cap thickness, and decreased fibrin and haemosiderin in unstable plaques, without affecting lesion monocytes and red blood cell markers, or circulating leukocytes and lipids. MPOgadolinium magnetic resonance imaging (MRI) demonstrated sustained enhancement of plaque with unstable phenotype on T1weighted imaging that was two-fold greater than in stable plaques, and was attenuated by both AZM198 treatment and deletion of the MPO gene. Thus, MPO is involved in plaque instability, and noninvasive imaging and pharmacological inhibition of plaque MPO activity hold promise for clinical translation in the management of high-risk coronary artery disease (CAD), as outlined in an Editorial by Willem Mulder from the Translational and Molecular Imaging Institute in New York, USA. Although IVUS, OCT, and, in the future, also molecular imaging provide insights into the vulnerability of plaques, they provide only indirect evidence as to their haemodynamic relevance. This is the domain of pressure wire assessment of coronary stenosis, which is considered the invasive reference standard today for the detection of ischaemia-generating lesions. Recently, methods to estimate the fractional flow reserve (FFR) from conventional angiography without