Vulnerable plaques and patients: state-of-the-art

Abstract

Despite advanced understanding of the biology of atherosclerosis, coronary heart disease remains the leading cause of death worldwide. Progress has been challenging as half of the individuals who suffer sudden cardiac death do not experience premonitory symptoms. Furthermore, it is well-recognized that also a plaque that does not cause a haemodynamically significant stenosis can trigger a sudden cardiac event, yet the majority of ruptured or eroded plaques remain clinically silent. In the past 30 years since the term 'vulnerable plaque' was introduced, there have been major advances in the understanding of plaque pathogenesis and pathophysiology, shifting from pursuing features of 'vulnerability' of a specific lesion to the more comprehensive goal of identifying patient 'cardiovascular vulnerability'. It has been also recognized that aside a thin-capped, lipid-rich plaque associated with plaque rupture, acute coronary syndromes (ACS) are also caused by plaque erosion underlying between 25% and 60% of ACS nowadays, by calcified nodule or by functional coronary alterations. While there have been advances in preventive strategies and in pharmacotherapy, with improved agents to reduce cholesterol, thrombosis, and inflammation, events continue to occur in patients receiving optimal medical treatment. Although at present the positive predictive value of imaging precursors of the culprit plaques remains too low for clinical relevance, improving coronary plaque imaging may be instrumental in guiding pharmacotherapy intensity and could facilitate optimal allocation of novel, more aggressive, and costly treatment strategies. Recent technical and diagnostic advances justify continuation of interdisciplinary research efforts to improve cardiovascular prognosis by both systemic and 'local' diagnostics and therapies. The present state-of-the-art document aims to present and critically appraise the latest evidence, developments, and future perspectives in detection, prevention, and treatment of 'high-risk' plaques occurring in 'vulnerable' patients.

Keywords: Thin-cap fibroatheroma; Acute coronary syndromes; Cardiovascular pharmacotherapy; Culprit plaque; New invasive coronary imaging modalities; Plaque erosion; Plaque rupture; Vulnerable plaque.

Take home figure

High-risk and culprit plaques in ‘vulnerable patients’. The combination of ‘vulnerable patient’ phenotype and ‘high-risk plaque’ is likely required to produce an adverse cardiac event. Plaque rupture, plaque erosion, calcified nodule and functional coronary alterations represent pathophysiological mechanisms underlying acute coronary syndromes. Photography adapted from Partida et al.   and Gijsen et al.   (Creative Commons Licence CC-BY-NC).

Figure 1

Coronary computed tomography angiography in cardiovascular risk prediction. (A) Coronary computed tomography angiography-adapted Leaman score. (B) Perivascular fat attenuation index. 95% CI, 95% confidence interval; HR, hazard ratio. Adapted from Mushtaq et al.   and Oikonomou et al.

Figure 2

Schematic summary of advances in non-invasive imaging of coronary plaque. CCTA, coronary computed tomography angiography; FFR, fractional flow reserve; ¹⁸F-FDG, ¹⁸F-fluorodeoxyglucose; ¹⁸F-NaF, 18F-sodium fluoride; MRA, magnetic resonance angiography; PET, positron emission tomography; USPIO, ultrasmall superparamagnetic iron oxide. Photography adapted from Joshi et al.   and Chiribiri et al.

Figure 3

Intravascular imaging modalities in studies on high-risk plaques and vulnerable patients. CA, calcium; ESS, endothelial shear stress; IVUS, intravascular ultrasound; LCBI, lipid core burden index; MACE, major adverse cardiac events; MLA, minimum lumen area; NA, not available; NIRS, near-infrared spectroscopy; OCT, optical coherence tomography; PB, plaque burden; TCFA, thin-cap fibroatheroma; VH, virtual histology.

Figure 4

Summary of potential advantages of hybrid catheters. FLIm, fluorescence lifetime imaging; IVPA, intravascular photoacoustics; IVUS, intravascular ultrasound; NA, not available; NIRF, near-infrared fluorescence; NIRS, near-infrared spectroscopy; OCT, optical coherence tomography; TRFS; time-resolved fluorescence spectroscopy.