Plaque Structural Stress Estimations Improve Prediction of Future Major Adverse Cardiovascular Events After Intracoronary Imaging

Abstract

A therosclerosis is a multifocal disease, with myocardial infarction (MI) remaining a leading cause of morbidity and mortality. Around two thirds of all spontaneous thrombotic coronary events resulting in MI or sudden cardiac death are caused by rupture of an atheromatous plaque.1,2 Repeated cycles of subclinical rupture and repair also underlie rapid plaque growth, 3 leading to luminal encroachment and symptoms of progressive angina. Morphologically, ruptured plaques exhibit large necrotic lipid cores, thin overlying fibrous caps, and evidence of microcalcification. 4 The precursor lesion for rupture, termed a thin-cap fibroatheroma (TCFA), displays several of these compositional features. 4 However, prospective studies have shown that future clinical event rates attributable to high-risk plaques were <10% for 3 years, 5 highlighting that novel, non-imaging-based markers are required to improve plaque-based risk stratification. See Editorial by Stone and Coskun See Clinical PerspectivePlaque rupture occurs when the plaque structural stress (PSS) exceeds the material strength of the tissue. 6 Autopsy studies have shown that PSS is increased after plaque rupture and that the location of peak PSS can accurately predict Background-Although plaque rupture is responsible for most myocardial infarctions, few high-risk plaques identified by intracoronary imaging actually result in future major adverse cardiovascular events (MACE). Nonimaging markers of individual plaque behavior are therefore required. Rupture occurs when plaque structural stress (PSS) exceeds material strength. We therefore assessed whether PSS could predict future MACE in high-risk nonculprit lesions identified on virtual-histology intravascular ultrasound. Methods and Results-Baseline nonculprit lesion features associated with MACE during long-term follow-up (median:1115 days) were determined in 170 patients undergoing 3-vessel virtual-histology intravascular ultrasound. MACE was associated with plaque burden ≥70% (hazard ratio: 8.6; 95% confidence interval, 2.5-30.6; P<0.001) and minimal luminal area ≤4 mm 2 (hazard ratio: 6.6; 95% confidence interval, 2.1-20.1; P=0.036), although absolute event rates for high-risk lesions remained <10%. PSS derived from virtual-histology intravascular ultrasound was subsequently estimated in nonculprit lesions responsible for MACE (n=22) versus matched control lesions (n=22). PSS showed marked heterogeneity across and between similar lesions but was significantly increased in MACE lesions at high-risk regions, including plaque burden ≥70% (13.9±11.5 versus 10.2±4.7; P<0.001) and thin-cap fibroatheroma (14.0±8.9 versus 11.6±4.5; P=0.02). Furthermore, PSS improved the ability of virtual-histology intravascular ultrasound to predict MACE in plaques with plaque burden ≥70% (adjusted log-rank, P=0.003) and minimal luminal area ≤4 mm 2 (P=0.002). Plaques responsible for MACE had larger superficial calcium inclusions, which acted to increase PSS (P<0.05). 9-11 Although direct in vivo measurement of PSS is currently impos...

Structural Stress of Coronary Plaques to Predict Risk for Clinical Events

“…14 Plaque rupture is ultimately a mechanical process and it occurs when the plaque structural stress exceeds the material strength of the tissue. In this issue of Circulation: Cardiovascular Imaging, Brown et al 15 provide a comprehensive assessment of plaque characteristics of 170 patients who underwent 3-vessel VH-IVUS assessment and were then followed up for 3 years. A 2-dimensional finite element simulation for plaque structural stress (PSS) was performed for 44 nonculprit lesions (NCLs; 22 MACE and 22 non-MACE) composed of arterial wall, fibrous tissue, necrotic core, and dense calcium, as determined from VH-IVUS categorization of end-diastolic images.…”

“…The sophisticated, multidimensional, validated approach presented by Brown et al 15 is extremely valuable to understand the constituents and vascular biology of coronary plaque, and also to predict which specific plaques will be most likely to rupture. Previous efforts to risk-assess plaque mechanical…”

“…That process has been successful, but it has become clear that anatomic characterization by traditional intracoronary imaging is not sufficient to identify the small numerator of high-risk plaques that cause a new clinical event from the large denominator of ostensibly high-risk plaques. The in vivo PSS study by Brown et al 15 has brought us a major step forward in understanding the detailed mechanical aspects of coronary plaque and, most importantly, how we can apply that information to predict the future course of individual plaques. The field of accurate plaque prognostication is again becoming invigorated by these more sophisticated analyses beyond plaque anatomy.…”

Impact of Fiber Structure on the Material Stability and Rupture Mechanisms of Coronary Atherosclerotic Plaques

“…On the other hand, high structural stress concentration within the plaque, which is about 10 3 –10 5 times higher than endothelial shear stress, has been shown to be associated with fissuring and rupture in both coronary29 and carotid38 plaques. Structural stress and stretch may also differentiate patient clinical presentations,15,41,53 and are associated with subsequent cerebrovascular32,44 and heart ischemic events in symptomatic patients 5. In general, stable lesions are protected by a thick FC, as increasing FC thickness results in decreasing structural stress 25,52.…”

Carotid Intraplaque Hemorrhage: A Biomarker for Subsequent Ischemic Cerebrovascular Event?

“…As the majority of ischemic events are induced by plaque rupture, high mechanical loading within the plaque structure due to blood pressure may be useful to assess the likelihood of rupture [11] , as fibrous cap integrity may be compromised if such loading exceeds its material strength. A pilot study in the coronary arteries demonstrated that mechanical analysis may improve the risk prediction 2-3 fold for individual high-risk features [12] .…”