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...