Abstract

Introduction: Thin-cap fibroatheromas are the pathologic cause of acute coronary syndromes and ischemic sudden death. Near infrared spectroscopy (NIRS) detects lipid concentration in the arterial wall and intravascular ultrasound (IVUS) identifies necrotic cores and vascular remodeling. We hypothesized that concurrent use of these two invasive technologies could predict development and progression of high-risk fibroatheromas as determined by histology. Methods: Multi-vessel coronary angiography, IVUS and NIRS were performed 3, 6 and 9 months (m) after induction of diabetes (DM) and hypercholesterolemia (HC) in 21 pigs. Five animals died of ischemic sudden death and 3 of other causes. The remaining animals were sacrificed at 9-m. Results: Longitudinal IVUS data demonstrated a progressive increase in plaque + media and necrotic core areas and positive remodeling. At 9-m NIRS positivity predicted the presence of TCFAs and ThFCAs (both p=0.0001 vs NIRS negative), greater plaque (p<0.0001) and necrotic core (p<0.0019) areas and thinner fibrous caps (p=0.04) by histology. Importantly, NIRS positive fibroatheromas possessed a higher number of activated macrophages (p=0.006), as well as greater number of proliferating (p=0.016) and apoptotic cells (p=0.04) in the fibrous cap. NIRS positivity also predicted greater necrotic core size on IVUS scan at the subsequent time point. Moreover, 88% of arterial segments which were NIRS positive at 3 and 6-m developed into a fibroatheroma at 9-m by histology compared to 35% of persistently NIRS negative segments (p<0.01). Conclusion: Results from IVUS and NIRS predicted the subsequent development of high-risk coronary fibroatheromas with greater plaque and larger necrotic core areas possessing characteristics of increased plaque instability.

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