Prognostic Value of Intraplaque Neovascularization Detected by Carotid Contrast-Enhanced Ultrasound in Patients Undergoing Stress Echocardiography

Background: Stress echocardiography (SE) is used for diagnosis and risk stratification of patients with known or suspected coronary artery disease (CAD). Contrast-enhanced ultrasound (CEUS) detects carotid intraplaque neovascularization (IPN). The aim of this study was to test the hypothesis that combining SE with carotid CEUS in patients with known or suspected CAD might provide incremental prognostic value beyond clinical risk factors and either test alone for the occurrence of cardiovascular events. Methods: One hundred eighty-five patients (mean age, 69 ± 8 years; 79% men) with known or suspected CAD referred for SE and found to have carotid plaque on screening were recruited for carotid CEUS imaging. IPN was graded by presence and location within plaque. Patients were followed for cardiovascular events (CVEs) including cardiac death, myocardial infarction, unstable angina, and transient ischemic attack or stroke. A subset of patients (n = 27) underwent carotid magnetic resonance imaging within 1 month of CEUS; carotid plaque was assessed for lipid-rich necrotic core, loose matrix, and presence of intraplaque hemorrhage. Results: Sixty-nine patients had abnormal findings on SE. IPN was identified in 112 patients; 52 patients had IPN localized to plaque shoulder (IPNS). Plaques with IPNS had larger lipid-rich necrotic cores and were more likely to have intraplaque hemorrhage. During follow-up (median, 31 months), 26 CVEs occurred. Multivariate Cox proportional-hazard analysis showed IPN and IPNS to be predictors of CVEs (hazard ratios, 3.34 [95% CI, 1.25–8.93; P =.02] and 4.88 [95% CI, 1.77–13.49; P =.002], respectively). The presence of IPNS increased the likelihood of CVEs beyond SE and history of CAD (χ² = 9.0, P =.02). Conclusions: Carotid IPN detected by CEUS and localized to plaque shoulder was an independent predictor of CVEs in patients referred for SE.