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BACKGROUND: Patients with symptomatic carotid stenosis are at high risk for recurrent stroke. The decision for carotid endarterectomy currently mainly relies on degree of stenosis (cutoff value >50% or 70%). Nevertheless, also, patients with mild-to-moderate stenosis still have a considerable recurrent stroke risk. Increasing evidence suggests that carotid plaque composition rather than degree of stenosis determines plaque vulnerability; however, it remains unclear whether this also provides additional information to improve clinical decision making. OBJECTIVES: The PARISK (Plaque At RISK) study aimed to improve the identification of patients at increased risk of recurrent ischemic stroke using multimodality carotid imaging. METHODS: The authors included 244 patients (71% men; mean age, 68 years) with a recent symptomatic mild-to-moderate carotid stenosis in a prospective multicenter cohort study. Magnetic resonance imaging (carotid and brain) and computed tomography angiography (carotid) were performed at baseline and after 2 years. The clinical endpoint was a recurrent ipsilateral ischemic stroke or transient ischemic attack (TIA). Cox proportional hazards models were used to assess whether intraplaque hemorrhage (IPH), ulceration, proportion of calcifications, and total plaque volume in ipsilateral carotid plaques were associated with the endpoint. Next, the authors investigated the predictive performance of these imaging biomarkers by adding these markers (separately and simultaneously) to the ECST (European Carotid Surgery Trial) risk score. RESULTS: During 5.1 years follow-up, 37 patients reached the clinical endpoint. IPH presence and total plaque volume were associated with recurrent ipsilateral ischemic stroke or TIA (HR: 2.12 [95% CI: 1.02-4.44] for IPH; HR: 1.07 [95% CI: 1.00-1.15] for total plaque volume per 100 µL increase). Ulcerations and proportion of calcifications were not statistically significant determinants. Addition of IPH and total plaque volume to the ECST risk score improved the model performance (C-statistics increased from 0.67 to 0.75-0.78). CONCLUSIONS: IPH and total plaque volume are independent risk factors for recurrent ipsilateral ischemic stroke or TIA in patients with mild-to-moderate carotid stenosis. These plaque characteristics improve current decision making. Validation studies to implement plaque characteristics in clinical scoring tools are needed. (PARISK: Validation of Imaging Techniques [PARISK]; NCT01208025).

The authors regret that there was a mistake in reporting the mol% of the microbubble coating composition used. For all experiments, the unit mg/mL was used, and the conversion mistake occurred only when converting to mol% to define the ratio between the coating formulation components. The correct molecular weight of PEG-40 stearate is 2046.54 g/mol (Shen et al. 2008; Kilic and Bolukcu 2018), not 328.53 g/mol. On page 494, the sentence should read “The coating was composed of 1,2-distearyol-sn-glycero-3-phosphocholine (84.8 mol%; P6517, Sigma-Aldrich, Zwijndrecht, The Netherlands); polyoxyethylene-40 stearate (8.2 mol%; P3440, Sigma-Aldrich); 1,2-distearyol-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)2000] (DSPE-PEG(2000); 5.9 mol%; 880125P, Avanti Polar Lipids, Alabaster, AL, USA); and DSPE-PEG(2000)-biotin (1.1 mol%; 880129C, Avanti Polar Lipids).” This correction does not change the conclusions published in this work. The authors apologize for any inconvenience caused.

The authors regret that there was a mistake in reporting the mol% of the microbubble coating composition used. For all experiments, the unit in mg/mL was used and the conversion mistake occurred only when converting to mol% to define the ratio between the coating formulation components. The correct molecular weight of PEG-40 stearate is 2046.54 g/mol (Shen et al. 2008; Kilic and Bolukcu 2018), not 328.53 g/mol. On page 1433, the sentence should read “The lipid coating was composed of 84.8 mol% DSPC (P6517, Sigma-Aldrich, Zwijndrecht, Netherlands) or DPPC (850355, Avanti Polar Lipids, Alabaster, AL, USA); 8.2 mol% polyoxyethylene-40-stearate (PEG40 stearate, P3440, Sigma-Aldrich); 5.9 mol% 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)2000 (DSPE-PEG2000, 880125, Avanti Polar Lipids); and 1.1 mol% 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[biotinyl(polyethylene glycol)-2000] (DSPE-PEG2000-biotin) (880129, Avanti Polar Lipids).” This correction does not change the conclusions published in this work. The authors apologize for any inconvenience caused.

The authors regret that there was a mistake in calculating the mol% of the microbubble coating composition used. For all experiments the unit in mg/ml was utilized and the conversion mistake only came when converting to mol% to define the ratio between the coating formulation components. The correct molecular weight of PEG-40 stearate is 2046.54 g/mol (Kilic & Bolukcu, 2018; Shen et al., 2008), not 328.53 g/mol. On page 221, it should read “The coating was composed of DSPC (84.8 mol%; Sigma-Aldrich), PEG-40 stearate (8.2 mol%; Sigma-Aldrich), DSPE-PEG(2000) (5.9 mol%; Avanti Polar Lipids) and DSPE-PEG(2000)-biotin (1.1 mol%; Avanti Polar Lipids).” This correction does not change the conclusions published in this study. The authors would like to apologize for any inconvenience caused. The published article can be found here: https://onlinelibrary.wiley.com/doi/10.1002/bit.25337.

The authors regret that there was a mistake in calculating the mol% of the microbubble coating composition used. For all experiments the unit in mg/ml was utilized and the conversion mistake only came when converting to mol% to define the ratio between the coating formulation components. The correct molecular weight of PEG-40 stearate is 2046.54 g/mol (Kilic & Bolukcu, 2018; Shen et al., 2008), not 328.53 g/mol. On page 221, it should read “The coating was composed of DSPC (84.8 mol%; Sigma-Aldrich), PEG-40 stearate (8.2 mol%; Sigma-Aldrich), DSPE-PEG(2000) (5.9 mol%; Avanti Polar Lipids) and DSPE-PEG(2000)-biotin (1.1 mol%; Avanti Polar Lipids).” This correction does not change the conclusions published in this study. The authors would like to apologize for any inconvenience caused. The published article can be found here: https://onlinelibrary.wiley.com/doi/10.1002/bit.25337.