Coronary computed tomography angiography (CCTA) allows for quantification of coronary atherosclerotic plaque. Overall plaque burden is a determinant of future major cardiovascular events. In addition, based on pathologic analysis and imaging results, lesions associated with acute coronary syndrome (ACS) or sudden coronary death exhibit necrotic lipid-laden cores, positive remodeling, spotty calcification, high cross-sectional plaque burden, high stenosis severity, and thin-cap fibroatheroma.^1,2 Evolution of fibroatheromas, the development of sheets of calcification and reduction in necrotic core size, is considered plaque stabilizing.³

Background: Diagnosis of coronary artery disease and management strategies have relied solely on the presence of diameter stenosis ≥50%. We assessed whether direct quantification of plaque burden (PB) and plaque characteristics assessed by coronary computed tomography angiography could provide additional value in terms of predicting rapid plaque progression. Methods and Results: From a 13-center, 7-country prospective observational registry, 1345 patients (60.4±9.4 years old; 57.1% male) who underwent repeated coronary computed tomography angiography >2 years apart were enrolled. For conventional angiographic analysis, the presence of stenosis ≥50%, number of vessel involved, segment involvement score, and the presence of high-risk plaque feature were determined. For quantitative analyses, PB and annual change in PB (△PB/y) in the entire coronary tree were assessed. Clinical outcomes (cardiac death, nonfatal myocardial infarction, and coronary revascularization) were recorded. Rapid progressors, defined as a patient with ≥median value of △PB/y (0.33%/y), were older, more frequently male, and had more clinical risk factors than nonrapid progressors (all P <0.05). After risk adjustment, addition of baseline PB improved prediction of rapid progression to each angiographic assessment of coronary artery disease, and the presence of high-risk plaque further improved the predictive performance (all P <0.001). For prediction of adverse outcomes, adding both baseline PB and △PB/y showed best predictive performance (C statistics, 0.763; P <0.001). Conclusions: Direct quantification of atherosclerotic PB in addition to conventional angiographic assessment of coronary artery disease might be beneficial for improving risk stratification of coronary artery disease. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02803411.

Background First pass effect (FPE) in mechanical thrombectomy is thought to be associated with good clinical outcomes. Objective To determine FPE rates as a function of thrombectomy technique and to compare clinical outcomes between patients with and without FPE. Methods In July 2020, a literature search on FPE (defined as modified Thrombolysis in Cerebral Infarction (TICI) 2c–3 after a single pass) and modified FPE (mFPE, defined as TICI 2b–3 after a single pass) and mechanical thrombectomy for stroke was performed. Using a random-effects meta-analysis, we evaluated the following outcomes for both FPE and mFPE: overall rates, rates by thrombectomy technique, rates of good neurologic outcome (modified Rankin Scale score ≤2 at day 90), mortality, and symptomatic intracerebral hemorrhage (sICH) rate. Results Sixty-seven studies comprising 16 870 patients were included. Overall rates of FPE and mFPE were 28% and 45%, respectively. Thrombectomy techniques shared similar FPE (p=0.17) and mFPE (p=0.20) rates. Higher odds of good neurologic outcome were found when we compared FPE with non-FPE (56% vs 41%, OR=1.78) and mFPE with non-mFPE (57% vs 44%, OR=1.73). FPE had a lower mortality rate (17% vs 25%, OR=0.62) than non-FPE. FPE and mFPE were not associated with lower sICH rate compared with non-FPE and non-mFPE (4% vs 18%, OR=0.41 for FPE; 5% vs 7%, OR=0.98 for mFPE). Conclusions Our findings suggest that approximately one-third of patients achieve FPE and around half of patients achieve mFPE, with equivalent results throughout thrombectomy techniques. FPE and mFPE are associated with better clinical outcomes.

Vascular endothelial growth factor (VEGF) is a crucial proangiogenic component in pancreatic ductal adenocarcinoma (PDA), and its high expression levels have been correlated with poor prognosis and early postoperative recurrence. Angiotensin II (AngII), which has been shown to increase VEGF production in a variety of cancers, is actively generated in the pancreas. We hypothesized that AngII plays a crucial role in PDA-associated angiogenesis. We analyzed the expression and localization of AngI converting enzyme (ACE) and AngII type 1 receptor (AT1R) in relation to VEGF in matched invasive human PDA (n=25) and surrounding nonmalignant tissues using real-time polymerase chain reaction, Western immunoblotting, and immunohistochemistry. VEGF levels in conditioned media of HS766T and PK9 PDA cells treated with or without AngII (10(-7) mol/L) were measured by ELISA. The effects of an AT1R blocker (losartan) and an ACE inhibitor (captopril) on VEGF production and cellular proliferation were also examined. ACE and AT1R mRNA and protein levels were significantly upregulated in 19 of the 25 neoplastic tissues examined (approximately 75%), when compared with matching controls. VEGF expression was significantly higher in tissues that expressed high levels of AT1R and ACE (n=19), compared with low levels (n=4) or negative (n=2) cases. ACE protein collocalized with AT1R and VEGF in the malignant ducts and in the stromal cells. Addition of AngII significantly enhanced VEGF mRNA production and protein secretion, an effect that was prevented when cells were preincubated with captopril or losartan. Blocking endogenous AngII by captopril or losartan significantly suppressed cell proliferation. Both ACE and AT1R are functionally expressed in PDA and may be involved in tumor angiogenesis. Because AT1R blockers and ACE inhibitors are already widely used clinically, they may represent a potential novel and promising strategy for controlling angiogenesis, prevention of metastasis, and prolongation of survival in patients with primary or metastatic PDA.