Perioperative and Long-Term Outcomes in Patients Undergoing Synchronous Carotid Endarterectomy and Coronary Artery Bypass Grafting: A Single-Center Experience.

INTRODUCTION: Patients requiring coronary artery bypass grafting (CABG) and carotid endarterectomy (CEA) can be managed with staged (CEA before CABG), reverse staged (CABG before CEA) or synchronous treatment. This single-center retrospective study evaluated the outcomes in patients undergoing planned synchronous CEA and CABG. METHODS: Between 2000 and 2020 a total of 185 patients with symptomatic triple-vessel or left main coronary artery disease associated with 70-99% asymptomatic or 50-99% symptomatic uni- or bilateral internal carotid artery (ICA) stenosis underwent synchronous CEA and CABG at our institution. Study endpoints were defined as mortality, stroke and myocardial infarction at 30 days. Additionally, the composite endpoint of these events was investigated. RESULTS: At 30 days, mortality, stroke and myocardial infarction rates were 5.9%, 8.1% (permanent [unresolved deficit at discharge] 5.4%) and 3.8%, respectively, and the composite endpoint was reached in 13.0% of patients. Patients suffering from a stroke more frequently had a contralateral 70-99% ICA stenosis (60.0% vs. 17.3%; p < 0.001), peripheral artery disease (73.3% vs. 38.9%; p = 0.013) and prolonged cardiopulmonary bypass time (mean 119 ± 62 min vs. 84 ± 29 min; p = 0.012). Multivariate logistic regression analysis revealed the duration of cardiopulmonary bypass (odds ratio [OR] 1.024; 95% confidence interval [CI] 1.002-1.046; p = 0.034), a history of type 2 diabetes mellitus (OR 5.097; 95% CI 1.161-22.367; p = 0.031) and peripheral artery disease (OR 5.814; 95% CI 1.231-27.457; p = 0.026) as independent risk factors for reaching the composite endpoint. CONCLUSION: Patients undergoing synchronous CEA and CABG face an elevated risk of perioperative cardiovascular events, particularly an increased stroke risk in patients with symptomatic and bilateral ICA stenosis. Graphical Abstract available for this article.

Histone citrullination as a novel biomarker and target to inhibit progression of abdominal aortic aneurysms.

Neutrophil extracellular traps (NETs) have been implicated in the pathogenesis of abdominal aortic aneurysms (AAAs). This study has addressed the notion that NET components might serve as AAA biomarkers or novel targets of AAA therapy. Thus, parameters of neutrophil activation and NET formation were measured in plasma. Their diagnostic marker value was explored in 41 AAA patients and 38 healthy controls. The NET parameter citrullinated histone H3 (citH3) was then validated in 63 AAA patients and 63 controls matched for cardiovascular disease. The prognostic marker potential was investigated in 54 observation periods of AAA growth over 6 months. NETs were further assessed in conditioned medium and sections of aortic tissue. CitH3 was found to be increased in blood (median 362 vs 304 ng/mL, P = 0.004) and aortic tissue (50 vs 1.5 ng/mg, P < 0.001) of AAA patients compared to healthy controls and accumulated in the intraluminal thrombus (629 ng/mg). The diagnostic potential of citH3 ranged at 0.705 area under the ROC curve (AUROC) and was validated with the independent sample set. Furthermore, plasma citH3 predicted AAA growth over the next 6 months (AUROC: 0.707, P = 0.015) and dropped significantly after surgical aneurysm repair. In an angiotensin II - based mouse model of experimental AAA, an inhibitor of histone citrullination was applied to block NET formation and AAA progression. Of note, further growth of an established aneurysm was prevented in mice treated with the NET inhibitor (P = 0.040). In conclusion, histone citrullination represents a promising AAA biomarker and potential therapeutic target to control disease progression.

A Novel Diagnostic and Prognostic Score for Abdominal Aortic Aneurysms Based on D-Dimer and a Comprehensive Analysis of Myeloid Cell Parameters.

The pathogenesis of abdominal aortic aneurysm (AAA) involves a central component of chronic inflammation which is predominantly mediated by myeloid cells. We hypothesized that the local inflammatory activity may be reflected in systemic alterations of neutrophil and monocyte populations as well as in soluble factors of myeloid cell activation and recruitment. To establish their marker potential, neutrophil and monocyte sub-sets were measured by flow cytometry in peripheral blood samples of 41 AAA patients and 38 healthy controls matched for age, sex, body mass index and smoking habit. Comparably, circulating factors reflecting neutrophil and monocyte activation and recruitment were assayed in plasma. Significantly elevated levels of CD16+ monocytes, activated neutrophils and newly released neutrophils were recorded for AAA patients compared with controls. In line, the monocyte chemoattractant C-C chemokine ligand 2 and myeloperoxidase were significantly increased in patients' plasma. The diagnostic value was highest for myeloperoxidase, a mediator which is released by activated neutrophils as well as CD16+ monocytes. Multivariable regression models using myeloid activation markers and routine laboratory parameters identified myeloperoxidase and D-dimer as strong independent correlates of AAA. These two biomarkers were combined to yield a diagnostic score which was subsequently challenged for confounders and confirmed in a validation cohort matched for cardiovascular disease. Importantly, the score was also found suited to predict rapid disease progression. In conclusion, D-dimer and myeloperoxidase represent two sensitive biomarkers of AAA which reflect distinct hallmarks (thrombus formation and inflammation) of the pathomechanism and, when combined, may serve as diagnostic and prognostic AAA score warranting further evaluation.