Aortic Dissection

ImportanceEmergency department (ED) triage may impact timeliness of care for high-risk conditions.ObjectiveTo determine the association of ED undertriage with delays in care for patients with subarachnoid hemorrhage (SAH), aortic dissection (AD), and ST-elevation myocardial infarction (STEMI).Design, setting, and participantsThis retrospective cohort study included adult ED patients diagnosed with SAH, AD, or STEMI from January 1, 2016, to December 31, 2020, from a multicenter, community-based health care delivery system. Data analysis were completed in March 2023 to October 2024.ExposureUndertriage vs correct triage, defined by operational measures of mistriage.Main outcomes and measuresUsing a lognormal distribution, the outcomes of interest for patients with SAH and AD were adjusted median time to noncontrast computed tomography (CT) (head CT for patients with SAH, chest CT for patients with AD), antihypertensive medication orders (SAH), and β-blocker orders (AD), and ED length of stay (LOS). For patients with STEMI, outcomes of interest were adjusted median time to electrocardiogram (ECG) and troponin orders.ResultsA total of 5929 patients (median [IQR] age, 63.0 [54.0 to 73.0] years; 3876 [65.4%] male) were identified, including 915 with SAH, 480 with AD, and 4534 with STEMI. There were 1129 Asian patients (19.0%), 553 Black patients (9.3%), 889 Hispanic patients (15.0%), and 2906 non-Hispanic White patients (49.0%). Overall, 2175 patients (36.7%) were undertriaged. For patients with SAH, the lognormal estimate for delay in time to head CT was 0.2 (95% CI, 0.0-0.3), or a delay of 2.4 minutes, and for antihypertensive orders, the lognormal estimate was 4.8 (95% CI, 3.6-5.9), or a delay of 33.3 minutes; the lognormal estimate for ED LOS was 0.1 (95% CI, 0.0-0.1), or 7.7 minutes longer. For patients with AD, the lognormal estimate for delays were 0.2 (95% CI, 0.0-0.4), or 8.9 minutes, for chest CT and 0.5 (95% CI, 0.2-0.7), or 17.6 minutes, for β-blocker orders, and ED LOS was 0.2 (95% CI, 0.1-0.3), or 64 minutes longer. For patients with STEMI, differences in time to ECG and troponin orders were not statistically significant, at less than 1 minute, comparing correctly and undertriaged patients.Conclusions and relevanceIn this cohort study of patients diagnosed with SAH, AD, or STEMI, ED undertriage was associated with small but significant delays in key diagnostic and therapeutic orders for patients with SAH and AD but not for patients with STEMI.

Acute aortic dissection (AAD) is a life-threatening cardiovascular emergency characterized by aortic layer separation and false lumen formation, with high mortality rates. Emerging evidence highlights the critical role of innate immunity in AD pathogenesis. Innate immune activation drives AAD progression through multiple mechanisms, including macrophage polarization (M1/M2 imbalance), neutrophil extracellular trap (NET) formation, and inflammasome activation. These processes amplify vascular inflammation via cytokine storms (IL-1β, IL-6, TNF-α) and oxidative stress, further promoting matrix metalloproteinase activation and smooth muscle cell phenotypic switching. The cGAS-STING pathway, triggered by mitochondrial DNA release, and TLR signaling act as central hubs connecting vascular injury to innate immune responses. This review synthesizes recent advances in the molecular mechanisms of AAD, focusing on aortic wall structural alterations, dysregulated signaling pathway, including TGF-β, Ang II, STING, and TLR cascades, and immune-inflammatory responses mediated by innate immune components. A deeper understanding of these innate immune components may lead to improved diagnostic biomarkers and targeted therapies for AAD management.

Thoracic aortic aneurysm and dissection (TAAD) encompasses a clinically heterogeneous group of diseases characterized by high morbidity and mortality. Genetic studies over the past two decades have significantly expanded our understanding of the molecular landscape underlying heritable TAAD, revealing contributions from multiple interconnected biological pathways. This review systematically summarizes more than 75 genes implicated in TAAD pathogenesis, categorizing them according to major mechanistic roles including TGF-β signaling, extracellular matrix remodeling, smooth muscle cell contractility and cytoskeletal regulation, cell-matrix and cell-cell adhesion, metabolic processes, ion transport, and transcriptional regulation. Special emphasis is placed on emerging genes with variable or overlapping clinical phenotypes, dual-mechanism candidates, and their implications for personalized clinical management, including surveillance and surgical intervention thresholds. The integration of molecular insights into clinical practice, along with cautious consideration of genes of uncertain significance, promises to enhance diagnostic precision and risk stratification in individuals and families affected by heritable aortic disease.

Thoracic aortic dissection (TAD), a life-threatening vascular emergency requiring urgent pharmacological intervention, prompted investigation into arachidonic acid metabolites based on their established roles in inflammation and vascular homeostasis. Through comprehensive plasma metabolomics analysis performed in both TAD patients and a β-aminopropionitrile monofumarate (BAPN)-induced mouse model, significant elevation of 12-hydroxyeicosatetraenoic acid (12-HETE) was identified, accompanied by marked upregulation of its synthetic enzyme 12/15-lipoxygenase (12/15-LOX) in dissected aortic tissues. The pathogenetic significance was further demonstrated by the substantial protection against TAD progression that was observed in Alox15-deficient mice. Mechanistically, 12-HETE was confirmed to function as an endogenous ligand for the BLT2 receptor on macrophages, leading to activation of the NOX-1/ROS/NF-κB signaling cascade. This signaling activation was shown to induce inflammatory cytokine release and promote inflammatory cell recruitment, ultimately resulting in pathological phenotype switching of vascular smooth muscle cells. The therapeutic potential was validated by significant reduction in dissection rupture rates that was achieved with either the 12/15-LOX inhibitor ML351 or the BLT2 antagonist LY255283, with maximal efficacy being demonstrated when both agents were administered in combination. These findings establish the 12-HETE-BLT2 axis as a key driver of TAD pathogenesis and validate its potential as a promising therapeutic target for clinical intervention.