OBJECTIVE:Many patients with peripheral artery disease (PAD) are frail and experience an increased risk of adverse outcomes, regardless of revascularization status. Hospital-free days (HFDs) represent an important patient-centered outcome as it accounts for both the early- and long-term utilization of hospital and emergency department care, as well as survival. We hypothesized that frail patients would experience fewer HFDs after lower-extremity revascularization for PAD. METHODS:We performed a retrospective analysis of adults undergoing an index lower-extremity revascularization for PAD (2016-2024) in a multihospital health care system. We defined frailty via the Risk Analysis Index adapted to the International Statistical Classification of Diseases, 10th Revision, Clinical Modification: not frail (<36) and frail (≥36). We defined our primary outcome, HFDs, as total days alive and outside of inpatient acute hospitals or emergency department visits, in a 90-day postoperative interval. Patients who died during the interval accrued zero additional HFDs after death. We modeled the association between frailty and PAD on HFDs using negative binomial regression, adjusting for age, demographics, and pertinent comorbidities not within the Risk Analysis Index. We generated adjusted rate ratios and 95% confidence intervals (CIs), as well as marginal adjusted mean HFDs. We compared secondary outcomes, including time-to-major amputation, major reintervention, and mortality using Kaplan-Meier curves and Cox models. RESULTS:In total, 11,436 adults (age, 71.1 ± 0.3 years; 62% male, 67% White) underwent revascularization for PAD, of which 17% were frail. Frail patients were more commonly older, men, and with comorbid diabetes, as well as pulmonary and coronary artery disease. Observed median HFDs was lowest among the frail patients (83 days [interquartile range, 73-88] vs 86 days [interquartile range, 80-89]) with PAD. On multivariable adjustment, the rate of HFDs was lower among frail patients (adjusted rate ratio, 0.95; 95% CI, 0.94-0.97; P = .01), which corresponded to 76 (95% CI, 75-77) vs 80 (95% CI, 79-80) adjusted HFDs in the 90 days after reintervention. Further, after multivariable Cox modeling, frailty was associated with a higher risk of major amputation [adjusted hazard ratio (aHR), 1.44; 95% CI, 1.12-1.84; P = .004] and mortality (aHR, 1.69; 95% CI, 1.49-1.92; P = .01), but a lower risk of major reintervention (aHR, 0.78; 95% CI, 0.64-0.94; P < .001). CONCLUSIONS:Among patients with PAD undergoing lower-extremity revascularization, frailty was associated with fewer HFDs. Frailty adversely affects limb and mortality outcomes, especially in the early postoperative period, reiterating the need for routine frailty screening, advanced perioperative care planning, and using data like these to inform shared decision-making between patient and clinicians.

Objective Clopidogrel remains the most prescribed antiplatelet medication following occlusive atherosclerotic revascularization. However, 20-50% of the population are clopidogrel non-responders. Loss-of-function (LOF) cytochrome P450 2C19 (CYP2C19) single-nucleotide polymorphisms (SNPs) decrease clopidogrel metabolism and activation, resulting in intermediate or poor metabolizer phenotypes reducing formation of clopidogrel’s active metabolite. The association of these SNPs with adverse clinical outcomes with clopidogrel treatment following coronary artery disease (CAD) revascularization is well-studied, but the impact of these SNPs in non-CAD revascularization outcomes remains unclear. We evaluated the hypothesis that CYP2C19 LOF carrier status is associated with worse cardiovascular and limb adverse events with clopidogrel treatment following peripheral arterial revascularization. Methods We included adults with peripheral artery disease (PAD) undergoing open and endovascular extracranial, extremity, or visceral arterial revascularization (2016-2024) at a multi-hospital institution who were also prescribed post-revascularization clopidogrel and had known pharmacogenetic data. Individuals were stratified into CYP2C19 LOF carriers and non-carriers based on CYP2C19 SNPs. Entropy-balanced weights of pre-revascularization patient- and procedure-specific variables were generated. Residual imbalances were addressed with covariate adjustment in Cox hazards models evaluating the association between CYP2C19 LOF genotype carrier status and risk of adverse outcomes, generating weighted hazard ratios (wHR) with 95% confidence intervals (95%CI), censoring loss to follow-up or death. The primary outcome was major adverse limb event (MALE), and secondary outcomes were major adverse cardiovascular events (MACE), major revascularizations, major amputations, any revascularization, and major bleeding. Results Among 211 patients (69.2±10.0 years, 64.0% male, 7.1% extracranial, 83.4% extremity, 9.5% visceral revascularization procedures), 42 (19.9%) were CYP2C19 LOF carriers. There was no significant association between LOF carrier status and MALE (wHR=0.76, 95%CI 0.40-1.45, p-value=.41), its individual components (major revascularization wHR=0.81, 95%CI 0.41-1.59, p-value=.54; major amputation wHR=0.40, 95%CI 0.10-1.52, p-value=.18), or any revascularizations (wHR=1.10, 95%CI 0.68-1.77, p-value=.70). Having a LOF genotype was significantly associated with a 79% increased risk of MACE (wHR 1.79, 95%CI 1.08-2.99, p-value=.03), but not major bleeding events (wHR=0.70, 95%CI 0.30-1.64, p-value=.41). Conclusion CYP2C19 LOF carriers were associated with an increased risk of MACE but not MALE or its components after PAD revascularization. Because MACE significantly impacts the outcomes of PAD patients undergoing intervention, prospective evaluation of genotype-guided antiplatelet therapy may reduce cardiac morbidity and mortality and improve overall outcomes.

BACKGROUND: Clopidogrel was added to the national formulary of the Veterans Health Administration (VHA) in 2000, with national guidance in the form of Criteria for Use (CFU) generated in 2007 by the Pharmacy Benefits Management office. Although the national CFU restricted the duration of clopidogrel to no more than 30 days following peripheral vascular intervention (PVI) for peripheral artery disease (PAD), each local VHA Veterans Affairs Medical Center (VAMC) determined its own strategies of implementation. Strategies ranged from passive diffusion of information to electronic health record-mandated pharmacist approval for noncompliant CFU prescribing. OBJECTIVE: To characterize patterns of compliance to restricted duration of clopidogrel and determine the factors associated with compliance. METHODS: In a retrospective cohort study, we used the Veterans Affairs Surgical Quality Initiative Program (2007-2022) to identify index PVI performed for PAD and integrated post-PVI medication information from the VA Clinical Data Warehouse. Our primary outcome was to evaluate compliance with the CFU. During the active CFU period (2007-2018), we compared patient, procedural, and VAMC features by CFU compliance and determined their associations with compliance using multivariable logistic regression. We also characterized variation in compliance across the Veterans Integrated Service Network (VISN), VAMC, and surgeons. RESULTS: Among 7,206 PVIs with postoperative clopidogrel, 35% and 26% had post-PVI clopidogrel durations of no more than 30 days during and after the CFU period, respectively. During the active CFU period, we found no strong association among patient, PVI, and VAMC characteristics with compliance. Compliance during the active CFU period varied significantly among VISNs (16%-55%), VAMCs (0%-93%), and surgeons (0%-100%). CONCLUSIONS: Adherence to no more than 30 days of clopidogrel post-PVI was low during and after the active CFU period and varied substantially among the VISNs, VAMCs, and surgeons. Given that national guidance implementation was directed by local VHA pharmacies, this study highlights the importance and limitations of local implementation strategies on national guidance compliance.

Introduction Atherosclerotic cardiovascular diseases, with peripheral artery disease (PAD) and coronary artery disease (CAD) being the most common, are leading causes of morbidity and mortality. Although PAD and CAD have nearly equivalent prevalences, PAD disproportionately affects low resourced and historically marginalized populations and is predominately cared for by surgeons with a growing interest in the PAD pathology by cardiologists. We hypothesize PAD is understudied with fewer and lower quality clinical trials (CTs) than CAD. Materials and methods We conducted a cross-sectional study and queried the ClinicalTrials.gov database for PAD and CAD entries (2000-2024) and abstracted the structured CT characteristic data available. Our primary outcome was the number of CT entries/year with trends compared CAD and PAD using linear regression. Secondary outcomes included CT design components compared using descriptive statistics. Results Of the 7805 CTs included, most were CAD entries (n = 6278 [79.4%]). CAD CT entries/year were 4x that of PAD (beta-coefficient [95% confidence interval]: 3.9 [3.5-4.2], P < 0.001). Overall, CTs most commonly evaluated treatments (67.3%), but diagnostic (4.5% versus 10.8%, P < 0.001) or prevention (5.9% versus 11.1%, P < 0.001) evaluations were more common in CAD trials. Fewer PAD CTs evaluated efficacy or effectiveness: PAD CTs were more commonly phase I (6.9% versus 3.9%, P < 0.001) and single-arm interventions (31.8% versus 20.1%; P < 0.001). PAD CT also utilized fewer bias reducing methods: less randomization (64.5% versus 77.4%; P < 0.001), less blinding (43.2% versus 46.9%; P = 0.006), and more industry funding (35.6% versus 20.6%; P < 0.001). Among completed CTs, PAD CTs enrolled fewer participants/CT (median: 50 [interquartile range: 20-123] versus 92 [38-269]; P < 0.001). Conclusions Atherosclerotic cardiovascular disease CTs have increased over time, with CAD having 4-fold more entries than PAD. Further, PAD CT methods less frequently evaluated treatment efficacy or effectiveness and had less rigorous design. Focused efforts targeting quality PAD CT development are needed.

Importance The rate of follow-up after endovascular aortic repair (EVAR) of an abdominal aortic aneurysm (AAA) is low despite guidelines recommending regular surveillance due to increased risk of stent-related complications, rupture, and death. Objective To identify existing barriers and facilitators to patient follow-up adherence after EVAR to inform future interventions to improve follow-up adherence. Design, Setting, and Participants This qualitative study used purposive diversity sampling in a multisite, academic health system to interview patients who underwent elective or emergency EVAR between October 2019 and October 2021 and had varying follow-up patterns; health care professionals (HCPs), including vascular surgeons and advanced practice providers ([APPs] nurse practitioners and physician associates); and key clinical personnel, including administrative assistants, schedulers, nurses, and medical assistants with diverse backgrounds and experience with EVAR. Data were collected between December 2021 and February 2023. Data were analyzed between December 2022 and April 2025. Exposure Participants engaged in a single semistructured phone interview. Interview guides and thematic analysis were informed by the Theoretical Domains Framework. Main Outcomes and Measures Barriers and facilitators to patient follow-up adherence after EVAR. Results The sample included 55 participants (25 patients [17 (68%) males], 16 HCPs [12 physicians and 4 APPs], and 14 key clinical personnel). Of the patients, 13 had complete follow-up and a median (IQR) age of 71.6 (63.8-75.6) years, and 12 had incomplete follow-up and a median (IQR) age of 72.0 (66.3-79.3) years. The HCPs had a median (range) 7 (3-16) years in practice, and key clinical personnel worked in their current position a median (range) 2 (1-4) years. Four main themes were identified during the qualitative analysis. In theme 1, patients’ perceptions of follow-up importance were primarily affected by beliefs about immediate consequences and physical reinforcements (ie, symptoms). In theme 2, despite attempts by HCPs to provide education, patients’ knowledge of anatomical concepts did not translate to better follow-up; however, explicit knowledge of clinical consequences (ie, rupture and death) did. In theme 3, patient memory and attention issues posed barriers to follow-up, but these barriers were partially mitigated by protocolization of follow-up processes (eg, appointment reminders, standardization of preoperative and postoperative resources, and optimization of discharge paperwork). In theme 4, social support and environmental circumstances, particularly transportation, were both substantial facilitators and barriers to follow-up. Conclusions and Relevance In this qualitative study, patient focus on immediate outcomes after EVAR and memory and attention factors were important barriers to follow-up. However, recognition of explicit long-term consequences, presence of social support, and protocolization facilitated follow-up. Potential interventions to improve follow-up could include enhanced protocolization, a robust recall system to identify and contact patients with missed appointments, careful expansion of telemedicine, and transportation adjuncts.

OBJECTIVE:Over a dozen ruptured abdominal aortic aneurysm (rAAA) mortality risk prediction models currently exist; however, lack of external validation limits their applicability. This study aimed to evaluate the accuracy of eight common rAAA mortality risk prediction models in a large, contemporary, external validation cohort. METHODS:A retrospective review of rAAA repairs at a multicentre integrated regional healthcare system with large central quaternary referral facility (2010 - 2020) was performed. Eight models were used to predict 30 day post-operative death, including the Updated Glasgow Aneurysm Score (GAS), Vascular Study Group of New England rAAA Risk Score, Harborview Pre-operative rAAA Risk Score, Modified Harborview Risk Score, Vancouver Scoring System (VSS), Artificial Neural Network Score, Dutch Aneurysm Score, and Edinburgh Ruptured Aneurysm Score. The models were assessed for discrimination, calibration, and clinical utility using receiver operating characteristic curves (area under the curve [AUC]), Hosmer-Lemeshow χ2 test, Brier scores, and decision curve analysis. The proportion of unexpected survivors (survival despite > 80% predicted 30 day death) to expected deaths was compared across calculators, and both groups were compared using the model demonstrating the highest unexpected survival frequency. RESULTS:Three hundred and fifteen rAAA repairs were included (mean age 73.6 ± 10.0 years; 72.1% male; 49.8% open repair) with a 30 day mortality rate of 32.1%. Three models had fair discrimination (AUC ≥ 0.70), with GAS having the highest AUC (0.74, 95% confidence interval 0.68 - 0.79). All models demonstrated poor to adequate calibration. Using VSS, unexpected survivors (n = 25) had less pre-operative shock (72% vs. 96%; p = .050) and statistically significantly less coagulopathy (median international normalised ratio 1.2 [interquartile range 1.1, 1.5] vs. 1.8 [1.3, 2.2]; p = .015) compared with expected deaths (n = 23). CONCLUSION:Current rAAA risk prediction models demonstrated only fair discrimination and poor to adequate calibration. These findings suggest that existing risk prediction models have not sufficiently captured important physiological characteristics associated with rAAA death and should be applied cautiously to clinical practice.

Importance:Postoperative red blood cell transfusion guidelines recommend transfusion for hemoglobin levels less than 7 g/dL. However, the safety of this strategy in patients at high risk of cardiac events undergoing major operations remains unclear. Objective:To evaluate the risk of death or major ischemic events within 90 days after a liberal transfusion strategy compared with a restrictive transfusion strategy in patients at high risk of cardiac events who had undergone major vascular or general surgery operations and developed postoperative anemia. Design, Setting, and Participants:This parallel, single-blind, randomized clinical superiority trial included 1428 veterans (≥18 y) at high cardiac risk undergoing major vascular or general surgery operations. Participants were enrolled from February 2018 to March 2023 across 16 Veterans Affairs Medical Centers in the US. Interventions:Seven hundred fourteen participants with postoperative hemoglobin less than 10 g/dL were randomized to a liberal strategy (transfusion trigger at hemoglobin level <10 g/dL) and 714 to a restrictive strategy (transfusion trigger at hemoglobin <7 g/dL). Main Outcomes and Measures:The primary end point was a composite of all-cause death, myocardial infarction, coronary revascularization, acute kidney failure, or ischemic stroke within 90 days after randomization. Secondary end points included a composite of cardiac complications other than myocardial infarction (arrhythmias, heart failure, and nonfatal cardiac arrest). Results:Of the 1424 analyzed veterans (mean age, 69.9 [SD, 7.9] years; 1393 male [97.8%]; 268 Black [18.8%]; 48 Hispanic [4.1%]; 1071 White [75.2%]), 1297 (91.1%) underwent vascular surgical procedures. The mean hemoglobin difference between transfusion strategies was 2.0 g/dL on day 5 after randomization. The primary outcome rate in the liberal group was 9.1% (61 of 670) compared with 10.1% (71 of 700) in the restrictive group (relative risk, 0.90; 95% CI, 0.65-1.24). The secondary end point of cardiac complications without myocardial infarction, which was 1 of 5 secondary end points, occurred in 5.9% (38 of 647) of patients in the liberal group and 9.9% (67 of 678) of patients in the restrictive group (relative risk, 0.59; 99% CI, 0.36-0.98). Conclusions and relevance:After major vascular or general surgery operations among patients at high risk of a cardiac event, a liberal transfusion strategy did not reduce 90-day death or major ischemic outcome rates compared with a restrictive strategy. Trial Registration:ClinicalTrials.gov Identifier: NCT03229941.

Introduction: The American Diabetes Association recommends use of glucagon-like-peptide-1 receptor agonists (GLP-1RAs) by patients with peripheral arterial disease (PAD) despite limited information regarding the impact of GLP-1RAs in these patients. Hypothesis: Patients using GLP-1RAs have lower rates of adverse events following revascularization. Methods: Our retrospective cohort (18-hospital, unified health care system; 2016-2024) included diabetic adults undergoing an index PAD revascularization, stratified by GLP-1RAs prescription. The primary outcome was overall mortality. Secondary outcomes included major adverse limb events (MALE), major adverse cardiac events (MACE), major amputation, and acute coronary syndromes (ACS). Outcomes were compared via Kaplan Meier analysis and entropy-balanced Cox regression using demographic, medical, healthy user parameters, intervention, and facility factors generating adjusted hazard ratios (aHR) and 95% confidence intervals (CI). Results: We included 5,008 patients (age 69±11 years; 1,858 [37.1%] females; 4,400 [87.8%] White; 1,766 [35.2%] open interventions) of which 468 (9.3%) were prescribed GLP-1RAs. On unadjusted analysis, GLP-1RAs prescriptions were correlated with lower mortality rates (60 [13%] vs 1,649 [36%], p<0.001) (Figure 1) and ACS events (42 [9%] vs 642 [14%], p=0.04). However, MALE (123 [26%] vs 1,306 [29%], p=0.45), MACE (81 [17%] vs1,048 [23%], p=0.18), and major amputation (38 [8%] vs 498 [11%], p=0.12) differences were non-significant. After entropy-balance, covariates were well balanced with all standardized mean differences <0.1. Entropy-balance and multivariable regression noted GLP-1RA prescriptions were associated with a reduced risk of mortality (aHR [95%CI]: 0.65 [0.44-0.96]), ACS (aHR [95%CI]: 0.61 [0.37-0.99]), and major amputation (aHR [95%CI]: 0.45 [0.28-0.73]) (Figure 2) but failed to reach significance for MALE (aHR [95%CI]: 0.76 [0.56-1.03]) and MACE (aHR [95%CI]: 0.89 [0.61-1.30]). Conclusions: GLP-1RAs use in diabetic patients undergoing revascularization for PAD was associated with significantly decreased rates of postoperative mortality, major amputation, and ACS events after lower extremity revascularization. These findings support the benefit of these medications in the diabetic PAD population and warrant further investigation to understand mechanism of protection of these medications and the potential expanded use in nondiabetic patients with PAD.

OBJECTIVE:Endovascular treatment of acute limb ischemia, primarily consisting of catheter-directed thrombolysis (CDT), has been shown to reduce mortality without affecting limb salvage. Percutaneous thrombectomy (PT) devices have expanded endovascular approaches while decreasing thrombolytic use. Although many advocate for an endovascular-first approach, it is unclear which patients would benefit most from each strategy. METHODS:We included adults (18+) who underwent revascularization for infrainguinal acute limb ischemia (January 2016 to December 2023) at a multi-hospital health care system. We compared amputation and mortality after endovascular vs open approaches using logistic regression, Kaplan-Meier curves, and Cox regression. RESULTS:We included 315 patients: 145 undergoing an endovascular-first strategy (89 CDT, 51 PT, 5 angioplasty/stent) and 170 undergoing open therapy (132 open thrombectomy, 38 bypass). Patients undergoing endovascular-first treatment were less ischemic, had more prior stenting, and more acute-on-chronic disease. Patients undergoing PT with suction devices were less likely to undergo overnight CDT compared with those with rheolytic devices (21% vs 67%; P = .004). There were no differences in 30-day amputation or mortality, but 30-day reintervention was increased in the endovascular group (adjusted odds ratio, 2.29; 95% confidence interval [CI], 1.06-4.91; P = .03). Three-year amputation rates were not significantly different on univariable or multivariable analysis when comparing the endovascular-first approach with open. PT alone trended toward increased amputation rates compared to open (adjusted hazard ratio [aHR], 1.96; 95% CI, 0.98-3.94; P = .058); however, this was mainly driven by the use of rheolytic devices with an amputation rate of 64% vs 8% in suction devices. Furthermore, those with embolic disease had significantly increased amputation rates (aHR, 2.92; 95% CI, 1.29-6.58; P = .01; Pinteraction = .02) with any endovascular-first strategy, when compared with open therapy. Endovascular-first patients had decreased mortality on univariable analysis (16% vs 37%; log-rank = .004) but not multivariable analysis (aHR, 0.60; 95% CI, 0.32-1.13; P = .12). When separated by endovascular modality, CDT had decreased mortality compared with open (aHR, 0.41; 95% CI, 0.18-0.93; P = .033), whereas PT did not (aHR, 1.05; 95% CI, 0.47-2.35; P = .91). Although effect of treatment modality on outcomes was not moderated by Rutherford classification, only 22 patients underwent endovascular-first treatment for Rutherford 2b ischemia. CONCLUSIONS:Endovascular-first therapy had increased 3-year amputation in patients with embolic etiology of disease compared with open therapy. We also saw increased 30-day reintervention with endovascular-first therapy when compared with open therapy. CDT had decreased 3-year mortality when compared with open therapy. PT devices had mixed results, indicating that this is a technology in evolution. Newer PT devices are effective at reducing thrombolytic usage, and their amputation and mortality rates were similar to open therapy. An endovascular-first approach to Rutherford 2b ischemia needs further evaluation.

Postoperative red blood cell transfusion guidelines recommend transfusion for hemoglobin levels less than 7 g/dL. However, the safety of this strategy in patients at high risk of cardiac events undergoing major operations remains unclear. To evaluate the risk of death or major ischemic events within 90 days after a liberal transfusion strategy compared with a restrictive transfusion strategy in patients at high risk of cardiac events who had undergone major vascular or general surgery operations and developed postoperative anemia. This parallel, single-blind, randomized clinical superiority trial included 1428 veterans (≥18 y) at high cardiac risk undergoing major vascular or general surgery operations. Participants were enrolled from February 2018 to March 2023 across 16 Veterans Affairs Medical Centers in the US. Seven hundred fourteen participants with postoperative hemoglobin less than 10 g/dL were randomized to a liberal strategy (transfusion trigger at hemoglobin level <10 g/dL) and 714 to a restrictive strategy (transfusion trigger at hemoglobin <7 g/dL). The primary end point was a composite of all-cause death, myocardial infarction, coronary revascularization, acute kidney failure, or ischemic stroke within 90 days after randomization. Secondary end points included a composite of cardiac complications other than myocardial infarction (arrhythmias, heart failure, and nonfatal cardiac arrest). Of the 1424 analyzed veterans (mean age, 69.9 [SD, 7.9] years; 1393 male [97.8%]; 268 Black [18.8%]; 48 Hispanic [4.1%]; 1071 White [75.2%]), 1297 (91.1%) underwent vascular surgical procedures. The mean hemoglobin difference between transfusion strategies was 2.0 g/dL on day 5 after randomization. The primary outcome rate in the liberal group was 9.1% (61 of 670) compared with 10.1% (71 of 700) in the restrictive group (relative risk, 0.90; 95% CI, 0.65-1.24). The secondary end point of cardiac complications without myocardial infarction, which was 1 of 5 secondary end points, occurred in 5.9% (38 of 647) of patients in the liberal group and 9.9% (67 of 678) of patients in the restrictive group (relative risk, 0.59; 99% CI, 0.36-0.98). After major vascular or general surgery operations among patients at high risk of a cardiac event, a liberal transfusion strategy did not reduce 90-day death or major ischemic outcome rates compared with a restrictive strategy. ClinicalTrials.gov Identifier: NCT03229941

Background: Aortic infection is associated with high morbidity and mortality, but the outcomes of prosthetic (surgical or endovascular) grafts compared with primary aortic infections are poorly defined. This large single-center retrospective study aims to compare the outcomes of primary and prosthetic aortic graft infections. Methods: Patients diagnosed with primary or infected aortic grafts between January 2000 and December 2022 were included. Patients were grouped based on the type of infection (primary, surgical graft, and endograft). Baseline demographics, symptoms, imaging, interventions, and outcomes were evaluated. Primary outcomes include overall and reintervention-free survival. Kaplan-Meier survival and Cox proportional hazards analysis were performed. Results: A total of 145 patients presented during the study period with primary infection of the native aorta (33.8%) or aortic graft infection (66.2%: 44.8% surgical graft and 21.4% endograft). In-hospital mortality (39% vs 15% vs 10%; P = .007) and 30-day complication rates (68% vs 40% vs 37%; P = .015) were highest among endografts, followed by surgical grafts, and lowest among primary infections, respectively. Primary aortic infections had the highest 30-day, 1-year, and 5-year survival on Kaplan-Meier analysis compared with surgical and endograft infections. Reintervention-free survival was also highest in primary infections at 1 and 5 years (log-rank P < .001). On multivariate analysis, infected surgical grafts and endografts were associated with a significantly higher 30-day mortality (hazard ratio, 8.1; P = .016 and hazard ratio, 5.8; P = .035, respectively). Visceral artery involvement was a major determinant of mortality at 1 year and 5 years but not at 30 days, whereas treatment type did not affect mortality across all groups. There was no difference in the duration of intravenous antibiotic treatment between groups (42 vs 45 vs 44 days; P = .68). Conclusions: Infected aortic endografts have lower short-and long-term survival as well as a lower rate of long-term intervention-free survival when compared with surgical graft and primary aortic infections. Visceral artery involvement was associated with increased mortality. Predictors of endograft infection need to be determined to minimize complications, and careful consideration is necessary before endovascular aortic interventions if there is concern an underlying infectious process.

Collagen-containing tissues show strain hardening behavior due to the alignment and the waviness of collagen fibers. As the fibers uncrimp and align with stretching, they become increasingly load-bearing and make the tissue strain hardening. We consider the mechanics of analogous synthetic composites comprising stiff crimped fibers dispersed in a soft elastomeric matrix. A novel workflow is developed wherein a random configuration of hundreds of finite-length crimped fibers embedded in a soft matrix can be created, meshed, and then simulated by 3D finite element methods. We show that the mechanical behavior of these composites is affected by the degree of fiber crimp, the fiber volume fraction, and fiber orientation. The degree of reinforcement of the soft matrix was found to increase with volume fraction of the fibers, and with better alignment of the fibers along the tension direction. Fibers with larger crimp amplitude were found to show strain hardening behavior, i.e. contribute little to the stress at small strain, but much more at large strain. The Holzapfel-Gasser-Ogden model is shown to capture the stress-strain behavior adequately. Further, we show that simulations of a single fiber embedded in a soft matrix can approximately predict the mechanical behavior of multifiber composites at much reduced computational cost. Such composites of chopped crimped fibers offer the benefit of reproducing the mechanical behavior of tissues, while still being flow-processable.

BACKGROUND:Among patients who suffer a ruptured abdominal aortic aneurysm (rAAA), ≤35% die perioperatively despite advancements in endovascular repair and intensive care. Patient rurality and associated disparities in local health services portend poorer cardiovascular outcomes; however, the effect of patient rurality on rAAA outcomes is unknown. Conversely, high-volume repair hospitals are associated with improved mortality outcomes for cardiovascular operations; however, the effects for patients residing rurally are unknown. We evaluated the association between in-hospital mortality, patient rurality, transfer status, and rAAA hospital repair volume among patients undergoing rAAA repair. METHODS:Using Healthcare Cost and Utilization Project's State Inpatient Database (New York and Florida), we identified adults with a primary diagnosis of rAAA who underwent repair (2015-2020). Exposures of interest included (1) patient rurality, (2) transfer status before repair, and (3) hospital rAAA repair volume. The Rural Urban Community Area classified patient residence as rural (rural/small town/micropolitan) or nonrural (metropolitan), the State Inpatient Database provided transfer status from another facility, and the top 25% of hospital rAAA volume defined high-volume repair hospitals. The primary outcome was in-hospital mortality. A multivariable logistic regression adjusted for patient demographics, comorbidities, frailty (by validated the Risk Analysis Index), income quartiles, repair type, and hospital case mix with a variance estimation clustered by unique hospital. Interaction terms evaluated the association between hospital repair volume and mortality among exposure subgroups. RESULTS:Of 1744 rAAA patients (median age, 75 years [interquartile range, 67-82 years]; 76.4% male; 78.8% White; 73.9% undergoing endovascular aneurysm repair), 148 (8.5%) resided in rural areas, 414 (23.7%) were transferred to a referral hospital for repair, and 1248 (71.6%) were repaired at high-volume hospitals. Rural patients were more often transferred in from another facility for repair (49.3% vs 21.4%; P < .001) and repaired at high-volume hospitals (82.6% vs 70.6%; P = .002). After multivariable adjustment, neither rurality (adjusted odds ratio [aOR], 0.78; 95% confidence interval [CI], 0.46-1.34) nor transfer status (aOR, 0.82; 95% CI, 0.61-1.10) were associated with in-hospital mortality; however, high-volume hospitals were associated with a 27% lower risk of in-hospital mortality (aOR, 0.73; 95% CI, 0.56-0.96). The association between high-volume repair hospitals and reduced in-hospital mortality was independent of rural residence and transfer status. CONCLUSIONS:Despite rural patients having fewer local health care resources, rurality was not associated with an increased risk of in-hospital mortality after rAAA repair. High-volume rAAA repair hospitals were associated with a 27% decreased in in-hospital mortality, independent of transfer status or patient rurality. These data underscore the importance of considering rAAA repair at high-volume repair hospitals for patients stable enough to survive rapid transport.

Background: Preoperative smoking cessation can reduce adverse postoperative outcomes. Investment in smoking cessation therapies has therefore proven cost effective prior to elective interventions across numerous disciplines. Despite high rates of smoking among patients with peripheral artery disease (PAD), the cost effectiveness of smoking cessation before elective revascularization is unclear. Methods: Using a Markov model, we evaluated the cost effectiveness of preoperative smoking cessation therapies (standard care, counseling, nicotine replacement therapy [NRT], varenicline, bupropion) for 65-year-old patients undergoing open or endovascular revascularization for symptomatic PAD. Local data quantified smoking cessation therapy costs. Established literature informed therapy effectiveness, postoperative outcomes (stroke, myocardial infarction, major amputation, patency, death) frequencies, and postoperative costs. Lifetime costs were quantified in US dollars and effectiveness in quality-adjusted life-years (QALYs), with a willingness-to-pay threshold of $100,000/QALY gained. Sensitivity analyses tested model robustness. Results: In the base-case scenario, standard care was least expensive ($326,280) and varenicline was costliest ($333,335). However, varenicline was the most effective (7.11 QALYs), while standard care was least effective (6.43 QALYs). NRT and varenicline were the most costeffective therapies. In the probabilistic simulation (randomly varying model parameters over 1,000 iterations), varenicline was favored in 80.3% at $100,000/QALY gained. Assuming no mortality differences by smoking status, in one-way sensitivity analyses varenicline dominated all other therapies. Conclusion: Smoking cessation adjuncts are cost effective prior to PAD interventions. Varenicline and NRT were the most cost-effective smoking cessation strategies. Our results highlight the value of supplemented coverage for smoking cessation therapies among patients with PAD undergoing revascularization.

BACKGROUND:Aging patients face increasing comorbid conditions, most commonly atherosclerotic cardiovascular diseases, which are often treated surgically; however, aging is also associated with frailty, which portends adverse postoperative outcomes. Assessing outcomes in a frail surgical cohort necessitates the use of valid patient-centered metrics such as hospital-free days (HFDs) quantifying patient time at home and out of the hospital. STUDY DESIGN:We included patients from the Florida State Inpatient Database undergoing coronary artery bypass grafting, carotid endarterectomy, or abdominal aortic aneurysm repair (2015 to 2018). The association between frailty (Risk Analysis Index) and 90-day HFD (HFD-90) was assessed using multivariable zero-inflated negative binomial and ordinal logistic regression models. Logistic regression evaluated the association between frailty and in-hospital mortality. RESULTS:Overall, 67,861 patients (age 69.3 ± 9.9 years; 28.3% women; 46.4% robust, 46.6% normal, and 7.0% frail) were included from 148 Florida hospitals. Median HFD-90 was 83 (interquartile range 79 to 86) days, and 2.6% of patients experienced in-hospital mortality. Compared with normal status, robust status was associated with higher HFD-90 (adjusted rate ratio 1.03, 95% CI 1.02 to 1.04), whereas frailty was associated with lower HFD-90 (adjusted rate ratio 0.95, 95% CI 0.94 to 0.96) risk. Similarly, robust patients had lower adjusted odds of in-hospital mortality (adjusted odds ratio 0.40, 95% CI 0.34 to 0.48), whereas frail patients had higher odds (adjusted odds ratio 6.20, 95% CI 4.90 to 7.77) as compared with normal. CONCLUSIONS:HFD-90 is a feasible, comprehensive, patient-centered metric to assess outcomes in frail patients which encompasses the most used postoperative outcomes assessment tools (mortality, length of stay, and readmission) into 1 inclusive measure.

Background: Acute limb ischemia (ALI) is a morbid and deadly diagnosis. However, existing epidemiologic studies describing ALI predate the introduction of the Affordable Care Act in 2010 and direct oral anticoagulants in 2011. Thus, we synergized the National Inpatient Sample (NIS) and United States Census to define contemporary trends in the incidence, treatment, and outcomes of ALI in the US. Methods: We included emergent admissions of adults with primary diagnosis of lower extremity ALI in survey-weighted NIS data (2005-2020). Mann-Kendal trend test evaluated ALI incidence (primary outcome), anticoagulation usage, insurance coverage, revascularization type, and in-hospital amputation/death. Multivariable logistic regression quantified covariate associations with in-hospital amputation/death. Results: Of the 582,322,862 estimated hospitalizations in the NIS, 227,440 met the inclusion criteria (mean age 68.80 years, 49.94% women, 76.66% White). ALI incidence peaked in 2006 (7.16/100,000 person-years) but has declined since 2015 to 4.16/100,000 person-years in 2020 (ptrend - 0.008). Endovascular revascularization, anticoagulation, and Medicaid coverage increased, while self-pay insurance decreased (ptrend < 0.05). Amputation rates significantly decreased from 8.04 to 6.54% (ptrend - 0.01) while death rate remained at 5.59% (ptrend - 0.16) over the study period. Prehospitalization anticoagulation was associated with decreased amputation (adjusted odds ratio [aOR] - 0.74 (95% confidence interval [CI] 0.65-0.84)) and death (aOR - 0.50 (95% CI 0.43-0.57)). When controlling for covariates, women had a higher risk of death (aOR - 1.17 (95% CI 1.07-1.27), P < 0.0001), while Black patients had a higher risk of amputation (aOR - 1.24 (95% CI 1.10-1.41), P < 0.0001). Conclusions: Our US population based epidemiological study demonstrates that ALI incidence and in-hospital amputation rates are decreasing, while mortality remains unchanged. We further highlight the ongoing need for ALI investigation specifically as it relates to access to care, antithrombotic therapy use, treatment strategy, and strategies to combat gender and racial disparities.