Single-Nuclei RNA-Sequencing of the Gastrocnemius Muscle in Peripheral Artery Disease.

BACKGROUND: Lower extremity peripheral artery disease (PAD) is a growing epidemic with limited effective treatment options. Here, we provide a single-nuclei atlas of PAD limb muscle to facilitate a better understanding of the composition of cells and transcriptional differences that comprise the diseased limb muscle. METHODS: We obtained gastrocnemius muscle specimens from 20 patients with PAD and 12 non-PAD controls. Nuclei were isolated and single-nuclei RNA-sequencing was performed. The composition of nuclei was characterized by iterative clustering via principal component analysis, differential expression analysis, and the use of known marker genes. Bioinformatics analysis was performed to determine differences in gene expression between PAD and non-PAD nuclei, as well as subsequent analysis of intercellular signaling networks. Additional histological analyses of muscle specimens accompany the single-nuclei RNA-sequencing atlas. RESULTS: Single-nuclei RNA-sequencing analysis indicated a fiber type shift with patients with PAD having fewer type I (slow/oxidative) and more type II (fast/glycolytic) myonuclei compared with non-PAD, which was confirmed using immunostaining of muscle specimens. Myonuclei from PAD displayed global upregulation of genes involved in stress response, autophagy, hypoxia, and atrophy. Subclustering of myonuclei also identified populations that were unique to PAD muscle characterized by metabolic dysregulation. PAD muscles also displayed unique transcriptional profiles and increased diversity of transcriptomes in muscle stem cells, regenerating myonuclei, and fibro-adipogenic progenitor cells. Analysis of intercellular communication networks revealed fibro-adipogenic progenitors as a major signaling hub in PAD muscle, as well as deficiencies in angiogenic and bone morphogenetic protein signaling which may contribute to poor limb function in PAD. CONCLUSIONS: This reference single-nuclei RNA-sequencing atlas provides a comprehensive analysis of the cell composition, transcriptional signature, and intercellular communication pathways that are altered in the PAD condition.

Activation of the Aryl Hydrocarbon Receptor in Muscle Exacerbates Ischemic Pathology in Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease (CKD) accelerates the development of atherosclerosis, decreases muscle function, and increases the risk of amputation or death in patients with peripheral artery disease (PAD). However, the mechanisms underlying this pathobiology are ill-defined. Recent work has indicated that tryptophan-derived uremic solutes, which are ligands for AHR (aryl hydrocarbon receptor), are associated with limb amputation in PAD. Herein, we examined the role of AHR activation in the myopathy of PAD and CKD. METHODS: AHR-related gene expression was evaluated in skeletal muscle obtained from mice and human PAD patients with and without CKD. AHRmKO (skeletal muscle-specific AHR knockout) mice with and without CKD were subjected to femoral artery ligation, and a battery of assessments were performed to evaluate vascular, muscle, and mitochondrial health. Single-nuclei RNA sequencing was performed to explore intercellular communication. Expression of the constitutively active AHR was used to isolate the role of AHR in mice without CKD. RESULTS: PAD patients and mice with CKD displayed significantly higher mRNA expression of classical AHR-dependent genes (Cyp1a1, Cyp1b1, and Aldh3a1) when compared with either muscle from the PAD condition with normal renal function (P<0.05 for all 3 genes) or nonischemic controls. AHRmKO significantly improved limb perfusion recovery and arteriogenesis, preserved vasculogenic paracrine signaling from myofibers, increased muscle mass and strength, as well as enhanced mitochondrial function in an experimental model of PAD/CKD. Moreover, viral-mediated skeletal muscle-specific expression of a constitutively active AHR in mice with normal kidney function exacerbated the ischemic myopathy evidenced by smaller muscle masses, reduced contractile function, histopathology, altered vasculogenic signaling, and lower mitochondrial respiratory function. CONCLUSIONS: These findings establish AHR activation in muscle as a pivotal regulator of the ischemic limb pathology in CKD. Further, the totality of the results provides support for testing of clinical interventions that diminish AHR signaling in these conditions.

A patient-centered textbook outcome measure effectively discriminates contemporary elective open abdominal aortic aneurysm repair quality.

BACKGROUND: There is persistent controversy surrounding the merit of surgical volume benchmarks being used solely as a sufficient proxy for assessing the quality of open abdominal aortic aneurysm (AAA) repair. Importantly, operative volume quotas may fail to reflect a more nuanced and comprehensive depiction of surgical outcomes most relevant to patients. Accordingly, we herein propose a patient-centered textbook outcome (TO) for AAA repair that is analogous to other large magnitude extirpative operations performed in other surgical specialties, and test its feasibility to discriminate hospital performance using Society for Vascular Surgery (SVS) volume guidelines. METHODS: All elective open infrarenal AAA repairs (OAR) in the SVS-Vascular Quality Initiative were examined (2009-2022). The primary end point was a TO, defined as a composite of no in-hospital complication or reintervention/reoperation, length of stay of ≤10 days, home discharge, and 1-year survival rates. The discriminatory ability of the TO measure was assessed by comparing centers that did or did not meet the SVS annual OAR volume threshold recommendation (high volume ≥10 OARs/year; low volume <10 OARs/year). Logistic regression and multivariable models adjusted for patient and procedure-related differences. RESULTS: A total of 9657 OARs across 198 centers were analyzed (mean age, 69.5 ± 8.4 years; female, 26%; non-White, 12%). A TO was identified in 44% (n = 4293) of the overall cohort. The incidence of individual TO components included no in-hospital complication (61%), no in-hospital reintervention or reoperation (92%), length of stay of ≤10 days (78%), home discharge (76%), and 1-year survival (91%). Median annual center volume was 6 (interquartile range, 3-10) and a majority of centers did not meet the SVS volume suggested threshold (<10 OARs/year, n = 148 [74%]). However, most patients (6265 of 9657 [65%]) underwent OAR in high-volume hospitals. When comparing high- and low-volume centers, a TO was more likely to occur in high-volume institutions: ≥10 OARs/year (46%) vs <10 OARs/year (42%; P = .0006). The association of a protective effect for higher center volume remained after risk adjustment (odds ratio, 1.1; 95% confidence interval, 1.05-1.26; P = .003). CONCLUSIONS: TOs for elective OAR reflect a more nuanced and comprehensive patient centered proxy to measure care delivery, consistent with other surgical specialties. Surprisingly, a TO was achieved in <50% of elective AAA cases nationally. Although the likelihood of a TO seems to correlate with SVS center volume recommendations, it more importantly reflects elements which may be prioritized by patients and thus offers insights into further improving real-world AAA care.

Patient decision-making in the era of transcarotid artery revascularization.

OBJECTIVE: The National Coverage Determination on carotid stenting by Medicare in October 2023 stipulates that patients participate in a shared decision-making (SDM) conversation with their proceduralist before an intervention. However, to date, there is no validated SDM tool that incorporates transcarotid artery revascularization (TCAR) into its decision platform. Our objective was to elicit patient and surgeon experiences and preferences through a qualitative approach to better inform the SDM process surrounding carotid revascularization. METHODS: We performed longitudinal perioperative semistructured interviews of 20 participants using purposive maximum variation sampling, a qualitative technique designed for identification and selection of information-rich cases, to define domains important to participants undergoing carotid endarterectomy or TCAR and impressions of SDM. We also performed interviews with nine vascular surgeons to elicit their input on the SDM process surrounding carotid revascularization. Interview data were coded and analyzed using inductive content analysis coding. RESULTS: We identified three important domains that contribute to the participants' ultimate decision on which procedure to choose: their individual values, their understanding of the disease and each procedure, and how they prefer to make medical decisions. Participant values included themes such as success rates, "wanting to feel better," and the proceduralist's experience. Participants varied in their desired degree of understanding of carotid disease, but all individuals wished to discuss each option with their proceduralist. Participants' desired medical decision-making style varied on a spectrum from complete autonomy to wanting the proceduralist to make the decision for them. Participants who preferred carotid endarterectomy felt outcomes were superior to TCAR and often expressed a desire to eliminate the carotid plaque. Those selecting TCAR felt it was a newer, less invasive option with the shortest procedural and recovery times. Surgeons frequently noted patient factors such as age and anatomy, as well as the availability of long-term data, as reasons to preferentially select one procedure. For most participants, their surgeon was viewed as the most important source of information surrounding their disease and procedure. CONCLUSIONS: SDM surrounding carotid revascularization is nuanced and marked by variation in patient preferences surrounding autonomy when choosing treatment. Given the mandate by Medicare to participate in a SDM interaction before carotid stenting, this analysis offers critical insights that can help to guide an efficient and effective dialog between patients and providers to arrive at a shared decision surrounding therapeutic intervention for patients with carotid disease.

Size thresholds for repair of abdominal aortic aneurysms warrant reconsideration.

BACKGROUND: The historical size threshold for abdominal aortic aneurysm (AAA) repair is widely accepted to be 5.5 cm for men and 5.0 cm for women. However, contemporary AAA rupture risks may be lower than historical benchmarks, which has implications for when AAAs should be repaired. Our objective was to use contemporary AAA rupture rates to inform optimal size thresholds for AAA repair. METHODS: We used a Markov chain analysis to estimate life expectancy for patients with AAA. The primary outcome was AAA-related mortality. We estimated survival using Social Security Administration life tables and published contemporary AAA rupture estimates. For those undergoing repair, we modified survival estimates using data from the Vascular Quality Initiative and Medicare on complications, late rupture, and open conversion. We used this model to estimate the AAA repair size threshold that minimizes AAA-related mortality for 60-year-old average-health men and women. We performed a sensitivity analysis of poor-health patients and 70- and 80-year-old base cases. RESULTS: The annual risk of all-cause mortality under surveillance for a 60-year-old woman presenting with a 5.0 cm AAA using repair thresholds of 5.5 cm, 6.0 cm, 6.5 cm, and 7.0 cm was 1.7%, 2.3%, 2.7%, and 2.8%, respectively. The corresponding risk for a man was 2.3%, 2.9%, 3.3%, and 3.4% for the same repair thresholds, respectively. For a 60-year-old average-health woman, an AAA repair size of 6.1 cm was the optimal threshold to minimize AAA-related mortality. Life expectancy varied by <2 months for repair at sizes from 5.7 cm to 7.1 cm. For a 60-year-old average-health man, an AAA repair size of 6.9 cm was the optimal threshold to minimize AAA-related mortality. Life expectancy varied by <2 months for repair at sizes from 6.0 cm to 7.4 cm. Women in poor health, at various age strata, had optimal AAA repair size thresholds that were >6.5 cm, whereas men in poor health, at all ages, had optimal repair size thresholds that were >8.0 cm. CONCLUSIONS: The optimal threshold for AAA repair is more nuanced than a discrete size. Specifically, there appears to be a range of AAA sizes for which repair is reasonable to minmized AAA-related mortality. Notably, they all are greater than current guideline recommendations. These findings would suggest that contemporary AAA size thresholds for repair should be reconsidered.

A dedicated risk prediction model of 1-year mortality following endovascular aortic aneurysm repair involving the renal-mesenteric arteries.

OBJECTIVE: Treatment goals of prophylactic endovascular aortic repair of complex aneurysms involving the renal-mesenteric arteries (complex endovascular aortic repair [cEVAR]) include achieving both technical success and long-term survival benefit. Mortality within the first year after cEVAR likely indicates treatment failure owing to associated costs and procedural complexity. Notably, no validated clinical decision aid tools exist that reliably predict mortality after cEVAR. The purpose of this study was to derive and validate a preoperative prediction model of 1-year mortality after elective cEVAR. METHODS: All elective cEVARs including fenestrated, branched, and/or chimney procedures for aortic disease extent confined proximally to Ishimaru landing zones 6 to 9 in the Society for Vascular Surgery Vascular Quality Initiative were identified (January 2012 to August 2023). Patients (n = 4053) were randomly divided into training (n = 3039) and validation (n = 1014) datasets. A logistic regression model for 1-year mortality was created and internally validated by bootstrapping the AUC and calibration intercept and slope, and by using the model to predict 1-year mortality in the validation dataset. Independent predictors were assigned an integer score, based on model beta-coefficients, to generate a simplified scoring system to categorize patient risk. RESULTS: The overall crude 1-year mortality rate after elective cEVAR was 11.3% (n = 456/4053). Independent preoperative predictors of 1-year mortality included chronic obstructive pulmonary disease, chronic renal insufficiency (creatinine >1.8 mg/dL or dialysis dependence), hemoglobin <12 g/dL, decreasing body mass index, congestive heart failure, increasing age, American Society of Anesthesiologists class ≥IV, current tobacco use, history of peripheral vascular intervention, and increasing extent of aortic disease. The 1-year mortality rate varied from 4% among the 23% of patients classified as low risk to 23% for the 24% classified as high risk. Performance of the model in validation was comparable with performance in the training data. The internally validated scoring system classified patients roughly into quartiles of risk (low, low/medium, medium/high and high), with 52% of patients categorized as medium/high to high risk, which had corresponding 1-year mortality rates of 11% and 23%, respectively. Aneurysm diameter was below Society for Vascular Surgery recommended treatment thresholds (<5.0 cm in females, <5.5 cm in males) in 17% of patients (n = 679/3961), 41% of whom were categorized as medium/high or high risk. This subgroup had significantly increased in-hospital complication rates (18% vs 12%; P = .02) and 1-year mortality (13% vs 5%; P < .0001) compared with patients in the low- or low/medium-risk groups with guideline-compliant aneurysm diameters (≥5.0 cm in females, ≥5.5 cm in males). CONCLUSIONS: This validated preoperative prediction model for 1-year mortality after cEVAR incorporates physiological, functional, and anatomical variables. This novel and simplified scoring system can effectively discriminate mortality risk and, when applied prospectively, may facilitate improved preoperative decision-making, complex aneurysm care delivery, and resource allocation.

Comparison of open and endovascular left subclavian artery revascularization for zone 2 thoracic endovascular aortic repair.

OBJECTIVE: In patients undergoing elective thoracic endovascular aortic repair (TEVAR) and left subclavian artery (LSA) coverage, routine preoperative LSA revascularization is recommended. However, in the current endovascular era, the optimal surgical approach is debated. We compared baseline characteristics, procedural details, and perioperative outcomes of patients undergoing open or endovascular LSA revascularization in the setting of TEVAR. METHODS: Adult patients undergoing TEVAR with zone 2 proximal landing and LSA revascularization between 2013-2023 were identified in the Vascular Quality Initiative. We excluded patients with traumatic aortic injury, aortic thrombus, or ruptured presentations, and stratified based on revascularization type (open vs. any endovascular). Open LSA revascularization included surgical bypass or transposition. Endovascular LSA revascularization included single-branch, fenestration, or parallel stent grafting. Primary outcomes were stroke, spinal cord ischemia, and perioperative mortality (Pearson's χ2-test). Multivariable logistic regression was used to evaluate associations between revascularization type and primary outcomes. Secondarily, we studied other in-hospital complications and 5-year mortality (Kaplan-Meier, multivariable Cox-regression). Sensitivity analysis was performed in patients undergoing concomitant LSA revascularization to TEVAR. RESULTS: Of 2,489 patients, 1,842 (74%) underwent open and 647 (26%) received endovascular LSA revascularization. Demographics and comorbidities were similar between open and endovascular cohorts. Compared with open, endovascular revascularization had shorter procedure times (median 135 vs. 174min, p<.001), longer fluoroscopy time (median 23 vs. 16min, p<.001), lower estimated blood loss (median 100 vs. 123ml, p<.001), and less preoperative spinal drain use (40% vs. 49%, p<.001). Patients undergoing endovascular revascularization were more likely to present urgently (24% vs. 19%) or emergently (7.4% vs. 3.4%) (p<.001). Compared with open, endovascular patients experienced lower stroke rates (2.6% vs. 4.8%, p=.026; aOR 0.50[95%C.I., 0.25-0.90]), but had comparable spinal cord ischemia (2.9% vs. 3.5%, p=.60; 0.64[0.31-1.22]) and perioperative mortality (3.1% vs. 3.3%, p=.94; 0.71[0.34-1.37]). Compared with open, endovascular LSA revascularization had lower rates of overall composite in-hospital complications (20% vs. 27%, p<.001; 0.64[0.49-0.83]) and shorter overall hospital stay (7 vs. 8 days, p<.001). After adjustment, 5-year mortality was similar among groups (aHR 0.85[0.64-1.13]). Sensitivity analysis supported the primary analysis with similar outcomes. CONCLUSIONS: In patients undergoing TEVAR starting in zone 2, endovascular LSA revascularization had lower rates of postoperative stroke and overall composite in-hospital complications, but similar spinal cord ischemia, perioperative and 5-year mortality rates compared with open LSA revascularization. Future comparative studies are needed to evaluate the mid- to long-term safety of endovascular LSA revascularization and assess differences between specific endovascular techniques.

Comparative outcomes of open mesenteric bypass after a failed endovascular or open mesenteric revascularization for chronic mesenteric ischemia.

INTRODUCTION: Clinical practice guidelines have recommended an endovascular-first approach (ENDO) for the management of patients with chronic mesenteric ischemia (CMI), whereas an open mesenteric bypass (OMB) is proposed for subjects deemed to be poor ENDO candidates. However, the impact of a previous failed endovascular or open mesenteric reconstruction on a subsequent OMB is unknown. Accordingly, this study was designed to examine the results of a remedial OMB (R-OMB) after a failed ENDO or a primary OMB (P-OMB) for patients with recurrent CMI. METHODS: All patients who underwent an OMB from 2002 to 2022 at the University of Florida were reviewed. Outcomes after an R-OMB (ie, history of a failed ENDO or P-OMB) and P-OMB were compared. The primary end point was 30-day mortality, whereas secondary outcomes included complications, reintervention, and survival. The Kaplan-Meier methodology was used to estimate freedom from reintervention and all-cause mortality, whereas multivariable Cox proportional hazards modeling identified predictors of death. RESULTS: A total of 145 OMB procedures (R-OMB, n = 48 [33%]; P-OMB, n = 97 [67%]) were analyzed. A majority of R-OMB operations were performed for a failed stent (prior ENDO, n = 39 [81%]; prior OMB, n = 9 [19%]). R-OMB patients were generally younger (66 ± 9 years vs P-OMB, 69 ± 11 years; P = .09) and had lower incidence of smoking exposure (29% vs P-OMB, 48%; P = .07); however, there were no other differences in demographics or comorbidities. R-OMB was associated with less intraoperative transfusion (0.6 units vs P-OMB, 1.4 units; P = .01), but there were no differences in conduit choice or bypass configuration.The overall 30-day mortality and complication rates were 7% (n = 10/145) and 53% (n = 77/145), respectively, with no difference between the groups. Notably, R-OMB had decreased cardiac (6% vs P-OMB, 21%; P < .01) and bleeding complication rates (2% vs P-OMB, 15%; P = .01). The freedom from reintervention (1 and 5 years: R-OMB: 95% ± 4%, 83% ± 9% vs P-OMB: 97% ± 2%, 93% ± 5%, respectively; log-rank P = .21) and survival (1 and 5 years: R-OMB: 82% ± 6%, 68% ± 9% vs P-OMB: 84% ± 4%, 66% ± 7%; P = .91) were similar. Independent predictors of all-cause mortality included new postoperative hemodialysis requirement (hazard ratio [HR], 7.4, 95% confidence interval [CI], 3.1-17.3; P < .001), pulmonary (HR, 2.7, 95% CI, 1.4-5.3; P = .004) and cardiac (HR, 2.4, 95% CI, 1.1-5.1; P = .04) complications, and female sex (HR, 2.1, 95% CI, 1.03-4.8; P = .04). Notably, R-OMB was not a predictor of death. CONCLUSIONS: The perioperative and longer-term outcomes for a remedial OMB after a failed intraluminal stent or previous open bypass appear to be comparable to a P-OMB. These findings support the recently updated clinical practice guideline recommendations for an endovascular-first approach to treating recurrent CMI due to the significant perioperative complication risk of OMB. However, among the subset of patients deemed ineligible for endoluminal reconstruction after failed mesenteric revascularization, R-OMB results appear to be acceptable and highlight the utility of this strategy in selected patients.

Most preoperative stress tests fail to comply with practice guideline indications and do not reduce cardiac events.

BACKGROUND: There is wide variation in stress test utilization before major vascular surgery and adherence to practice guidelines is unclear. We defined rates of stress test compliance at our institution and led a quality improvement initiative to improve compliance with American Heart Association (ACC/AHA) guidelines. METHODS: We implemented a stress testing order set in the electronic medical record at one tertiary hospital. We reviewed all patients who underwent elective, major vascular surgery in the 6 months before (Jan 1, 2022 - Jul 1, 2022) and 6 months after (Aug 1, 2022 - Jan 31, 2023) implementation. We studied stress test guideline compliance, changes in medical or surgical management, and major adverse cardiac events (MACE). RESULTS: Before order set implementation, 37/122 patients (30%) underwent stress testing within the past year (29 specifically ordered preoperatively) with 66% (19/29) guideline compliance. After order set implementation, 50/173 patients (29%) underwent stress testing within the past year (41 specifically ordered preoperatively) with 80% (33/41) guideline compliance. In the pre- and postimplementation cohorts, stress testing led to a cardiovascular medication change or preoperative coronary revascularization in 24% (7/29) and 27% (11/41) of patients, and a staged surgery or less invasive anesthetic strategy in 14% (4/29) and 4.9% (2/41) of patients, respectively. All unindicated stress tests were surgeon-ordered and none led to a change in management. There was no change in MACE after order set implementation. CONCLUSIONS: Electronic medical record-based guidance of perioperative stress testing led to a slight decrease in overall stress testing and an increase in guideline-compliant testing. Our study highlights a need for improved preoperative cardiovascular risk assessment prior to major vascular surgery, which may eliminate unnecessary testing and more effectively guide perioperative decision-making.

Perioperative Cerebrospinal Fluid Drain Placement Does Not Increase Venous Thromboembolism Risk After Thoracic and Fenestrated Endovascular Aortic Repair.

BACKGROUND: Venous thromboembolism (VTE) incidence after thoracic and fenestrated endovascular aortic repair (TEVAR/FEVAR) is high (up to 6-7%) relative to other vascular procedures; however, the etiology for this discrepancy remains unknown. Notably, patients undergoing TEVAR/FEVAR commonly receive cerebrospinal fluid drains (CSFDs) for neuroprotection, requiring interruption of perioperative anticoagulation and prolonged immobility. We hypothesized that CSFDs are a risk factor for VTE after TEVAR/FEVAR. METHODS: Consecutive TEVAR/FEVAR patients at a single center were reviewed (2011-2020). Cerebrospinal fluid drains (CSFDs) were placed based on surgeon preference preoperatively or for spinal cord ischemia (SCI) rescue therapy postoperatively. The primary end-point was VTE occurrence, defined as any new deep venous thrombosis (DVT) or pulmonary embolism (PE) confirmed on imaging within 30 days postoperatively. Routine postoperative VTE screening was not performed. Patients with and without VTE, and subjects with and without CSFDs were compared. Logistic regression was used to explore associations between VTE incidence and CSFD exposure. RESULTS: Eight hundred ninety-seven patients underwent TEVAR/FEVAR and 43% (n = 387) received a CSFD at some point during their care (preoperative: 94% [n = 365/387]; postoperative SCI rescue therapy: 6% [n = 22/387]). CSFD patients were more likely to have previous aortic surgery (44% vs. 37%; P = 0.028) and received more postoperative blood products (780 vs. 405 mL; P = 0.005). The overall VTE incidence was 2.2% (n = 20). 70% (14) patients with VTE had DVT, 50% (10) had PE, and 20% (4) had DVT and PE. Among TEVAR/FEVAR patients with VTE, 65% (n = 13) were symptomatic. Most VTEs (90%, n = 18) were identified inhospital and the median time to diagnosis was 12.5 (interquartile range 7.5-18) days postoperatively. Patients with VTE were more likely to have nonelective surgery (95% vs. 41%; P < 0.001), had higher American Society of Anesthesiologists classification (4.1 vs. 3.7; P < 0.001), required longer intensive care unit admission (24 vs. 12 days; P < 0.001), and received more blood products (1,386 vs. 559 mL; P < 0.001). Venous thromboembolism (VTE) incidence was 1.8% in CSFD patients compared to 3.5% in non-CSFD patients (odds ratio 0.70 [95% confidence interval 0.28-1.78, P = 0.300). However, patients receiving CSFDs postoperatively for SCI rescue therapy had significantly greater VTE incidence (9.1% vs. 1.1%; P = 0.044). CONCLUSIONS: CSFD placement was not associated with an increased risk of VTE in patients undergoing TEVAR/FEVAR. Venous thromboembolism (VTE) risk was greater in patients undergoing nonelective surgery and those with complicated perioperative courses. Venous thromboembolism (VTE) risk was greater in patients receiving therapeutic CSFDs compared to prophylactic CSFDs, highlighting the importance of careful patient selection for prophylactic CSFD placement.

N-acetylcysteine treatment attenuates hemodialysis access-related limb pathophysiology in mice with chronic kidney disease.

The objective of the present study was to determine if treatment with N-acetylcysteine (NAC) could reduce access-related limb dysfunction in mice. Male and female C57BL6J mice were fed an adenine-supplemented diet to induce chronic kidney disease (CKD) prior to the surgical creation of an arteriovenous fistula (AVF) in the iliac vascular bundle. AVF creation significantly increased peak aortic and infrarenal vena cava blood flow velocities, but NAC treatment had no significant impact, indicating that fistula maturation was not impacted by NAC treatment. Hindlimb muscle and paw perfusion recovery and muscle capillary density in the AVF limb were unaffected by NAC treatment. However, NAC treatment significantly increased the mass of the tibialis anterior (P = 0.0120) and soleus (P = 0.0452) muscles post-AVF. There was a significant main effect of NAC treatment on hindlimb grip strength at postoperative day 12 (POD 12) (P = 0.0003), driven by significantly higher grip strength in both male (P = 0.0273) and female (P = 0.0031) mice treated with NAC. There was also a significant main effect of NAC treatment on the walking speed at postoperative day 12 (P = 0.0447), and post hoc testing revealed an improvement in NAC-treated male mice (P = 0.0091). The area of postsynaptic acetylcholine receptors (P = 0.0263) and motor endplates (P = 0.0240) was also increased by NAC treatment. Interestingly, hindlimb skeletal muscle mitochondrial oxidative phosphorylation trended higher in NAC-treated female mice but was not statistically significant (P = 0.0973). Muscle glutathione levels and redox status were not significantly impacted by NAC treatment in either sex. In summary, NAC treatment attenuated some aspects of neuromotor pathology in mice with chronic kidney disease following AVF creation.NEW & NOTEWORTHY Hemodialysis via autogenous arteriovenous fistula (AVF) is the preferred first-line modality for renal replacement therapy in patients with end-stage kidney disease. However, patients undergoing AVF surgery frequently experience a spectrum of hand disability symptoms postsurgery including weakness and neuromotor dysfunction. Unfortunately, no treatment is currently available to prevent or mitigate these symptoms. Here, we provide evidence that daily N-acetylcysteine supplementation can attenuate some aspects of limb neuromotor function in a preclinical mouse model of AVF.

Increased Preoperative Stress Test Utilization is Not Associated With Reduced Adverse Cardiac Events in Current US Surgical Practice.

OBJECTIVE: To measure the frequency of preoperative stress testing and its association with perioperative cardiac events. BACKGROUND: There is persistent variation in preoperative stress testing across the United States. It remains unclear whether more testing is associated with reduced perioperative cardiac events. METHODS: We used the Vizient Clinical Data Base to study patients who underwent 1 of 8 elective major surgical procedures (general, vascular, or oncologic) from 2015 to 2019. We grouped centers into quintiles by frequency of stress test use. We computed a modified revised cardiac risk index (mRCRI) score for included patients. Outcomes included in-hospital major adverse cardiac events (MACEs), myocardial infarction (MI), and cost, which we compared across quintiles of stress test use. RESULTS: We identified 185,612 patients from 133 centers. The mean age was 61.7 (±14.2) years, 47.5% were female, and 79.4% were White. Stress testing was performed in 9.2% of patients undergoing surgery, and varied from 1.7% at lowest quintile centers, to 22.5% at highest quintile centers, despite similar mRCRI comorbidity scores (mRCRI>1: 15.0% vs 15.8%; P =0.068). In-hospital MACE was less frequent among lowest versus highest quintile centers (8.2% vs 9.4%; P <0.001) despite a 13-fold difference in stress test use. Event rates were similar for MI (0.5% vs 0.5%; P =0.737). Mean added cost for stress testing per 1000 patients who underwent surgery was $26,996 at lowest quintile centers versus $357,300 at highest quintile centers. CONCLUSIONS: There is substantial variation in preoperative stress testing across the United States despite similar patient risk profiles. Increased testing was not associated with reduced perioperative MACE or MI. These data suggest that more selective stress testing may be an opportunity for cost savings through a reduction of unnecessary tests.

Incidence, reintervention, and survival associated with type II endoleak at hospital discharge after elective endovascular aneurysm repair in the Vascular Quality Initiative.

BACKGROUND: The longitudinal clinical significance of type II endoleaks (T2ELs) remains controversial. Specifically, the real-world incidence, need for reintervention, and associated mortality referable to T2ELs remain unknown. Moreover, current professional society clinical practice guidelines recommend differing aneurysm sac growth thresholds to prompt intervention. Therefore, the purpose of this analysis was to better quantify the prevalence of early T2ELs after infrarenal endovascular aortic aneurysm repair (EVAR) and determine its association with reintervention and survival. METHODS: All elective EVARs from the Vascular Quality Initiative (2010-2020) were examined to identify patients with isolated T2ELs vs no endoleak (NONE) at discharge. Procedures with a type I or III endoleak were excluded. A subgroup analysis was performed on patients surviving beyond the first postoperative year with follow-up data available on endoleaks. The primary outcome was overall survival. Secondary outcomes included perioperative mortality and reinterventions. Outcomes were assessed by multivariable logistic and Cox proportional hazards regression to adjust for covariates. RESULTS: We identified 53,697 patients who underwent EVAR. The overall incidence of isolated T2ELs at discharge was 16%. In-hospital mortality was lower for those with isolated T2ELs vs NONE (0.8% vs 1.9%, odds ratio: 0.6, 95% confidence interval: 0.5-0.8, P < .0001). Unadjusted overall survival was marginally higher at 5 years for patients with T2ELs vs NONE (84% vs 82%); however, after risk adjustment, survival was similar (hazard ratio: 0.95, 95% confidence interval: 0.9-1.0). Among 44,345 patients with 1-year follow-up, 66% had data on endoleak status for assessment. Survival was similar regardless of endoleak status (NONE, at discharge only, at follow-up only, or at both time points). Among patients with documented T2ELs during follow-up, 6.1% and 2.5% had abdominal aortic aneurysm sac diameter growth ≥5 mm and ≥10 mm, respectively. Reinterventions occurred in 12%. Rupture (1%) and any open reintervention (4%) were rare among patients with 1-year follow-up. For patients with T2ELs, 5-year survival was similar between those with and without reintervention by 1 year (89% vs 91%, log-rank P = .06). CONCLUSIONS: T2ELs remain common after EVAR within the Vascular Quality Initiative and are not associated with long-term mortality. Reinterventions for T2ELs were not associated with improved overall survival among patients with T2ELs. Although additional data surrounding the appropriate role of reintervention for T2ELs remain necessary, it appears that the natural history of T2ELs is benign.

Assessing the quality of reporting of studies using Vascular Quality Initiative (VQI) data.

OBJECTIVE: The Society for Vascular Surgery Vascular Quality Initiative (VQI) has become an increasingly popular data source for retrospective observational vascular surgery studies. There are published guidelines on the reporting of data in such studies to promote transparency and rigor, but these have not been used to evaluate studies using VQI data. Our objective was to appraise the methodological reporting quality of studies using VQI data by evaluating their adherence to these guidelines. METHODS: The Society for Vascular Surgery VQI publication repository was queried for all articles published in 2020. The REporting of studies Conducted using Observational Routinely-collected Health Data (RECORD) statement and the Journal of American Medical Association-Surgical Section (JAMA-Surgery) checklist were utilized to assess the quality of each article's reporting. Five and three items from the RECORD statement and JAMA-Surgery checklist were excluded, respectively, because they were either inapplicable or nonassessable. Journal impact factor (IF) was queried for each article to elucidate any difference in reporting standards between high and low IF journals. RESULTS: Ninety studies were identified and analyzed. The median score on the RECORD checklist was 6 (of 8). The most commonly missed item was discussing data cleaning methods (93% missed). The median score on the JAMA-Surgery checklist was 3 (of 7). The most commonly missed items were the identification of competing risks (98% missed), the use of a flow chart to clearly define sample exclusion and inclusion criteria (84% missed), and the inclusion of a solid research question and hypothesis (81% missed). There were no differences in JAMA-Surgery checklist or RECORD statement median scores among studies published in low vs high IF journals. CONCLUSIONS: Studies using VQI data demonstrate a poor to moderate adherence to reporting standards. Key areas for improvement in research reporting include articulating a clear hypothesis, using flow charts to clearly define inclusion and exclusion criteria, identifying competing risks, and discussing data cleaning methods. Additionally, future efforts should center on creating tailored instruments to better guide reporting in studies using VQI data.

The Contemporary Impact of Body Mass Index on Open Aortic Aneurysm Repair.

INTRODUCTION: The Centers for Disease Control and Prevention (CDC) has deemed obesity a national epidemic and contributor to other leading causes of death including heart disease, stroke, and diabetes. Accordingly, the role of body mass index (BMI) and its impact on surgical outcomes has been a focus of persistent investigation. The purpose of this study was to quantify the effect of BMI on open abdominal aortic aneurysm repair (oAAA) outcomes in contemporary practice. METHODS: All elective oAAAs in the VQI (2010-2021) were identified. End-points included 30-day death, in-hospital complications and 1-year mortality. Patients were stratified into four BMI cohorts (BMI<18.5, 18.5≤BMI<25, 25≤BMI<30, BMI≥30). Spline interpolation was used to explore a potential non-linear association between BMI and perioperative mortality. Mixed-effects Cox regression was used to assess the association between BMI and 1-year survival. RESULTS: 9,479 patients underwent oAAA over the study interval (median age-70, 74%-male, BMI 27±6). Lower BMI patients(<18.5) compared to higher BMI(>30) patients were more likely to be women (53% vs. 32%;p<.0001), current smokers(65% vs. 50%;p<.0001), and have COPD(58% vs. 37%;p<.0001). In contrast, an increased BMI was associated with a greater prevalence of diabetes and CAD (DM-26% vs. 6%;p<.0001; CAD-27% vs. 20%;p=.01). There was no difference in cross-clamp position or visceral/renal bypass between groups, though low BMI patients necessitated more frequent infrainguinal bypass(5% vs. 2%;p=.0002). 30-day mortality and in-hospital complications were greater among low BMI patients(30-day mortality:12% vs. 4%;p<.0001;complications-47% vs. 37%;p<.0001). Interestingly, low BMI conferred a nearly 2-fold increase in observed pulmonary complications(18% vs. 11%;p<.0001). Surgical site infections were twice as common among the lowest and highest BMI groups(4% vs. 2%;p<.0001). 1-year mortality was greatest among low BMI patients(23% vs. 9%;p<.0001). Adjusted spline-fit analysis demonstrated increased mortality among patients with BMI<21 or >34(BMI<18.5-HR 2.1, 95%CI 1.6-2.8;p<.0001; BMI>34-HR 1.3, 95%CI 1.1-1.6;p=.009). CONCLUSION: Both low (<18.5) and high (>34) BMI were associated with increased oAAA mortality in current practice. Despite the perception that obesity confers substantial surgical risk during oAAA, diminished BMI was associated with a 3-fold increase in 30-day and 1-year mortality. It appears that BMI extremes are distinct proxies for differential clinical phenotypes and should inform risk stratification for oAAA repair.

Clinical presentation, outcomes, and threshold for repair by sex in degenerative saccular vs fusiform aneurysms in the descending thoracic aorta.

OBJECTIVE: Saccular-shaped thoracic aortic aneurysms (TAAs) are often treated at smaller diameters compared with fusiform TAAs, despite a lack of strong clinical evidence to support this practice. The aim of this study was to examine differences in presentation, treatment, and outcomes between saccular TAAs and fusiform TAAs in the descending thoracic aorta. We also examined the need for sex-specific treatment thresholds for TAAs. METHODS: All Vascular Quality Initiative (VQI) patients undergoing thoracic endovascular aneurysm repair (TEVAR) for degenerative TAAs in the descending thoracic aorta from 2012 through 2022 were reviewed. Patients were stratified by urgency: emergent/urgent vs elective repairs (ruptured/symptomatic). Demographics, comorbidities, anatomical/procedural characteristics, and outcomes for fusiform TAAs and saccular TAAs were compared. Cumulative distribution curves were used to plot the proportion of patients who underwent emergent/urgent repair according to sex-stratified aortic diameter. RESULTS: Among 655 emergent/urgent TEVARs, 37% were performed for saccular TAAs, whereas among 1352 elective TEVARs, 35% had saccular TAA morphology. Compared with fusiform TAAs, saccular TAAs more frequently underwent emergent/urgent (ruptured/symptomatic) TEVAR below the repair threshold in both females (<50 mm: 38% vs 10%; relative risk, 3.39; 95% confidence interval [CI], 2.04-5.70; P < .001), and males (<55 mm: 47% vs 21%; relative risk, 2.26; 95% CI, 1.60-3.18; P < .001). Moreover, among patients with emergent/urgent fusiform TAAs, females presented at smaller diameters compared with males, whereas there was no difference in preoperative aneurysm diameter among patients with saccular TAAs. Regarding outcomes, emergent/urgent treated saccular TAAs had similar postoperative outcomes and 5-year mortality compared with fusiform TAAs. Nevertheless, in the elective cohort, patients with saccular TAAs had similar postoperative mortality compared with those with fusiform TAAs, but a lower rate of postoperative spinal cord ischemia (0.7% vs 3.2%; P = .010). Furthermore, patients with saccular TAAs had a higher rate of 5-year mortality compared with their fusiform counterparts (23% vs 17%; hazard ratio, 1.53; 95% CI, 1.12-2.10; P = .010). CONCLUSIONS: Patients with saccular TAAs underwent emergent/urgent TEVAR at smaller diameters than those with fusiform TAAs, supporting current clinical practice guideline recommendations that saccular TAAs warrant treatment at smaller diameters. Furthermore, these data support a sex-specific treatment threshold for patients with fusiform TAAs, but not for those with saccular TAAs. Although there were no differences in outcomes following TEVAR between morphologies in the emergent/urgent cohort, patients with saccular TAAs who were treated electively were associated with higher 5-year mortality compared with those with fusiform TAAs.

Thoracic endovascular aortic repair of metachronous thoracic aortic aneurysms following prior infrarenal abdominal aortic aneurysm repair.

OBJECTIVE: Thoracic endovascular aortic repair (TEVAR) of metachronous thoracic aortic aneurysms (M-TAAs) following previous infrarenal abdominal aortic aneurysm (AAA) repair has been associated with higher spinal cord ischemia (SCI) risk compared with TEVAR of primary thoracic aortic aneurysms (TAAs). However, data on the impact of the type of prior infrarenal aortic repair on outcomes are scarce. In this study, we examined perioperative outcomes and long-term mortality following TEVAR M-TAA compared with primary TEVAR of TAA. METHODS: We identified all Vascular Quality Initiative (VQI) patients who underwent TEVAR of TAA in the descending thoracic aorta from 2013 to 2022. Only patients undergoing primary TEVAR or TEVAR following infrarenal open (OAR) or endovascular (EVAR) repair were included. We performed univariate analyses to identify differences in baseline and procedural characteristics, and multivariable analyses for perioperative outcomes and 5-year mortality using logistic and Cox regression, respectively. RESULTS: We included 1493 patients who underwent primary TEVAR (81%) or TEVAR following prior OAR (9.0%) or prior EVAR (9.7%). Compared with primary TEVAR, patients undergoing TEVAR M-TAA were older, more commonly male, white, and had higher rates of hypertension, smoking, and renal dysfunction. Patients with M-TAA were more likely to be asymptomatic and have larger diameters at presentation but were exposed to greater contrast volume and procedural times relative to primary TEVAR patients. Following risk-adjustment, compared with primary TEVAR, TEVAR after prior EVAR was associated with higher perioperative mortality (9.7% vs 3.9%; odds ratio [OR], 5.3; 95% confidence interval [CI], 2.3-12; P < .001) and 5-year mortality (40% vs 24%; hazard ratio [HR], 2.1; 95% CI, 1.4-3.1; P = .001). Specifically, among octogenarians (n = 375; 25%), the perioperative and 5-year mortality differences were even more pronounced (perioperative mortality: 17% vs 8.4%; OR, 6.7; 95% CI, 2.2-21; P = .001; 5-year mortality: 50% vs 27%; HR, 3.0; 95% CI, 1.5-5.7; P = .010). However, in-hospital complications, including SCI (2.6% vs 2.8%; OR, 1.2; 95% CI, 0.33-3.3; P = .77), were not notably different. In contrast, TEVAR after previous OAR was associated with comparable perioperative mortality (4.4% vs 3.9%; OR, 1.2; 95% CI, 0.32-3.8; P = .73), 5-year mortality (28% vs 24%; HR, 1.3; 95% CI, 0.80-2.1; P = .54), and in-hospital complications, including SCI (2.6% vs 0.7%; OR, 0.21; 95% CI, 0.01-1.1; P = .16). CONCLUSIONS: Patients undergoing TEVAR of M-TAAs after prior EVAR, particularly octogenarians, have higher perioperative and 5-year mortality and therefore, represent a high-risk group. Future efforts should strive to discern the underlying factors leading to these poorer outcomes; meanwhile, these findings emphasize the need for careful patient selection and appropriate preoperative counseling in these high-risk individuals.

National Institutes of Health funding among vascular surgeons is rare.

BACKGROUND: The National Institutes of Health (NIH) is an essential source of funding for vascular surgeons conducting research. NIH funding is frequently used to benchmark institutional and individual research productivity, help determine eligibility for academic promotion, and as a measure of scientific quality. We sought to appraise the current scope of NIH funding to vascular surgeons by appraising the characteristics of NIH-funded investigators and projects. In addition, we also sought to determine whether funded grants addressed recent Society for Vascular Surgery (SVS) research priorities. METHODS: In April 2022, we queried the NIH Research Portfolio Online Reporting Tools Expenditures and Results (RePORTER) database for active projects. We only included projects that had a vascular surgeon as a principal investigator. Grant characteristics were extracted from the NIH Research Portfolio Online Reporting Tools Expenditures and Results database. Principal investigator demographics and academic background information were identified by searching institution profiles. RESULTS: There were 55 active NIH awards given to 41 vascular surgeons. Only 1% (41/4037) of all vascular surgeons in the United States receive NIH funding. Funded vascular surgeons are an average of 16.3 years out of training; 37% (n = 15) are women. The majority of awards (58%; n = 32) were R01 grants. Among the active NIH-funded projects, 75% (n = 41) are basic or translational research projects, and 25% (n = 14) are clinical or health services research projects. Abdominal aortic aneurysm and peripheral arterial disease are the most commonly funded disease areas and together accounted for 54% (n = 30) of projects. Three SVS research priorities are not addressed by any of the current NIH-funded projects. CONCLUSIONS: NIH funding of vascular surgeons is rare and predominantly consists of basic or translational science projects focused on abdominal aortic aneurysm and peripheral arterial disease research. Women are well-represented among funded vascular surgeons. Although the majority of SVS research priorities receive NIH funding, three SVS research priorities are yet to be addressed by NIH-funded projects. Future efforts should focus on increasing the number of vascular surgeons receiving NIH grants and ensuring all SVS research priorities receive NIH funding.

Market competition influences practice patterns in management of patients with intermittent claudication in the vascular quality initiative.

OBJECTIVE: The Society for Vascular Surgery (SVS) clinical practice guidelines recommend best medical therapy (BMT) as first-line therapy before offering revascularization to patients with intermittent claudication (IC). Notably, atherectomy and tibial-level interventions are generally discouraged for management of IC; however, high regional market competition may incentivize physicians to treat patients outside the scope of guideline-directed therapy. Therefore, we sought to determine the association between regional market competition and endovascular treatment of patients with IC. METHODS: We examined patients with IC undergoing index endovascular peripheral vascular interventions (PVI) in the SVS Vascular Quality Initiative from 2010 to 2022. We assigned the Herfindahl-Hirschman Index as a measure of regional market competition and stratified centers into very high competition (VHC), high competition, moderate competition, and low competition cohorts. We defined BMT as preoperative documentation of being on antiplatelet medication, statin, nonsmoking status, and a recorded ankle-brachial index. We used logistic regression to evaluate the association of market competition with patient and procedural characteristics. A sensitivity analysis was performed in patients with isolated femoropopliteal disease matched by the TransAtlantic InterSociety classification of disease severity. RESULTS: There were 24,669 PVIs that met the inclusion criteria. Patients with IC undergoing PVI were more likely to be on BMT when treated in higher market competition centers (odds ratio [OR], 1.07 per increase in competition quartile; 95% confidence interval [CI], 1.04-1.11; P < .0001). The probability of undergoing aortoiliac interventions decreased with increasing competition (OR, 0.84; 95% CI, 0.81-0.87; P < .0001), but there were higher odds of receiving tibial (OR, 1.40; 95% CI, 1.30-1.50; P < .0001) and multilevel interventions in VHC vs low competition centers (femoral + tibial OR, 1.10; 95% CI, 1.03-1.14; P = .001). Stenting decreased as competition increased (OR, 0.89; 95% CI, 0.87-0.92; P < .0001), whereas exposure to atherectomy increased with higher market competition (OR, 1.15; 95% CI, 1.11-1.19; P < .0001). When assessing patients undergoing single-artery femoropopliteal intervention for TransAtlantic InterSociety A or B lesions to account for disease severity, the odds of undergoing either balloon angioplasty (OR, 0.72; 95% CI, 0.625-0.840; P < .0001) or stenting only (OR, 0.84; 95% CI, 0.727-0.966; P < .0001) were lower in VHC centers. Similarly, the likelihood of receiving atherectomy remained significantly higher in VHC centers (OR, 1.6; 95% CI, 1.36-1.84; P < .0001). CONCLUSIONS: High market competition was associated with more procedures among patients with claudication that are not consistent with guideline-directed therapy per the SVS clinical practice guidelines, including atherectomy and tibial-level interventions. This analysis demonstrates the susceptibility of care delivery to regional market competition and signifies a novel and undefined driver of PVI variation among patients with claudication.

Contemporary outcomes after treatment of aberrant subclavian artery and Kommerell's diverticulum.

OBJECTIVE: Aberrant subclavian artery (ASA) and Kommerell's diverticulum (KD) are rare vascular anomalies that may be associated with lifestyle-limiting and life-threatening complications. The aim of this study is to report contemporary outcomes after invasive treatment of ASA/KD using a large international dataset. METHODS: Patients who underwent treatment for ASA/KD (2000-2020) were identified through the Vascular Low Frequency Disease Consortium, a multi-institutional collaboration to investigate uncommon vascular disorders. We report the early and mid-term clinical outcomes including stroke and mortality, technical success, and other operative outcomes including reintervention rates, patency, and endoleak. RESULTS: Overall, 285 patients were identified during the study period. The mean patient age was 57 years; 47% were female and 68% presented with symptoms. A right-sided arch was present in 23%. The mean KD diameter was 47.4 mm (range, 13.0-108.0 mm). The most common indication for treatment was symptoms (59%), followed by aneurysm size (38%). The most common symptom reported was dysphagia (44%). A ruptured KD was treated in 4.2% of cases, with a mean diameter of 43.9 mm (range, 18.0-100.0 mm). An open procedure was performed in 101 cases (36%); the most common approach was ASA ligation with subclavian transposition. An endovascular or hybrid approach was performed in 184 patients (64%); the most common approach was thoracic endograft and carotid-subclavian bypass. A staged operative strategy was employed more often than single setting repair (55% vs 45%). Compared with endovascular or hybrid approach, those in the open procedure group were more likely to be younger (49 years vs 61 years; P < .0001), female (64% vs 36%; P < .0001), and symptomatic (85% vs 59%; P < .0001). Complete or partial symptomatic relief at 1 year after intervention was 82.6%. There was no association between modality of treatment and symptom relief (open 87.2% vs endovascular or hybrid approach 78.9%; P = .13). After the intervention, 11 subclavian occlusions (4.5%) occurred; 3 were successfully thrombectomized resulting in a primary and secondary patency of 95% and 96%, respectively, at a median follow-up of 39 months. Among the 33 reinterventions (12%), the majority were performed for endoleak (36%), and more reinterventions occurred in the endovascular or hybrid approach than open procedure group (15% vs 6%; P = .02). The overall survival rate was 87.3% at a median follow-up of 41 months. The 30-day stroke and death rates were 4.2% and 4.9%, respectively. Urgent or emergent presentation was independently associated with increased risk of 30-day mortality (odds ratio [OR], 19.8; 95% confidence interval [CI], 3.3-116.6), overall mortality (OR, 3.6; 95% CI, 1.2-11.2) and intraoperative complications (OR, 8.3; 95% CI, 2.8-25.1). Females had a higher risk of reintervention (OR, 2.6; 95% CI, 1.0-6.5). At an aneurysm size of 44.4 mm, receiver operator characteristic curve analysis suggested that 60% of patients would have symptoms. CONCLUSIONS: Treatment of ASA/KD can be performed safely with low rates of mortality, stroke and reintervention and high rates of symptomatic relief, regardless of the repair strategy. Symptomatic and urgent operations were associated with worse outcomes in general, and female gender was associated with a higher likelihood of reintervention. Given the worse overall outcomes when symptomatic and the inherent risk of rupture, consideration of repair at 40 mm is reasonable in most patients. ASA/KD can be repaired in asymptomatic patients with excellent outcomes and young healthy patients may be considered better candidates for open approaches versus endovascular or hybrid modalities, given the lower likelihood of reintervention and lower early mortality rate.