2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The "2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease" provides recommendations to guide clinicians in the treatment of patients with lower extremity peripheral artery disease across its multiple clinical presentation subsets (ie, asymptomatic, chronic symptomatic, chronic limb-threatening ischemia, and acute limb ischemia). METHODS: A comprehensive literature search was conducted from October 2020 to June 2022, encompassing studies, reviews, and other evidence conducted on human subjects that was published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through May 2023 during the peer review process, were also considered by the writing committee and added to the evidence tables where appropriate. STRUCTURE: Recommendations from the "2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease" have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with peripheral artery disease have been developed.

Cocoa flavanols, Nrf2 activation, and oxidative stress in peripheral artery disease: mechanistic findings in muscle based on outcomes from a randomized trial.

The pathophysiology of muscle damage in peripheral artery disease (PAD) includes increased oxidant production and impaired antioxidant defenses. Epicatechin (EPI), a naturally occurring flavanol, has antioxidant properties that may mediate the beneficial effects of natural products such as cocoa. In a phase II randomized trial, a cocoa-flavanol-rich beverage significantly improved walking performance compared with a placebo in people with PAD. In the present work, the molecular mechanisms underlying the therapeutic effect of cocoa flavanols were investigated by analyzing baseline and follow-up muscle biopsies from participants. Increases in nuclear factor erythroid 2-related factor 2 (Nrf2) target antioxidants heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase [quinone] 1 (NQO1) in the cocoa group were significantly associated with reduced accumulation of central nuclei, a myopathy indicator, in type II muscle fibers (P = 0.017 and P = 0.023, respectively). Protein levels of the mitochondrial respiratory complex III subunit, cytochrome b-c1 complex subunit 2 (UQCRC2), were significantly higher in the cocoa group than in the placebo group (P = 0.032), and increases in UQCRC2 were significantly associated with increased levels of Nrf2 target antioxidants HO-1 and NQO1 (P = 0.001 and P = 0.035, respectively). Exposure of non-PAD human myotubes to ex vivo serum from patients with PAD reduced Nrf2 phosphorylation, an indicator of activation, increased hydrogen peroxide production and oxidative stress, and reduced mitochondrial respiration. Treatment of myotubes with EPI in the presence of serum from patients with PAD increased Nrf2 phosphorylation and protected against PAD serum-induced oxidative stress and mitochondrial dysfunction. Overall, these findings suggest that cocoa flavanols may enhance antioxidant capacity in PAD via Nrf2 activation.NEW & NOTEWORTHY The current study supports the hypothesis that in people with PAD, cocoa flavanols activate Nrf2, thereby increasing antioxidant protein levels, protecting against skeletal muscle damage, and increasing mitochondrial protein abundance. These results suggest that Nrf2 activation may be an important therapeutic target for improving walking performance in people with PAD.

Trimethylamine N-oxide: a meta-organismal axis linking the gut and fibrosis.

BACKGROUND: Tissue fibrosis is a common pathway to failure in many organ systems and is the cellular and molecular driver of myriad chronic diseases that are incompletely understood and lack effective treatment. Recent studies suggest that gut microbe-dependent metabolites might be involved in the initiation and progression of fibrosis in multiple organ systems. MAIN BODY OF THE MANUSCRIPT: In a meta-organismal pathway that begins in the gut, gut microbiota convert dietary precursors such as choline, phosphatidylcholine, and L-carnitine into trimethylamine (TMA), which is absorbed and subsequently converted to trimethylamine N-oxide (TMAO) via the host enzyme flavin-containing monooxygenase 3 (FMO3) in the liver. Chronic exposure to elevated TMAO appears to be associated with vascular injury and enhanced fibrosis propensity in diverse conditions, including chronic kidney disease, heart failure, metabolic dysfunction-associated steatotic liver disease, and systemic sclerosis. CONCLUSION: Despite the high prevalence of fibrosis, little is known to date about the role of gut dysbiosis and of microbe-dependent metabolites in its pathogenesis. This review summarizes recent important advances in the understanding of the complex metabolism and functional role of TMAO in pathologic fibrosis and highlights unanswered questions.

An Analysis of Water Used and Wasted at Operating Room (OR) Scrub Sinks and Call to Action for Reducing Water Waste.

OBJECTIVE: To model the volume of water used and wasted during wet scrubs at operating room (OR) scrub sinks and identify factors for reducing water waste. BACKGROUND: Wasteful consumption of water by US healthcare systems has not been well characterized. METHODS: This is a two-component observational study. The first was an observational study of handwashing practices and water usage at scrub sinks in the OR at a single medical center. The second component was a series of two anonymous surveys of surgeons and OR staff to assess hand scrub practices and perspectives. Data from both components were used to estimate the volume of water used and wasted annually at OR scrub sinks. RESULTS: The median total volume of water wasted at OR scrub sinks for 34,554 cases over one year is 337,595.6 L (interquartile range 139,010.0;911,210.5). This represents approximately 34.2% of the total volume of water usage associated with wet scrubs (i.e.,water used during scrubbing and wasted after the conclusion of the scrub). Other pertinent findings are that attending surgeons and OR staff perform water scrubs in 25.9% of cases; there are significant differences in scrub type preferences among OR users; the median volume of water wasted in a single wet scrub at timer-controlled sinks is 10 L; and significantly more water is wasted at timer-controlled sinks than knee-operated sinks. CONCLUSIONS: OR wet scrubs are a source of enormous water waste. We identified scrub sink characteristics and OR user beliefs and behaviors as modifiable factors for water waste reduction. We encourage all institutions and OR users to carefully examine their facility characteristics and practices to implement plans that will conserve water without compromising patient safety.

Discordance of patient-reported outcome measures with objectively assessed walking decline in peripheral artery disease.

OBJECTIVE: Among people with peripheral artery disease (PAD), perceived change in walking difficulty over time, compared with people without PAD, is unclear. Among people reporting no change in walking difficulty over time, differences in objectively measured change in walking performance between people with and without PAD are unknown. METHODS: A total of 1289 participants were included. Eight hundred seventy-four participants with PAD (aged 71.1 ± 9.1 years) were identified from noninvasive vascular laboratories and 415 without PAD (aged 69.9 ± 7.6 years) were identified from people with normal vascular laboratory testing or general medical practices in Chicago. The Walking Impairment Questionnaire and 6-minute walk were completed at baseline and 1-year follow-up. The Walking Impairment Questionnaire assessed perceived difficulty walking due to symptoms in the calves or buttocks on a Likert scale (range, 0-4). Symptom change was determined by comparing difficulty reported at 1-year follow-up to difficulty reported at baseline. RESULTS: At 1-year follow-up, 31.9% of participants with and 20.6% of participants without PAD reported walking difficulty that was improved (P < .01), whereas 41.2% vs 55%, respectively, reported walking difficulty that was unchanged (P < .01). Among all reporting no change in walking difficulty, participants with PAD declined in 6-minute walk, whereas participants without PAD improved (-10 vs +15 meters; mean difference, -25; 95% confidence interval, -38 to -13; P < .01). CONCLUSIONS: Most people with PAD reported improvement or no change in walking difficulty from calf or buttock symptoms at one-year follow-up. Among all participants who perceived stable walking ability, those with PAD had significant greater declines in objectively measured walking performance, compared with people without PAD.

The ankle-brachial index, gastrocnemius mitochondrial respirometry, and walking performance in people with and without peripheral artery disease.

Background: Mitochondrial abnormalities exist in lower-extremity peripheral artery disease (PAD), yet the association of the ankle-brachial index (ABI) with mitochondrial respiration in gastrocnemius muscle is unknown. The association of gastrocnemius mitochondrial respiration with 6-minute walk distance in PAD is unknown. Objective: To describe associations of the ABI with mitochondrial respiratory function in gastrocnemius muscle biopsies and associations of gastrocnemius mitochondrial respirometry with 6-minute walk distance in people with and without PAD. Methods: People with (ABI ⩽ 0.90) and without (ABI 1.00-1.40) PAD were enrolled. ABI and 6-minute walk distance were measured. Mitochondrial function of permeabilized myofibers from gastrocnemius biopsies was measured with high-resolution respirometry. Results: A total of 30 people with PAD (71.7 years, mean ABI: 0.64) and 68 without PAD (71.8 years, ABI: 1.17) participated. In non-PAD participants, higher ABI values were associated significantly with better mitochondrial respiration (Pearson correlation for maximal oxidative phosphorylation PCI+II: +0.29, p = 0.016). In PAD, the ABI correlated negatively and not significantly with mitochondrial respiration (Pearson correlation for PCI+II: -0.17, p = 0.38). In people without PAD, better mitochondrial respiration was associated with better 6-minute walk distance (Pearson correlation: +0.51, p < 0.001), but this association was not present in PAD (Pearson correlation: +0.10, p = 0.59). Conclusions: Major differences exist between people with and without PAD in the association of gastrocnemius mitochondrial respiration with ABI and 6-minute walk distance. Among people without PAD, ABI and walking performance were positively associated with mitochondrial respiratory function. These associations were not observed in PAD.

Prosthetic vascular grafts engineered to combat calcification: Progress and future directions.

Calcification in prosthetic vascular conduits is a major challenge in cardiac and vascular surgery that compromises the long-term performance of these devices. Significant research efforts have been made to understand the etiology of calcification in the cardiovascular system and to combat calcification in various cardiovascular devices. Novel biomaterial design and tissue engineering strategies have shown promise in preventing or delaying calcification in prosthetic vascular grafts. In this review, we highlight recent advancements in the development of acellular prosthetic vascular grafts with preclinical success in attenuating calcification through advanced biomaterial design. We also discuss the mechanisms of action involved in the designs that will contribute to the further understanding of cardiovascular calcification. Lastly, recent insights into the etiology of vascular calcification will guide the design of future prosthetic vascular grafts with greater potential for translational success.

Identifying gaps in disease knowledge among patients with peripheral artery disease.

OBJECTIVE: An individual's understanding of disease risk factors and outcomes is important for the ability to make healthy lifestyle choices and decisions about disease treatment. Peripheral artery disease (PAD) is a condition with increasing global prevalence and high risk of adverse patient outcomes. This study seeks to understand the adequacy of disease understanding in patients with PAD. METHODS: This was an observational study of patients with PAD recruited from vascular surgery outpatient clinic and PAD clinical studies at a single academic medical center over an 8-month period. A 44-item paper survey assessed demographic and socioeconomic information, knowledge of personal medical history, PAD risk factors, consequences of PAD, and health education preferences. Patients with documented presence of PAD were offered the survey. Patients unable to complete the survey or provide informed consent were not considered eligible. Disease "awareness" was defined as correct acknowledgement of the presence or absence of a disease, including PAD, in the personal medical history. "PAD knowledge score" was the percentage of correct responses to questions on general PAD risk factors and consequences. Of 126 eligible patients, 109 participated. Bivariate analysis was used to study factors associated with awareness of PAD diagnosis. Factors associated with the PAD knowledge score were studied using the Pearson correlation coefficient, two-sample t test, or one-way analysis of variance. P value < .05 was considered statistically significant. RESULTS: The mean participant age was 69.4 ± 11.0 years, and 39.4% (n = 43) were female. Most participants (78.9%; n = 86) had critical limb-threatening ischemia. Only 65.4% (n = 70) of participants were aware of a diagnosis of PAD, which was less than their awareness of related comorbidities. Factors positively associated with PAD diagnosis awareness were female sex (81.4% vs 54.7%; P = .004) and history of percutaneous leg revascularization (78.6% vs 47.9%; P = .001). Among 17 patients who had undergone major leg amputation, 35% (n = 6) were unaware of a diagnosis of PAD. PAD knowledge scores correlated positively with an awareness of PAD diagnosis (59.1% vs 48.7%; P = .02) and negatively with a history of hypertension (53.4% vs 68.1%; P = .001). Most participants (86.5%; n = 90) expressed a desire to be further educated on PAD. The most popular education topics were dietary recommendations, causes, and treatment for PAD. CONCLUSIONS: Patients with PAD have deficits in their awareness of this diagnosis and general knowledge about PAD. Future research priorities should further define these deficits and their causes in order to inform new strategies that foster information-seeking behavior and effective educational programs for PAD.

Limb ischemia and bleeding in patients requiring venoarterial extracorporeal membrane oxygenation.

OBJECTIVE: Acute limb ischemia (ALI) and cannulation site bleeding are frequent complications of venoarterial (VA) extracorporeal membrane oxygenation (ECMO) and are associated with worse outcomes. The goals of this study were to assess our rates of ECMO-related ALI and bleeding and to evaluate the efficacy of strategies to prevent them, such as distal perfusion cannula (DPC) and ultrasound-guided cannulation. METHODS: This is a single-center retrospective cohort study of adult patients placed on peripheral VA-ECMO at a tertiary medical center between 2014 and 2018. ALI was defined as new ischemia of the extremity ipsilateral to arterial cannulation. Significant cannulation site bleeding was defined as excessive bleeding requiring intervention (eg, transfusion or reoperation). Univariate analyses were used to identify factors associated with ALI, bleeding, and in-hospital mortality. RESULTS: During the study period, 105 patients were placed on peripheral VA-ECMO (61.3% female; mean age, 54.9 ± 14.8 years). Nearly half (46.6%) had ECMO implantation in an extracorporeal cardiopulmonary resuscitation setting and 37 (44.0%) had a DPC. Average duration of support was 5.6 ± 5.0 days. Overall in-hospital mortality and death on ECMO support were 65.1% and 50%, respectively. ALI occurred in 21 (20%) and cannulation-related bleeding occurred in 24 (22.9%) patients who were treated with a total of 27 procedures, including thromboembolectomy (22.2%), vascular repair (18.5%), and fasciotomy (25.9%). On univariate analysis, cannulation in the operating room (odds ratio [OR], 0.25; 95% confidence interval [CI], 0.08-0.77; P = .02) was associated with decreased risk of ALI, whereas cannulation in the operating room (OR, 2.65; 95% CI, 1.09-6.45; P = .03) and cutdown approach (OR, 4.96; 95% CI, 2.32-10.61; P < .0001) were associated with increased risk of bleeding. Ultrasound-guided placement was associated with decreased risk of bleeding (OR, 0.81; 95% CI, 0.04-0.84; P = .03). DPC was not associated with either ALI (P = .47) or bleeding (P = .06). ALI (OR, 2.68; 95% CI 1.03-6.98; P = .04), age (OR, 1.94; 95% CI, 1.03-3.69; P = .04), and worse baseline heart failure (OR, 2.01; 95% CI, 1.02-3.97; P = .04) were associated with greater risk of in-hospital mortality. Ultrasound-guided cannulation (OR, 0.41; 95% CI, 0.20-0.87; P = .02) was associated with decreased risk of in-hospital mortality. CONCLUSIONS: ALI and significant bleeding are common occurrences after peripheral VA-ECMO cannulation. Whereas DPC placement did not significantly decrease risk of ALI, ultrasound-guided cannulation decreased the risk of bleeding. Cannulation in the operating room is associated with decreased risk of ALI at the expense of increased risk of bleeding. ALI, older age (≥65 years), and worse heart failure increased risk of in-hospital mortality.

Targeted Inhibition of Gut Microbial Trimethylamine N-Oxide Production Reduces Renal Tubulointerstitial Fibrosis and Functional Impairment in a Murine Model of Chronic Kidney Disease.

OBJECTIVE: Gut microbial metabolism of dietary choline, a nutrient abundant in a Western diet, produces trimethylamine (TMA) and the atherothrombosis- and fibrosis-promoting metabolite TMA-N-oxide (TMAO). Recent clinical and animal studies reveal that elevated TMAO levels are associated with heightened risks for both cardiovascular disease and incident chronic kidney disease development. Despite this, studies focusing on therapeutically targeting gut microbiota-dependent TMAO production and its impact on preserving renal function are limited. Approach and Results: Herein we examined the impact of pharmacological inhibition of choline diet-induced gut microbiota-dependent production of TMA, and consequently TMAO, on renal tubulointerstitial fibrosis and functional impairment in a model of chronic kidney disease. Initial studies with a gut microbial choline TMA-lyase mechanism-based inhibitor, iodomethylcholine, confirmed both marked suppression of TMA generation, and consequently TMAO levels, and selective targeting of the gut microbial compartment (ie, both accumulation of the drug in intestinal microbes and limited systemic exposure in the host). Dietary supplementation of either choline or TMAO significantly augmented multiple indices of renal functional impairment and fibrosis associated with chronic subcutaneous infusion of isoproterenol. However, the presence of the gut microbiota-targeting inhibitor iodomethylcholine blocked choline diet-induced elevation in TMAO, and both significantly improved decline in renal function, and significantly attenuated multiple indices of tubulointerstitial fibrosis. Iodomethylcholine treatment also reversed many choline diet-induced changes in cecal microbial community composition associated with TMAO and renal functional impairment. CONCLUSIONS: Selective targeting of gut microbiota-dependent TMAO generation may prevent adverse renal structural and functional alterations in subjects at risk for chronic kidney disease.

Ankle-brachial index to monitor limb perfusion in patients with femoral venoarterial extracorporeal membrane oxygenation.

BACKGROUND: Limb ischemia is a major complication of femoral venoarterial extracorporeal membrane oxygenation (VA-ECMO). Use of ankle-brachial index (ABI) to monitor limb perfusion in VA-ECMO has not been described. We report our experience monitoring femoral VA-ECMO patients with serial ABI and the relationships between ABI and near infrared spectroscopy (NIRS). METHODS: This is a retrospective single-center review of consecutive adult patients placed on femoral VA-ECMO between January 2019 and October 2019. Data were collected on patients with paired ABI and NIRS values. Relationships between NIRS and ABI of the cannulated (E-NIRS and E-ABI) and non-cannulated legs (N-NIRS and N-ABI) along with the difference between legs (d-NIRS and d-ABI) were determined using Pearson correlation. RESULTS: Overall, 22 patients (mean age 56.5 ± 14.0 years, 72.7% male) were assessed with 295 E-ABI and E-NIRS measurements, and 273 N-ABI and N-NIRS measurements. Mean duration of ECMO support was 129.8 ± 78.3 h. ECMO-mortality was 13.6% and in-hospital mortality was 45.5%. N-ABI and N-NIRS were significantly higher than their ECMO counterparts (ABI mean difference 0.16, 95% confidence interval [CI]: 0.13-0.19, p < .0001; NIRS mean difference 2.51, 95% CI: 1.48-3.54, p < .0001). There was no correlation between E-ABI versus E-NIRS (r = .032, p = .59), N-ABI versus N-NIRS (r = .097, p = .11), or d-NIRS versus d-ABI (r = .11, p = .069). CONCLUSION: ABI is a quantitative metric that may be used to monitor limb perfusion and supplement clinical exams to identify limb ischemia in femorally cannulated VA-ECMO patients. More studies are needed to characterize the significance of ABI in femoral VA-ECMO and its value in identifying limb ischemia in this patient population.

Microbiota composition modulates inflammation and neointimal hyperplasia after arterial angioplasty.

BACKGROUND: Neointimal hyperplasia is a major contributor to restenosis after arterial interventions, but the genetic and environmental mechanisms underlying the variable propensity for neointimal hyperplasia between individuals, including the role of commensal microbiota, are not well understood. We sought to characterize how shifting the microbiome using cage sharing and bedding mixing between rats with differing restenosis phenotypes after carotid artery balloon angioplasty could alter arterial remodeling. METHODS: We co-housed and mixed bedding between genetically distinct rats (Lewis [LE] and Sprague-Dawley [SD]) that harbor different commensal microbes and that are known to have different neointimal hyperplasia responses to carotid artery balloon angioplasty. Sequencing of the 16S ribosomal RNA gene was used to monitor changes in the gut microbiome. RESULTS: There were significant differences in neointimal hyperplasia between non-co-housed LE and SD rats 14 days after carotid artery angioplasty (mean intima + media [I + M] area, 0.117 ± 0.014 mm2 LE vs 0.275 ± 0.021 mm2 SD; P < .001) that were diminished by co-housing. Co-housing also altered local adventitial Ki67 immunoreactivity, local accumulation of leukocytes and macrophages (total and M2), and interleukin 17A concentration 3 days after surgery in each strain. Non-co-housed SD and LE rats had microbiomes distinguished by both weighted (P = .012) and unweighted (P < .001) UniFrac beta diversity distances, although without significant differences in alpha diversity. The difference in unweighted beta diversity between the fecal microbiota of SD and LE rats was significantly reduced by co-housing. Operational taxonomic units that significantly correlated with average I + M area include Parabacteroides distasonis, Desulfovibrio, Methanosphaera, Peptococcus, and Prevotella. Finally, serum concentrations of microbe-derived metabolites hydroxyanthranilic acid and kynurenine/tryptophan ratio were significantly associated with I + M area in both rat strains independent of co-housing. CONCLUSIONS: We describe a novel mechanism for how microbiome manipulations affect arterial remodeling and the inflammatory response after arterial injury. A greater understanding of the host inflammatory-microbe axis could uncover novel therapeutic targets for the prevention and treatment of restenosis.

The Comorbidity-Polypharmacy Score is an Objective and Practical Predictor of Outcomes and Mortality after Vascular Surgery.

BACKGROUND: The comorbidity-polypharmacy score (CPPS) was developed to quantify the severity of comorbidities of patients with geriatric trauma. CPPS is the sum of the number of medications and comorbidities, and is thus objective, user-friendly, and potentially adaptable to many clinical situations. We sought to understand if CPPS associates with outcomes and mortality after common vascular surgery procedures. METHODS: This is a retrospective single-center study. A total of 466 patients who underwent carotid endarterectomy, infrainguinal bypass, percutaneous lower extremity revascularization, or endovascular abdominal aortic aneurysm repair at a single medical center were included. CPPS were classified as mild, moderate, severe, and morbid based on scores of 0-7, 8-15, 15-21, and ≥21, respectively. End points were reinterventions, 30-day readmission, and mortality. We used chi-squared tests to analyze differences in categorical variables; Kruskal-Wallis tests to analyze differences in continuous variables; Kaplan-Meier estimation and Cox proportional hazard modeling to examine survival data; and receiver operator characteristic (ROC) curve analyses to assess sensitivity and specificity. RESULTS: The mean preoperative CPPS was 14.1 ± 6.1. Higher CPPS were associated with longer hospital and postoperative length of stay (P < 0.001). Severe and morbid CPPS categories had higher rates of ICU admission, reintervention, and 30-day readmission which did not reach statistical significance after correction for multiple comparisons. CPPS was independently associated with 1- and 5-year mortality in a multivariable Cox model (hazard ratio = 2.2, 95% confidence interval: 1.3-3.3). ROC analysis revealed C-statistics of 0.81 and 0.72 for 1-year and 5-year all-cause mortality, respectively (P < 0.001). CONCLUSIONS: CPPS is a simple and pragmatic clinical tool for quantifying risk of postoperative outcomes and mortality after common vascular surgery procedures. Further investigation is needed to validate the use of CPPS in enhancing existing predictors of patient outcomes and in serving as an adjunctive tool for determining resource allocation and discharge planning in patients who underwent vascular surgery.

Predictors and Consequences of Loss to Follow-up after Vascular Surgery.

BACKGROUND: Loss to follow-up (LTF) after surgery impacts quality of care and can adversely affect short- and long-term clinical outcomes. This study identifies modifiable factors contributing to LTF after vascular surgery and the factors' effect on short- and long-term clinical outcomes. METHODS: This is a retrospective single-center cohort study of 440 consecutive adult patients who underwent carotid endarterectomy, infrainguinal bypass, percutaneous lower extremity revascularization, or endovascular aortic aneurysm repair at Northwestern Memorial Hospital between November 2011 and November 2013. Twenty-six patients who died within 9 months after surgery were excluded because of competing risks with the study end points. Demographics, medical history and medications, hospitalization and procedure-related factors, and postoperative complications were collected from the medical record. The primary end point was LTF 1 month after surgery (LTF1M), defined as lack of an in-person outpatient visit with a vascular surgeon 1 month after the index procedure. Secondary outcomes were LTF 1 year after surgery (LTF1Y), defined as lack of an in-person outpatient visit with a vascular surgeon between 9 and 22 months after discharge, and overall 5-year survival. RESULTS: Overall LTF1M and LTF1Y rates were 27.3% and 46.8%, respectively. Kaplan-Meier analysis revealed no difference in survival based on the LTF1M status (P = 0.72), but patients who were LTF1Y had significantly worse survival at 5 years (P < 0.001). Seeing a nonvascular surgeon specialist at our institution (odds ratio (OR) 0.58, 95% confidence interval (CI): 0.35-0.94, P = 0.03) and having a reintervention (OR 0.17, 95% CI: 0.08-0.37, P < 0.001) were associated with decreased LTF1Y in a multivariable model. Overall mortality was more likely with LTF1Y (hazard ratio (HR) 3.27, 95% CI: 1.86-5.76, P < 0.001) and less likely with seeing another specialist at our institution (HR 0.38, 95% CI: 0.20-0.75, P = 0.005). CONCLUSIONS: LTF rates after vascular surgery are high and associated with poor long-term outcomes. Patients who did not see a nonvascular surgeon specialist at our institution had higher rates of LTF1Y and worse overall mortality, suggesting that improved integration of care can improve LTF and survival.

Identifying a Safe Carotid Stump Pressure Threshold for Selective Shunting During Carotid Endarterectomy.

BACKGROUND: There is no current consensus on the best criteria for selective shunting during carotid endarterectomy (CEA). The choice of continuous neurologic assessment during awake CEA, intraoperative electroencephalogram, or carotid stump pressure monitoring as the basis for shunt placement is primarily dependent on surgeon preference. Our goal is to define a safe stump pressure threshold as a guide for selective shunting. METHODS: The study is a single-surgeon retrospective review of consecutive patients who underwent CEA under general anesthesia with selective shunting based on intraoperative stump pressure measurements from 2001 to 2019. Demographic and periprocedural variables were analyzed using standard statistical techniques. RESULTS: Among 399 patients, 68% were male with a mean age of 70. One-third of the patients were symptomatic, with amaurosis fugax in 12%, transient ischemic attack in 7%, and stroke in 16%. In total, 60 (15%) patients underwent shunting: 34 for a confirmed preoperative acute ischemic stroke, 22 for a stump pressure <30 mm Hg, and 4 for other indications. Overall 30-day death, ischemic ipsilateral stroke, myocardial infarction, and cranial nerve palsy rates were 0.5%, 0.8%, 1.8%, and 1.0%, respectively. No strokes occurred due to hypoperfusion, and all stroke symptoms resolved prior to discharge with a mean length of stay of 1.6 days. CONCLUSIONS: This is one of the largest contemporary series of CEA using a 30 mm Hg threshold for selective shunting that demonstrated exceedingly low 30-day death and stroke events. Intraoperative carotid stump pressure measurements are a useful guide for selective shunting and reduction in perioperative stroke complications after CEA.

Peripheral artery reconstructions using cryopreserved arterial allografts in infected fields.

OBJECTIVE: Cryopreserved human arterial allografts are a recognized acceptable alternative for vascular reconstruction when other traditional conduits are either unavailable or contraindicated. We reviewed our experience using cryopreserved arterial allografts for peripheral artery reconstructions in contaminated and infected surgical fields. METHODS: A single-center, retrospective review was conducted of 57 patients who underwent a peripheral vascular reconstruction using a cryopreserved arterial allograft from January 2002 through July 2017. Indications for repair included removal of infected prosthetic bypass (n = 29), revascularizations in contaminated fields (n = 11), primary arterial repair in the setting of infection (n = 10), and infected vascular closure devices (n = 7). Aorta-based repairs were excluded. Demographics, index procedural details, postoperative complications, and conduit patency were analyzed. Primary end points included conduit-related mortality and graft failure as measured by reinfection, hemorrhage, or aneurysmal degeneration. Mean follow-up for the study is 27.8 months (range, 2-125 months). RESULTS: A total of 57 peripheral vascular reconstructions using cryopreserved arterial allografts were performed during the 15-year period. Among the 22 women and 35 men treated, the mean age was 61 years. The vascular beds involved included iliofemoral (n = 39), femoropopliteal or femoral-distal (n = 10), axillosubclavian or brachial (n = 2), mesenteric (n = 3), and carotid (n = 3) arteries. Adjunctive muscle flap coverage of the allograft conduit was performed in the majority of cases (61%; n = 35). The 30-day mortality was 9%; one death was directly related to conduit insertion. The 30-day conduit-related complication rate was 14% and included hemorrhage from the graft requiring return to the operating room (n = 4) and graft infection (n = 4). The late conduit-related complication rate was 15.8% and included graft infection (n = 1), graft thrombosis (n = 3), major amputation resulting from conduit failure (n = 1), pseudoaneurysm degeneration requiring repair (n = 2), graft hemorrhage (n = 1), and symptomatic graft stenosis (n = 1). CONCLUSIONS: A cryopreserved arterial allograft is a useful alternative conduit for peripheral vascular reconstruction in infected or contaminated surgical fields when other autologous or prosthetic conduits are either unavailable or contraindicated. In the immediate postoperative period, these repairs demonstrate acceptable resistance to graft failure and reinfection, particularly in conjunction with adjunctive rotational muscle flap coverage. Late conduit-related complications appear to be infrequent.

Plasma microbiome-modulated indole- and phenyl-derived metabolites associate with advanced atherosclerosis and postoperative outcomes.

OBJECTIVE: Multiple studies have shown that gut microbes contribute to atherosclerosis, and there is mounting evidence that microbial metabolism of dietary nutrients influences pathophysiology. We hypothesized that indole- and phenyl-derived metabolites that originate solely or in part from bacterial sources would differ between patients with advanced atherosclerosis and age- and sex-matched controls without clinically apparent atherosclerosis. METHODS: Plasma from the advanced atherosclerosis cohort (n = 100) was from patients who underwent carotid endarterectomy, open infrainguinal leg revascularization, or major leg amputation for critical limb ischemia. The controls (n = 22) were age- and sex-matched participants who had no peripheral arterial disease or history of stroke or myocardial infarction. Patients with chronic kidney disease were excluded. Metabolites and internal standards were measured using high-performance liquid chromatography and tandem mass spectrometry. RESULTS: Plasma metabolite concentrations differed significantly between the advanced atherosclerosis and control cohorts. After adjustment for traditional atherosclerosis risk factors, indole (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.75-0.95; P = .004), tryptophan (OR, <0.001; 95% CI, <0.001-0.003; P < .001), indole-3-propionic acid (OR, 0.27; 95% CI, 0.019-0.91; P = .02), and indole-3-aldehyde (OR, 0.12; 95% CI, 0.014-0.92; P = .04) concentrations negatively associated with advanced atherosclerosis, whereas the kynurenine/tryptophan ratio (OR, 61.7; 95% CI, 1.9->999; P = .02) was positively associated. Furthermore, tryptophan and indole-3-propionic acid concentrations (Spearman coefficients of 0.63 and 0.56, respectively; P < .001) correlated with the ankle-brachial index, a surrogate for overall atherosclerotic disease burden. Fourteen patients experienced a major postoperative cardiac complication within 30 days in the advanced atherosclerosis cohort, which was associated with baseline kynurenine/tryptophan ratio (P = .001) and hippuric acid (P = .03). In a multivariate analysis, only the kynurenine/tryptophan ratio remained significantly associated with a postoperative cardiac complication (OR, 44.1; 95% CI, 3.3-587.1; P = .004). Twenty patients in the advanced atherosclerosis cohort experienced a major adverse cardiac event during the follow-up period, which was associated with hippuric acid (P = .002) and the kynurenine/tryptophan ratio (P < .001) at baseline. Both hippuric acid and the kynurenine/tryptophan ratio were independently associated with a major adverse cardiac event in multivariate analyses that included diabetes mellitus. CONCLUSIONS: Specific microbe-derived metabolite signatures associate with advanced human atherosclerosis and postoperative cardiac complications. We suggest that these metabolites are potential novel biomarkers for atherosclerotic disease burden and that further investigation into mechanistic links between defined microbial metabolic pathways and cardiovascular disease is warranted.

Comparison of Direct and Less Invasive Techniques for the Treatment of Severe Aorto-Iliac Occlusive Disease.

BACKGROUND: Severe aorto-iliac occlusive disease (AIOD) is traditionally treated with aorto-bifemoral bypass (ABF) or aorto-unifemoral bypass (AUF). However, cross-femoral bypass (CFB) and hybrid femoral endarterectomy and patch angioplasty with iliac stenting (EPS) have gained popularity as less invasive options. We sought to compare 1-year survival, primary patency, and major amputation rates between open surgical (ABF and AUF) and 2 less invasive reconstruction techniques (CFB and EPS) using a large, multicenter cohort. STUDY DESIGN: This is a retrospective cohort study of patients who underwent either ABF/AUF or CFB/EPS for AIOD between 2006 and 2013 in the Society for Vascular Surgery Vascular Quality Initiative registry. Baseline patient and periprocedural variables were compared. Propensity score matching (PSM) was performed to predict the likelihood of more invasive repair. Kaplan-Meier analysis and Cox models were performed for 1-year survival, primary patency, and major amputation. RESULTS: 1872 patients underwent procedures for AIOD, including 1,133 ABF/AUF and 739 CFB/EPS, during the study period. Indication was critical limb ischemia in 47.3% (n = 886). Median follow-up time was 305 days (range, 10-406). After PSM, the matched cohort included 1,094 ABF/AUF and 711 CFB/EPS patients. Multivariate analysis revealed that patient factors and procedure indication were significant predictors of 1-year mortality and major amputation, but not procedure type. ABF/AUF was associated with improved primary patency over CFB/EPS at 1 year (94.1% ± 1.1% vs. 92.3% ± 1.5%, hazard ratio 0.65, 95% confidence interval 0.45-0.94; P = 0.02). CONCLUSIONS: In a propensity-matched cohort from a multicenter vascular surgery registry, a direct approach to AIOD (ABF/AUF) demonstrated better 1-year primary patency than commonly used less invasive strategies. However, treatment approach was not a predictor of 1-year survival or limb salvage, suggesting that patient factors and procedure indication have a greater impact on outcome.

Diagnosis, classification, and treatment of femoropopliteal artery in-stent restenosis.

In-stent restenosis is a pervasive challenge to the durability of stenting for the treatment of lower extremity ischemia. There is considerable controversy about the criteria for diagnosis, indications for treatment, and preferred algorithm for addressing in-stent restenosis. This evidence summary seeks to review existing information on strategies for the treatment of this difficult problem.

High dose-rate brachytherapy for the treatment of lower extremity in-stent restenosis.

OBJECTIVE: Historically, edge stenosis and late thrombosis limited the effectiveness of adjunctive endovascular brachytherapy (EVBT) for in-stent restenosis (ISR) after percutaneous transluminal angioplasty (PTA) and stenting. We evaluated an updated protocol of PTA and EVBT for ISR among patients with lower extremity occlusive disease. METHODS: This is a retrospective, single-center review of patients treated with PTA and EVBT for ISR in the iliac and femoropopliteal segments between 2004 and 2012. A dose of 20 Gy was given at a depth of 0.5 mm beyond the radius of the largest PTA balloon using iridium 192, with at least 2-cm-long margins of radiation coverage proximal and distal to the injured area. Stents were assessed for patency by duplex ultrasound imaging at 1, 3, 6, 9, 12, and 18 months and then yearly. The primary end point was freedom from ≥50% restenosis in the treated segment at 6 months, 1 year, and 2 years. Patency data were estimated using the Kaplan-Meier method. Secondary end points were early and late thrombotic occlusion. RESULTS: Among 42 consecutive cases in 35 patients of EVBT for ISR in common or external iliac (9 [20.8%]) and superficial femoral or popliteal (33 [76.7%]) arteries, or both, 21 patients (50%) had claudication, asymptomatic hemodynamically significant stenoses were identified on duplex ultrasound imaging in 16 (38.1%), and 4 (9.8%) had critical limb ischemia. Mean treated length was 23.5 ± 12.3 cm over a mean duration of 16.1 ± 9.6 minutes. There was one technical failure (2.3%). Median post-EVBT follow-up time was 682 days (range, 1-2262 days). There were two (4.9%) and five (11.9%) cases of early and late thrombotic occlusions, respectively. There was one death, believed to be secondary to acute coronary syndrome. Primary, assisted primary, and secondary patency in the entire cohort was 75.2%, 89.1%, and 89.1%, respectively, at 1 year and 63.7%, 80.6%, and 85.6%, respectively, at 2 years. CONCLUSIONS: This contemporary protocol of PTA and adjunctive EVBT for lower extremity ISR, which is updated from those used in prior trials and includes a surveillance strategy that identifies at-risk stents for reintervention before occlusion, may be a promising treatment for lower extremity ISR at institutions where a close collaboration between vascular surgeons and radiation oncologists is feasible.