Midterm outcomes and predictors of failure of lower extremity bypass to para-malleolar and pedal targets.

OBJECTIVES: The frequency of distal lower extremity bypass (LEB) for infra-popliteal critical limb threatening ischemia (IP-CLTI) has significantly decreased. Our goal was to analyze the contemporary outcomes and factors associated with failure of LEB to para-malleolar and pedal targets. METHODS: We queried the VQI infra-inguinal database from 2003-2021 to identify LEB to para-malleolar or pedal/plantar targets. Primary outcomes were graft patency, major adverse limb events [vascular re-intervention, above ankle amputation] (MALE), and amputation-free survival at 2 years. Standard statistical methods were utilized. RESULTS: We identified 2331 LEB procedures (1265 anterior tibial at ankle/dorsalis pedis, 783 posterior tibial at ankle, 283 tarsal/plantar). The prevalence of LEB bypasses to distal targets has significantly decreased from 13.37% of all LEB procedures in 2003 to 3.51% in 2021 (p<0.001). The majority of cases presented with tissue loss (81.25. Common post-operative complications included major adverse cardiac events (8.9%) and surgical site infections (3.6%). Major amputations occurred in 16.8% of patients at 1 year. Post-operative mortality at 1 year was 10%. On unadjusted Kaplan-Meier survival analysis at 2 years, primary patency was 50.56%±3.6%, MALE was 63.49%±3.27%, and amputation-free survival was 71.71%±0.98%. In adjusted analyses [adjusted for comorbidities, indication, conduit type, urgency, prior vascular interventions, graft inflow vessel (femoral/popliteal), concomitant inflow procedures, surgeon and center volume] conduits other than GSV (p<0.001) were associated with loss of primary patency and increased MALE. High center volume (>5 procedures/year) was associated with improved primary patency (p=0.015), and lower MALE (p=0.021) at 2 years. CONCLUSIONS: Despite decreased utilization, open surgical bypass to distal targets at the ankle remains a viable option for treatment of IP-CLTI with acceptable patency and amputation-free survival rates at 2 years. Bypasses to distal targets should be performed at high volume centers to optimize graft patency and limb salvage and minimize re-interventions.

Percutaneous thrombectomy for acute limb ischemia is associated with equivalent limb and mortality outcomes compared with open thrombectomy.

BACKGROUND: Acute limb ischemia (ALI) carries a 15% to 20% risk of combined death or amputation at 30 days and 50% to 60% at 1 year. Percutaneous mechanical thrombectomy (PT) is an emerging minimally invasive alternative to open thrombectomy (OT). However, ALI thrombectomy cases are omitted from most quality databases, limiting comparisons of limb and survival outcomes between PT and OT. Therefore, our aim was to compare in-hospital outcomes between PT and OT using the National Inpatient Sample. METHODS: We analyzed survey-weighted National Inpatient Sample data (2015-2020) to include emergent admissions of aged adults (50+ years) with a primary diagnosis of lower extremity ALI undergoing index procedures within 2 days of hospitalization. We excluded hospitalizations with concurrent trauma or dissection diagnoses and index procedures using catheter-directed thrombolysis. Our primary outcome was composite in-hospital major amputation or death. Secondary outcomes included in-hospital major amputation, death, in-hospital reintervention (including angioplasty/stent, thrombolysis, PT, OT, or bypass), and extended length of stay (eLOS; defined as LOS >75th percentile). Adjusted odds ratios (aORs) with 95% confidence intervals (95% CIs) were generated by multivariable logistic regression, adjusting for demographics, frailty (Risk Analysis Index), secondary diagnoses including atrial fibrillation and peripheral artery disease, hospital characteristics, and index procedure data including the anatomic thrombectomy level and fasciotomy. A priori subgroup analyses were performed using interaction terms. RESULTS: We included 23,795 survey-weighted ALI hospitalizations (mean age: 72.2 years, 50.4% female, 79.2% White, and 22.3% frail), with 7335 (30.8%) undergoing PT. Hospitalization characteristics for PT vs OT differed by atrial fibrillation (28.7% vs 36.5%, P < .0001), frequency of intervention at the femoropopliteal level (86.2% vs 88.8%, P = .009), and fasciotomy (4.8% vs 6.9%, P = .006). In total, 2530 (10.6%) underwent major amputation or died. Unadjusted (10.1% vs 10.9%, P = .43) and adjusted (aOR = 0.96 [95% CI, 0.77-1.20], P = .74) risk did not differ between the groups. PT was associated with increased odds of reintervention (aOR = 2.10 [95% CI, 1.72-2.56], P < .0001) when compared with OT, but this was not seen in the tibial subgroup (aOR = 1.31 [95% CI, 0.86-2.01], P = .21, Pinteraction < .0001). Further, 79.1% of PT hospitalizations undergoing reintervention were salvaged with endovascular therapy. Lastly, PT was associated with significantly decreased odds of eLOS (aOR = 0.80 [95% CI, 0.69-0.94], P = .005). CONCLUSIONS: PT was associated with comparable in-hospital limb salvage and mortality rates compared with OT. Despite an increased risk of reintervention, most PT reinterventions avoided open surgery, and PT was associated with a decreased risk of eLOS. Thus, PT may be an appropriate alternative to OT in appropriately selected patients.

Socioeconomic factors predict successful supervised exercise therapy completion.

OBJECTIVE: Supervised exercise therapy (SET) for patients with intermittent claudication (IC) can lower the risk of progression to chronic limb-threatening ischemia and amputation, while preserving and restoring functional status. Despite supporting evidence, it remains underutilized, and among those who initiate programs, attrition rates are extremely high. We hypothesize that socioeconomic factors may represent significant barriers to SET completion. METHODS: Patients with IC referred to SET at a multi-hospital, single-institution health care system (2018-2022) from a prospectively maintained database were retrospectively analyzed. Our primary endpoint was SET program completion and graduation, defined as completion of 36 sessions. Our secondary endpoints were vascular intervention within 1 year of referral and change in ankle-brachial index (ABI). Baseline demographics were assessed using standard statistical methods. Predictors of SET graduation were analyzed using multivariable logistic regression generating adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Change in ABI was analyzed using t-test between subgroups. Reasons for attrition were tabulated. Patient Health Questionnaire-9 (PHQ-9), metabolic equivalent level, Vascular QOL, Duke Activity Status, and ABI were analyzed using paired t-tests across the entire cohort. RESULTS: Fifty-two patients met inclusion criteria: mean age 67.85 ± 10.69 years, 19 females (36.54%), mean baseline ABI of 0.77 ± 0.16. The co-pays for 100% of patients were fully covered by primary and secondary insurance plans. Twenty-one patients (40.38%) completed SET. On multivariable analysis, residence in a ZIP code with median household income <$47,000 (aOR, 0.10; 95% CI, 0.01-0.76; P = .03) and higher body mass index (aOR, 0.81; 95% CI, 0.67-0.99; P = .04) were significant barriers to SET graduation. There were no differences in ABI change or vascular intervention within 1 year between graduates and non-graduates. Non-graduates reported transportation challenges (25.00%), lack of motivation (20.83%), and illness/functional limitation (20.83%) as primary reasons for SET attrition. Metabolic Equivalent Level (P ≤ .01) and Duke Activity Status scores (P = .04) were significantly greater after participating in a SET program. CONCLUSIONS: Although SET participation improves lower extremity and functionality outcomes, only 40% of referred patients completed therapy in our cohort. Our findings suggest that both socioeconomic and functional factors influence the odds of completing SET programs, indicating a need for holistic pre-referral assessment to facilitate enhanced program accessibility for these populations.

Selective Publication within Vascular Surgery: Characteristics of Discontinued and Unpublished Randomized Clinical Trials.

BACKGROUND: Discontinued and unpublished randomized clinical trials (RCTs) are common resulting in biased publication and loss of potential knowledge. The magnitude of selective publication within vascular surgery remains unknown. METHODS: RCT relevant to vascular surgery registered (01/01/2010-10/31/2019) on ClinicalTrials.gov were included. Trials ending normally with conclusion of participant treatment and examination were considered completed whereas discontinued trials stopped early. Publications were identified through automatically indexed PubMed citations on ClinicalTrials.gov or manually identified on PubMed or Google Scholar >30 months after the completion date, the date the final participant was examined, allowing time for publication. RESULTS: Of 108 RCT (n = 37, 837), 22.2% (24/108) were discontinued, including 16.7% (4/24) stopped prior to and 83.3% (20/24) after starting enrollment. Only 28.4% of estimated enrollment was achieved for all discontinued RCT. Nineteen (79.2%) investigators provided a reason for discontinuation, which most commonly included poor enrollment (45.8%), inadequate supplies or funding (12.5%), and trial design concerns (8.3%). Of the 20 trials terminated following enrollment, 20.0% (4/20) were published in peer-reviewed journals and 80.0% (16/20) failed to reach publication. Of the 77.8% trials completed, 75.0% (63/84) were published and 25.0% (21/84) remain unpublished. In a multivariate regression of completed trials, industry funding was significantly associated with decreased likelihood of peer-reviewed publication (OR = 0.18, (95% CI 0.05-0.71), P = 0.01). Of the discontinued and completed trials remaining unpublished, 62.5% and 61.9% failed to report results on ClinicalTrials.gov, respectively, encompassing a total of 4,788 enrollees without publicly available results. CONCLUSIONS: Nearly 25% of registered vascular RCT were discontinued. Of completed RCT, 25% remain unpublished with industry funding associated with decreased likelihood of publication. This study identifies opportunities to report all findings for completed and discontinued vascular surgery RCT, whether industry sponsored, or investigator initiated.

Cognitive function after carotid endarterectomy in asymptomatic patients.

Asymptomatic carotid stenosis has been shown to be associated with progressive neurocognitive decline, but the effects of carotid endarterectomy (CEA) on this are not well defined. Due to the wide heterogeneity of studies and lack of standardization in cognitive function tests and study design, there is mounting scientific evidence to support the notion that CEA is effective in reversing or slowing neurocognitive decline; however, definitive conclusions are difficult to make. Further, while the association between ACS and cognitive decline has been well document, a direct etiological role has not been established. More research is required to elucidate the relationship between asymptomatic carotid stenosis and the benefit of carotid endarterectomy and its potential protective effects regarding cognitive decline. This article aims to review current evidence in preoperative and postoperative cognitive function in asymptomatic patients with carotid stenosis undergoing CEA.

Acute limb ischemia secondary to vaccine-induced thrombotic thrombocytopenia.

Vaccine-associated thrombosis has previously been described in patients presenting with cerebral sinus thrombosis, deep venous thrombosis/pulmonary embolism, or mesenteric venous thrombosis. Only recently has arterial thrombosis gained attention. A new entity known as vaccine-induced thrombotic thrombocytopenia (VITT) has been associated with the coronavirus disease of 2019 (COVID-19) vaccines produced by AstraZeneca and Johnson & Johnson. We describe a case series of three patients who presented with acute limb ischemia with vaccine-associated arterial occlusions, one of whom was diagnosed with VITT.

Carotid endarterectomy remains cost-effective for the surgical management of carotid stenosis.

OBJECTIVE: Transcarotid arterial revascularization (TCAR) has gained popularity as an alternative to carotid endarterectomy (CEA) and transfemoral carotid artery stenting (TFCAS), potentially combining the benefits of a minimally invasive approach with a lower risk of procedural stroke compared with TFCAS. Emerging evidence shows TCAR to have excellent perioperative outcomes. However, the cost-effectiveness of TCAR is not well-understood. METHODS: Incorporating data from Carotid Revascularization Endarterectomy vs Stenting Trial (CREST), the Vascular Quality Initiative Surveillance Project, and local cost data, we compared the cost-effectiveness of these three treatment modalities (TFCAS, CEA, and TCAR) for both symptomatic and asymptomatic carotid stenosis using a Markov state-transition model to quantify lifetime costs in United States dollars and effectiveness in quality-adjusted life-years (QALYs). We accounted for perioperative stroke and myocardial infarction, as well as long-term risks of stroke and restenosis. Based on CREST, we assumed a start age of 69 years and a cost-effectiveness acceptability threshold of $100,000/QALYs gained. Sensitivity analyses were performed. RESULTS: In the base-case scenario, TCAR cost $160,642/QALY gained compared with CEA, greater than the frequently cited $100,000/QALY gained threshold. TFCAS was more expensive and less effective than other strategies, largely due to a greater periprocedural stroke risk. In one-way sensitivity analysis, if TCAR stroke risk was <0.9% (base-case risk, 1.4%), than it was economically favorable compared with CEA at its current procedural cost. Alternatively, if TCAR procedural costs were reduced by approximately $2000 (base-case cost, $15,182), it would also become economically favorable. In a probabilistic sensitivity analysis, varying all parameters simultaneously over distributions, CEA was favored in 80% of model iterations at $100,000/QALY, with TCAR favored in 19%. CONCLUSIONS: At current cost and outcomes, TCAR does not meet a traditional cost-effectiveness threshold to replace CEA as the primary treatment modality for carotid stenosis. TFCAS is the least cost-effective strategy for carotid revascularization. Given these observations, TCAR should be limited to select patients, specifically those at high physiologic and anatomic risk from CEA. However, TCAR can become cost-effective if its cost is reduced. Given the current outcomes and cost, CEA remains the most cost-effective treatment for carotid revascularization.

Any Postoperative Surveillance Improves Survival after Endovascular Repair of Ruptured Abdominal Aortic Aneurysms.

BACKGROUND: Endovascular aortic repair (EVAR) has advanced the care of patients with ruptured abdominal aortic aneurysms (rAAA) with improved early postoperative morbidity and mortality. However, this comes at the cost of a rigorous postoperative surveillance schedule to monitor for further aneurysmal degeneration. Adherence to surveillance recommendations is known to be poor in the elective setting, but has yet to be studied in the ruptured population. The aim of this study is to investigate predictors of incomplete surveillance after EVAR for rAAA (rEVAR) and examine how adherence impacts outcomes. METHODS: This was a retrospective case control study of patients undergoing rEVAR at a multiple hospital single healthcare center (2003-2020). Patients were excluded if they underwent open conversion during their index hospitalization or died within 60 days of surgery. Follow-up was broadly categorized as complete surveillance (60-day postoperative visit and annually thereafter) or incomplete surveillance, comprising both patients with less than recommended surveillance (minimal surveillance) and completely lost to follow-up (LTF). Any follow-up was defined as patients with complete or minimal surveillance. We investigated predictors of complete versus incomplete surveillance by multivariate logistic regression. Secondary outcomes included overall survival and cumulative incidence of reintervention controlling for the competing risk of mortality, generating hazard ratios (HR) and subdistribution hazard ratios (SHR). RESULTS: One-hundred and sixty patients (mean age 74 ± 10.1 years, 81.2% male) out of 673 total rAAA met study inclusion criteria. Complete surveillance was seen in 41.3% of our cohort, with the remainder with minimal surveillance (29.4%) or LTF (29.4%). Incomplete surveillance was associated with male sex (odds ratio [OR] 2.56; 95% CI 1.02-6.43), lack of a primary care provider (PCP; OR 0.20; 95% CI 0.04-0.99), and longer driving distance from home to treating hospital (OR 2.37; 95% CI 1.08-5.20). Survival was not different between complete and incomplete surveillance groups, however any follow-up conferred improved survival over LTF (HR 0.57; 95% CI 0.331-0.997; P = 0.049). Reintervention was associated with incomplete surveillance (SHR 0.29; 95% CI 0.11-0.75), and discharge to a facility (SHR 0.25; 95% CI 0.067-0.94). CONCLUSIONS: Incomplete surveillance was observed in over 50% of patients who underwent rEVAR and was associated with male sex, lack of PCP, and longer driving distance. Any follow-up conferred a survival benefit, yet incomplete surveillance was associated with a lower risk of reintervention. Targeted strategies to prevent LTF, and less stringent, personalized follow-up plans that may confer similar survival benefit with better patient adherence should be investigated.

Predictive Factors of Perioperative Stroke-Related Mortality Following Vascular Surgery: A Retrospective Analysis.

OBJECTIVE: Vascular surgical procedures have one of the highest risks of perioperative stroke and stroke-related mortality, yet the independent risk factors contributing to this increased mortality have not been described. Perioperative strokes are thought to result from a combination of embolism and hypoperfusion mechanisms. The purpose of this study is to describe the independent predictors of perioperative stroke-related mortality in the vascular surgical population using the Pennsylvania Health Care Cost Containment Council (PHC4) database which collects cause of death data. METHODS: This retrospective, case-control study evaluated 4,128 patients aged 18-99 who underwent a vascular, non-carotid surgical procedure and subsequently suffered perioperative mortality. Common surgical comorbidities and risk factors for perioperative stroke, including carotid stenosis and atrial fibrillation, were evaluated in multivariate regression analysis. RESULTS: Patients with carotid stenosis were 2.6 (aOR, 95% CI 1.4-4.5) times more likely to suffer perioperative mortality from stroke than from other causes. Additionally, in-hospital stroke, history of stroke, admission from a healthcare facility, and cancer were all positive predictive factors, whereas atrial fibrillation, emergency admission, hypertension, and diabetes were associated with decreased risk of perioperative stroke-related mortality. CONCLUSIONS: Identification of vascular surgical population-specific predictors of stroke-related mortality can help to enhance preoperative risk-stratification tools and guide perioperative management of identified high-risk patients. Increased neurophysiologic monitoring in the perioperative period to prevent delays in diagnosis of perioperative stroke offers a strategy to reduce risk of perioperative stroke-related mortality in vascular surgical patients.

Rationale and Design for the Remote Ischemic Preconditioning for Carotid Endarterectomy Trial.

BACKGROUND: While the perioperative stroke rate after carotid endarterectomy (CEA) is low, "silent" microinfarctions identified by magnetic resonance imaging (MRI) are common and have been correlated with postoperative neurocognitive decline. Our study will investigate the role of remote ischemic preconditioning (RIPC) as a potential neuroprotective mechanism. RIPC is a well-tolerated stimulus that, through neuronal and humoral pathways, generates a systemic environment of greater resistance to subsequent ischemic insults. We hypothesized that patients undergoing RIPC before CEA will have improved postoperative neurocognitive scores compared with those of patients undergoing standard care. METHODS: Patients undergoing CEA will be randomized 1:1 to RIPC or standard clinical care. Those randomized to RIPC will undergo a standard protocol of 4 cycles of RIPC. Each RIPC cycle will involve 5 min of forearm ischemia with 5 min of reperfusion. Forearm ischemia will be induced by a blood pressure cuff inflated to 200 mm Hg or at least 15 mm Hg higher than the systolic pressure if it is >185 mm Hg. This will occur after anesthesia induction and during incision/dissection but before manipulation or clamping of the carotid; thus, patients will be blinded to their assignment. Before carotid endarterectomy, all patients will undergo baseline neurocognitive testing in the form of a Montreal Cognitive Assessment (MoCA) and National Institutes of Health (NIH) Toolbox. MoCA testing only will be conducted on postoperative day 1 in the hospital. The full neurocognitive testing battery will again be conducted at 1-month follow-up in the office. Changes from baseline will be compared between arms at the follow-up time points. Assuming no drop-ins or dropouts and a 10% loss to follow-up, we would need a sample size of 43 patients for 80% power per treatment arm. The primary endpoint, change in MoCA scores, will be analyzed using a random effects model, and secondary outcomes will be analyzed using either linear or logistic regression where appropriate. CONCLUSIONS: RIPC, if shown to be effective in protecting patients from neurocognitive decline after CEA, represents a safe, inexpensive, and easily implementable method of neuroprotection.

Cost-effectiveness analysis of drug-coated therapies in the superficial femoral artery.

OBJECTIVE: Drug-coated balloons (DCBs) may increase durability of endovascular treatment of superficial femoral artery (SFA) disease while avoiding stent-related risks. The purpose of this study was to use meta-analytic data of DCB studies to compare the cost-effectiveness of potential SFA treatments: DCB, drug-eluting stent (DES), plain old balloon angioplasty (POBA), or bare-metal stent (BMS). METHODS: A search for randomized controlled trials comparing DCB with POBA for treatment of SFA disease was performed. Hazard ratios were extracted to account for the time-to-event primary outcome of target lesion revascularization. Odds ratios were calculated for the secondary outcomes of primary patency (PP) and major amputation. Incorporating pooled data from the meta-analysis, cost-effectiveness analysis, assuming a payer perspective, used a decision model to simulate patency at 1 year and 2 years for each index treatment modality: POBA, BMS, DCB, or DES. Costs were based on current Medicare outpatient reimbursement rates. RESULTS: Eight studies (1352 patients) met inclusion criteria for meta-analysis. DCB outperformed POBA with respect to target lesion revascularization over time (pooled hazard ratio, 0.41; P < .001). Risk of major amputation at 12 months was not significantly different between groups. There was significantly improved 1-year PP in the DCB group compared with POBA (pooled odds ratio, 3.30; P < .001). In the decision model, the highest PP at 1 year was seen in the DES index therapy strategy (79%), followed by DCB (74%), BMS (71%), and POBA (64%). With a baseline cost of $9259.39 per patent limb at 1 year in the POBA-first group, the incremental cost per patent limb for each other strategy compared with POBA was calculated: $14,136.10/additional patent limb for DCB, $38,549.80/limb for DES, and $59,748,85/limb for BMS. The primary BMS option is dominated by being more expensive and less effective than DCB. Compared directly with DCB, DES costs $87,377.20 per additional patent limb at 1 year. Based on the projected PP at 1 year in the decision model, the number needed to treat for DES compared with DCB is 20. At current reimbursement, the use of more than two DCBs per procedure would no longer be cost-effective compared with DES. At 2 years, DCB emerges as the most cost-effective index strategy with the lowest overall cost and highest patency rates over that time horizon. CONCLUSIONS: Current data and reimbursements support the use of DCB as a cost-effective strategy for endovascular intervention in the SFA; any additional effectiveness of DES comes at a high price. Use of more than one DCB per intervention significantly decreases cost-effectiveness.

An Accumulated Deficits Model Predicts Perioperative and Long-term Adverse Events after Carotid Endarterectomy.

BACKGROUND: There is increasing recognition that decreased reserve in multiple organ systems, known as accumulated deficits (AD), may better stratify perioperative risk than traditional risk indices. We hypothesized that an AD model would predict both perioperative adverse events and long-term survival after carotid endarterectomy (CEA), particularly important in asymptomatic patients. METHODS: Consecutive patients undergoing CEA between 1st January 2000 and 31st December 2010 were retrospectively identified. Seven of the deficit items from the Canadian Study of Health and Aging-frailty index (coronary disease, renal insufficiency, pulmonary disease, peripheral vascular disease, heart failure, hypertension, and diabetes) were tabulated for each patient. Predictors of perioperative and long-term outcomes were evaluated using regression analysis. RESULTS: About 1,782 CEAs in 1,496 patients (mean age: 71.3 ± 9.3 years, 56.3% male, 35.4% symptomatic) were included. The risk of major adverse events (stroke, death, or myocardial infarction) at 30 days for patients with ≤3 deficits was 2.53% vs. 8.81% for patients with ≥4 deficits (P < 0.001). For patients with ≥5 deficits, the risk was 15.18%. Each additional deficit increased the odds of a 30-day major adverse event and hospital stay >2 days by 1.64 (P < 0.001) and 1.15 (P < 0.001), respectively. In multivariate analysis, the presence of ≥4 deficits was more predictive of perioperative major adverse events (odds ratio [OR] = 3.62, P < 0.001) than symptomatology within 6 months (OR = 1.57, P = 0.08) or octogenarian status (OR = 2.00, P = 0.02). Kaplan-Meier analysis showed significantly decreased survival over time with accumulating deficits (P < 0.001). Patients with ≥4 deficits have a hazards ratio for death of 2.6 compared to patients with ≤3 deficits (P < 0.001). Overall survival is estimated at 79.5% (95% confidence interval [CI]: 0.77-0.82) at 5 years in patients with ≤3 deficits versus 52.4% (95% CI: 0.46-0.58) in patients with ≥4 deficits, respectively. In subgroup analysis of asymptomatic patients, 5-year survival for octogenarian male patients with ≥4 deficits was only 26.8%. For asymptomatic males aged 70-79 years with ≥4 deficits, 5-year survival was 59.9%. CONCLUSIONS: An AD model is more predictive of perioperative adverse events after CEA than age or symptomatic status. This model remains predictive of long-term survival. In asymptomatic male octogenarians with 4 or more AD, 5-year survival is severely limited.