Multi-modality imaging for assessment of the microcirculation in peripheral artery disease: Bench to clinical practice.

Peripheral artery disease (PAD) is a highly prevalent disorder with a high risk of mortality and amputation despite the introduction of novel medical and procedural treatments. Microvascular disease (MVD) is common among patients with PAD, and despite the established role as a predictor of amputations and mortality, MVD is not routinely assessed as part of current standard practice. Recent pre-clinical and clinical perfusion and molecular imaging studies have confirmed the important role of MVD in the pathogenesis and outcomes of PAD. The recent advancements in the imaging of the peripheral microcirculation could lead to a better understanding of the pathophysiology of PAD, and result in improved risk stratification, and our evaluation of response to therapies. In this review, we will discuss the current understanding of the anatomy and physiology of peripheral microcirculation, and the role of imaging for assessment of perfusion in PAD, and the latest advancements in molecular imaging. By highlighting the latest advancements in multi-modality imaging of the peripheral microcirculation, we aim to underscore the most promising imaging approaches and highlight potential research opportunities, with the goal of translating these approaches for improved and personalized management of PAD in the future.

Long-Term Mortality Predictors Using a Machine-Learning Approach in Patients With Chronic Limb-Threatening Ischemia After Peripheral Vascular Intervention.

BACKGROUND: Patients with chronic limb-threatening ischemia (CLTI) face a high long-term mortality risk. Identifying novel mortality predictors and risk profiles would enable individual health care plan design and improved survival. We aimed to leverage a random survival forest machine-learning algorithm to identify long-term all-cause mortality predictors in patients with CLTI undergoing peripheral vascular intervention. METHODS AND RESULTS: Patients with CLTI undergoing peripheral vascular intervention from 2017 to 2018 were derived from the Medicare-linked VQI (Vascular Quality Initiative) registry. We constructed a random survival forest to rank 66 preprocedural variables according to their relative importance and mean minimal depth for 3-year all-cause mortality. A random survival forest of 2000 trees was built using a training sample (80% of the cohort). Accuracy was assessed in a testing sample (20%) using continuous ranked probability score, Harrell C-index, and out-of-bag error rate. A total of 10 114 patients were included (mean±SD age, 72.0±11.0 years; 59% men). The 3-year mortality rate was 39.1%, with a median survival of 1.4 years (interquartile range, 0.7-2.0 years). The most predictive variables were chronic kidney disease, age, congestive heart failure, dementia, arrhythmias, requiring assisted care, living at home, and body mass index. A total of 41 variables spanning all domains of the biopsychosocial model were ranked as mortality predictors. The accuracy of the model was excellent (continuous ranked probability score, 0.172; Harrell C-index, 0.70; out-of-bag error rate, 29.7%). CONCLUSIONS: Our random survival forest accurately predicts long-term CLTI mortality, which is driven by demographic, functional, behavioral, and medical comorbidities. Broadening frameworks of risk and refining health care plans to include multidimensional risk factors could improve individualized care for CLTI.

Impact of Early Intervention on Health Status Outcomes in Peripheral Artery Disease Patients with Chronic Total Occlusion Lesions Using the PORTRAIT Registry.

OBJECTIVES: To analyze the impact of non-invasive and early invasive treatments on health status in patients with lower extremity peripheral arterial disease (PAD) without and with chronic total occlusions (CTO) after 12 months of follow-up. METHODS: Using the international (U.S., Netherlands, and Australia) observational longitudinal PORTRAIT registry, we included patients with recent PAD symptoms between June 2011 and December 2015. We assessed the PAD-specific health status at initial visit, 3-, 6- and 12-month follow-up using the Peripheral Arterial Questionnaire (PAQ). On a propensity matched-weighted cohort, we compared patients' characteristics by CTO status and treatment groups as early invasive (revascularization in the 3 months) vs. non-invasive (exercise, medical therapies, or smoking cessation). We then assessed the health status trajectory over 12 months, as 3-way interaction between CTO status, and treatment groups, and months, using a multilevel generalized linear regression model for repeated measures adjusted for baseline health status with random effects at sites- and patients-level. RESULTS: We included 581 participants, with mean age of 66.62±9.33 years, 34.3% female, and 90.8% White, of whom 353 (60.8%) without and 228 (39.2%) with a CTO lesion. Respectively, 96 (27.2%) and 70 (30.7%) patients underwent early invasive treatment (d=0.07). While patients with CTO were more likely to have lower resting ABI, multilevel disease, and to experience severe claudication vs. their counterparts (|d|≥0.20); the patients' health status at baseline with CTO was not different from those without CTO, with mean Summary scores of 45.14±20.26 vs. 45.90±21.24 (d=0.04), respectively. The trajectory did not differ by CTO status (interaction CTO status*month: p=0.517) and was higher in early invasive vs. non-invasive treatment (treatment*month: p<0.001), regardless of CTO status (CTO status*treatment: p=0.981 and CTO status*treatment*month: p=0.264). The score increased over time with the largest improvement occurring at 3 months in both non-invasive (non-CTO: +7.82 95%CI 4.03;11.60 and CTO: +9.27 95%CI 4.45;14.09) and early invasive (non-CTO: +26.17 95%CI 20.06; 32.28 and CTO: +24.52 95%CI 17.40;31.64) groups. The mean score in CTO vs. non-CTO did not differ at each timepoint, with the 12-month mean score of 70.26 (95%CI 67.87; 74.65) vs. 71.17 (95% CI 65.91; 76.44) (p=0.99) in the non-invasive treatment and 84.93 (95%CI 78.90;90.97) vs. 79.20 (95%CI 72.77;86.14) (p=0.31) in the early invasive treatment. CONCLUSIONS: Patients with symptomatic PAD undergoing early revascularization exhibited higher health status over time vs. those undergoing non-invasive treatment strategy, irrespective of the presence of CTOs. The degree of the improvement was greater in the 3 months following the initial visit, especially in patients undergoing early revascularization.

Variability in short-term mortality following repair of ruptured abdominal aortic aneurysms across centers and physicians.

BACKGROUND: Variation in the care management of repairs for ruptured infrarenal abdominal aortic aneurysms between centers and physicians, such as procedural volumes, may explain differences in mortality outcomes. First, we quantified the center and physician variability associated with 30- and 90-day mortality risk after ruptured open surgical repair (rOSR) and ruptured endovascular aneurysm repair (rEVAR). Second, we explored wheter part of this variability was attributable to procedural volume at the center and physician levels. METHODS: Two cohorts including rOSR and rEVAR procedures between 2013 and 2019 were analyzed from the Vascular Quality Initiative database. Thirty- and 90-day all-cause mortality rates were derived from linked Medicare claims data. The median odds ratio (MOR) (median mortality risk from low- to high-risk cluster) and intraclass correlation coefficient (ICC) (variability attributable to each cluster) for 30- and 90-day mortality risks associated with center and physician variability were derived using patient-level adjusted multilevel logistic regression models. Procedural volume was calculated at the center and physician levels and stratified by quartiles. The models were sequentially adjusted for volumes, and the difference in ICCs (without vs with accounting for volume) was calculated to describe the center and physician variability in mortality risk attributable to volumes. RESULTS: We included 450 rOSRs (mean age, 74.5 ± 7.6 years; 23.5% female) and 752 rEVARs (76.4 ± 8.4 years; 26.1% female). After rOSRs, the 30- and 90-day mortality rates were 32.9% and 38.7%, respectively. No variability across centers and physicians was noted (30- and 90-day MORs ≈1 and ICCs ≈0%). Neither center nor physician volume was associated with 30-day (P = .477 and P = .796) or 90-day mortality (P = .098 and P = .559). After rEVAR, the 30- and 90-day mortality rates were 21.3% and 25.5%, respectively. Significant center variability (30-day MOR, 1.82 [95% confidence interval (CI), 1.33-2.22]; ICC, 11% [95% CI, 2%-36%]; and 90-day MOR, 1.76 [95% CI, 1.37-2.09]; ICC, 10% [95% CI, 3%-30%]), but negligeable variability across physicians (30- and 90-day MORs ≈1 and ICCs ≈0%) were noted. Neither center nor physician volume were associated with 30-day (P = .076 and P = .336) or 90-day mortality risk (P = .066 and P = .584). The center variability attributable to procedural volumes was negligeable (difference in ICCs, 1% for 30-day mortality; 0% for 90-day mortality). CONCLUSIONS: Variability in practice from center to center was associated with short-term mortality outcomes in rEVAR, but not for rOSR. Physician variability was not associated with short-term mortality for rOSR or rEVAR. Annualized center and physician volumes did not significantly explain these associations. Further work is needed to identify center-level factors affecting the quality of care and outcomes for ruptured abdominal aortic aneurysms.

Comparison of mortality and amputation after lower extremity bypass versus peripheral vascular intervention in patients with chronic limb-threatening ischemia and comorbid chronic kidney disease.

OBJECTIVE: Comorbid chronic kidney disease (CKD) is associated with worse outcomes for patients with chronic limb-threatening ischemia (CLTI). However, comparative effectiveness data are limited for lower extremity bypass (LEB) vs peripheral vascular intervention (PVI) in patients with CLTI and CKD. We aimed to evaluate (1) 30-day all-cause mortality and amputation and (2) 5-year all-cause mortality and amputation for LEB vs PVI in patients with comorbid CKD. METHODS: Individuals who underwent LEB and PVI were queried from the Vascular Quality Initiative with Medicare claims-linked outcomes data. Propensity scores were calculated using 13 variables, and a 1:1 matching method was used. The mortality risk at 30 days and 5 years in LEB vs PVI by CKD was assessed using Kaplan-Meier and Cox proportional hazards models, with interaction terms added for CKD. For amputation, cumulative incidence functions and Fine-Gray models were used to account for the competing risk of death, with interaction terms for CKD added. RESULTS: Of 4084 patients (2042 per group), the mean age was 71.0 ± 10.8 years, and 69.0% were male. Irrespective of CKD status, 30-day mortality (hazard ratio [HR]: 0.94, 95% confidence interval [CI]: 0.63-1.42, P = .78) was similar for LEB vs PVI, but LEB was associated with a lower risk of 30-day amputation (sub-HR [sHR]: 0.66, 95% CI: 0.44-0.97, P = .04). CKD status, however, did not modify these results. Similarly, LEB vs PVI was associated with a lower risk of 5-year mortality (HR: 0.79, 95% CI: 0.71-0.88, P < .001) but no difference in 5-year amputation (sHR: 1.03, 95% CI: 0.89-1.20, P = .67). CKD status did not modify these results. CONCLUSIONS: Regardless of CKD status, patients had a lower risk of 5-year all-cause mortality and 30-day amputation with LEB vs PVI. Results may help inform preference-sensitive treatment decisions on LEB vs PVI for patients with CLTI and CKD, who may commonly be deemed too high risk for surgery.

Clinician perspectives regarding CYP2C19 genotype testing in patients with critical limb ischemia: A Delphi approach.

OBJECTIVES: Antiplatelet therapy is an essential element in the management of patients with arterial vascular disease. In peripheral arterial disease (PAD), dual antiplatelet therapy (DAPT), primarily clopidogrel and aspirin, is routinely prescribed following intervention. There is sparse data regarding the need for DAPT, the appropriate duration, or the heterogeneity of treatment effects for antiplatelet regimens across patients, leading to potential uncertainty and heterogeneity around treatment practices. An example of heterogeneity of treatment effects is a patients' metabolizer status for the use of clopidogrel. The aim of the study was to (1) assess clinicians' knowledge of and attitudes toward managing patients with CYP2C19 mutations, (2) identify barriers to implementation of CYP2C19 testing and management policies, and (3) reach consensus for CYP2C19 testing and management strategies for patients with PAD who undergo peripheral vascular interventions (PVI). METHODS: A modified Delphi method was used to establish consensus amongst PAD interventionalists around CYP2C19 testing. All practicing Yale New Haven Hospital PAD interventionalists with backgrounds in interventional cardiology, vascular surgery, or interventional radiology were approached by email for participation. Round 1 included the collection of baseline demographic questions, knowledge questions, and three statements for consensus. Knowledge questions were rated on a 0-10 Likert scale with the following anchors: 0 ("Not at all"), 5 ("Neutral), and 10 ("Very Much"). Participants were asked to rate the importance of the three consensus statements on a 9-point Likert scale from 1 ("Strongly Disagree") to 10 ("Strongly Agree"). In Round 2, participants were shown the same consensus statements, the median response of the group from the previous round, and their previous answers. Participants were instructed to revise their rating using the results from the previous round. This process was repeated for Round 3. RESULTS: Of the 28 experts invited to participate, 13 agreed (46%). Participants were predominantly male (92.3%) and white (61.5%) with representation from interventional cardiology (46.2%) and vascular surgery (53.8%). Most participants reported more than 10+ years in practice (61.5%). PAD interventionalists felt they would benefit from more education regarding CYP2C19 mutations (median score 8.0, interquartile range 5.0-8.5). They indicated some familiarity with CYP2C19 mutations (7.0, 6.0-9.5) but did not feel strongly that CYP2C19 was important to their practice (6.0, 5.5-7.5). In each round, the median responses for the three consensus statements were 5, 6, and 9, respectively. With each successive round the interquartile range narrowed indicative of evolving consensus but did not reach the prespecified interquartile range for consensus of 1 for any of the statements. CONCLUSIONS: PAD interventionalists practicing at an academic health system recognize the heterogenous response of their patients to clopidogrel therapy but are unsure when to leverage genetic testing to improve outcomes for their patients. Our study identified gaps regarding PAD interventionalists' knowledge, perceived barriers, and attitudes toward CYP2C19 testing in PAD. This information highlights the need for randomized data on genetic testing for clopidogrel responsiveness in peripheral vascular disease following intervention to help guide antiplatelet management.

Anticoagulation in Patients with Premature Peripheral Artery Disease Undergoing Lower Extremity Revascularization.

BACKGROUND: Premature peripheral artery disease (PAD), defined by lower extremity revascularization (LER) at age ≤ 50 years, is associated with poor major adverse limb events. The early onset of disease is thought to be influenced by genetic factors that regulate homeostasis of the vascular wall and coagulation. The aim of this study is to investigate the effect of anticoagulation as an adjunct to antiplatelet therapy on the outcomes of LER in patients with premature PAD. METHODS: There were 8,804 patients with premature PAD on preoperative and postoperative antiplatelet therapy only and 1,236 patients on preoperative and postoperative anticoagulation plus antiplatelet therapy in the Vascular Quality Initiative peripheral vascular intervention, infrainguinal, and suprainguinal files. Propensity score matching (2:1) was performed between patients with premature PAD who were on antiplatelet therapy and those on anticoagulation plus antiplatelet therapy. Perioperative and 1-year outcomes were analyzed including reintervention, major amputation, and mortality. RESULTS: Patients on anticoagulation were more likely to have coronary artery disease (48.7% vs. 41.2%, P < 0.001), congestive heart failure (20.2% vs. 13.1%, P < 0.001), and have undergone prior LER (73.9% vs. 49.2%, P < 0.001) compared to patients on antiplatelet therapy only. They were also less likely to be independently ambulatory (74.2% vs. 81.8%, P < 0.001) and be on a statin medication (66.8% vs. 74.3%, P < 0.001) compared to patients on antiplatelet therapy only. Patients on anticoagulation were also less likely to be treated for claudication (38.1% vs. 48.6%, P < 0.001), and less likely to be treated with an endovascular procedure (64.8% vs. 73.8%, P < 0.001). After matching for baseline characteristics, there were 1,256 patients on antiplatelet therapy only and 628 patients on anticoagulation. Patients on anticoagulation were more likely to require a return to the operating room (3.7% vs. 1.6%, P < 0.001) and had higher perioperative mortality (1.1% vs. 0.3%, P = 0.032), but major amputation was not significantly different (1.8% vs. 1.6%, P = 0.798) compared to patients on antiplatelet therapy alone. At 1 year, amputation-free survival was higher in patients on antiplatelets only compared to patients on anticoagulation and antiplatelet medications (87.5% vs. 80.9%, log-rank P = 0.001). CONCLUSIONS: Anticoagulation in addition to antiplatelet therapy in patients with premature PAD undergoing LER is associated with increased reintervention and mortality at 1 year.

Inter-Rater Reliability for the Amputation Endpoint in the National Vascular Quality Initiative.

BACKGROUND: National quality reporting efforts after revascularization for peripheral artery disease (PAD) are ongoing. Validation of endpoints are necessary in national quality registries. OBJECTIVES: This study sought to examine the interrater reliability for the endpoint of major amputation at 1 year in the Vascular Quality Initiative (VQI) registry and the Medicare-linked Vascular Quality Initiative registry (VQI-VISION) against electronic health record (EHR) review. METHODS: Surgical or endovascular revascularization procedures between January 1, 2010, and December 31, 2017, in the VQI registry and VQI-VISION for 2 academic health systems were queried. Major amputation data were abstracted by trained data collectors for the VQI and derived from Current Procedural Terminology codes for VQI-VISION. Cases underwent protocolized adjudication for the endpoint of major amputation by EHR review. Paired tests were used to evaluate the sensitivity and specificity. Spearman's ρ and Cohen's κ were used to evaluate interrater reliability. RESULTS: Amputation endpoints for 1,936 revascularizations were examined. Compared with major amputation data in EHR review, the sensitivity for the VQI registry was 35.9% and the specificity was 99.4% (ρ = 0.53; κ = 0.48). For VQI-VISION, sensitivity was 67.7% and specificity was 98.9% (ρ = 0.75; κ = 0.74). For any amputation in VQI data, sensitivity was 35.3% and specificity was 99.3% (ρ = 0.53; κ = 0.46), and for VQI-VISION, they were 71.6% and 97.7%, respectively (ρ = 0.75; κ = 0.74). CONCLUSIONS: Almost two-thirds of the amputations in the VQI registry and one-third of amputations in VQI-VISION were missing at 1 year compared against adjudicated EHR review. In preparing for national reporting systems for major amputation tracking, data collection system reform is needed.

Evaluation of short-term mortality in patients with Medicare undergoing endovascular interventions for chronic limb-threatening ischemia.

INTRODUCTION: Patients with chronic limb-threatening ischemia (CLTI) have high mortality rates after revascularization. Risk stratification for short-term outcomes is challenging. We aimed to develop machine-learning models to rank predictive variables for 30-day and 90-day all-cause mortality after peripheral vascular intervention (PVI). METHODS: Patients undergoing PVI for CLTI in the Medicare-linked Vascular Quality Initiative were included. Sixty-six preprocedural variables were included. Random survival forest (RSF) models were constructed for 30-day and 90-day all-cause mortality in the training sample and evaluated in the testing sample. Predictive variables were ranked based on the frequency that they caused branch splitting nearest the root node by importance-weighted relative importance plots. Model performance was assessed by the Brier score, continuous ranked probability score, out-of-bag error rate, and Harrell's C-index. RESULTS: A total of 10,114 patients were included. The crude mortality rate was 4.4% at 30 days and 10.6% at 90 days. RSF models commonly identified stage 5 chronic kidney disease (CKD), dementia, congestive heart failure (CHF), age, urgent procedures, and need for assisted care as the most predictive variables. For both models, eight of the top 10 variables were either medical comorbidities or functional status variables. Models showed good discrimination (C-statistic 0.72 and 0.73) and calibration (Brier score 0.03 and 0.10). CONCLUSION: RSF models for 30-day and 90-day all-cause mortality commonly identified CKD, dementia, CHF, need for assisted care at home, urgent procedures, and age as the most predictive variables as critical factors in CLTI. Results may help guide individualized risk-benefit treatment conversations regarding PVI.

Impact of comorbid opioid use disorder and major depressive disorder on healthcare utilization outcomes in patients with peripheral artery disease: A National Readmission Database analysis.

BACKGROUND: Prior research has demonstrated that individuals with peripheral artery disease (PAD) often have comorbid opioid use disorder (OUD) and major depressive disorder (MDD), with limited data regarding their impact on readmission outcomes, length of stay, and cost. This study aimed to investigate these healthcare utilization outcomes in patients with PAD who have comorbid OUD and MDD. METHODS: Data were obtained from the National Readmission Database from 2011 through 2018. The study population included all hospitalizations with PAD as the primary or secondary diagnosis, from which hospitalizations with OUD and MDD were extracted using appropriate ICD-9/10 diagnosis codes. Primary outcomes were 30-day and 90-day readmission, total cost, and total length of stay within the calendar year. We created hierarchical multivariable logistic regression models examining OUD with and without MDD, with a random effect for healthcare facility location. RESULTS: From 2011 to 2018, 13,265,817 weighted admissions with PAD were identified. These admissions were segmented into four categories: No OUD/No MDD (12,056,466), OUD/No MDD (323,762), No OUD/MDD (867,641), and OUD/MDD (17,948). The group with No OUD/No MDD was used as the reference group for all subsequent comparisons. Regarding 30-day and 90-day readmissions, patients with OUD/MDD had odds of 1.14 (95% CI 1.10, 1.18) and 1.09 (95% CI 1.06, 1.13), respectively. Patients with OUD/No MDD bore the highest median cost of $64,354 (IQR $30,797-137,074), and patients with OUD/MDD marked the lengthiest median stay of 6.01 days (IQR 2.01-13.30). CONCLUSION: This study found a significant association between these comorbidities and outcomes and therefore calls for targeted interventions and pain management strategies.

Secondary interventions following open vs endovascular revascularization for chronic limb threatening ischemia in the BEST-CLI trial.

OBJECTIVES: Patients undergoing revascularization for chronic limb-threatening ischemia experience a high burden of target limb reinterventions. We analyzed data from the Best Endovascular versus Best Surgical Therapy in Patients with Critical Limb Ischemia (BEST-CLI) randomized trial comparing initial open bypass (OPEN) and endovascular (ENDO) treatment strategies, with a focus on reintervention-related study endpoints. METHODS: In a planned secondary analysis, we examined the rates of major reintervention, any reintervention, and the composite of any reintervention, amputation, or death by intention-to-treat assignment in both trial cohorts (cohort 1 with suitable single-segment great saphenous vein [SSGSV], n = 1434; cohort 2 lacking suitable SSGSV, n = 396). We also compared the cumulative number of major and all index limb reinterventions over time. Comparisons between treatment arms within each cohort were made using univariable and multivariable Cox regression models. RESULTS: In cohort 1, assignment to OPEN was associated with a significantly reduced hazard of a major limb reintervention (hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.28-0.49; P < .001), any reintervention (HR, 0.63; 95% CI, 0.53-0.75; P < .001), or any reintervention, amputation, or death (HR, 0.68; 95% CI, 0.60-0.78; P < .001). Findings were similar in cohort 2 for major reintervention (HR, 0.53; 95% CI, 0.33-0.84; P = .007) or any reintervention (HR, 0.71; 95% CI, 0.52-0.98; P = .04). In both cohorts, early (30-day) limb reinterventions were notably higher for patients assigned to ENDO as compared with OPEN (14.7% vs 4.5% of cohort 1 subjects; 16.6% vs 5.6% of cohort 2 subjects). The mean number of major (mean events per subject ratio [MR], 0.45; 95% CI, 0.34-0.58; P < .001) or any target limb reinterventions (MR, 0.67; 95% CI, 0.57-0.80; P < .001) per year was significantly less in the OPEN arm of cohort 1. The mean number of reinterventions per limb salvaged per year was lower in the OPEN arm of cohort 1 (MR, 0.45; 95% CI, 0.35-0.57; P < .001 and MR, 0.66; 95% CI, 0.55-0.79; P < .001 for major and all, respectively). The majority of index limb reinterventions occurred during the first year following randomization, but events continued to accumulate over the duration of follow-up in the trial. CONCLUSIONS: Reintervention is common following revascularization for chronic limb-threatening ischemia. Among patients deemed suitable for either approach, initial treatment with open bypass, particularly in patients with available SSGSV conduit, is associated with a significantly lower number of major and minor target limb reinterventions.

Insulin Requirement and Infrainguinal Bypass Outcomes in Patients with Peripheral Arterial Disease.

BACKGROUND: Diabetes mellitus (DM) is a major risk factor for peripheral artery disease. The association of DM with major adverse limb events (MALE) after lower extremity revascularization remains controversial, as patients with diabetes are typically analyzed as a single, homogenous group. Using a large national database, this study examines the impact of insulin use and glycemic control on the outcomes following infrainguinal bypass. The hypothesis is that prevalent insulin therapy and elevated hemoglobin A1c (HbA1c) are associated with an increased risk of MALEs after infrainguinal bypass in patients with DM and could therefore be used for risk stratification. METHODS: The Vascular Quality Initiative database files for infrainguinal bypass (2007-2021) were retrospectively reviewed. Patients with DM undergoing bypass for peripheral artery disease were included. Patients on dialysis or with prior kidney transplantation were excluded. The characteristics and outcomes of patients with insulin-requiring diabetes mellitus (IRDM) were compared to those of patients not requiring insulin (noninsulin-requiring diabetes mellitus [NIRDM]) prior to the bypass procedure. RESULTS: A total of 9,686 patients with DM (56% IRDM) underwent bypass. Patients with IRDM were significantly younger than patients with NIRDM, more likely to be female (P < 0.01), African American (P < 0.01), and Hispanic (P = 0.031), and more likely to have comorbidities and be categorized into American Society of Anesthesiologist classes IV-V. They were more likely to be treated for chronic limb-threatening ischemia (P < 0.001). Patients with IRDM had significantly higher perioperative complications with no difference in perioperative mortality between the 2 groups. Beyond the perioperative period, with a mean follow-up of 427 days, patients with IRDM had significantly lower crude rates of primary patency and higher crude rates of major amputation, MALE, and mortality compared to patients with NIRDM. Regression analyses demonstrated that insulin requirement, but not HbA1c, was independently associated with a higher risk of MALE (hazard ratio = 1.17 [1.06-1.29]) and mortality (hazard ratio = 1.28 [1.16-1.43]). CONCLUSIONS: Insulin requirement, but not HbA1c, is significantly associated with MALEs and survival after infrainguinal bypass in the Vascular Quality Initiative. Stratification of patients with DM based on their prevalent insulin use prior to infrainguinal bypass surgery could improve the prediction of outcomes of peripheral arterial bypass surgery in patients with diabetes.

Variability in guideline-directed medical therapy across sites and operators and long-term mortality and amputation outcomes risk in patients undergoing peripheral vascular interventions.

BACKGROUND: The use of guideline-directed medical therapy (GDMT) in patients undergoing peripheral vascular interventions (PVIs) decreases the risk of death and amputation and may decrease hospital readmissions. The variability of GDMT prescription across sites and operators and the proportionality of risk is not well understood. We aimed to study the association between variability of GDMT prescription at the site and operator level and outcomes (including 90-day readmissions and 24-month all-cause mortality and major amputation). METHODS: We examined GDMT discharge rates in PVIs performed between 2017 and 2018 using Medicare-linked Vascular Quality Initiative registry. GDMT included a statin, antiplatelet therapy, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACE-i/ARB) if hypertensive. Quartiles (Q1-4) of GDMT rates were documented by operators and sites and variability was quantified using median odds ratios (MOR) and intraclass correlation (ICC). The association between lower GDMT rates (per 10%) by sites and operators with 90-day readmission were calculated using logistic regression, and with 24-month mortality and major amputation using parametric survival model. Models were adjusted for patient-level factors and included sites and operators nested within sites as 2 random effects. RESULTS: GDMT rates for 17,147 patients across 223 sites and 1,263 operators ranged from 0% to 38% (Q1, MOR 1.43, 95%CI 1.39-1.47, P ≤ .001) to 57%-100% (Q4, MOR 1.48, 95%CI 1.44-1.51, P ≤ .001). Four percent of variance in GDMT use was explained by sites (ICC 3.9, 95%CI 2.9-5.3) and operators (ICC 4.1, 95%CI 3.1-5.4). A dose-response relationship was noted between lower GDMT rates and increased risk of 90-day readmission risk by sites (P = .021) and operators (P < .001). Lower GDMT prescription by site was associated with higher risk of 24-month mortality (HR = 1.07, 95%CI 1.02-1.13) and major amputation (HR = 1.08, 95%CI 1.01-1.15). Similar associations were found for GDMT use by provider (mortality HR = 1.05, 95%CI 1.02-1.08 and amputation HR = 1.04, 95%CI 1.00-1.08). CONCLUSION: Both at the operator and health system level, there was significant variability in GDMT prescription following PVI, proportionally translating into risk for readmission, mortality, and major amputation. Targeted quality efforts should prioritize both operator and site levels to improve GDMT use and outcomes for patients undergoing PVI.

Psychosocial and socioeconomic factors are most predictive of health status in patients with claudication.

BACKGROUND: As a key treatment goal for patients with symptomatic peripheral artery disease (PAD), improving health status has also become an important end point for clinical trials and performance-based care. An understanding of patient factors associated with 1-year PAD health status is lacking in patients with PAD. METHODS: The health status of 1073 consecutive patients with symptomatic PAD in the international multicenter PORTRAIT (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) registry was measured at baseline and 1 year with the Peripheral Artery Questionnaire (PAQ). The association of 47 patient characteristics with 1-year PAQ scores was assessed using a random forest algorithm. Variables of clinical significance were retained and included in a hierarchical multivariable linear regression model predicting 1-year PAQ summary scores. RESULTS: The mean age of patients was 67.7 ± 9.3 years, and 37% were female. Variables with the highest importance ranking in predicting 1-year PAQ summary score were baseline PAQ summary score, Patient Health Questionnaire-8 depression score, Generalized Anxiety Disorder-2 anxiety score, new onset symptom presentation, insurance status, current or prior diagnosis of depression, low social support, initial invasive treatment, duration of symptoms, and race. The addition of 19 clinical variables in an extended model marginally improved the explained variance in 1-year health status (from R2 0.312 to 0.335). CONCLUSIONS: Patients' 1-year PAD-specific health status, as measured by the PAQ, can be predicted from 10 mostly psychosocial and socioeconomic patient characteristics including depression, anxiety, insurance status, social support, and symptoms. These characteristics should be validated and tested in other PAD cohorts so that this model can inform risk adjustment and prediction of PAD health status in comparative effectiveness research and performance-based care.

Examining Outcomes in Patients Admitted With Comorbid Peripheral Artery Disease and Microvascular Disease.

BACKGROUND: Peripheral artery disease (PAD) and microvascular disease (MVD) are highly prevalent conditions that share common risk factors. This observational study aimed to characterize patients with both conditions and determine the impact of comorbid PAD/MVD on outcomes. METHODS AND RESULTS: Patients admitted across 31 states January 2011 through December 2018 with a primary or secondary diagnosis of PAD or MVD were included from the National Readmissions Database and weighted to approximate a national sample. Those age <18 years or with nonatherosclerotic leg injuries were excluded. Patients were divided into 3 groups: PAD-only, MVD-only, or comorbid PAD/MVD. Multiple logistic regression was used to evaluate associations with major and minor amputations, major adverse cardiac events, and in-hospital mortality. Cox regression was used to evaluate associations with readmission within 1 year. The PAD group was used as reference. The final cohort included 33 972 772 admissions: 9.1 million with PAD, 21.3 million with MVD, and 3.6 million with both. Annual admissions for PAD/MVD increased to >500 000 in 2018. Major and minor amputations increased ≈50% for PAD/MVD between 2011 and 2018. Compared with PAD-only, PAD/MVD was associated with a higher risk for major amputation (odds ratio [OR], 1.30 [95% CI, 1.28-1.32]), minor amputation (OR, 2.15 [95% CI, 2.12-2.18]), major adverse cardiac events (OR, 1.04 [95% CI, 1.03-1.04]), in-hospital mortality (OR, 1.07 [95% CI, 1.05-1.09]), and readmission (hazard ratio, 1.02 [95% CI, 1.02-1.02]) after adjustment for baseline factors. CONCLUSIONS: Comorbid MVD is present in a large and growing number of patients with PAD and is associated with augmented risk for adverse outcomes. Further prospective research is merited to understand this vulnerable population.

Successful percutaneous management of hypothenar hammer syndrome with thrombosuction and catheter-directed intra-arterial thrombolysis.

Hypothenar hammer syndrome (HHS) is a rare vascular disorder leading to ulnar artery thrombosis or aneurysm and causing acute or chronic limb ischemia. The optimal approaches to managing this condition lack a definitive consensus and are essentially empirical, typically necessitating conservative methods for symptomatic relief, with surgical intervention reserved for cases for which conservative measures prove inadequate or when acute limb ischemia ensues. Limited data are available on percutaneous management for this condition. We present the case of a 36-year-old male powerlifter who developed acute digital ischemia due to HHS in the left hand that was managed successfully through an innovative approach using antegrade left brachial artery access and combining percutaneous thrombosuction and intra-arterial thrombolysis. This comprehensive approach resulted in restoration of blood flow and resolution of acute limb ischemia. The patient was subsequently prescribed short-term anticoagulation therapy and remained symptom free at 3 months of follow-up. This innovative strategy challenges traditional surgical approaches in HHS management, underscoring the importance of using minimally invasive techniques as a promising alternative and highlighting potential avenues for further research.

Developmental or Procedural Vena Cava Interruption and Venous Thromboembolism: A Review.

The inferior vena cava (IVC) and superior vena cava are the main conduits of the systemic venous circulation into the right atrium. Developmental or procedural interruptions of vena cava might predispose to stasis and deep vein thrombosis (DVT) distal to the anomaly and may impact the subsequent rate of pulmonary embolism (PE). This study aimed to review the various etiologies of developmental or procedural vena cava interruption and their impact on venous thromboembolism. A systematic search was performed in PubMed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines per each clinical question. For management questions with no high-quality evidence and no mutual agreements between authors, Delphi methods were used. IVC agenesis is the most common form of congenital vena cava interruption, is associated with an increased risk of DVT, and should be suspected in young patients with unexpected extensive bilateral DVT. Surgical techniques for vena cava interruption (ligation, clipping, and plication) to prevent PE have been largely abandoned due to short-term procedural risks and long-term complications, although survivors of prior procedures are occasionally encountered. Vena cava filters are now the most commonly used method of procedural interruption, frequently placed in the infrarenal IVC. The most agreed-upon indication for vena cava filters is for patients with acute venous thromboembolism and coexisting contraindications to anticoagulation. Familiarity with different forms of vena cava interruption and their local and systemic adverse effects is important to minimize complications and thrombotic events.

Chronic Cough: Characterizing and Quantifying Burden in Adults Using a Nationwide Electronic Health Records Database.

Chronic cough is a common condition; until recently, no International Classification of Diseases (ICD) code for chronic cough existed; therefore, the true scope and burden of chronic cough is unclear. Using established algorithms, we examined chronic cough patients and their risk profiles, recurrent cough episodes, and subsequent 1-year health care utilization in the nationwide Cerner EHR data resource, compared with those with acute cough. An ICD-based algorithm was applied to the Cerner Health Facts EHR database to derive a phenotype of chronic cough defined as three ICD-based "cough" encounters 14-days apart over a 56-to-120-day period from 2015 to 2017. Demographics, comorbidities, and outcomes (1-year outpatient, emergency, and inpatient encounters) were collected for the chronic cough cohort and acute cough cohort. The chronic cough cohort was 61.5% female, 70.4% white, and 15.2% African American, with 13.7% being of Asian, Native American, or unknown race. Compared with the acute cough cohort, chronic cough patients were more likely to be older, female, and have chronic pulmonary disease, obesity, and depression. Predictors of recurrent chronic cough were older age and race. Those with chronic cough had more outpatient (2.48 ± 2.10 vs. 1.48 ± 0.99; SMD = 0.94), emergency (1.90 ± 2.26 vs. 1.23 ± 0.68; SMD = 0.82), and inpatient (1.11 ± 0.36 vs. 1.05 ± 0.24, SMD = 0.24) encounters compared with acute cough. While EHR-based data may provide a useful resource to identify chronic cough phenotypes, supplementary data approaches and screening methods for chronic cough can further identify the scope of the problem.

The Impact of Ejection Fraction on Major Adverse Limb Events after Lower Extremity Revascularization.

BACKGROUND: Peripheral arterial disease (PAD) is commonly associated with coronary artery disease, and echocardiography is frequently performed before lower extremity revascularization (LER). However, the incidence of various echocardiographic findings in patients with PAD and their impact on the outcomes of LER has not been well studied. Reduced ejection fraction (EF) ≤ 40% is associated with increased major adverse limb events (MALE) after LER. METHODS: The electronic medical records of patients undergoing LER in a single center were reviewed. Patients were divided based on the presence or absence of reduced EF. Patient, transthoracic echocardiogram, procedural characteristics, and outcomes were compared between the 2 groups. RESULTS: A total of 1,114 patients (N = 131, 11.8% with reduced EF) underwent LER between 2013 and 2019. Patients with reduced EF were more likely to be male and have a history of coronary artery disease and heart failure. Furthermore, they were more likely to have diastolic dysfunction with moderate to severe mitral and tricuspid valve regurgitation. Patients with reduced EF were more likely to undergo LER for chronic limb-threatening ischemia, and to be treated with endovascular procedures. Perioperatively, patients with reduced EF were more likely to develop myocardial infarction. Lastly, the 2 groups had no difference in overall MALE or major amputation. However, on Kaplan-Meier curves, MALE-free survival was significantly lower for patients with reduced EF. Regression analysis demonstrated that indication and not EF was associated with MALE and MALE-free survival. CONCLUSIONS: Reduced EF is associated with decreased MALE-free survival for patients with PAD undergoing LER.