Quality of Life in Patients With Chronic Limb-Threatening Ischemia Treated With Revascularization.

BACKGROUND: In the BEST-CLI trial (Best Endovascular Versus Best Surgical Therapy for Patients With Chronic Limb-Threatening Ischemia), a prespecified secondary objective was to assess the effects of revascularization strategy on health-related quality of life (HRQoL). METHODS: Patients with chronic limb-threatening ischemia were randomized to surgical bypass (Bypass) or endovascular intervention (Endo) in 2 parallel trials. Cohort 1 included patients with single-segment great saphenous vein; cohort 2 included those lacking suitable single-segment great saphenous vein. HRQoL was assessed over the trial duration using Vascular Quality-of-Life (VascuQoL), European Quality-of-Life-5D (EQ-5D), the Short Form-12 (SF-12) Physical Component Summary (SF-12 PCS), SF-12 Mental Component Summary (SF-12 MCS), Utility Index Score (SF-6D R2), and numeric rating scales of pain. HRQoL was summarized by cohort and compared within and between groups using mixed-model linear regression. RESULTS: A total of 1193 and 335 patients in cohorts 1 and 2 with a mean follow-up of 2.9 and 2.0 years, respectively, were analyzed. In cohort 1, HRQoL significantly improved from baseline to follow-up for both groups across all measures. For example, mean (SD) VascuQoL scores were 3.0 (1.3) and 3.0 (1.2) for Bypass and Endo at baseline and 4.7 (1.4) and 4.8 (1.5) over follow-up. There were significant group differences favoring Endo when assessed with VascuQoL (difference, -0.14 [95% CI, -0.25 to -0.02]; P=0.02), SF-12 MCS (difference, -1.03 [95% CI, -1.89 to -0.18]; P=0.02), SF-6D R2 (difference, -0.01 [95% CI, -0.02 to -0.001]; P=0.03), numeric rating scale pain at present (difference, 0.26 [95% CI, 0.03 to 0.49]; P=0.03), usual level during previous week (difference, 0.26 [95% CI, 0.04 to 0.48]; P=0.02), and worst level during previous week (difference, 0.29 [95% CI, 0.02 to 0.56]; P=0.04). There was no difference between treatment arms on the basis of EQ-5D (difference, -0.01 [95% CI, -0.03 to 0.004]; P=0.12) or SF-12 PCS (difference, -0.41 [95% CI, -1.2 to 0.37]; P=0.31). In cohort 2, HRQoL also significantly improved from baseline to the end of follow-up for both groups based on all measures, but there were no differences between Bypass and Endo on any measure. CONCLUSIONS: Among patients with chronic limb-threatening ischemia deemed eligible for either Bypass or Endo, revascularization resulted in significant and clinically meaningful improvements in HRQoL. In patients with an available single-segment great saphenous vein for bypass, but not among those without one, Endo was statistically superior on some HRQoL measures; however, these differences were below the threshold of clinically meaningful difference.

Current Status and Principles for the Treatment and Prevention of Diabetic Foot Ulcers in the Cardiovascular Patient Population: A Scientific Statement From the American Heart Association.

Despite the known higher risk of cardiovascular disease in individuals with type 2 diabetes, the pathophysiology and optimal management of diabetic foot ulcers (DFUs), a leading complication associated with diabetes, is complex and continues to evolve. Complications of type 2 diabetes, such as DFUs, are a major cause of morbidity and mortality and the leading cause of major lower extremity amputation in the United States. There has recently been a strong focus on the prevention and early treatment of DFUs, leading to the development of multidisciplinary diabetic wound and amputation prevention clinics across the country. Mounting evidence has shown that, despite these efforts, amputations associated with DFUs continue to increase. Furthermore, due to increasing patient complexity of management secondary to comorbid conditions, such as cardiovascular disease, the management of peripheral artery disease associated with DFUs has become increasingly difficult, and care delivery is often episodic and fragmented. Although structured, process-specific approaches exist at individual institutions for the management of DFUs in the cardiovascular patient population, there is insufficient awareness of these principles in the general medicine communities. Furthermore, there is growing interest in better understanding the mechanistic underpinnings of DFUs to better define personalized medicine to improve outcomes. The goals of this scientific statement are to provide salient background information on the complex pathogenesis and current management of DFUs in cardiovascular patients, to guide therapeutic and preventive strategies and future research directions, and to inform public policy makers on health disparities and other barriers to improving and advancing care in this expanding patient population.

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.

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

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

Bioengineering Cell Therapy for Treatment of Peripheral Artery Disease.

Peripheral artery disease is an atherosclerotic disease associated with limb ischemia that necessitates limb amputation in severe cases. Cell therapies comprised of adult mononuclear or stromal cells have been clinically tested and show moderate benefits. Bioengineering strategies can be applied to modify cell behavior and function in a controllable fashion. Using mechanically tunable or spatially controllable biomaterials, we highlight examples in which biomaterials can increase the survival and function of the transplanted cells to improve their revascularization efficacy in preclinical models. Biomaterials can be used in conjunction with soluble factors or genetic approaches to further modulate the behavior of transplanted cells and the locally implanted tissue environment in vivo. We critically assess the advances in bioengineering strategies such as 3-dimensional bioprinting and immunomodulatory biomaterials that can be applied to the treatment of peripheral artery disease and then discuss the current challenges and future directions in the implementation of bioengineering strategies.

Intravascular ultrasound-guided drug-coated balloon angioplasty for femoropopliteal artery disease: a clinical trial.

BACKGROUND AND AIMS: Drug-coated balloons (DCBs) have demonstrated favourable outcomes following endovascular therapy for femoropopliteal artery (FPA) disease. However, uncertainty remains whether the use of intravascular ultrasound (IVUS) can improve the outcomes of DCBs. METHODS: This prospective, multicentre, randomized trial, conducted at seven centres in South Korea, compared the outcomes of IVUS-guided vs. angiography-guided angioplasty for treating FPA disease with DCBs. Patients were assigned to receive IVUS-guided (n = 119) or angiography-guided (n = 118) angioplasty using DCBs. The primary endpoint was 12-month primary patency. RESULTS: Between May 2016 and August 2022, 237 patients were enrolled and 204 (86.0%) completed the trial (median follow-up; 363 days). The IVUS guidance group showed significantly higher primary patency [83.8% vs. 70.1%; cumulative difference 19.6% (95% confidence interval 6.8 to 32.3); P = .01] and increased freedom from clinically driven target lesion revascularization [92.4% vs. 83.0%; difference 11.6% (95% confidence interval 3.1 to 20.1); P = .02], sustained clinical improvement (89.1% vs. 76.3%, P = .01), and haemodynamic improvement (82.4% vs. 66.9%, P = .01) at 12 months compared with the angiography guidance group. The IVUS group utilized larger balloon diameters and pressures for pre-dilation, more frequent post-dilation, and higher pressures for post-dilation, resulting in a greater post-procedural minimum lumen diameter (3.90 ± 0.59 vs. 3.71 ± 0.73 mm, P = .03). CONCLUSIONS: Intravascular ultrasound guidance significantly improved the outcomes of DCBs for FPA disease in terms of primary patency, freedom from clinically driven target lesion revascularization, and sustained clinical and haemodynamic improvement at 12 months. These benefits may be attributed to IVUS-guided optimization of the lesion before and after DCB treatment.

Critical limb-threatening ischaemia and microvascular transformation: clinical implications.

BACKGROUND AND AIMS: Clinical management of critical limb-threatening ischaemia (CLTI) is focused on prevention and treatment of atherosclerotic arterial occlusions. The role of microvascular pathology in disease progression is still largely unspecified and more importantly not utilized for treatment. The aim of this explorative study was to characterize the role of the microvasculature in CLTI pathology. METHODS: Clinical high-resolution imaging of CLTI patients (n = 50) and muscle samples from amputated CLTI limbs (n = 40) were used to describe microvascular pathology of CLTI at the level of resting muscle blood flow and microvascular structure, respectively. Furthermore, a chronic, low arterial driving pressure-simulating ischaemia model in rabbits (n = 24) was used together with adenoviral vascular endothelial growth factor A gene transfers to study the effect of microvascular alterations on muscle outcome. RESULTS: Resting microvascular blood flow was not depleted but displayed decreased capillary transit time (P < .01) in CLTI muscles. Critical limb-threatening ischaemia muscle microvasculature also exhibited capillary enlargement (P < .001) and further arterialization along worsening of myofibre atrophy and detaching of capillaries from myofibres. Furthermore, CLTI-like capillary transformation was shown to worsen calf muscle force production (P < .05) and tissue outcome (P < .01) under chronic ischaemia in rabbits and in healthy, normal rabbit muscle. CONCLUSIONS: These findings depict a progressive, hypoxia-driven transformation of the microvasculature in CLTI muscles, which pathologically alters blood flow dynamics and aggravates tissue damage under low arterial driving pressure. Hypoxia-driven capillary enlargement can be highly important for CLTI outcomes and should therefore be considered in further development of diagnostics and treatment of CLTI.

Mitochondrial respiration in peripheral arterial disease depends on stage severity.

Peripheral arterial disease (PAD) is an increasing cause of morbidity and its severity is graded based on clinical manifestation. To investigate the influence of the different stages on myopathy of ischemic muscle we analysed severity-dependent effects of mitochondrial respiration in PAD. Eighteen patients with severe PAD, defined as chronic limb-threatening ischemia, 47 patients with intermittent claudication (IC) and 22 non-ischemic controls were analysed. High-resolution respirometry (HRR) was performed on muscle biopsies of gastrocnemius and vastus lateralis muscle of patients in different PAD stages to investigate different respiratory states. Results from HRR are given as median and interquartile range and were normalized to citrate synthase activity (CSA), a marker for mitochondrial content. In order to account for inter-individual differences between patients and controls, we calculated the ratio of O2-flux in gastrocnemius muscle over vastus muscle ('GV ratio'). CSA of the gastrocnemius muscle as a proxy for mitochondrial content was significantly lower in critical ischemia compared to controls. Mitochondrial respiration normalized to CSA was higher in IC compared to controls. Likewise, the GV ratio was significantly higher in IC compared to control. Mitochondrial respiration and CSA of PAD patients showed stage-dependent modifications with greater changes in the mild PAD stage group (IC).

Rivaroxaban Plus Aspirin Versus Aspirin Alone After Endovascular Revascularization for Symptomatic PAD: Insights From VOYAGER PAD.

BACKGROUND: Rivaroxaban plus aspirin compared with aspirin alone reduced major cardiac and ischemic limb events after lower extremity revascularization (LER) in the VOYAGER PAD (Vascular Outcomes Study of ASA Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease) trial. The effect has not been described in patients undergoing endovascular LER. METHODS: The VOYAGER PAD trial randomized 6564 patients with symptomatic peripheral artery disease to a double-blinded treatment with 2.5 mg of rivaroxaban BID or matching placebo and 100 mg of aspirin daily. The primary efficacy outcome was a composite of acute limb ischemia, major amputation of a vascular pathogenesis, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety end point was Thrombolysis in Myocardial Infarction major bleeding. A prespecified subgroup of patients who underwent endovascular revascularization was included. RESULTS: Endovascular LER occurred in 4379 (66.7%) patients and surgical LER in 2185 (33.3%). Over a 3-year follow-up, rivaroxaban reduced the risk of the primary outcome by 15% (hazard ratio [HR], 0.85 [95% CI, 0.76-0.96]) with an absolute risk reduction of 0.92% at 6 months and 1.04% at 3 years and a consistent benefit in those receiving endovascular (HR, 0.89 [95% CI, 0.76-1.03]) or surgical LER (HR, 0.81 [95% CI, 0.67-0.98]; P interaction=0.43). For endovascular-treated patients, rivaroxaban reduced the risk of acute limb ischemia or major amputation of a vascular pathogenesis by 30% (HR, 0.70 [95% CI, 0.54-0.90]; P=0.005) with an absolute risk reduction of 1.0% at 6 months and 2.0% at 3 years compared with aspirin alone. Among endovascular-treated patients, the median duration of concomitant dual antiplatelet therapy with clopidogrel treatment was 31 days (interquartile range, 30-58). There was a consistent benefit for rivaroxaban regardless of background clopidogrel. Thrombolysis in Myocardial Infarction major bleeding was significantly higher for the rivaroxaban and aspirin group for the endovascular cohort (HR, 1.66 [95% CI, 1.06-2.59]) with an absolute risk increase of 0.9% at 3 years with no increase in intracranial or fatal bleeding observed (HR, 0.86 [95% CI, 0.40-1.87]; P=0.71). Mortality with rivaroxaban was higher in the endovascular-treated patients (HR, 1.24 [95% CI, 1.02-1.52]), although this finding was isolated to specific regions. CONCLUSIONS: Rivaroxaban added to aspirin or dual antiplatelet therapy after LER for peripheral artery disease reduces ischemic risk and increases major bleeding without an increased risk of intracranial or fatal bleeding. These benefits are consistent in those treated with endovascular and surgical approaches with significant benefits for major adverse limb events. These data support the use of rivaroxaban in addition to aspirin or dual antiplatelet therapy after endovascular intervention for symptomatic peripheral artery disease.

Health Disparities in Peripheral Artery Disease: A Scientific Statement From the American Heart Association.

Peripheral artery disease (PAD) affects 200 million individuals worldwide. In the United States, certain demographic groups experience a disproportionately higher prevalence and clinical effect of PAD. The social and clinical effect of PAD includes higher rates of individual disability, depression, minor and major limb amputation along with cardiovascular and cerebrovascular events. The reasons behind the inequitable burden of PAD and inequitable delivery of care are both multifactorial and complex in nature, including systemic and structural inequity that exists within our society. Herein, we present an overview statement of the myriad variables that contribute to PAD disparities and conclude with a summary of potential novel solutions.

Cardiovascular and renal diseases in type 2 diabetes patients: 5-year cumulative incidence of the first occurred manifestation and hospitalization cost: a cohort within the French SNDS nationwide claims database.

BACKGROUND: Myocardial infarction (MI), stroke, peripheral arterial disease (PAD), heart failure (HF) and chronic kidney disease (CKD) are common cardiovascular renal diseases (CVRD) manifestations for type 2 diabetes. The objective was to estimate the incidence of the first occurring CVRD manifestation and cumulative hospitalization costs of each CVRD manifestation for type 2 diabetes without CVRD history. METHODS: A cohort study of all type 2 diabetes free of CVRD as of January 1st 2014, was identified and followed-up for 5 years within the French SNDS nationwide claims database. The cumulative incidence of the first occurring CVRD manifestation was estimated using the cumulative incidence function, with death as a competing risk. Cumulative hospitalization costs of each CVRD manifestations were estimated from the perspective of all payers. RESULTS: From 2,079,089 type 2 diabetes without cancer or transplantation, 76.5% were free of CVRD at baseline with a mean age of 65 years, 52% of women and 7% with microvascular complications history. The cumulative incidence of a first CVRD manifestation was 15.3% after 5 years of follow-up with a constant linear increase over time for all CVRD manifestations: The most frequent was CKD representing 40.6% of first occurred CVRD manifestation, followed by HF (23.0%), then PAD (13.5%), stroke (13.2%) and MI (9.7%). HF and CKD together reached about one patient out of ten after 5 years and represented 63.6% of first CVRD manifestations. The 5-year global cost of all CVRD hospitalizations was 3.9 billion euros (B€), i.e. 2,450€ per patient of the whole cohort, with an exponential increase over time for each specific CVRD manifestation. The costliest was CKD (2.0 B€), followed by HF (1.2 B€), then PAD (0.7 B€), stroke (0.6 B€) and MI (0.3 B€). CONCLUSIONS/INTERPRETATION: While MI, stroke and PAD remain classic major risks of complications for CVRD-free type 2 diabetes, HF and CKD nowadays represent individually a higher risk and cost than each of these classic manifestations, and jointly represents a risk and a cost twice as high as these three classic manifestations all together. This should encourage the development of specific HF and CKD preventive strategies.

Impact of routine surveillance duplex ultrasound and subsequent reintervention after superficial femoral artery stenting.

OBJECTIVE: Superficial femoral artery (SFA) stenting is a common treatment for peripheral artery disease. It is effective in the short term; however, in-stent restenosis (ISR) limits long-term success. Surveillance with duplex ultrasound (DUS) can identify patients who develop ISR leading to early reintervention, but data to support this practice is sparce. The purpose of this study was to evaluate whether surveillance and subsequent reintervention improves outcomes in patients with SFA stents. METHODS: A single-center, retrospective study was performed with patients undergoing SFA stenting between 2005 and 2020 who had a follow-up with DUS. Five groups were identified based on the presence of ISR on DUS (ISR vs no ISR [NISR]), recurrence of symptoms (symptomatic [SX] vs asymptomatic [ASX]), and if any reintervention was performed (reintervention [R] vs no reintervention [NR]): (1) ISR+SX+R; (2) ISR+SX+NR; (3) ISR+ASX+R; (4) ISR+ASX+NR; and (5) NISR+NR. The primary endpoint was amputation-free survival, and the secondary endpoint was patency. Predictors of mortality and surveillance were identified by multivariable logistic regressions and Cox multivariate regression models. Survival curves were presented as Kaplan-Meier plots using log-rank test for subgroup comparison. RESULTS: Two hundred fifty-seven patients were included in the analysis. The indication for intervention was claudication in 28% and chronic limb-threatening ischemia in 72%. A total of 161 patients (63%) underwent reintervention for ISR. Of patients who had restenosis on DUS, those who were symptomatic and did not undergo reintervention (ISR+SX+NR) did the worst, with 50% amputation rate. In contrast, those who were asymptomatic but did undergo reintervention (ISR+ASX+R) had the lowest amputation rate of 13%. Active smoking was a predictor of both loss of patency and amputation (1.72; 95% confidence interval [CI], 1.00-2.98; P = .050; 3.55; 95% CI, 1.53-8.25; P = .003). Post procedure dual antiplatelet therapy had a positive association with limb salvage (hazard ratio [HR], 0.23; 95% CI, 0.09-0.58; P = .001), whereas diabetes (HR, 2.61; 95% CI, 1.21-6.01; P = .019), stent occlusion (HR, 17.0; 95% CI, 5.93-63.1; P < .001), and chronic limb-threatening ischemia presentations (HR, 4.31; 95% CI, 1.86-11.7; P=.002) were negatively associated with limb salvage. CONCLUSIONS: Routine surveillance DUS and subsequent reintervention on ISR after SFA stenting is associated with improved patency and amputation-free survival. Surveillance DUS should be routine for patients after stenting, with reintervention strongly considered if ISR is identified for both symptomatic and asymptomatic.

Anatomic patterns in claudicants who fail supervised exercise therapy.

OBJECTIVE: Patients with intermittent claudication (IC) from peripheral arterial disease (PAD) have significant improvement with supervised exercise therapy (SET). However, many patients have progressive disease that will ultimately require revascularization. We sought to determine whether the anatomic patterns of PAD were associated with response to SET. METHODS: We prospectively enrolled patients with IC at the West Haven, Connecticut Veterans Health Administration between June 2019 and June 2022. Patients were classified based on the level of their arterial disease with >50% obstruction. SET failure was defined as progressive symptoms or development of critical limb-threatening ischemia (CLTI) requiring revascularization. RESULTS: Thirty-eight patients with PAD were included. Thirteen patients (34.2%) had significant common femoral artery (CFA) disease, and 25 (65.8%) had non-CFA disease. Over a median follow-up of 1407 days, 11 patients (84.6%) with CFA disease failed SET as compared with three patients (12.0%) with non-CFA disease (P < .001). Patients with CFA disease were more likely to develop CLTI (46.2% vs 4.0%; P = .001) and have persistent symptoms (38.5% vs 8.0%; P = .02). Patients with CFA disease had significantly lower post-SET ankle-brachial index (0.58 ± 0.14 vs 0.77 ± 0.19; P = .03). In multivariate analysis, the only variable associated with SET failure was CFA disease location (odds ratio, 68.75; 95% confidence interval, 5.05-936.44; P = .001). CONCLUSIONS: Patients with IC from high-grade CFA atherosclerosis are overwhelmingly likely to fail SET, potentially identifying a subset of patients who benefit from upfront revascularization.

Arterial dissection during peripheral vascular interventions.

OBJECTIVE: Arterial dissection (AD) is a known complication of peripheral vascular interventions (PVIs), but its incidence and significance have not been well-characterized. This study examines AD in the Vascular Quality Initiative database for patients treated for peripheral arterial disease. Our hypothesis is that AD is associated with decreased patency and worse limb outcomes. METHODS: The Vascular Quality Initiative PVI registry (2016-2021) was reviewed. Patients were divided based on the presence or absence of reported AD during the procedure. Trend of incidence and management of AD was derived. The characteristics and outcomes of patients with and without AD were compared. The primary endpoint was primary patency. RESULTS: There was a total of 177,790 cases, and 3% had AD. The incidence of AD significantly increased over the study period from 2.4% to 3.6% (P = .007). Endovascular therapy was used to treat AD in 83.7% of cases, 14.5% were treated medically, and only 1.8% required open surgery. Patients with AD were significantly more likely to be female (47.4% vs 39.7%; P < .001). Patient with AD were more likely to have a history of smoking (79.7% vs 77.2%; P < .001), but were significantly less likely to be on dialysis (8.2% vs 9.3%; P < .001) compared with patients without AD. Patients with AD were more likely to have femoropopliteal disease (45.2% vs 38.0%; P < .001) and undergo treatment of more complex disease as denoted by higher mean number of lesions treated (1.95 ± 1.01 vs 1.71 ± 0.89; P < .001), longer occlusion length (8 ± 16 vs 7 ± 15 cm; P < .001), and more severe TransAtlantic Inter-Society Consensus grade (Grade D: 36.2% vs 29.1%; P < .001). The proportion of stenting as a treatment modality was higher in the dissection group (55.4% vs 41.1%; P < .001). After a mean follow-up of 828 days, patients with AD had significantly lower primary patency than patients without AD. Kaplan-Meier curves demonstrated that the AD group had lower primary patency (86.9% vs 91%; P < .001) and reintervention-free survival (79.5 % vs 84.1%; P < .001) at 1 year with difference in amputation-free survival. Cox proportional hazard regression confirmed the independent association of AD with primary patency and reintervention-free survival. CONCLUSIONS: AD is more common in women and is more likely to occur during treatment of the femoropopliteal segment. AD is associated with decreased primary patency and reintervention-free survival after PVI for peripheral arterial disease.

A systematic review and meta-analysis on the influence of sociodemographic factors on amputation in patients with peripheral arterial disease.

OBJECTIVE: To identify disparities in sociodemographic factors that are associated with major lower limb amputation in patients with peripheral arterial disease (PAD). METHODS: A systematic review of the literature was performed to identify studies that reported major lower limb amputation rates in patients with PAD among different sociodemographic groups. Data that compared amputation rates on the basis of sex, race, ethnicity, income, insurance, geography, and hospital type were collected and described. Outcomes were then aggregated and standardized, and a meta-analysis was performed to synthesis data into single odds ratios (ORs). RESULTS: Forty-one studies were included in the review. There was no association found between males and females (OR, 0.95; 95% confidence interval [CI], 0.90-1.00). Compared with Whites, higher rates of amputation were seen among Blacks/African Americans (OR, 2.02; 95% CI, 1.81-2.26) and Native Americans (OR, 1.22; 95% CI, 1.04-1.45). No significant association was found between Whites and Asians, Native Hawaiians, or Pacific Islanders (OR, 1.15; 95% CI, 1.00-1.33). Hispanics had higher rates of amputation compared with non-Hispanics (OR, 1.36; 95% CI, 1.22-1.52). Compared with private insurance, higher rates of amputation were seen among Medicare patients (OR, 1.38; 95% CI, 1.27-1.50), Medicaid patients (OR, 1.59; 95% CI, 1.44-1.76), and noninsured patients (OR, 1.41; 95% CI, 1.02-1.95). Compared with the richest income quartile, higher rates of amputation were seen among the second income quartile (OR, 1.10; 95% CI, 1.05-1.15), third income quartile (OR, 1.20; 95% CI, 1.07-1.35), and bottom income quartile (OR, 1.36; 95% CI, 1.24-1.49). There was no association found between rural and urban populations (OR, 1.35; 95% CI, 0.92-1.97) or between teaching and nonteaching hospitals (OR, 1.01; 95% CI, 0.91-1.12). CONCLUSIONS: Our study has identified a number of disparities and quantified the influence of sociodemographic factors on major lower limb amputation rates owing to PAD between groups. We believe these findings can be used to better target interventions aimed at decreasing amputation rates, although further research is needed to better understand the mechanisms behind our findings.

Platelet function testing and clinical outcomes in peripheral arterial disease: Systematic review and narrative synthesis.

OBJECTIVE: This systematic review aims to comprehensively assess the contemporary literature on platelet function testing (PFT) in individuals undergoing revascularization therapy for peripheral arterial disease (PAD). The goal is to identify whether PFT can aid in detecting antiplatelet resistance, predicting post-procedural thrombotic complications, and informing tailored treatment strategies. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a literature review was conducted using PubMed databases. Search terms included relevant medical subject headings (MeSH) terms. Eligible articles published in English between 1990 and 2023 were analyzed. Studies that examined PFT outcomes in patients with PAD after lower extremity revascularization were included. RESULTS: Ten studies met the inclusion criteria. Various PFT methods were used, including thromboelastography with platelet mapping, multiplate analyzer, Cytochrome P450 2C19 testing, VerifyNow, corrected whole blood aggregometry, platelet function analyzer-100, and light transmission aggregometry. PFT identified individuals who were resistant or non-sensitive to antiplatelet therapy, with such patients facing increased risks of graft/stent thrombosis, amputation, and reintervention. However, substantial heterogeneity in surgical procedures, drug regimens, and testing methods was observed among the studies. CONCLUSIONS: PFTs can play a crucial role in detecting resistance and non-sensitivity to antiplatelet drugs in patients with PAD post-revascularization. However, heterogeneity of data and methods underlines the need for standardized protocols and consensus-building among PFTs. Enhancing clinical utility and reliability could help optimize antiplatelet thromboprophylaxis, minimize thrombotic complications, and improve treatment strategies in vascular surgery. Further research is necessary to solidify the role of PFTs in guiding antiplatelet therapy post-revascularization in patients with PAD.

Impact of early intervention on health status outcomes in peripheral artery disease patients with chronic total occlusion lesions using the PORTRAIT registry.

OBJECTIVE: To analyze the impact of noninvasive and early invasive treatments on health status in patients with lower extremity peripheral arterial disease (PAD) without and with chronic total occlusions (CTOs) after 12 months of follow-up. METHODS: Using the international (the United States, the Netherlands, and Australia) observational longitudinal Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories registry, we included patients with recent PAD symptoms between June 2011 and December 2015. We assessed the PAD-specific health status at initial visit and the 3-, 6-, and 12-month follow-up using the Peripheral Arterial Questionnaire. 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 noninvasive (exercise, medical therapies, or smoking cessation). We then assessed the health status trajectory over 12 months, as a three-way interaction between CTO status, treatment groups, and months, using a multilevel generalized linear regression model for repeated measures adjusted for baseline health status with random effects at the site and patient levels. RESULTS: We included 581 participants, with a mean age of 66.62 ± 9.33 years, 34.3% female, and 90.8% White, of whom 353 (60.8%) were without and 228 (39.2%) had a CTO lesion. Respectively, 96 (27.2%) and 70 (30.7%) patients underwent early invasive treatment (d = 0.07). Although patients with CTO were more likely to have lower resting ABI, multilevel disease, and to experience severe claudication vs their counterparts (|d| ≥ 0.20), patient 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 = .517) and was higher in early invasive vs noninvasive treatment (treatment × month; P < .001), regardless of CTO status (CTO status × treatment; P = .981 and CTO status × treatment × month; P = .264). The score increased over time with the largest improvement occurring at 3 months in both noninvasive (non-CTO, +7.82 [95% confidence interval (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 groups did not differ at each timepoint, with a 12-month mean score of 70.26 (95% CI, 67.87-74.65) vs 71.17 (95% CI, 65.91-76.44) (P = .99) in the noninvasive treatment and 84.93 (95% CI, 78.90-90.97) vs 79.20 (95% CI, 72.77-86.14) (P = .31) in the early invasive treatment. CONCLUSIONS: Patients with symptomatic PAD undergoing early revascularization exhibited better health status over time vs those undergoing noninvasive treatment strategy, irrespective of the presence of CTOs. The degree of the improvement was greater in the 3 months after the initial visit, especially in patients undergoing early revascularization.

The mid-term effect of intravascular ultrasound on endovascular interventions for lower extremity peripheral arterial disease: A systematic review and meta-analysis.

OBJECTIVE: Intravascular ultrasound (IVUS) is an important adjunctive tool for patients with lower extremity peripheral arterial disease (PAD) undergoing endovascular therapy (EVT). The evidence regarding the advantages of IVUS use is evolving, and recent studies have reported conflicting results. We aimed to perform a meta-analysis to evaluate the efficacy of IVUS during angiography-guided EVT for patients with PAD. METHODS: MEDLINE and EMBASE were searched through April 2023 to identify studies that investigated the outcomes of IVUS with angiography-guided EVT vs angiography-alone-guided EVT. The primary outcome was restenosis/occlusion rate; secondary outcomes were target lesion revascularization, major amputation, and mortality. RESULTS: One randomized controlled trial and 14 observational studies, largely of moderate quality, were included, yielding a total of 708,808 patients with 709,189 lesions that were treated with IVUS-guided EVT (n = 101,405) vs angiography-alone (n = 607,784). Compared with angiography alone, IVUS-guided EVT was associated with a non-significant trend towards decreased restenosis/occlusion (relative risk [RR], 0.74; 95% confidence interval [CI], 0.54-1.00; I2 = 60%). Although the risk of target lesion revascularization and mortality were comparable (RR, 0.85; 95% CI, 0.65-1.10; I2 = 70%; RR, 1.01; 95% CI, 0.79-1.28; I2 = 43%, respectively), the use of IVUS was also associated with significantly lower risk of major amputation (RR, 0.74; 95% CI, 0.67-0.82; I2 = 47%). Subgroup analysis focusing on femoropopliteal disease demonstrated significantly higher patency (RR, 0.72; 95% CI, 0.52-0.98; I2 = 73%). However, superiority with major amputation was not observed. CONCLUSIONS: IVUS-guided EVT for PAD may possibly be associated with a lower major amputation rate compared with angiography alone-guided EVT, although the difference in patency remained an insignificant trend in favor of IVUS-guided EVT. Adjunctive use of IVUS during EVT may be beneficial, and further prospective studies are warranted to delineate this relationship and the applicability of this technology in routine practice.

Safety and efficacy of mechanical aspiration thrombectomy for patients with acute lower extremity ischemia.

OBJECTIVE: Acute limb ischemia (ALI) is associated with high rates of amputation and consequent morbidity and mortality. The objective of this study is to report on the safety and efficacy of aspiration thrombectomy using the Indigo Aspiration System in patients with lower extremity (LE) ALI. METHODS: The STRIDE study was an international, multicenter, prospective, study that enrolled 119 participants presenting with LE-ALI. Patients were treated firstline with mechanical thrombectomy using the Indigo Aspiration System, before stenting or angioplasty, or other therapies as determined by treating physician. The primary end point was target limb salvage at 30 days after the procedure. Secondary end points within 30 days included technical success, defined as core laboratory-adjudicated Thrombolysis in Myocardial Infarction (TIMI) 2/3 flow rate immediately after the procedure, changes in modified Society for Vascular Surgery runoff score, improvement of Rutherford classification compared with before the procedure, patency, rate of device-related serious adverse events, and major periprocedural bleeding. Secondary end points that will be evaluated at 12 months include target limb salvage and mortality. RESULTS: Of the 119 participants enrolled at 16 sites, the mean age was 66.3 years (46.2% female). At baseline (n = 119), ischemic severity was classified as Rutherford I in 10.9%, Rutherford IIa in 54.6%, and Rutherford IIb in 34.5%. The mean target thrombus length was 125.7 ± 124.7 mm. Before the procedure, 93.0% (of patients 107/115) had no flow (TIMI 0) through the target lesion. The target limb salvage rate at 30 days was 98.2% (109/111). The rate of periprocedural major bleed was 4.2% (5/119) and device-related serious adverse events was 0.8% (1/119). Restoration of flow (TIMI 2/3) was achieved in 96.3% of patients (105/109) immediately after the procedure. The median improvement in the modified Society for Vascular Surgery runoff score (before vs after the procedure) was 6.0 (interquartile range, 0.0-11.0). Rutherford classifications also improved after discharge in 86.5% of patients (83/96), as compared with preprocedural scores. Patency at 30 days was achieved in 89.4% of patients (101/113). CONCLUSIONS: In the STRIDE (A Study of Patients with Lower Extremity Acute Limb Ischemia to Remove Thrombus with the Indigo Aspiration System) study, aspiration thrombectomy with the Indigo System provided a safe and effective endovascular treatment for patients with LE-ALI, resulting in a high rate (98.2%) of successful limb salvage at 30 days, with few periprocedural complications.

Outcomes of lower extremity arterial bypass using the Human Acellular Vessel in patients with chronic limb-threatening ischemia.

OBJECTIVE: Patients with chronic limb-threatening ischemia (CLTI) and no great saphenous vein to use as a conduit for arterial bypass have a high risk for amputation despite advances in medical and endovascular therapies. This report presents findings from a U.S. Food and Drug Administration (FDA) supported study of the Human Acellular Vessel (HAV) (Humacyte Inc.) used as a conduit for arterial bypass in patients with CLTI and inadequate or absent autologous conduit. METHODS: The HAV is a 6-mm, 40-cm vessel created from human vascular smooth muscle cells seeded onto a polyglycolic acid scaffold pulsed in a bioreactor for 8 weeks as cells proliferate and the scaffold dissolves. The resultant vessel is decellularized, creating a nonimmunogenic conduit composed of collagen, elastin, and extracellular matrix. The FDA issued an Investigational New Drug for an intermediate-sized, single-center study of the HAV under the agency's Expanded Access Program in patients with advanced CLTI and inadequate or absent autologous conduit. Technical results and clinical outcomes were analyzed and reported. RESULTS: Between March 2021 and July 2023, 29 patients (20 males; mean age, 71 ± 11 years) underwent limb salvage operation using the HAV as a bypass conduit. Most patients had advanced CLTI (Rutherford class 5/6 in 72%; wound, ischemia, and foot infection stage 3/4 in 83%), and 97% had previously failed revascularization(s) of the extremity. Two HAVs were sewn together to attain the needed bypass length in 24 patients (83%). Bypasses were to tibial arteries in 23 patients (79%) and to the popliteal artery in 6 (21%). Technical success was 100%, and the 30-day mortality rate was 7% (2 patients). With 100% follow-up (median, 9.3 months), the limb salvage rate was 86% (25/29 patients). There were 16 reinterventions to restore secondary patency, of which 15 (94%) were successful. Primary and secondary patency of the HAV at 9 months were 59% and 71%, respectively. CONCLUSIONS: The HAV has demonstrated short- to intermediate-term safety and efficacy as an arterial bypass conduit in a complex cohort of patients with limb-threatening ischemia and no autologous options. This experience using the FDA's Expanded Access Program provides real-world data to inform regulatory deliberations and future trials of the HAV, including the study of the vessel as a first-line bypass conduit in less severe cases of chronic limb ischemia.