Biologic and Clinical Efficacy of LentiGlobin for Sickle Cell Disease.

BACKGROUND: Sickle cell disease is characterized by the painful recurrence of vaso-occlusive events. Gene therapy with the use of LentiGlobin for sickle cell disease (bb1111; lovotibeglogene autotemcel) consists of autologous transplantation of hematopoietic stem and progenitor cells transduced with the BB305 lentiviral vector encoding a modified ß-globin gene, which produces an antisickling hemoglobin, HbAT87Q. METHODS: In this ongoing phase 1-2 study, we optimized the treatment process in the initial 7 patients in Group A and 2 patients in Group B with sickle cell disease. Group C was established for the pivotal evaluation of LentiGlobin for sickle cell disease, and we adopted a more stringent inclusion criterion that required a minimum of four severe vaso-occlusive events in the 24 months before enrollment. In this unprespecified interim analysis, we evaluated the safety and efficacy of LentiGlobin in 35 patients enrolled in Group C. Included in this analysis was the number of severe vaso-occlusive events after LentiGlobin infusion among patients with at least four vaso-occlusive events in the 24 months before enrollment and with at least 6 months of follow-up. RESULTS: As of February 2021, cell collection had been initiated in 43 patients in Group C; 35 received a LentiGlobin infusion, with a median follow-up of 17.3 months (range, 3.7 to 37.6). Engraftment occurred in all 35 patients. The median total hemoglobin level increased from 8.5 g per deciliter at baseline to 11 g or more per deciliter from 6 months through 36 months after infusion. HbAT87Q contributed at least 40% of total hemoglobin and was distributed across a mean (±SD) of 85±8% of red cells. Hemolysis markers were reduced. Among the 25 patients who could be evaluated, all had resolution of severe vaso-occlusive events, as compared with a median of 3.5 events per year (range, 2.0 to 13.5) in the 24 months before enrollment. Three patients had a nonserious adverse event related or possibly related to LentiGlobin that resolved within 1 week after onset. No cases of hematologic cancer were observed during up to 37.6 months of follow-up. CONCLUSIONS: One-time treatment with LentiGlobin resulted in sustained production of HbAT87Q in most red cells, leading to reduced hemolysis and complete resolution of severe vaso-occlusive events. (Funded by Bluebird Bio; HGB-206 ClinicalTrials.gov number, NCT02140554.).

Coronary bypass surgery guided by computed tomography in a low-risk population.

BACKGROUND AND AIMS: In patients with three-vessel disease and/or left main disease, selecting revascularization strategy based on coronary computed tomography angiography (CCTA) has a high level of virtual agreement with treatment decisions based on invasive coronary angiography (ICA). METHODS: In this study, coronary artery bypass grafting (CABG) procedures were planned based on CCTA without knowledge of ICA. The CABG strategy was recommended by a central core laboratory assessing the anatomy and functionality of the coronary circulation. The primary feasibility endpoint was the percentage of operations performed without access to the ICA. The primary safety endpoint was graft patency on 30-day follow-up CCTA. Secondary endpoints included topographical adequacy of grafting, major adverse cardiac and cerebrovascular (MACCE), and major bleeding events at 30 days. The study was considered positive if the lower boundary of confidence intervals (CI) for feasibility was ≥75% (NCT04142021). RESULTS: The study enrolled 114 patients with a mean (standard deviation) anatomical SYNTAX score and Society of Thoracic Surgery score of 43.6 (15.3) and 0.81 (0.63), respectively. Unblinding ICA was required in one case yielding a feasibility of 99.1% (95% CI 95.2%-100%). The concordance and agreement in revascularization planning between the ICA- and CCTA-Heart Teams was 82.9% with a moderate kappa of 0.58 (95% CI 0.50-0.66) and between the CCTA-Heart Team and actual treatment was 83.7% with a substantial kappa of 0.61 (95% CI 0.53-0.68). The 30-day follow-up CCTA in 102 patients (91.9%) showed an anastomosis patency rate of 92.6%, whilst MACCE was 7.2% and major bleeding 2.7%. CONCLUSIONS: CABG guided by CCTA is feasible and has an acceptable safety profile in a selected population of complex coronary artery disease.

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.

Rationale and design of a single-center randomized trial to compare the graft patency between the radial artery and the no-touch saphenous vein in coronary artery bypass grafting surgery (GRAFT-CAB Study).

BACKGROUND: Previous studies suggested only the radial artery and the No-touch (NT) technique were effective in reducing graft occlusion after coronary artery bypass grafting (CABG) surgery. However, there is no randomized trial comparing these 2 graft conduits. The optimum second conduit for CABG remains undetermined. MATERIALS AND METHODS: This study is a prospective, single-center randomized clinical trial, aiming to compare the graft patency between the radial artery and the NT vein graft. All patients undergoing isolated CABG with left internal mammary artery (LIMA) plus at least 2 additional grafts will be considered eligible. About 774 cases (516 in the radial artery group and 258 in the NT vein group) will be enrolled in over 1 to 2 years. Participants will be randomized and allocated to two bypass strategies: the LIMA plus 1 radial artery and 1 conventional vein graft, or the LIMA plus 2 NT vein grafts. The primary outcome is graft occlusion at 1 year after CABG evaluated by CT angiography. The secondary outcomes include graft occlusion at 3 and 5 years and major adverse cardiac or cerebrovascular events at 1, 3, and 5 years follow-ups. DISCUSSION: This study will define whether or not the NT vein has a lower graft occlusion rate than the radial artery in short and mid-term follow-ups, and provide new evidence for the second conduit choice in CABG surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT06014047. Registered on October 15th, 2023.

Association between diabetes mellitus and primary restenosis following endovascular treatment: a comprehensive meta-analysis of randomized controlled trials.

IMPORTANCE: Diabetes mellitus (DM) is thought to be closely related to arterial stenotic or occlusive disease caused by atherosclerosis. However, there is still no definitive clinical evidence to confirm that patients with diabetes have a higher risk of restenosis. OBJECTIVE: This meta-analysis was conducted to determine the effect of DM on restenosis among patients undergoing endovascular treatment, such as percutaneous transluminal angioplasty (PTA) or stenting. DATA SOURCES AND STUDY SELECTION: The PubMed/Medline, EMBASE and Cochrane Library electronic databases were searched from 01/1990 to 12/2022, without language restrictions. Trials were included if they satisfied the following eligibility criteria: (1) RCTs of patients with or without DM; (2) lesions confined to the coronary arteries or femoral popliteal artery; (3) endovascular treatment via PTA or stenting; and (4) an outcome of restenosis at the target lesion site. The exclusion criteria included the following: (1) greater than 20% of patients lost to follow-up and (2) a secondary restenosis operation. DATA EXTRACTION AND SYNTHESIS: Two researchers independently screened the titles and abstracts for relevance, obtained full texts of potentially eligible studies, and assessed suitability based on inclusion and exclusion criteria.. Disagreements were resolved through consultation with a third researcher. Treatment effects were measured by relative ratios (RRs) with 95% confidence intervals (CIs) using random effects models. The quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. MAIN OUTCOMES AND MEASURES: The main observation endpoint was restenosis, including > 50% stenosis at angiography, or TLR of the primary operation lesion during the follow-up period. RESULTS: A total of 31,066 patients from 20 RCTs were included. Patients with DM had a higher risk of primary restenosis after endovascular treatment (RR = 1.43, 95% CI: 1.25-1.62; p = 0.001). CONCLUSIONS AND RELEVANCE: This meta-analysis of all currently available RCTs showed that patients with DM are more prone to primary restenosis after endovascular treatment.

Short-term mortality and revisions to promote maturation after arteriovenous fistula creation.

OBJECTIVE: Arteriovenous fistula (AVF) for hemodialysis access is traditionally considered superior to grafts due to infection resistance and purported improved patency. However, challenges to AVF maturation and limited patient survival may reduce AVF benefits. The objective of this study is to identify factors associated with risk of AVF requiring revision before maturation and/or mortality within 2 years of creation. METHODS: We performed a retrospective review of 250 AVFs created between May 2017 and November 2020 at a single institution. Maturation was defined as the date the surgeon deemed the AVF ready for use or the patient successfully used the AVF for dialysis. The Risk Analysis Index was used to calculate frailty. The primary outcome was a composite of endovascular/surgical revision to promote maturation and/or mortality within 2 years of AVF creation (REVDEAD). The primary outcome was categorized as met if the patient required a revision to promote maturation or if the patient experienced mortality within 2 years of AVF creation, or if both occurred. REVDEAD was compared with those who did not meet the primary outcome and will be referred to as NOREVDEAD. RESULTS: Survival at 2 years after AVF creation was 82%, and 54 (22%) patients underwent AVF revision. Of those, 31 (59%) patients progressed to AVF maturation. Of the 250 AVFs, 91 (36%) met the primary outcome of REVDEAD and 159 (64%) did not (NOREVDEAD). There was no difference between the REVDEAD and NOREVDEAD groups in age (P = .18), sex (P = .75), White race (P = .97), Hispanic ethnicity (P = .62), obesity (P = .76), coronary artery disease (P = .07), congestive heart failure (P = .29), diabetes mellitus (P = .78), chronic obstructive pulmonary disease (P = .10), dialysis status (P = .63), hypertension (P = .32), peripheral arterial disease (P = .34), or dysrhythmia (P = .13). There was no difference between the groups in the forearm vs the upper arm location of AVF (P = .42) or the vein diameter (P = .58). Forearm access, as opposed to upper arm AVF creation, was associated with higher rate of revision before maturation (P = .05). More patients in REVDEAD were frail or very frail (60% vs 48%, P = .05). Of the AVFs that matured, maturation required longer time in REVDEAD at 110.0 ± 9.1 days vs 78.8 ± 5.6 days (mean ± standard deviation) (P = .003). Adjusted for the vein diameter and the forearm vs the upper arm, frailty increased the odds of REVDEAD by 1.9 (95% confidence interval: 1.1, 3.3). CONCLUSIONS: Frail patients who underwent AVF were significantly more likely to die within 2 years of AVF creation with no significant association between frailty and the need for revisions to promote maturation. Forearm AVFs were more likely to require revisions; in patients who are frail, with a high likelihood of 2-year mortality, graft may be more appropriate than AVF. If AVF is being considered in a frail patient, upper arm AVFs should be prioritized over forearm AVFs.

Direct oral anticoagulants over warfarin at discharge associated with improved survival and patency in infra-geniculate bypasses with prosthetic conduits.

OBJECTIVE: There is no consensus on the optimal anticoagulant regimen following lower extremity bypass. Historically, warfarin has been utilized for prosthetic or compromised vein bypasses. Direct-acting oral anticoagulants (DOACs) are increasingly replacing warfarin in this context, but their efficacy in bypass preservation has not been well-studied. Recent studies have shown that DOACs may improve outcomes following bypasses; however, it is unclear if this is dependent upon type of bypass conduit. The goal of this study was to evaluate whether a difference exists between vein and prosthetic infra-geniculate bypasses outcomes based on the anticoagulant utilized on discharge, warfarin or DOAC. METHODS: The Vascular Quality Initiative infra-inguinal bypass database was queried for all patients who underwent an infra-geniculate bypass and were anticoagulation-naive at baseline but were discharged on either warfarin or DOACs. A survival analysis was performed for patients up to 1 year to determine whether the choice of discharge anticoagulation was associated with differences between those with vein vs prosthetic conduits in overall survival, primary patency, risk of amputation, or risk of major adverse limb events (MALE). A multivariable Cox proportional hazards analysis was performed to control for differences in baseline demographic factors between the groups. RESULTS: During the study period (2003-2020), 57,887 patients underwent infra-geniculate bypass. Of these, 3230 (5.5%) were anticoagulated on discharge. There was a similar distribution of anticoagulation between vein (n = 1659; 51.4%) and prosthetic conduits (n = 1571; 48.6%). Thirty-two percent were discharged on DOACs, and 68.0% were discharged on warfarin. For prosthetic conduits, being discharged on a DOAC was associated with improved outcomes on univariate and multivariable analyses revealing lower risk of overall mortality (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.41-0.93; P = .021), loss of primary patency (HR, 0.70; 95% CI, 0.55-0.89; P = .003), risk of amputation (HR, 0.71; 95% CI, 0.54-0.93; P = .013), and risk of MALE (HR, 0.80; 95% CI, 0.64-1.00; P = .048). Patients with a vein bypass had improved univariate outcomes for survival and primary patency; however, with multivariable analysis, there were no significant differences in outcomes between DOAC and warfarin. CONCLUSIONS: Anticoagulation-naive patients who underwent an infra-geniculate prosthetic bypass had higher rates of overall survival, bypass patency, amputation-free survival, and freedom from MALE when discharged on a DOAC compared with warfarin. Those with vein bypasses had similar outcomes regardless of the choice of anticoagulation.

Cryopreserved arterial allografts vs autologous vein for arterial reconstruction in infected fields.

OBJECTIVE: Peripheral arterial infections are rare and difficult to treat when an in situ reconstruction is required. Autologous vein (AV) is the conduit of choice in many scenarios. However, cryopreserved arterial allografts (CAAs) are an alternative. We aimed to assess our experience with CAAs and AVs for reconstruction in primary and secondary peripheral arterial infections. METHODS: Data from patients with peripheral arterial infections undergoing reconstruction with CAA or AV from January 2002 through August 2022 were retrospectively analyzed. Patients with aortic- or iliac-based infections were excluded. RESULTS: A total of 42 patients (28 CAA, 14 AV) with a mean age of 65 and 69 years, respectively, were identified. Infections were secondary in 31 patients (74%) and primary in 11 (26%). Secondary infections included 10 femoral-femoral grafts, 10 femoropopliteal or femoral-distal grafts, five femoral patches, four carotid-subclavian grafts, one carotid-carotid graft, and one infected carotid patch. Primary infection locations included six femoral, three popliteal, and two subclavian arteries. In patients with lower extremity infections, associated groin infections were present in 19 (56%). Preoperative blood cultures were positive in 17 patients (41%). AVs included saphenous vein in eight and femoral vein in six. Intraoperative cultures were negative in nine patients (23%), polymicrobial in eight (21%), and monomicrobial in 22 (56%). Thirty-day mortality occurred in four patients (10%), two due to multisystem organ failure, one due to graft rupture causing acute blood loss and myocardial infarction, and one due to an unknown cause post-discharge. Median follow-up was 20 months and 46 months in the CAA and AV group, respectively. Graft-related reintervention was performed in six patients in the CAA group (21%) and one patient in the AV group (7%). Freedom from graft-related reintervention rates at 3 years were 82% and 92% in the CAA and AV group, respectively (P = .12). Survival rates at 1 and 3 years were 85% and 65% in the CAA group and 92% and 84% in the AV group (P = .13). Freedom from loss of primary patency was similar with 3-year rates of 77% and 83% in the CAA and AV group, respectively (P = .25). No patients in either group were diagnosed with reinfection. CONCLUSIONS: CAAs are an alternative conduit for peripheral arterial reconstructions when AV is not available. Although there was a trend towards higher graft-related reintervention rates in the CAA group, patency is similar and reinfection is rare.

Frailty screening for determination of hemodialysis access placement.

OBJECTIVE: Choosing the right hemodialysis vascular access for frail patients remains difficult because the patient's preferences and the likelihood of access function and survival must be considered. We hypothesize that patients identified before arteriovenous (AV) access as frail by the PRISMA-7 score may have worse outcomes, indicating that fistula creation may not be the most clinically beneficial option and it would be in the best interest of the patient to receive either AV graft (AVG) placement or dialysis through a percutaneous catheter. Our pilot study aims to determine whether an association exists between patient frailty as defined by PRISMA-7 and newly created AV fistula (AVF) and AVG access outcomes. METHODS: This was a single institutional prospective cohort study of patients undergoing new AVF or AVG intervention from April 2021 to May 2023. Patients were assessed using the PRISMA-7 frailty questionnaire before their AV access surgery. Patients were grouped by frailty score and score groups were examined for trends. Univariable analysis was performed for baseline differences between frail and nonfrail patients. Failure to achieve maturation, postoperative infection, and 180-day mortality difference was also investigated for frail vs nonfrail patients. Univariable analysis was performed for nonmaturation using standard comorbidities, arterial and venous diameters, and frailty. Multivariable binary logistic regression was performed for the outcome of nonmaturation using frailty as one of the variables in conjunction with the univariable risks associated with nonmaturation. RESULTS: A total of 40 patients undergoing new AV access placement were investigated, among whom 53% were designated as frail (PRISMA-7 score ≥3). When comparing the frail and nonfrail new AV access groups, the access (AVF and AVG combined) failed in 48% (10/21) of the frail patients, but only failed in 5% (1/19) of the nonfrail patients 1 (P = .012). When distinguishing between AV access types, AVF creations followed the overall trend with 60% of AVF access (9/15) sites in frail patients failing to mature when compared with nonfrail patients, who all had fistulas that matured to use (P = .049). Surgical site infection was absent in all frail patients and present in 5% of nonfrail patients (1/19). Both 30-day and 60-day readmission rates were higher in the frail group compared with the nonfrail group. There was 180-day mortality present in 5 of frail patients % (1/21) and absent in nonfrail patients. Multivariable analysis revealed that both frailty (adjusted odd ratio, 10.19; 95% confidence interval, 1.20-82.25); P = .033) and younger age (adjusted odd ratio, 0.953; 95% confidence interval, 0.923-0.983; P = .002) both had a significant association with nonmaturation. Power analysis revealed a power statistic of 0.898 indicating a probability of type 2 error of 10.02% with a P value of .002. Hosmer-Lemeshow goodness of fit for the logistic regression had 75% overall accuracy for the model. CONCLUSIONS: Patient frailty is significantly associated with an increased incidence of AV access failure to mature.

Midterm outcomes of arteriovenous fistula aneurysm repair with simultaneous inflow revision or outflow tract revascularization.

OBJECTIVE: The aim of this study was to investigate the 2-year outcomes of extensive revisions aimed at simultaneously addressing arteriovenous fistula (AVF) aneurysms, outflow stenosis, and/or high flow volumes. METHODS: This was a retrospective cohort study in a tertiary referral center. The study population comprised hemodialysis patients with aneurysmal AVFs requiring revision. Subjects were eligible if they were ≥18 years of age and had aneurysm repair associated with inflow revision or treatment of outflow lesions. Patients were followed-up for a minimum of 2 years, and the primary outcome measure was cumulative patency. RESULTS: Our cohort comprised 93 patients with a mean age of 56 ± 12 years. The most frequent access type was brachiocephalic fistula (61%), and the median access age at the time of revision was 66 months (interquartile range, 46-93 months). The median access flow volume was 2300 ml/min (interquartile range, 1281-2900), and 31 subjects (33%) presented aneurysms associated with both high flow and venous obstruction. Aneurysm repair consisted of aneurysmorraphy in the overwhelming majority (95%). Inflow revision was performed in a total of 49 cases (53%), and outflow tract obstruction was treated in 71 patients (72%), with 27 patients (29%) receiving a simultaneous 3-component revision. At 2 years, the primary, primary assisted, and cumulative patencies were 60% ± 1%, 91% ± 3%, and 94% ± 3%, respectively. The most frequent indication for first-time reinterventions was outflow tract stenosis (24%). Aneurysm recurrence was observed in 13 subjects (14%) during the entire follow-up and was responsible for reinterventions in seven of them (8%), with a 2-year freedom from aneurysm-related reintervention rate of 95% ± 3%. CONCLUSIONS: Extensive AVF revision with simultaneous aneurysm repair, inflow revision, and outflow tract revascularization is feasible, safe, and associated with favorable 2-year patency rates.

Creating hemodialysis autogenous access in children and adolescents.

OBJECTIVE: End-stage renal disease (ESRD) in childhood and adolescence is rare, with relatively few published reports of pediatric ESRD vascular access. This study analyzes a 10-year experience creating arteriovenous fistulas (AVFs) in children and adolescents. Our goal is to review our strategy for creating functional autogenous vascular access in younger patients and report our results. METHODS: We retrospectively reviewed data and outcomes for consecutive vascular access patients aged ≤19 years during a 10-year period. Each patient had preoperative vascular ultrasound mapping by the operating surgeon in addition to physical examination. A distal forearm radiocephalic AVF was the first access choice when feasible, and a proximal radial artery inflow AVF was the next option. Demographic data, inflow artery, venous outflow target, and required transposition vs direct AVFs were variables included in the analysis. Primary and cumulative patency were calculated by Kaplan-Meier analysis. RESULTS: Thirty-seven AVFs were created in 35 patients. No grafts were used. Ages were 6 to 19 years (mean, 15 years), and 20 were male. Causes of ESRD included glomerular disease (n = 18) and urinary obstruction or reflux (n = 7), among others. Three had previous AVFs, and 10 were obese. The proximal radial artery supplied AVF inflow in 25 patients and the brachial artery in only seven. Eleven individuals required a transposition and one a vein translocation to the contralateral arm. No patients developed hand ischemia, although two later required banding procedures for high flow. Eleven patients had successful transplants. A single patient died, unrelated to the vascular access. Five AVFs failed. Of these, two had new successful AVFs created, two regained renal function, one was transplanted, and one declined other procedures. Primary and cumulative patency rates were 75% and 85% at 12 months, 70% and 85% at 24 months, and 51% and 85% at 36 months, respectively. Median follow-up was 16 months. CONCLUSIONS: Creating an AVF for hemodialysis is a successful vascular access strategy for pediatric and adolescent patients. Proximal radial artery AVFs provided safe and functional access when a distal AVF was not feasible. Cumulative AVF patency was 85% at 36 months.

Slowly moving the needle away from Fistula First.

OBJECTIVE: In 2019, the management of end-stage kidney disease (ESKD) shifted away from "Fistula First" (FF) to "ESKD Life-Plan: Patient Life-Plan First then Access Needs." Indeed, some patients exhibit such excessive comorbidity that even relatively minor vascular surgery may be complicated. The purpose of this study was to retrospectively assess complications and mortality (and delineate operative futility) in patients undergoing arteriovenous fistula (AVF) creation in the FF era. METHODS: Consecutive AVFs created in a single institution before 2021 were retrospectively reviewed. Operative futility was defined as never-accessed fistula, no initiation of dialysis, failure of access maturation (despite secondary intervention), hemodialysis access-induced distal ischemia requiring ligation, early loss of secondary patency, and/or patient mortality within the first 6 postoperative months. RESULTS: A total of 401 AVFs were created including radial-cephalic (44%), brachial-cephalic (41%), and brachial-basilic (15%) constructions. Patients exhibited a mean age of 69 ± 15 years; 63% were male, and most (74%) were already being hemodialyzed at the time of fistula creation. Forty-five patients (11%) suffered a cardiac event, and five patients died (1%) within 90 days of their access surgery. Perioperative cardiac events were significantly more common after age 80 (19% vs 8%; P = .004); age >80 years was an independent predictor of major 90-day complications (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.04-3.39; P = .036) and the sole independent predictor of major morbidity defined as cardiopulmonary complications, stroke, or death within the first year (OR, 2.01; 95% CI, 1.24-3.25; P = .004). Operative futility was encountered in 52% of the cohort (n = 208 patients): 40% (n = 160) of primary AVFs failed to mature despite assistance, 19% (n = 77) had lost secondary patency by 6 months, 13% of patients (n = 53) were never started on dialysis after access creation, 4% (n = 16) were dead by 6 months, 2% of AVFs (n = 10) matured but were never accessed, and 2% (n = 9) required ligation for hemodialysis access-induced distal ischemia. Not surprisingly, the sole independent protector against operative futility was that catheter-based dialysis had been established prior to AVF creation (OR, 0.36; 95% CI, 0.22-0.59; P < .01). CONCLUSIONS: Approximately 50% of primary AVF operations performed in the aggressive FF era were deemed futile. Octogenarians were particularly prone to futility and complications during this era. A paradigm shift, from FF to an "ESKD Life-Plan" will, hopefully, more thoughtfully match vascular access strategies to individual patient needs.

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.

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.

Outcomes of covered vs bare metal stents for the treatment of aortoiliac occlusive disease.

OBJECTIVE: We retrospectively compared the clinical outcomes of self-expanding covered stents (CSs) and bare metal stents (BMSs) in the treatment of aortoiliac occlusive disease (AIOD) at a single center between 2016 and 2022. METHODS: All patients with AIOD receiving endovascular therapy at a single center from January 2016 to October 2022 were continuously analyzed, including patients with lesions of all classes according to the Trans-Atlantic Inter-Society Consensus II (TASC-II). Relevant clinical and baseline data were collected, and propensity score matching was performed to compare CSs and BMSs in terms of baseline characteristics, surgical factors, 30-day outcomes, 5-year primary patency, and limb salvage. The follow-up results were analyzed by Kaplan-Meier curves. Cox proportional hazard models were used to identify predictors of primary patency. RESULTS: A total of 209 patients with AIOD were enrolled in the study, including 135 patients (64.6%) in the CS group and 74 patients (35.4%) in the BMS group. Surgical success rates (100% vs 100%; P = 1.00), early (<30-day) mortality rates (0% vs 0%; P = 1.00), cumulative surgical complication rate (12.0% vs 8.0%; P = .891), 5-year primary patency rate (83.4% vs 86.9%; P = .330), secondary patency rate (96% vs 100%; P = .570), and limb salvage rate (100% vs 100%; P = 1.00) did not exhibit significant differences between the two groups. Patients in the CS group had a lower preoperative ankle-brachial index (0.48 ± 0.26 vs 0.52 ± 0.19; P = .032), more cases of complex AIOD (especially TASC D) (47.4% vs 9.5%; P < .001), more chronic total occlusive lesions (77.0% vs 31.1%; P < .001), and more severe calcification (20.7% vs 14.9%; P < .036). After propensity score matching, 50 patients (25 with CS and 25 with BMS) were selected. The results showed that only severe calcification (32.0% vs 8.0%; P = .034) and ankle-brachial index increase (0.45 ± 0.15 vs 0.41 ± 0.22; P = .038) were significantly different between the groups. In terms of surgical factors, patients in the CS group had more use of bilateral femoral or combined brachial artery percutaneous access (60.0% vs 12.0%; P < .001), more number of stents used (2.3 ± 1.2 vs 1.3 ± 0.7; P < .001), longer mean stent length (9.3 ± 3.3 vs 5.8 ± 2.6 cm; P < .001), and more catheter-directed thrombolysis treatment (32.0% vs 4.0%; P = .009). Multivariate Cox survival analysis showed that severe calcification (hazard ratio, 1.32; 95% confidence interval, 1.04-1.85; P = .048) was the only independent predictor of the primary patency rate. CONCLUSIONS: All patients with AIOD who underwent endovascular therapy were included and achieved good outcomes with both CSs and BMSs. The influence of confounding factors in the two groups was minimized by propensity score matching, and the 5-year patency rates were generally similar in the unmatched and matched cohorts. Postoperative hemodynamic improvement was more obvious in patients in the CS group. For more complex lesions, CS is recommended to be preferred. Especially for severe calcification lesions, which is the only independent predictor of primary patency, CS showed obvious advantages. Further studies with more samples are needed to investigate the role of stent types in AIOD treatment.

Outcomes of brachial artery transposition in hemodialysis patients.

OBJECTIVE: In hemodialysis patients with a difficult access extremity who are not suitable for an arteriovenous fistula or arteriovenous graft creation, the concept of cannulating a superficialized artery for arterial outflow in dialysis sessions has been adopted as a tertiary alternative. However, its long-term patency and complications have not been recognized widely. We report our 16-year experience with hemodialysis access creation using the brachial artery transposition (BAT) technique. METHODS: This single-center retrospective study included consecutive patients who underwent BAT for hemodialysis vascular access between June 1, 2006, and December 31, 2022. The patency of the whole access circuit and the transposed brachial artery itself was evaluated independently. RESULTS: In total, 193 surgical procedures were included. The success rate was 93.2%. The mean operative time was 128 minutes. The median interval from access placement to first cannulation was 21 days. The primary patency rates for BAT were 92.3%, 91.3%, 90.3%, 86.1%, and 71.9% at 1, 2, 3, 5, and 10 years, respectively. The secondary patency rates for BAT were 96.3%, 96.3%, 95.0%, 90.1%, and 74.9% at 1, 2, 3, 5, and 10 years, respectively. The primary patency rates for the whole access circuit were 61.4%, 49.2%, 45.8%, and 26.9% at 1, 2, 3, and 5 years, respectively. The secondary patency rates for the whole access circuit were 85.1%, 83.3%, 82.0%, and 68.6% at 1, 2, 3, and 5 years, respectively. The overall patient survival rates were 79.6%, 69.6%, 54.6%, 36.5%, and 13.4% at 1, 2, 3, 5 and 10 years, respectively. The abandonments of BAT were brachial artery thrombosis (n = 6), pseudoaneurysm (n = 2), aneurysmal change (n = 1), and other reasons (n = 1). The abandonments of the whole access circuit were exhaustion of venous return (n = 26), abandonment of BAT (n = 7), and other reasons (n = 2). Complications were exhaustion of venous return (n = 26), aneurysmal change (n = 12), pseudoaneurysm (n = 6), brachial artery thrombosis (n = 7), impaired wound healing (n = 19), lymphorrhea (n = 9), skin infection (n = 5), hematoma on cannulation (n = 3), and reduced peripheral blood flow (n = 2). CONCLUSIONS: The patency of BAT was excellent, and that of the whole access circuit was adequate, with a few complications. BAT is an effective alternative from a long-term perspective for patients who are unsuitable for conventional hemodialysis access creation.

Intraoperative transit time flow measurement predicts maturation of radiocephalic arteriovenous fistulas.

OBJECTIVE: The arteriovenous fistula (AVF) is the first choice for gaining vascular access for hemodialysis. However, 20% to 50% of AVFs fail within 4 months after creation. Although demographic risk factors have been described, there is little evidence on the intraoperative predictors of AVF maturation failure. The aim of this study was to assess the predictive value of intraoperative transit time flow measurements (TTFMs) on AVF maturation failure. METHODS: In this retrospective cohort study, intraoperative blood flow, measured using TTFM, was compared with AVF maturation after 6 weeks in 55 patients. Owing to its significantly higher prevalence and risk of nonmaturation, the radiocephalic AVF (RCAVF) was the main focus of this study. A recommended cutoff point for high vs low intraoperative blood flow was determined for RCAVFs, using a receiver operating characteristic curve. RESULTS: The average intraoperative blood flow in RCAVFs was 156 mL/min. Patients with an intraoperative blood flow equal or lower than the determined cutoff point of 160 mL/min, showed a 3.03 times increased risk of AVF maturation failure after 6 weeks, compared with patients with a higher intraoperative blood flow (P < .001). CONCLUSIONS: The intraoperative blood flow in RCAVFs measured by TTFM provides an adequate means of predicting AVF nonmaturation 6 weeks after surgery. For RCAVFs, a cutoff point for intraoperative blood flow of 160 mL/min is recommended for maximum sensitivity and specificity to predict AVF maturation failure after 6 weeks.

Outcomes and predictors of amputation-free survival in patients undergoing below-knee popliteal-distal bypass.

OBJECTIVE: The infrageniculate popliteal artery is a potential source for inflow in lower extremity bypass surgery in patients with isolated tibial artery disease. The objective of our study was to assess the short- and long-term outcomes of popliteal-distal bypasses using data from the Vascular Quality Initiative (VQI). METHODS: The VQI registry was queried between 2003 and 2021 for patients undergoing surgical revascularizations with the below-knee popliteal artery serving as inflow. Demographics, comorbidities, intraoperative characteristics, and postoperative complications were analyzed. Kaplan-Meier models were used to estimate amputation-free survival, survival, and freedom from amputation. Cox regression analysis was conducted to determine factors associated with major amputation or death. RESULTS: A total of 1884 procedures were analyzed. The mean age of the included patients was 67.7 years. The most frequently observed preoperative comorbidities included insulin-dependent diabetes (52.3%), coronary disease (32.4%), and end-stage renal disease (14.4%). Of all the patients, 670 (35.6%) had a history of ipsilateral endovascular intervention. The procedures were performed for a variety of indications, including tissue loss (84.3%), rest pain (10.9%), and claudication (4.8%). Intraoperatively, the outflow targets were the dorsalis pedis (31.4%), the posterior tibial (24.4%), and the anterior tibial arteries (15.6%). Vein conduit was used in 92.1% of cases. The rate of perioperative myocardial infarction (MI) was 2.4%, and the 30-day mortality was 1.9%. The median length of follow up was 371 days. Amputation-free survival was found to be 85.6% (95% confidence interval [CI], 84.0%-87.2%) at 6 months and 78.6% (95% CI, 76.6%-80.4%) at 12 months. Survival was found to be 93.4% (95% CI, 92.2%-94.5%) at 6 months and 88.6% (95% CI, 87.1%-90.0%) at 12 months. Freedom from amputation was found to be 92.0% (95% CI, 90.7%-93.3%) at 6 months and 89.0% (95% CI, 87.3%-90.4%) at 12 months. Cox regression analysis demonstrated that age greater than 65 years, congestive heart failure, coronary artery disease, and end-stage renal disease were associated with a higher risk of major amputation or death (P < .05). CONCLUSIONS: Below-knee popliteal-distal bypass is a safe and effective approach to treat severe tibial vessel occlusive disease in this challenging patient cohort. Patients exhibited low perioperative complication rates and good amputation-free survival at 1 year.

The effect of cilostazol on late outcomes after endovascular treatment for occlusive femoropopliteal disease.

OBJECTIVE: Restenosis and late occlusion remain a significant problem for endovascular treatment of peripheral artery disease. This meta-analysis aims to evaluate the effect of cilostazol on late outcomes after endovascular repair of occlusive femoropopliteal disease. METHODS: A systematic literature review was conducted conforming to established criteria to identify articles published up to September 2023 evaluating late outcomes after endovascular treatment for atherosclerotic femoropopliteal disease. Eligible studies should compare outcomes between patients treated with cilostazol and patients not treated with cilostazol. Both prospective and retrospective studies were eligible. Late outcomes included primary patency (PP), restenosis, target lesion revascularization (TLR), and major amputation during follow-up. RESULTS: Overall, 10 clinical studies were identified for analysis including 4721 patients (1831 with cilostazol vs 2890 without cilostazol) that were treated for 5703 lesions (2235 with cilostazol vs 3468 without cilostazol). All studies were performed in Japan. Mean follow-up was 24.1 ± 12.5 months. Cilostazol was associated with a lower risk for restenosis (pooled odds ratio [OR], 0.503; 95% confidence interval [CI], 0.383-0.660; P < .0001). However, no association was found between cilostazol and TLR (pooled OR, 0.918; 95% CI, 0.300-2.812; P = .881) as well as major amputation (pooled OR, 1.512; 95% CI, 0.734-3.116; P = .263). Regarding primary patency, cilostazol was associated with a higher 12-month PP (OR, 3.047; 95% CI, 1.168-7.946; P = .023), and a higher 36-month PP (OR, 1.616; 95% CI, 1.412-1.850; P < .0001). No association was found between cilostazol and mortality during follow-up (pooled OR, .755; 95% CI, 0.293-1.946; P = .561). CONCLUSIONS: Cilostazol seems to have a positive effect on 1- to 3-year PP and restenosis rates among patients treated endovascularly for atherosclerotic femoropopliteal disease. A positive effect on TLR and amputation risk was not verified in this review.

Systemic immunosuppression does not affect revascularization outcomes in patients with chronic limb-threatening ischemia.

OBJECTIVE: Many patients with chronic limb-threatening ischemia (CLTI) have additional comorbidities requiring systemic immunosuppression. Few studies have analyzed whether these medications may inhibit graft integration and effectiveness, or conversely, whether they may prevent inflammation and/or restenosis. Therefore, our study aim was to examine the effect of systemic immunosuppression vs no immunosuppression on outcomes after any first-time lower extremity revascularization for CLTI. METHODS: We identified all patients undergoing first-time infrainguinal bypass graft (BPG) or percutaneous transluminal angioplasty with or without stenting (PTA/S) for CLTI at our institution between 2005 and 2014. Patients were stratified by procedure type and immunosuppression status, defined as ≥6 weeks of any systemic immunosuppression therapy ongoing at the time of intervention. Immunosuppression vs nonimmunosuppression were the primary comparison groups in our analyses. Primary outcomes included perioperative complications, reintervention, primary patency, and limb salvage, with Kaplan-Meier and Cox proportional hazard models used for univariate and multivariate analyses, respectively. RESULTS: Among 1312 patients, 667 (51%) underwent BPG and 651 (49%) underwent PTA/S, of whom 65 (10%) and 95 (15%) were on systemic immunosuppression therapy, respectively. Whether assessing BPG or PTA/S patients, there were no differences noted in perioperative outcomes, including perioperative mortality, myocardial infarction, stroke, hematoma, or surgical site infection (P > .05). For BPG patients, Kaplan-Meier analysis and log-rank testing demonstrated no significant difference in three-year reintervention (37% vs 33% [control]; P = .75), major amputation (27% vs 15%; P = .64), or primary patency (72% vs 66%; P = .35) rates. Multivariate analysis via Cox regression confirmed these findings (immunosuppression hazard ratio [HR] for reintervention, 0.95; 95% CI, 0.56-1.60; P = .85; for major amputation, HR, 1.44; 95% CI, 0.70-2.96; P = .32; and for primary patency. HR, 0.97; 95% CI, 0.69-1.38; P = .88). For PTA/S patients, univariate analysis revealed similar rates of reintervention (37% vs 39% [control]; P = .57) and primary patency (59% vs 63%; P = .21); however, immunosuppressed patients had higher rates of major amputation (23% vs 12%; P = .01). After using Cox regression to adjust for baseline demographics, as well as operative and anatomic characteristics, immunosuppression was not associated with any differences in reintervention (HR, 0.75; 95% CI, 0.49-1.16; P = .20), major amputation (HR, 1.46; 95% CI, 0.81-2.62; P = .20), or primary patency (HR, 0.84; 95% CI, 0.59-1.19; P = .32). Sensitivity analyses for the differences in makeup of immunosuppression regimens (steroids vs other classes) did not alter the interpretation of any findings in either BPG or PTA/S cohorts. CONCLUSIONS: Our findings demonstrate that patients with chronic systemic immunosuppression, as compared with those who are not immunosuppressed, does not have a significant effect on late outcomes after lower extremity revascularization, as measured by primary patency, reintervention, or major amputation.