Drug-Eluting Resorbable Scaffold versus Angioplasty for Infrapopliteal Artery Disease.

BACKGROUND: Among patients with chronic limb-threatening ischemia (CLTI) and infrapopliteal artery disease, angioplasty has been associated with frequent reintervention and adverse limb outcomes from restenosis. The effect of the use of drug-eluting resorbable scaffolds on these outcomes remains unknown. METHODS: In this multicenter, randomized, controlled trial, 261 patients with CLTI and infrapopliteal artery disease were randomly assigned in a 2:1 ratio to receive treatment with an everolimus-eluting resorbable scaffold or angioplasty. The primary efficacy end point was freedom from the following events at 1 year: amputation above the ankle of the target limb, occlusion of the target vessel, clinically driven revascularization of the target lesion, and binary restenosis of the target lesion. The primary safety end point was freedom from major adverse limb events at 6 months and from perioperative death. RESULTS: The primary efficacy end point was observed (i.e., no events occurred) in 135 of 173 patients in the scaffold group and 48 of 88 patients in the angioplasty group (Kaplan-Meier estimate, 74% vs. 44%; absolute difference, 30 percentage points; 95% confidence interval [CI], 15 to 46; one-sided P<0.001 for superiority). The primary safety end point was observed in 165 of 170 patients in the scaffold group and 90 of 90 patients in the angioplasty group (absolute difference, -3 percentage points; 95% CI, -6 to 0; one-sided P<0.001 for noninferiority). Serious adverse events related to the index procedure occurred in 2% of the patients in the scaffold group and 3% of those in the angioplasty group. CONCLUSIONS: Among patients with CLTI due to infrapopliteal artery disease, the use of an everolimus-eluting resorbable scaffold was superior to angioplasty with respect to the primary efficacy end point. (Funded by Abbott; LIFE-BTK ClinicalTrials.gov number, NCT04227899.).

Outcomes of early transcarotid artery revascularization versus carotid endarterectomy after acute neurologic events.

OBJECTIVE: Carotid revascularization within 14 days of a neurologic event has been recommended by society guidelines. Transcarotid artery revascularization (TCAR) carries the lowest overall stroke rate for any carotid artery stenting technique. However, the outcomes of TCAR within 14 days of a neurologic event have not been directly compared with those after carotid endarterectomy (CEA). METHODS: We compared the 30-day outcomes of symptomatic patients who had undergone TCAR and CEA within 14 days of a stroke or transient ischemic attack (TIA) from January 2016 to February 2020 using the Society for Vascular Surgery Vascular Quality Initiative carotid artery stenting and CEA databases. Propensity score matching was used to adjust for patient risk factors. The primary outcome was a composite of postoperative ipsilateral stroke, death, and myocardial infarction (MI). RESULTS: A total of 1281 symptomatic patients had undergone TCAR and 13,429 patients had undergone CEA within 14 days of a neurologic event. After 1:1 propensity matching, 728 matched pairs were included for analysis. The primary composite outcome of stroke, death, or MI was more frequent in the TCAR group (4.7% vs 2.6%; P = .04). This was driven by a higher rate of postoperative ipsilateral stroke in the TCAR group (3.8% vs 1.8%; P = .005). No differences were found between TCAR and CEA in terms of death (0.7% vs 0.8%; P = .8) or MI (0.8% vs 1%; P = .7). Although TCAR procedures were shorter (median, 69 minutes [interquartile range, 53-85 minutes]; vs median, 120 minutes [interquartile range, 93-150 minutes]; P < .001) and the postoperative length of stay was similar (2 days; P = .3) compared with CEA, the TCAR patients were more likely to be discharged to a facility other than home (26% vs 19%; P < .01). Performing TCAR within 48 hours of a stroke was an independent predictor of postoperative stoke or TIA (odds ratio, 5.4; 95% confidence interval, 1.8-16). This increased risk of postoperative stroke or TIA was not found when performing TCAR within 48 hours of a TIA. CONCLUSIONS: TCAR within 14 days of a neurologic event resulted in higher ipsilateral postoperative stroke rates compared with CEA, especially when performed within 48 hours after a stroke.

Transcarotid artery revascularization versus carotid endarterectomy and transfemoral stenting in octogenarians.

OBJECTIVE: Transfemoral carotid artery stenting (TFCAS) has higher combined stroke and death rates in elderly patients with carotid artery stenosis compared with carotid endarterectomy (CEA). However, transcarotid artery revascularization (TCAR) may have similar outcomes to CEA. This study compared outcomes after TCARs relative to those after CEAs and TFCAS, focusing on elderly patients. METHODS: We included all patients with carotid artery stenosis and no prior endarterectomy or stenting who underwent either a CEA, TFCAS, or TCAR in the Vascular Quality Initiative from September 2016 (TCAR commercially available) to December 2019. We categorized patients into age decades: 60 to 69 years, 70 to 79 years, and 80 to 90 years. Outcomes included 30-day and 1-year composite rates of stroke or death. Cox proportional hazards models evaluated both outcomes after adjusting for patient demographics, clinical factors, symptomatology, hospital CEA volume, and clustering. RESULTS: We identified 33,115 patients who underwent either a CEA, TFCAS, or TCAR for carotid artery stenosis (35% in their 60s, 44% in their 70s, and 21% in their 80s), where one-half (50%) were symptomatic. The majority of patients had CEAs (80%), followed by TFCAS (11%) and TCARs (9.1%). The overall rate of 30-day stroke/death was 1.5% and of 1-year stroke/death was 4.4%. Octogenarians had the highest 30-day and 1-year stroke/death rates relative to their peers (2.3% and 6.3%, respectively). Among all patients, the adjusted hazards of TCARs relative to CEAs was similar for 30-day stroke/death (hazard ratio [HR] 1.10; 95% confidence interval [CI], 0.75-1.62) and slightly higher for 1-year stroke/death (HR, 1.34; 95% CI, 1.02-1.76). Among octogenarians, however, the adjusted hazards of TCARs relative to CEAs was similar for both 30-day stroke/death (HR, 1.12; 95% CI, 0.59-2.13) and 1-year stroke/death (HR, 1.28; 95% CI, 0.85-1.94). TFCAS relative to CEAs had higher hazards of both 30-day stroke/death (HR, 1.78; 95% CI, 1.10-2.89) and 1-year stroke/death (HR, 1.85; 95% CI, 1.35-2.54) in octogenarians. CONCLUSIONS: TCARs had similar outcomes relative to CEAs among octogenarians with respect to 30-day and 1-year rates of stroke/death. TCAR may serve as a promising less invasive treatment for carotid disease in older patients who are deemed high anatomic, surgical, or clinical risk for CEAs.

The variable impact of aneurysm size on outcomes after open abdominal aortic aneurysm repairs.

OBJECTIVE: Previous studies evaluating the association between abdominal aortic aneurysm (AAA) size with postoperative outcomes after open repairs seldom accounted for renal or visceral artery involvement, proximal clamp site, intraoperative renal ischemia time, and hospital volume. This study examined the association between aneurysm size with outcomes after open repairs. METHODS: We identified patients who underwent open repairs of infrarenal versus juxtarenal nonruptured AAAs, defined by proximal clamp site, in the 2004-2019 Vascular Quality Initiative. Outcomes included 30-day mortality, postoperative complications, failure to rescue, and 1-year mortality. Multivariable logistic regressions adjusted for patient characteristics, operative factors, hospital volume, and hospital clustering. RESULTS: We identified 8011 patients (54% infrarenal, 46% juxtarenal). The median aneurysm size did not differ between infrarenal versus juxtarenal aneurysms (5.7 cm vs 5.9 cm; P = .12). For infrarenal aneurysms, every 1-cm increase in size increase the adjusted odds ratio (OR) or hazard ratio (HR) of 30-day mortality by 18% (OR, 1.18; 95% CI, 1.06-1.31), failure to rescue by 20% (OR, 1.20; 95% CI, 1.06-1.34), 1-year mortality by 18% (HR, 1.18; 95% CI, 1.10-1.26), but not complications (OR, 1.03; 95% CI, 0.98-1.07). For juxtarenal aneurysm, larger aneurysm sizes were not associated with any outcome. Proximal clamp site, ischemia time, and volume were associated with outcomes. CONCLUSIONS: The association between AAA size and outcomes matters less with renal and visceral artery aneurysmal involvement, having important implications for surgical decision-making, operative planning, and patient counseling.

Small apolipoprotein(a) isoforms may predict primary patency following peripheral arterial revascularization.

Background: High lipoprotein (a) [Lp(a)] is associated with adverse limb events in patients undergoing lower extremity revascularization. Lp(a) levels are genetically pre-determined, with LPA gene encoding for two apolipoprotein (a) [apo(a)] isoforms. Isoform size variations are driven by the number of kringle IV type 2 (KIV-2) repeats. Lp(a) levels are inversely correlated with isoform size. In this study, we examined the role of Lp(a) levels, apo(a) size and inflammatory markers with lower extremity revascularization outcomes. Methods: 25 subjects with chronic peripheral arterial disease (PAD), underwent open or endovascular lower extremity revascularization (mean age of 66.7±9.7 years; F=12, M=13; Black=8, Hispanic=5, and White=12). Pre- and post-operative medical history, self-reported symptoms, ankle brachial indices (ABIs), and lower extremity duplex ultrasounds were obtained. Plasma Lp(a), apoB100, lipid panel, and pro-inflammatory markers (IL-6, IL-18, hs-CRP, TNFα) were assayed preoperatively. Isoform size was estimated using gel electrophoresis and weighted isoform size ( wIS ) calculated based on % isoform expression. Firth logistic regression was used to examine the relationship between Lp(a) levels, and wIS with procedural outcomes: symptoms (better/worse), primary patency at 2-4 weeks, ABIs, and re-intervention within 3-6 months. We controlled for age, sex, history of diabetes, smoking, statin, antiplatelet and anticoagulation use. Results: Median plasma Lp(a) level was 108 (44, 301) nmol/L. The mean apoB100 level was 168.0 ± 65.8 mg/dL. These values were not statistically different among races. We found no association between Lp(a) levels and w IS with measured plasma pro-inflammatory markers. However, smaller apo(a) wIS was associated with occlusion of the treated lesion(s) in the postoperative period [OR=1.97 (95% CI 1.01 - 3.86, p<0.05)]. The relationship of smaller apo(a) wIS with re-intervention was not as strong [OR=1.57 (95% CI 0.96 - 2.56), p=0.07]. We observed no association between wIS with patient reported symptoms or change in ABIs. Conclusions: In this small study, subjects with smaller apo(a) isoform size undergoing peripheral arterial revascularization were more likely to experience occlusion in the perioperative period and/or require re-intervention. Larger cohort studies identifying the mechanism and validating these preliminary data are needed to improve understanding of long-term peripheral vascular outcomes. Key Findings: 25 subjects with symptomatic PAD underwent open or endovascular lower extremity revascularization in a small cohort. Smaller apo(a) isoforms were associated with occlusion of the treated lesion(s) within 2-4 weeks [OR=1.97 (95% CI 1.01 - 3.86, p<0.05)], suggesting apo(a) isoform size as a predictor of primary patency in the early period after lower extremity intervention. Take Home Message: Subjects with high Lp(a) levels, generally have smaller apo(a) isoform sizes. We find that, in this small cohort, patients undergoing peripheral arterial revascularization subjects with small isoforms are at an increased risk of treated vessel occlusion in the perioperative period. Table of Contents Summary: Subjects with symptomatic PAD requiring lower extremity revascularization have high median Lp(a) levels. Individuals with smaller apo(a) weighted isoform size (wIS) have lower primary patency rates and/or require re-intervention.

Postintervention monitoring of peripheral arterial disease wound healing using dynamic vascular optical spectroscopy.

Significance: Due to the persistence of chronic wounds, a second surgical intervention is often necessary for patients with peripheral arterial disease (PAD) within a year of the first intervention. The dynamic vascular optical spectroscopy system (DVOS) may assist physicians in determining patient prognosis only a month after the first surgical intervention. Aim: We aim to assess the DVOS utility in characterizing wound healing in PAD patients after endovascular intervention. Approach: The DVOS used near-infrared light ( 670 < λ < 850 nm ) to record hemodynamic response to a cuff inflation in 14 PAD patients with lower limb ulcers immediately before, immediately after, and at a first follow-up 3 to 4 weeks after intervention. Ankle-brachial index (ABI) and arterial duplex ultrasound (A-DUS) measurements were obtained when possible. Results: The total hemoglobin plateau time differed significantly between patients with ulcers that reduced in size ( N = 9 ) and patients with ulcers that did not ( N = 5 ) 3 to 4 weeks after intervention ( p value < 0.001 ). Data correlated strongly (89% sensitivity, 100% specificity, and AUC = 0.96 ) with long-term wound healing. ABI and A-DUS measurements were not statistically associated with wound healing. Conclusions: This pilot study demonstrates the potential of the DVOS to aid physicians in giving accurate long-term wound healing prognoses 1 month after intervention.

Injectable Therapeutic Organoids Using Sacrificial Hydrogels.

Organoids are becoming widespread in drug-screening technologies but have been used sparingly for cell therapy as current approaches for producing self-organized cell clusters lack scalability or reproducibility in size and cellular organization. We introduce a method of using hydrogels as sacrificial scaffolds, which allow cells to form self-organized clusters followed by gentle release, resulting in highly reproducible multicellular structures on a large scale. We demonstrated this strategy for endothelial cells and mesenchymal stem cells to self-organize into blood-vessel units, which were injected into mice, and rapidly formed perfusing vasculature. Moreover, in a mouse model of peripheral artery disease, intramuscular injections of blood-vessel units resulted in rapid restoration of vascular perfusion within seven days. As cell therapy transforms into a new class of therapeutic modality, this simple method-by making use of the dynamic nature of hydrogels-could offer high yields of self-organized multicellular aggregates with reproducible sizes and cellular architectures.

Power-pulse spray thrombectomy for treatment of Paget-Schroetter syndrome.

OBJECTIVE: This initial single-center study describes three cases of axillary-subclavian vein thrombosis (Paget-Schroetter syndrome) treated with a rapid, novel thrombectomy technique, termed "power-pulse spray thrombectomy," in which a thrombolytic agent is directly infused into the clot via a catheter, followed by intravascular mechanical clot fracture and removal. CONCLUSION: All patients in this series were treated in a single session. Complete clot removal was successfully achieved without the development of any complications. This is the first description of the application of this technique in the treatment of Paget-Schroetter syndrome to our knowledge.

Successful management of carotid stenosis in a high-risk population at an inner-city hospital.

This is a retrospective review of all carotid endarterectomies (CEA) (n=91) done from 1993 to 2002 at an inner-city hospital (Group I). This group was compared to a randomly selected group of patients (n=445) treated at a private hospital (Group II). The same high-volume surgeons performed CEAs at both hospitals. The majority of Group I patients (71.4%) were members of racial minority groups. They were also more likely to be younger (p<0.001), hypertensive (p<0.03), diabetic (p<0.001), and current smokers (p<0.001); have contralateral carotid artery occlusion (p=0.04); and present with stroke (p<0.001) than Group II patients. Despite this, the incidence of postoperative myocardial infarction (2.2% vs 0.2%, p=0.08), stroke (1.1% vs 1.6%, NS), and death (1.1% vs 0%, NS) was comparable between the 2 groups. Aggressive preoperative workup for occult cardiac disease in Group I revealed an incidence of 25.9% (n=15). Of these, 5 (33.3%) were found to have coronary artery disease severe enough to warrant intervention before CEA. In an inner-city population with increased medical comorbidities, more severe cerebrovascular disease, and relatively low volume of carotid surgery, the results of CEA were comparable to those in patients treated at a high-volume private hospital. The presence of high-volume surgeons, operating at the low-volume municipal hospital, may contribute to the low complication rate. Finally, aggressive preoperative cardiac workup in this underserved population revealed a meaningful incidence of occult coronary artery disease requiring intervention before CEA.

Impact of carotid artery angioplasty and stenting on management of recurrent carotid artery stenosis.

Citing the higher perioperative risk of redo carotid surgery, balloon angioplasty and stenting of the carotid artery (CAS) has been advocated for recurrent carotid stenosis (RCS). To examine the impact of CAS on the management and outcome of recurrent stenosis, a retrospective review of a prospectively compiled database was performed. From a registry of patients treated for carotid disease, 105 procedures were performed from 1992 to 2002 for RCS. For comparison, two study groups were examined. Time I consisted of 77 reoperations performed through 1998, before CAS was introduced at our institution. Time II included 12 reoperations and 16 CAS procedures performed for RCS from 1999 through 2002. Using perioperative stroke as a measure of outcome, the results for time II were poorer than for time I (7.2% vs. 5.2%, p = NS). Overall, the risk of perioperative stroke was the same for reoperation (5/89) and CAS (1/16) (5.6% vs. 6.3%, p = NS). Although not statistically significant, there was a trend toward a higher risk of perioperative stroke for patients treated with reoperation during the latter time period (8.3% vs. 5.2%, p = NS). This probably relates to the finding that during time II, CAS was most likely to be used in asymptomatic patients (68.6% vs. 41.7%, p = NS) with early (<3 years) RCS (87.5% vs. 41.7%, p= 0.01). No patient with asymptomatic, early RCS had a perioperative stroke with either surgery or CAS (0/35 cases, 0%). The presence of preoperative neurologic symptoms was significantly predictive of a perioperative stroke among all procedures performed for RCS (13.6% vs. 0%, p = 0.004). Contrary to suggestions that CAS might improve the management of RCS, a review of our data shows the overall risk of periprocedural stroke to be no better since CAS has become available. The bias for using CAS for asymptomatic myointimal hyperplastic lesions, and reoperation for frequently symptomatic late recurrent atherosclerotic disease, makes direct comparisons of the two techniques for treating RCS difficult. It is expected that the overall risk for redo carotid surgery will increase, as fewer low-risk patients will be receiving open procedures. However, the increased risk among symptomatic patients undergoing reoperation suggests that endovascular techniques should be investigated among this group of cases as well.