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.).

DETOUR2 trial outcomes demonstrate clinical utility of percutaneous transmural bypass for the treatment of long segment, complex femoropopliteal disease.

OBJECTIVE: Percutaneous transmural arterial bypass (PTAB) using the DETOUR system aims to create a percutaneous, endovascular femoropopliteal bypass for the treatment of long segment, complex superficial femoral and proximal popliteal artery disease. The goal of the DETOUR2 study is to investigate the safety and effectiveness of the therapy in comparison with pre-established performance goals. METHODS: The DETOUR2 investigational device exemption study is a prospective, single-arm, multicenter, international trial of symptomatic peripheral arterial disease patients (Rutherford classes 3-5) undergoing the DETOUR procedure for long segment (>20 cm) superficial femoral artery disease. Prespecified end points included primary safety (composite of major adverse events) at 30 days, and effectiveness (primary patency defined as freedom from restenosis or clinically driven target lesion revascularization) at 1 year. RESULTS: We enrolled 202 patients at 32 sites with 200 treated with the DETOUR system. The mean lesion length was 32.7 cm, of which 96% were chronic total occlusions (CTO) and 70% were severely calcified. Technical success was achieved in 100% of treated patients. The primary safety end point was met with a 30-day freedom from major adverse event rate of 93.0%. The 1-year primary effectiveness end point was met with 72.1% primary patency at 12 months. Primary-assisted and secondary patency were 77.7% and 89.0%, respectively, at 12 months. The 12 month deep venous thrombosis incidence was 4.1% with no pulmonary emboli reported. Venous quality-of-life scores showed no significant changes from baseline. There was a Rutherford improvement of at least one class through 12 months in 97.2% of patients. The mean ankle-brachial index also improved from 0.61 to 0.95 during this period. There were marked improvements in quality-of-life and functional status measures. CONCLUSIONS: The DETOUR2 study met both the primary safety and effectiveness end points, demonstrating clinical usefulness of this novel therapeutic strategy in long femoropopliteal lesions.

Outcomes of Stented vs Nonstented Femoropopliteal Lesions Treated With Drug-Coated Balloon Angioplasty.

PURPOSE: Drug-coated balloon (DCB) angioplasty has been increasingly used for the treatment of lower limb peripheral artery disease (PAD). However, bail-out stenting may be necessary in cases of suboptimal angioplasty. This study investigated the outcomes of femoropopliteal disease treated with DCB with/without bail-out stenting. MATERIALS AND METHODS: This was a single-center retrospective study enrolling 166 consecutive patients (DCB+stent: n=81 vs DCB: n=85) with 253 femoropopliteal lesions (DCB+stent: n=99 vs DCB: n=154) treated with DCB with/without stenting. Bail-out stenting was performed at the operator discretion for postangioplasty dissections or otherwise suboptimal angiographic result (>30% residual stenosis). Cox regression analysis was performed to examine the outcomes of DCB with/without stenting during 2-year follow-up. RESULTS: The baseline clinical characteristics were similar between the 2 groups. About half of the patients presented with critical limb ischemia, with most of the lesions located at the superficial femoral artery. The overall mean lesion length was 147±67 mm. The most frequent bail-out stent types were bare metal stents (BMS) (53.5%) followed by drug-eluting stents (DES) (41.4%). Lesions requiring bail-out stenting were on average longer (177±67 mm vs 127±59 mm; p<0.01) and on average had higher prevalence of flow-limiting postangioplasty dissections. The overall procedural success rate was 94% without any differences between the 2 groups. Both the stented and nonstented treatment modalities were effective and safe, demonstrating similar rates of 2-year freedom from major adverse limb event (stented: 71.3% vs nonstented: 64.4%) and 2-year freedom from target lesion revascularization (stented: 77.1% vs nonstented: 72.3%) during following up. The use of DES as bail-out therapy was associated with a lower risk of 2-year death compared with the use of BMS (DES: 97.2% vs BMS: 75.8%; p=0.01). CONCLUSION: Drug-coated balloon with bail-out stenting is a viable treatment option for cases of suboptimal DCB results, promising similar efficacy with DCB-alone procedures. However, as the patency of stents at the femoropopliteal segment may be a challenge due to the biomechanical stress of the artery, the efficacy of DCB+bail-out stenting should be further evaluated. In addition, future studies are needed to determine which grades of post-DCB dissections should be treated and optimize current bail-out strategies.

Clinical Outcomes of Additional Below-The-Ankle Intervention Compared to Below-The-Knee Intervention Alone: A Post-Hoc Analysis of a Prospective Multicenter Study.

PURPOSE: To investigate the clinical implication of additional below-the-ankle (BTA) intervention in patients with chronic limb-threatening ischemia (CLTI) undergoing below-the-knee (BTK) intervention. MATERIALS AND METHODS: A sub-analysis was performed using data from the LIBERTY trial (ClinicalTrials.gov identifier NCT01855412), a prospective, observational, core-laboratory adjudicated, multicenter study of endovascular intervention in 1204 patients. Patients with CLTI (Rutherford Classification 4-6) who underwent BTK intervention were included in this sub-analysis. Participants were then stratified into 2 treatment groups according to whether at least one lesion intervened on was BTA (n=66) or not (n=273). The decision on whether and where to intervene was made during the procedure. The main outcome measures included major amputation, target vessel revascularization (TVR), major adverse events (MAE), survival, amputation-free survival, major adverse limb events or peri-operative death (MALE-POD), and all-cause death. Other outcome measures included procedural success, procedural complications, and wound healing rate. RESULTS: There were no differences in procedural success or severe angiographic complications between the 2 groups. At 1-year post-procedure, patients in the BTK group had a higher rate of freedom from major amputation (95.0% vs. 86.9%, respectively; HR: 2.87, 95% CI: 1.17-7.03), a higher rate of freedom from TVR (80.1% vs. 66.9%, respectively; HR: 1.94, 95% CI: 1.14-3.32), a higher rate of freedom from MALE-POD (94.6% vs. 86.9%, respectively; HR: 2.65, 95% CI: 1.10-6.41), and a higher rate of freedom from MAE at both 1 (76.0% vs. 60.1%, respectively; HR: 2.00, 95% CI: 1.24-3.22) and 3 years post procedure (67.5% vs. 55.8%, respectively; HR: 1.69, 95% CI: 1.08-2.65). There was a significantly lower rate of survival in the BTK group at 3 years (74.3% vs. 91.1%, respectively; HR: 0.35, 95% CI: 0.14-0.87). After risk adjustment, there was a higher rate of all-cause death in the BTK group at 3 years (19.4% vs. 9.1%, respectively; p=0.023) post-intervention. CONCLUSION: Patients with disease requiring intervention to BTA lesions have a potential increased amputation rate in the short term, but BTA intervention carries a potential survival benefit in the long term when compared to BTK intervention alone.

Primary results of the SAVAL randomized trial of a paclitaxel-eluting nitinol stent versus percutaneous transluminal angioplasty in infrapopliteal arteries.

BACKGROUND: Effective and durable options for infrapopliteal artery revascularization for patients with chronic limb-threatening ischemia (CLTI) are limited. METHODS: The SAVAL trial is a prospective, multicenter, randomized trial of patients with CLTI and infrapopliteal artery lesions with total lesion length ⩽ 140 mm, stenosis ⩾ 70%, and Rutherford category 4-5 assigned 2:1 to treatment with the SAVAL self-expandable paclitaxel drug-eluting stent (DES) or percutaneous transluminal angioplasty (PTA) with an uncoated balloon. The primary effectiveness endpoint was primary vessel patency (i.e., core lab-adjudicated duplex ultrasound-based flow at 12 months in the absence of clinically driven target lesion revascularization or surgical bypass of the target lesion). The primary safety endpoint was the 12-month major adverse event (MAE)-free rate; MAEs were defined as a composite of above-ankle index limb amputation, major reintervention, and 30-day mortality. The endpoints were prespecified for superiority (effectiveness) and noninferiority (safety) at a one-sided significance level of 2.5%. RESULTS: A total of 201 patients were enrolled and randomly assigned to treatment (N = 130 DES, N = 71 PTA). Target lesion length was 68.1 ± 35.2 mm for the DES group and 68.7 ± 49.2 mm for the PTA group, and 31.0% and 27.6% of patients, respectively, had occlusions. The 12-month primary patency rates were 68.0% for the DES group and 76.0% for the PTA group (Psuperiority = 0.8552). The MAE-free rates were 91.6% and 95.3%, respectively (Pnoninferiority = 0.0433). CONCLUSION: The SAVAL trial did not show benefit related to effectiveness and safety with the nitinol DES compared with PTA in infrapopliteal artery lesions up to 140 mm in length. Continued innovation to provide optimal treatments for CLTI is needed. (ClinicalTrials.gov Identifier: NCT03551496).

Randomized evaluation of vessel preparation with orbital atherectomy prior to drug-eluting stent implantation in severely calcified coronary artery lesions: Design and rationale of the ECLIPSE trial.

BACKGROUND: Severe coronary artery calcification has been associated with stent underexpansion, procedural complications, and increased rates of early and late adverse clinical events in patients undergoing percutaneous coronary intervention. To date, no lesion preparation strategy has been shown to definitively improve outcomes of percutaneous coronary intervention for calcified coronary artery lesions. STUDY DESIGN AND OBJECTIVES: ECLIPSE (NCT03108456) is a prospective, randomized, multicenter trial designed to evaluate two different vessel preparation strategies in severely calcified coronary artery lesions. The routine use of the Diamondback 360 Coronary Orbital Atherectomy System is compared with conventional balloon angioplasty prior to drug-eluting stent implantation. The trial aims to enroll approximately 2000 subjects with a primary clinical endpoint of target vessel failure, defined as the composite of cardiac death, target vessel-related myocardial infarction, or ischemia-driven target vessel revascularization assessed at 1 year. The co-primary endpoint is the acute post-procedural in-stent minimal cross-sectional area as assessed by optical coherence tomography in a 500-subject cohort. Enrollment is anticipated to complete in 2022 with total clinical follow-up planned for 2 years. CONCLUSIONS: ECLIPSE is a large-scale, prospective randomized trial powered to demonstrate whether a vessel preparation strategy of routine orbital atherectomy system is superior to conventional balloon angioplasty prior to implantation of drug-eluting stents in severely calcified coronary artery lesions.

Orbital atherectomy of calcified coronary ostial lesions.

OBJECTIVES: To evaluate the feasibility and safety of coronary orbital atherectomy (OA) for the treatment of calcified ostial lesions. BACKGROUND: Percutaneous coronary intervention (PCI) is increasingly being completed in complex patients and lesions. OA is effective for severely calcified coronary lesions; however, there is a dearth of evidence on the use of OA in ostial lesions, especially with long-term outcome data. METHODS: Data were obtained from a retrospective analysis of patients who underwent OA of heavily calcified ostial lesions followed by stent implantation from December 2010 to June 2019 at two high-volume PCI centers. Kaplan-Meier analysis was utilized to assess the primary endpoints of 30-day, 1-year, and 2-year freedom-from (FF) major adverse cardiac events (MACE: death, myocardial infarction, or target vessel revascularization), stroke, and stent thrombosis (ST). RESULTS: A total of 56 patients underwent OA to treat heavily calcified ostial coronary lesions. The mean age was 72 years with a high prevalence of diabetes (55%) and heart failure (36%), requiring hemodynamic support (14%). There was high FF angiographic complications (93%), and at 30-day, 1-year, and 2-year, a high FF-MACE (96%, 91%, and 88%), stroke (98%, 96%, and 96%), and ST (100%), respectively. CONCLUSIONS: This study represents the largest real-world experience of coronary OA use in heavily calcified ostial lesions with long-term outcomes over 2 years. The main finding in this retrospective analysis is that, despite the complex patients and lesions included in this analysis, OA appears to be a feasible and safe treatment option for calcified coronary ostial lesions.

Intravascular Lithotripsy for Treatment of Calcified Infrapopliteal Lesions: Results from the Disrupt PAD III Observational Study.

PURPOSE: To evaluate the safety and effectiveness of the Shockwave S4 intravascular lithotripsy (IVL) catheter in an "all-comers" cohort of patients with calcified infrapopliteal lesions. MATERIALS AND METHODS: The Disrupt PAD III Observational Study (NCT02923193) is a prospective, nonrandomized, multicenter single-arm study designed to assess the "real-world" acute safety and effectiveness of the Shockwave Peripheral IVL System for the treatment of de novo calcified, stenotic peripheral arteries. Patients were eligible for enrollment if they had claudication or critical limb ischemia (CLI) and at least moderate calcification as assessed by angiography. This subanalysis includes consecutive patients enrolled with angiographic core lab-assessed treatment of infrapopliteal arteries using the Shockwave S4 IVL catheter. RESULTS: From July 2018 to August 2020, 101 patients with 114 calcified infrapopliteal arteries treated with the S4 IVL catheter were enrolled at 15 sites in 3 countries. CLI was present in 69.3% of patients. The anterior tibial and tiboperoneal trunk were the most commonly treated vessels with an overall mean reference vessel diameter (RVD) of 3.1±0.8 mm, minimum lumen diameter (MLD) of 0.5±0.6 mm, and a corresponding diameter stenosis of 83.4%±15.8% by core lab assessment. Mean lesion length was 64.7±54.7 mm with moderate to severe calcification in 69.3% of lesions by the Peripheral Academic Research Consortium (PARC) criteria. Adjunctive calcium-modifying technology, defined as scoring or cutting balloon and/or atherectomy, was used in 22.7% of procedures. The average acute gain at the end of the procedure was 2.0±0.7 mm with a residual stenosis <50% achieved in 99.0% of lesions and a mean residual stenosis of 23.3±12.5%. There were no flow-limiting dissection, embolization, slow flow/no-reflow, or abrupt closure events at the end of the procedure. CONCLUSION: This subanalysis of the PAD III Observational Study represents the largest report to-date of IVL treatment of heavily calcified below-the-knee (BTK) lesions in a "real-world" patient cohort. The use of S4 IVL demonstrated consistent acute safety and effectiveness outcomes consistent with prior IVL peripheral studies. These consistent outcomes were achieved with the initial use of the S4 IVL catheter for treatment of complex BTK lesions.

Orbital Atherectomy Prior to Drug-Coated Balloon Angioplasty in Calcified Infrapopliteal Lesions: A Randomized, Multicenter Pilot Study.

PURPOSE: Optimal balloon angioplasty for infrapopliteal lesions is often limited by severe calcification, which has been associated with decreased procedural success and lower long-term patency. MATERIALS AND METHODS: This was a prospective, randomized, multicenter pilot trial that included adult subjects with calcified lesions located from the popliteal segment below the knee (BTK) joint to within 5 cm above the ankle with ≥70% diameter stenosis by angiography. Patients were randomized 1:1 to undergo orbital atherectomy (OA) with adjunctive drug-coated balloon (DCB) angioplasty versus plain balloon angioplasty (BA) and DCB angioplasty (control). The periprocedural and 12 month outcomes of both procedures were compared. RESULTS: Overall, 66 subjects (OA + DCB = 32 vs control = 34) were included in an intention to treat analysis. Baseline demographics and lesion characteristics were well-balanced. The mean lesion length was 101.3 mm (SD = 72.8 mm) and 78.8 (SD = 61.0 mm) in the OA + DCB and control groups, respectively, with almost all lesions having severe calcification per the Peripheral Academic Research Consortium (PARC) criteria. Chronic total occlusions (CTOs) were present in 43.8% and 35.3% of the patients in the OA + DCB and control groups, respectively. The technical success of OA + DCB versus DCB was 81.8% and 89.2%, respectively, with 3 slow flow/no reflow, 1 perforation, 1 severe dissection occurred in OA + DCB group, and one distal embolization occurred in the control group. The target lesion primary patency rate was numerically higher in the OA + DCB versus control group at 6 (88.2% vs 50.0%, p=0.065) and 12 month follow-up (88.2% vs 54.5%, p=0.076). The 12 month freedom from major adverse events, clinically-driven target lesion revascularization, major amputation, and all-cause mortality rates were similar between both groups. CONCLUSION: The results of the Orbital Vessel PreparaTIon to MaximIZe Dcb Efficacy in Calcified BTK (OPTIMIZE BTK) pilot study indicated that utilization of OA + DCB is safe for infrapopliteal disease. Further prospective adequately powered studies should investigate the potential benefit of combined OA + DCB for BTK lesions.

Temsirolimus Adventitial Delivery to Improve ANGiographic Outcomes Below the Knee.

BACKGROUND: Current endovascular treatments of below the knee (BTK) popliteal or tibial/peroneal arteries including investigational drug-coated balloons have limited long-term efficacy. OBJECTIVES: This Phase 2 trial assessed the feasibility of adventitial deposition of temsirolimus to reduce neointimal hyperplasia and clinically relevant target lesion failure (CR-TLF) 6 months after BTK arterial revascularization. METHODS: This prospective, multicenter, double-blinded, comparative, dose-escalation trial enrolled 61 patients with Rutherford 3 to 5 symptoms undergoing endovascular revascularization of ≥1 angiographically significant BTK lesions. Perivascular infusion after completion of arterial revascularization was randomized into control (saline) vs low-dose (0.1 mg/mL) temsirolimus groups for the first 30 patients. In the second part of the trial, patients were randomized to control versus high-dose (0.4 mg/mL) temsirolimus groups. Primary and secondary efficacy endpoints were target lesion (TL) transverse-view vessel area loss percentage (TVAL%) and CR-TLF at 6 months, respectively. CR-TLF was defined as a composite of ischemia-driven major amputation of the target limb, clinically driven target lesion revascularization (CD-TLR), and clinically relevant TL occlusion. The primary safety endpoint was freedom from major adverse limb events or perioperative death (MALE+POD) at 30 days. RESULTS: There was no discernable difference in effect between temsirolimus doses; therefore, the low- and high-dose cohorts were pooled for the analyses. The principal analysis on the per protocol (PP) group of 53 patients revealed superior primary efficacy of the treatment arm, with reduction in TVAL% of 13.9% absolute (37.3% relative) and the rate of CR-TLF reduced by 27.1% absolute (51.3% relative), at 6 months. Subgroup analysis of all Trans-Atlantic Inter-Society Consensus (TASC) B to D lesions (N=36) revealed TVAL% reduction of 22.3% absolute (48.3% relative) and the rate of CR-TLF reduced by 39.2% absolute (56.6% relative). Freedom from 30-day MALE+POD was 100% in all groups. CONCLUSIONS: This hypothesis-generating trial suggests that adventitial infusion of temsirolimus in BTK arteries improves TVAL% and CR-TLF with no adverse safety signals through 6 months, supporting the move to a Phase 3 trial. CLINICAL IMPACT: There remain gaps in the endovascular treatment of patients with atherosclerotic lesions of below-the-knee (BTK) arteries. The TANGO trial evaluated the use of sub-adventitial temsirolimus with the Bullfrog micro-infusion device during BTK interventions. The therapy was safe and effective. Compared with controls, vessel lumen area patency was improved, and target lesion failure was less frequent. The effects were most appreciable in subjects with higher baseline TASC lesions (B, C, or D). Sub-adventitial temsirolimus offers the potential to improve the results of BTK interventions in this challenging patient population.

Implementation of supervised exercise therapy in a veteran population with symptomatic claudication.

BACKGROUND: Real-world implementation of supervised exercise therapy (SET) referral for symptomatic intermittent claudication has been limited by poor provider awareness around reimbursement and low patient adherence owing to factors including limited center availability and long travel distances to sites. METHODS: In this study, 76 of 77 consecutive male veteran patients with intermittent claudication managed at a single-center vascular specialty clinic were referred to SET prior to revascularization. Pre- and post-SET submaximal exercise treadmill testing was performed for assessment of exercise capacity in metabolic equivalents (METs). RESULTS: In the 48.7% of subjects who completed 36 sessions of SET (n = 37), the average improvement in METs was 60.3%, reflecting improvement from baseline average of 3.4 METs to 5.5 METs after SET. Another 14 patients pursued self-guided exercise therapy and 25 patients declined any participation in exercise therapy. Reasons for declining participation in SET included inadequate transportation, cost of copayment, and interference with full-time work schedules. There was a nonsignificant numeric trend toward improved change in ankle-brachial index in the combined SET and self-guided exercise groups compared to those that declined exercise therapy (0.011 ± 0.124 vs -0.040 ± 0.105, p = 0.156). CONCLUSION: High acceptance of referral to SET is possible, despite the limitations to implementation. Incorporation of novel pre- and post-SET submaximal exercise treadmill testing allows for assessment of change in exercise capacity and aids in risk stratification and management of intermittent claudication symptoms.

Statins and statin intensity in peripheral artery disease.

Background: Peripheral artery disease (PAD) affects more than 202 million people worldwide. Several studies have shown that patients with PAD are often undertreated, and that statin utilization is suboptimal. European and American guidelines highlight statins as the first-line lipid-lowering therapy to treat patients with PAD. Our objective with this meta-analysis was to further explore the impact of statins on lower extremities PAD endpoints and examine whether statin dose (high vs. low intensity) impacts outcomes. Patients and methods: We performed a systematic review and meta-analysis according to the PRISMA guidelines. Any study that presented a comparison of use of statins vs. no statins for PAD patients or studies comparing high vs. low intensity statins were considered to be potentially eligible. We excluded studies with only critical limb threatening ischemia (CLTI) patients. The Medline (PubMed) database was searched up to January 31, 2021. A random effects meta-analysis was performed. Results: In total, 39 studies and 275,670 patients were included in this meta-analysis. In total, 136,025 (49.34%) patients were on statins vs. 139,645 (50.66%) who were not on statins. Statin use was associated with a reduction in all cause-mortality by 42% (HR: 0.58, 95% CI: 0.49-0.67, p<0.01) and cardiovascular death by 43% (HR: 0.57, 95% CI: 0.40-0.74, p<0.01). Statin use was associated with an increase in amputation-free survival by 56% (HR: 0.44, 95% CI: 0.30-0.58, p<0.01). The risk of amputation and loss of patency were reduced by 35% (HR: 0.65, 95% CI: 0.41-0.89, p<0.01) and 46% (HR: 0.54, 95% CI: 0.34-0.74, p<0.01), respectively. Statin use was also associated with a reduction in the risk of major adverse cardiovascular events (MACE) by 35% (HR: 0.65, 95% CI: 0.51-0.80, p<0.01) and myocardial infarction rates by 41% (HR: 0.59, 95% CI: 0.33-0.86, p<0.01). Among patients treated with statins, the high-intensity treatment group was associated with a reduction in all cause-mortality by 36% (HR: 0.64, 95% CI: 0.54-0.74, p<0.01) compared to patients treated with low intensity statins. Conclusions: Statin treatment among patients with PAD was associated with a statistically significant reduction in all-cause mortality, cardiovascular mortality, MACE, risk for amputation, or loss of patency. Higher statin dose seems to be associated with improved outcomes.

Anterior, posterior, or all-vessel infrapopliteal revascularization in patients with moderate-severe claudication: Insights from the LIBERTY 360 study.

BACKGROUND: Little data guides revascularization of infrapopliteal peripheral arterial disease (PAD) in patients with claudication. We assessed outcomes after infrapopliteal-only intervention for claudication in the LIBERTY 360 observational study. METHODS: In this post hoc analysis, LIBERTY 360 patients (N = 128) with claudication and isolated infrapopliteal disease undergoing endovascular revascularization were divided by territory into anterior-vessel, posterior-vessel, or all-vessel groups. Patients were followed for periprocedural, in-hospital, and long-term outcomes. Logistic regression for odds ratios, Cox proportional hazard models, ANOVA, and Kaplan-Meier estimates were utilized to compare outcomes. RESULTS: Patients underwent anterior (N = 37), posterior (N = 76), or all-vessel (N = 15) infrapopliteal revascularization. Initial procedural success was 86%, 86%, and 69% for anterior, posterior, and all-vessel groups, respectively. Each group had improvements in Rutherford classification (RC) from baseline to 2 years (mean RC change: -1.3, -1.5, and -1.5, respectively). Compared with all-vessel intervention, both anterior and posterior groups had lower rate of major adverse events (MAE) and target vessel revascularization (TVR) at 3 years (MAE: 12% and 15% in anterior and posterior groups, respectively compared with 51% in the all-vessel group; hazard ratios and 95% CIs 0.22 [0.06-0.74], p = .015; 0.24 [0.09-0.64], p = .004). Other outcomes were similar among the three groups. The anterior group showed more improvement in pain subdomain and total VascuQoL scores compared with posterior and all-vessel groups at 2 years (p = .016, p = .020 and p = .068, p = .009, respectively). CONCLUSIONS: Both anterior or posterior revascularization have favorable outcomes and may be beneficial for improvement of symptoms in claudicants with isolated infrapopliteal PAD.

Comparison of rotational and orbital atherectomy for the treatment of calcific coronary lesions: Insights from the VA clinical assessment reporting and tracking (CART) program.

BACKGROUND: Previous studies suggested that pre-treatment of coronary artery calcification (CAC) with rotational atherectomy (RA) prior to stent deployment improved procedural success but was not associated with a concomitant improvement in clinical outcomes. Orbital atherectomy (OA) has demonstrated similar benefits, though there are few data comparing the safety and efficacy of the two modalities. METHODS: Patients who underwent PCI of a native coronary lesion with RA or OA from 2014 to 2018 within the Veterans Affairs Healthcare System were identified. Propensity matched cohorts were generated to compare the clinical and safety outcomes following either RA or OA. The primary endpoint was the rate of 30-day major adverse cardiovascular and cerebrovascular events (MACCE), including all-cause mortality, repeat myocardial infarction, target vessel revascularization, and stroke. RESULTS: We identified 1,091 patients that underwent atherectomy during the study period, 640 (59%) treated with RA and 451 (41%) treated with OA. Among a propensity-matched cohort consisting of 950 patients, there was no significant difference in MACCE for patients who underwent RA or OA (7.1 vs. 8.2%, p = .36). Components of the primary outcome including 30-day mortality, myocardial infarction, target vessel revascularization, and stroke were also similar in the matched cohort. Additionally, procedural complications including perforation, no-reflow, dissection, and in-stent thrombosis were comparable across both treatment strategies. CONCLUSIONS: Both rotational and orbital atherectomy are safe and effective strategies for the treatment of calcified coronary plaque prior to stent deployment, with similarly low rates of peri-procedural adverse events.

Association of Postangioplasty Femoropopliteal Dissections With Outcomes After Drug-Coated Balloon Angioplasty in the Femoropopliteal Arteries.

PURPOSE: Balloon angioplasty for the treatment of femoropopliteal lesions is often complicated by postangioplasty dissections. While dissections are known to affect patency and reintervention after balloon angioplasty, the association between dissections and major adverse limb event (MALE) after drug-coated balloon (DCB) angioplasty remains uncertain. Thus, the postangioplasty dissection and bailout stenting patterns were investigated. MATERIALS AND METHODS: This was a single-center retrospective study enrolling patients with de novo femoropopliteal lesions treated with DCB with/without stenting. Postangioplasty target vessel dissection was graded based to the coronary artery classification grades A-F, with grade C-F considered "severe." Cox regression analysis was performed to examine the association of dissection severity with outcomes during 2-year follow up, among nonstented cases. RESULTS: In 85.3% of the cases (N=203/238) a postangioplasty dissection was observed. The average dissection length was 55.57 mm (SD 36.71 mm), with 1 dissection present in 91.8% (N=180/196) and 2 or more dissections present in 8.2% (N=16/196). Dissection severity was grade A (19.8%), B (20.6%), C (23.1%), D (10.9%), E (10.1%), and F (0.8%). Bailout stenting was required in 40.4% of the patients, being more prevalent among grade C and grade E cases. Among 142 nonstented cases, dissections were present in 85.2%. A total of 75 (52.8%) of these dissections were grade A and B, while 46 (32.4%) were grade C to F. Among nonstented cases, grade C (hazard ratio [HR] 5.83; 95% CI 1.25 to 27.31; p=0.025) and grade D (HR 6.32; 95% CI 1.39 to 28.86; p=0.017) vs grade A dissections were associated with a higher risk for 2-year MALE. Multivariate analysis adjusting for several lesion characteristics demonstrated a statistically significant higher risk for 2-year MALE among the severe dissection group (HR 2.94; 95% CI 1.27 to 6.79; p = 0.012). Interestingly, the risks of limb loss (HR 1.30; 95% CI 0.22 to 7.79; p=0.774) and repeat revascularization (HR 0.95; 95% CI 0.40 to 2.26; p=0.905) during follow-up were similar between the 2 groups. CONCLUSION: This study indicated that nonstented moderate and severe postangioplasty dissections after DCB angioplasty were associated with higher risk for MALE. Future studies are needed to validate our results and determine other dissection characteristics (eg, total dissection length, lumen area, total number of dissections) that may affect the efficacy of DCB.

Three-Year Outcomes From the LIBERTY 360 Study of Endovascular Interventions for Peripheral Artery Disease Stratified by Rutherford Category.

PURPOSE: To report the 3-year results of the LIBERTY 360 study, which investigated outcomes of endovascular treatment of symptomatic peripheral artery disease (PAD). MATERIALS AND METHODS: The LIBERTY trial (ClinicalTrials.gov identifier NCT01855412) was a prospective, observational, core laboratory-assessed, multicenter study of endovascular interventions enrolling >1200 participants treated at 51 sites. Data from 1189 patients were stratified according to Rutherford category (RC) and analyzed [RC 2-3 (n=500), RC 4-5 (n=589), and RC 6 (n=100)]. The primary outcomes were major amputation of the target limb and all-cause death; secondary outcomes were target vessel revascularization (TVR) or target lesion revascularization (TLR); major adverse events (MAEs; death within 30 days, TVR or TLR, and major amputation); death or major amputation combined; and change in self-reported quality of life (QoL) measures (VascuQol-25). The Kaplan-Meier (KM) method was employed to estimate the outcomes; estimates are presented with the 95% confidence intervals (CI). Predictors of 3-year MAE, death, TVR, and major amputation were analyzed using Cox proportional hazard regression modeling. RESULTS: The 36-month KM survival rates were 86.0% in RC 2-3, 79.8% in RC 4-5, and 62.0% in RC 6 groups. The KM estimates of freedom from major amputation at 36 months were 98.5% in RC 2-3, 94.0% in RC 4-5, and 79.9% in RC 6. The 36-month KM estimates for freedom from TVR/TLR were 71.1% in RC 2-3, 64.2% in RC 4-5 and 61.9% in RC 6 groups. Patients with claudication at baseline were at lower risk for MAEs compared with RC 4-5 and RC 6 patients during the 36-month follow-up. Vascular QoL improved from baseline and persisted up to 36 months in all patients. CONCLUSION: Endovascular therapy is a viable treatment option for patients with symptomatic PAD, with sustained improved quality of life in both claudicants and patients with chronic limb-threatening ischemia. These results provide important point estimates for midterm outcomes after modern endovascular interventions for PAD.

Health Care Utilization Following Inpatient Femoropopliteal Revascularization With Drug-Coated Balloon Angioplasty: A Nationwide Cohort Analysis.

PURPOSE: To examine nationwide variations in inpatient use of drug-coated balloons (DCBs) for treating femoropopliteal segment occlusive disease and whether DCBs are associated with reduced early out-of-hospital health care utilization. MATERIALS AND METHODS: The study included 24,022 patients who survived hospitalization for femoropopliteal revascularization using DCB angioplasty (n=7850) or uncoated balloon angioplasty (n=16,172) in the 2016-2017 Nationwide Readmissions Database. Differences in patient, hospitalization, and institutional characteristics were compared between treatment strategies. Adjusted logistic regression models were used to examine differences in 6-month rates of readmission, amputation, and repeat intervention. Results are presented as the odds ratio (OR) and 95% confidence interval (CI). RESULTS: Patients treated with DCBs had a higher prevalence of chronic limb-threatening ischemia, diabetes, hypertension, and tobacco use. Revascularization with a DCB was associated with shorter hospitalizations, lower median hospitalization costs, and fewer inpatient lower extremity amputations. Readmissions at 6 months were decreased in patients treated with DCBs compared with uncoated balloon angioplasty (OR 0.90, 95% CI 0.83 to 0.98, p=0.014). The most common reasons for readmission were complications related to procedures (15.4%) and diabetes (15.4%). Compared to patients treated with DCBs, patients treated with uncoated balloon angioplasty were more often readmitted with early procedure-related complications (13.3% vs 17.5%). There were no between-group differences in readmission for sepsis, myocardial infarction, or congestive heart failure. CONCLUSION: DCBs are less often used compared to uncoated balloons during inpatient femoropopliteal procedures. While DCB utilization is associated with more severe comorbidities and advanced peripheral artery disease, readmission rates are decreased through the first 6 months.

Intravascular Lithotripsy for Treatment of Calcified Lesions During Carotid Artery Stenting.

PURPOSE: To report the use of intravascular lithotripsy (IVL) in the treatment of calcified carotid artery lesions. MATERIALS AND METHODS: The records of 21 high-surgical-risk patients (mean age 75.1±8.1 years; 17 men) who were treated at 8 centers for carotid artery stenosis ≥70% were retrospectively reviewed. Twelve patients had a history of cerebrovascular disease. All patients had heavily calcified carotid artery lesions: 19 de novo and 2 in-stent restenoses (ISR). The mean baseline stenosis was 82.3%±9.7%. IVL was utilized at the discretion of the operator, followed by balloon angioplasty. Embolic protection devices were used in all cases. RESULTS: In 19 patients, IVL was followed by stent implantation; the 2 ISR lesions were dilated only. The mean IVL balloon diameter was 4.64±1.13 mm, and the mean number of IVL pulses applied was 67.2±61.4 (range 10-180). All procedures were technically successful (<30% residual stenosis). No patients developed symptomatic bradycardia or hypotension due to IVL, and there were no adverse events associated with IVL delivery. All patients were discharged on dual antiplatelet therapy. Seventeen days after the procedure, 1 patient experienced an ischemic stroke that was deemed due to aortic arch manipulation during transfemoral access. Carotid duplex ultrasound examination identified significant restenosis (>70%) in 1 asymptomatic patient at 12 months after the index procedure. No patients required reintervention during a median follow-up of 6 months (range 1-12). CONCLUSION: This preliminary experience demonstrates that IVL can be a safe and effective approach for the management of severely calcified carotid lesions. Further research is warranted to determine the longer-term safety and efficacy of IVL for dilation of calcified carotid artery lesions as an adjunct to carotid artery stenting.

JetStream Atherectomy for the Treatment of In-Stent Restenosis of the Femoropopliteal Segment: One-Year Results of the JET-ISR Study.

PURPOSE: To report the results of a study evaluating JetStream atherectomy for the treatment of in-stent restenosis (ISR). MATERIALS AND METHODS: The JetStream XC atherectomy device, a rotational cutter with aspiration capacity, was evaluated in a prospective, multicenter study (JET-ISR) of 60 patients (mean age 70.2±10.8 years; 40 men) with femoropopliteal ISR (ClinicalTrials.gov identifier NCT02730234). Lesion length was 19.9±13.5 cm; 33 (55%) were chronic total occlusions and 26 (45%) were TransAtlantic Inter-Society Consensus class D. No drug-bearing device was allowed, and stenting was performed only for bailout. Lesion characteristics and stent integrity were evaluated by an independent core laboratory. The primary endpoint was target lesion revascularization (TLR) at 6 months with bailout stenting considered as TLR. Secondary endpoints included TLR (without bailout stenting) and clinical patency (no restenosis or TLR) at 1 year. The Kaplan-Meier method was employed to evaluate time-to-event endpoints; estimates are given with 95% confidence interval (CI). RESULTS: Bailout stenting was required in 6 of 60 limbs (10%). There were no stent fractures or deformities after atherectomy + adjunctive angioplasty reported by the core laboratory. Kaplan-Meier estimates of freedom from TLR at 6 months and 1 year were 79.3% (95% CI 68.9% to 89.8%) and 60.7% (95% CI 47.8% to 73.6%), respectively. When bailout stenting at the index procedure was not considered a TLR event, freedom from TLR estimates at 6 months and 1 year were 89.3% (95% CI 81.2% to 97.4%) and 66.8% (95% CI 54.3% to 74.2%), respectively. Clinical patency rates at 6 months and 1 year were 77.5% (31/40) and 51.7% (15/29), respectively. CONCLUSION: JetStream atherectomy using the XC device and no drug-eluting devices is feasible, with good clinical patency and 1-year freedom from TLR.

Technical Success and Complication Rates of Retrograde Arterial Access for Endovascular Therapy for Critical Limb Ischaemia: A Systematic Review and Meta-Analysis.

OBJECTIVE: Antegrade crossing techniques via transfemoral access are often challenging and may be associated with technical and clinical failure when treating patients with critical limb ischaemia (CLI). The objective of this study was to summarise all available literature regarding retrograde endovascular treatment of patients with CLI and to investigate the technical success and complication rate of retrograde access. METHODS: A systematic literature search was performed in PubMed, Scopus, and Cochrane Central until May 2020. A meta-analysis of 31 observational studies (29 retrospective and two prospective; 26 and five studies with low and moderate risk of bias, respectively) was conducted with random effects modelling. The incidence of adverse events peri-procedurally and during follow up were calculated. RESULTS: The 31 studies enrolled 1 910 patients who were treated endovascularly for femoropopliteal and/or infrapopliteal lesions causing CLI. Most of the patients had diabetes while more than half of the overall population had coronary artery disease and dyslipidaemia. All lesions were located in the infra-inguinal segment and most were chronic total occlusions (96%; 95% CI 85%-100%). Seven studies reported moderate or severe calcification in approximately half of the cases (45%; 95% CI 30%-60%). The overall technical success of the retrograde approach was 96% (18 studies; 95% CI 92%-100%). Perforation, flow limiting dissection, distal embolisation, and local haematoma at the retrograde access site were infrequent and observed in 2.1%, 0.6%, 0.1%, and 1.3% of the patients, respectively. The six month primary patency rate was 78% (five studies; 95% CI 46%-99%), the six month limb salvage rate was 77% (four studies; 95% CI 70%-84%). CONCLUSION: The results indicated that the retrograde or bidirectional antegrade/retrograde approach is safe and effective and facilitates angioplasty when antegrade treatment fails. However, prospective studies with standardised wound care and surveillance protocols are needed to investigate retrograde techniques in patients with CLI who failed antegrade revascularisation, to improve long term limb salvage and survival.