Drug-Coated Balloons for Dysfunctional Dialysis Arteriovenous Fistulas.

BACKGROUND: Standard percutaneous transluminal angioplasty is the current recommended treatment for dysfunctional hemodialysis fistulas, yet long-term outcomes of this treatment are poor. Drug-coated balloons delivering the antirestenotic agent paclitaxel may improve outcomes. METHODS: In this prospective, single-blinded, 1:1 randomized trial, we enrolled 330 participants at 29 international sites. Patients with new or restenotic lesions in native upper-extremity arteriovenous fistulas were eligible for participation. After successful high-pressure percutaneous transluminal angioplasty, participants were randomly assigned to receive treatment with a drug-coated balloon or a standard balloon. The primary effectiveness end point was target-lesion primary patency, defined as freedom from clinically driven target-lesion revascularization or access-circuit thrombosis during the 6 months after the index procedure. The primary safety end point, serious adverse events involving the arteriovenous access circuit within 30 days, was assessed in a noninferiority analysis (margin of noninferiority, 7.5 percentage points). The primary analyses included all participants with available end-point data. Additional sensitivity analyses were performed to assess the effect of missing data. RESULTS: A total of 330 participants underwent randomization; 170 were assigned to receive treatment with a drug-coated balloon, and 160 were assigned to receive treatment with a standard balloon. During the 6 months after the index procedure, target-lesion primary patency was maintained more often in participants who had been treated with a drug-coated balloon than in those who had been treated with a standard balloon (82.2% [125 of 152] vs. 59.5% [88 of 148]; difference in risk, 22.8 percentage points; 95% confidence interval [CI], 12.8 to 32.8; P<0.001). Drug-coated balloons were noninferior to standard balloons with respect to the primary safety end point (4.2% [7 of 166] and 4.4% [7 of 158], respectively; difference in risk, -0.2 percentage points; 95% CI, -5.5 to 5.0; P = 0.002 for noninferiority). Sensitivity analyses confirmed the results of the primary analyses. CONCLUSIONS: Drug-coated balloon angioplasty was superior to standard angioplasty for the treatment of stenotic lesions in dysfunctional hemodialysis arteriovenous fistulas during the 6 months after the procedure and was noninferior with respect to access circuit-related serious adverse events within 30 days. (Funded by Medtronic; IN.PACT AV Access Study ClinicalTrials.gov number, NCT03041467.).

Five-year results of the LEOPARD trial of commercially available endografts.

OBJECTIVE: The LEOPARD (Looking at EVAR Outcomes by Primary Analysis of Randomized Data) trial is a randomized controlled trial comparing the outcomes of endovascular aneurysm repair (EVAR) using commercially available devices in a real-world population. METHODS: A prospective, randomized, multi-center trial was performed to compare the anatomically fixated (AF) AFX/AFX2 endograft system (Endologix) with endografts with proximal fixation (PF) (Cook Medical Zenith Flex; Gore Excluder; and Medtronic Endurant II) in patients with infrarenal abdominal aortic aneurysms. The primary endpoint was freedom from aneurysm-related complications (ARCs), a composite endpoint consisting of perioperative death (≤30 days), aneurysm rupture, conversion to open surgical repair, postoperative endoleaks, endograft migration (≥10 mm), aneurysm enlargement (≥5 mm), endograft limb occlusion, and device- or aneurysm-related reintervention. RESULTS: The study population was 455 patients enrolled at 56 United States centers: 235 patients were treated with AF devices and 220 with PF devices. The primary endpoint supported noninferiority of the AF cohort at 1 year. The 5-year freedom from ARC Kaplan-Meier estimates were 63.8% for AF patients and 55.5% for PF patients (P = .10). Kaplan-Meier estimates for freedom from aneurysm-related mortality were 98.7% and 97.0% in the AF group and 99.5% and 98.5% in the PF group at 1 and 5 years. There was no difference in aneurysm-related mortality, all-cause mortality, rupture, secondary interventions, and type I and type III endoleak between the two cohorts. The type III endoleak rate at 5 years for the AFX cohort was 1.5% and 0.0% for the comparator cohort (P = .11). There was a lower type II endoleak rate in the AF group at 5 years (78.8% vs 68.4%; P = .037). There were zero open surgical conversions (0.0%) in the AF group and four (2.0%) in the PF group. CONCLUSIONS: The 5-year results from the LEOPARD study demonstrated that there was no clinically significant difference in overall aneurysm-related outcomes between patients randomized to the AFX endograft system or commercially available endografts with proximal fixation.

Percutaneous arteriovenous fistula creation with the 4F WavelinQ EndoAVF System.

BACKGROUND: Percutaneous devices for creation of native arteriovenous fistulae offer an alternative to traditional open surgical techniques. The 4F WavelinQ EndoAVF System was developed as a lower profile alternative to facilitate access through smaller vessels and minimize access site complications; The current report is the original first experience of this device, assessing outcome in 120 patients followed for 6 months. METHODS: The use of the 4F WavelinQ system in three studies, EASE (32 patients), EASE-2 (24 patients), and the EU postmarket clinical follow-up study (64 patients) was aggregated and analyzed. Patients were followed with duplex ultrasound at discharge and follow-up visits at 1, 3, and 6 months. Primary, assisted primary, and secondary patency rates were evaluated as Kaplan-Meier estimates and standard errors. Time to maturity and time to successful cannulation were defined as the mean ± standard deviation days from the procedure in patients enrolled on dialysis. RESULTS: Procedural success was achieved in 116 patients (96.7%). Primary, assisted-primary, and secondary 6-month patency rates were 71.9% ± 4.5%, 80.7% ± 4.1%, and 87.8% ± 3.3%, respectively. Time to maturity averaged 41 ± 17 days. Time to successful cannulation averaged 68 ± 51 days. Device-related serious adverse events were reported in 3 of 120 patients (2.5%) and procedure-related serious adverse events occurred in 7 of 120 patients (5.8%). Arterial or venous access complications were not reported in any of the patients. Access circuit reinterventions were performed in 23 patients (19.2%), split between those performed for EndoAVF maturation (13/120 [10.8%]) and maintenance (11/120 [9.2%]). CONCLUSIONS: Percutaneous creation of native dialysis fistulae with the 4F WavelinQ EndoAVF System is safe and effective, with favorable durability and a low rate of serious complications and reinterventions through 6-month follow-up. Use of the 4F device allows for percutaneous fistula creation between the radial artery and radial vein or the ulnar artery and ulnar vein. These findings suggest that the 4F device is a useful percutaneous alternative to open surgical AVF or endovascular AVF with larger bore devices.

United States Investigational Device Exemption study of the Revolution Peripheral Atherectomy System.

OBJECTIVE: Atherectomy has become commonplace as an adjunct to interventional treatments for peripheral arterial disease, but the procedures have been complicated by risks including distal embolization and arterial perforation. This study aimed to examine the safety and effectiveness of a novel atherectomy system to treat femoropopliteal and below-knee peripheral arterial disease. METHODS: The Revolution Peripheral Atherectomy System (Rex Medical LP, Conshohocken, Pa) was studied in 121 patients with 148 femoropopliteal and below-knee lesions, enrolled at 17 United States institutions. Technical success was defined when the post-atherectomy angiographic stenosis was ≤50%, as assessed by an independent core laboratory. Major adverse events were adjudicated by an independent Clinical Events Committee. RESULTS: Among 148 site-identified target lesions in 121 patients, 21.4% were in the superficial femoral artery, 13.7% involved the popliteal artery, and 67.9% were in tibial arteries; 3.1% involved more than one segment. Technical success was 90.2%, with stenoses decreasing from 73% ± 19% at baseline to 42% ± 14% after atherectomy. Adjunctive treatment after atherectomy included angioplasty with uncoated balloons in 91%, drug-coated balloons in 11%, bare stent deployment in 8%, and drug-eluting stent placement in 3%. Procedural success (<30% residual stenosis) was achieved in 93.7% of target lesions. Complications during the procedure included one target vessel perforation and two distal embolizations; each of which were adjudicated by the Clinical Events Committee as unrelated to the device and were not visualized angiographically by the core laboratory. Freedom from major adverse events was 97.3% through 30 days. The Kaplan-Meier estimates of primary, assisted primary, and secondary patency were 81.6%, 87.7%, and 91.6% at 6 months, respectively. CONCLUSIONS: The use of the Revolution Peripheral Atherectomy System was associated with few procedural complications and a high rate of success at the index procedure and through 6 months.

Four-year patient-level pooled mortality analysis of the ILLUMENATE US Pivotal and EU randomized controlled trials.

OBJECTIVE: To perform a meta-analysis of two concordant randomized controlled trials (RCTs) examining the long-term, 4-year safety profile of the Stellarex drug-coated balloon (DCB) vs percutaneous transluminal angioplasty (PTA) for the treatment of peripheral artery disease. METHODS: An independent, third-party, meta-analysis of homogeneous, patient-level data from the ILLUMENATE Pivotal and ILLUMENATE EU RCTs was performed to assess mortality (time to death) in patients treated for symptomatic femoropopliteal disease. The Kaplan-Meier (KM) methodology was used to estimate hazard rates [HRs] of all-cause mortality, and Cox proportional hazard modeling was used to assess predictors of mortality. All serious adverse events, including deaths, were adjudicated by an independent, blinded clinical events committee. RESULTS: In total, 589 (419 DCB; 170 PTA) patients were included in the pooled analysis of the ILLUMENATE Pivotal and ILLUMENATE EU RCTs. The median follow-up was 1735 days (interquartile range, 1434-1829 days), equivalent to 4.75 years. Vital status compliance was >95% in each RCT. The total number of deaths through 4 years was 81 of 589 (13.8%): 58 of 419 (13.8%) in the DCB arm and 23 of 170 (13.5%) in the PTA arm. The 1-year KM estimate of all-cause mortality was 1.9% ± 0.7% (estimate ±standard error) in those treated with DCB vs 1.2% ± 0.9% in those treated with PTA. At 2, 3, and 4 years, the respective KM estimates were 6.6% ± 1.2% vs 4.9% ± 1.7%, 9.3% ± 1.4% vs 9.9% ± 2.4%, and 14.0% ± 1.7% vs 14.4% ± 2.8% (P = .864). There were no significant differences in clinical events committee-adjudicated deaths between the two cohorts. In multivariate analysis, predictors of 4-year mortality were age (HR, 1.048; 95% confidence interval [CI], 1.026-1.071; P < .0001), renal insufficiency (HR, 2.440; 95% CI, 1.566-3.800; P < .0001), and lesion length (HR, 1.004; 95% CI, 1.000-1.008; P = .041). Neither paclitaxel exposure (DCB vs PTA; HR, 1.086; 95% CI, 0.709-1.664; P = .705) nor dose (mg; HR, 1.043; 95% CI, 0.971-1.119; P = .248) was the predictor of all-cause mortality at 4 years. CONCLUSIONS: This systematic meta-analysis of two concordant ILLUMENATE RCTs shows no difference in all-cause mortality through 4 years between Stellarex DCB and PTA, confirming the acceptable, long-term safety profile of the Stellarex DCB.

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.

Percutaneous Femoropopliteal Bypass: 2-Year Results of the DETOUR System.

PURPOSE: This study investigated the 2-year safety and effectiveness of the PQ Bypass DETOUR system as a percutaneous femoropopliteal bypass. MATERIALS AND METHODS: Seventy-eight patients with 82 long-segment femoropopliteal lesions were enrolled in this prospective, single-arm, multicenter study. The DETOUR system deployed Torus stent grafts directed through a transvenous route. Eligible patients included those with lesions of >10 cm and average of 371±55 mm. Key safety endpoints included major adverse events (MAEs) and symptomatic deep venous thrombosis in the target limb. Effectiveness endpoints included primary patency defined as freedom from ≥50% stenosis, occlusion, or clinically-driven target vessel revascularization (CD-TVR), primary assisted, and secondary patency. RESULTS: Chronic total occlusions and severe calcium occurred in 96% and 67% of lesions, respectively. Core laboratory-assessed total lesion length averaged 371±51 mm with a mean occlusion length of 159±88 mm. The rates of technical and procedural success were 96%, with satisfactory delivery and deployment of the device without in-hospital MAEs in 79/82 limbs. The MAE rate was 22.0%, with 3 unrelated deaths (4%), 12 CD-TVRs (16%), and 1 major amputation (1%). Deep venous thrombosis developed in 2.8% of target limbs, and there were no reported pulmonary emboli. Primary, assisted primary, and secondary patency rates by the Kaplan-Meier analysis were 79±5%, 79±5%, and 86±4%, respectively. CONCLUSIONS: The PQ Bypass DETOUR system is a safe and effective percutaneous alternative to femoropopliteal open bypass with favorable results through 2 years. The DETOUR system provides a durable alternative to conventional endovascular modalities and open surgery for patients with long, severely calcified, or occluded femoropopliteal lesions.

A preliminary analysis of late structural failures of the Navion stent graft in the treatment of descending thoracic aortic aneurysms.

OBJECTIVE: Patients in the Valiant Evo U.S. and international clinical trials had positive short-term outcomes; however, late structural failures, including type IIIb endoleaks have been recently discovered. Type IIIb endoleaks are serious adverse events because the repressurization of the aneurysm sac increases the risk of rupture. The purpose of the present study was to detail the imaging patterns associated with the structural failures with the aim of increasing awareness of failing graft presentation, early recognition, and prompt treatment. METHODS: The Valiant Evo clinical trial was a prospective, single-arm investigation of a thoracic stent graft system. With the recent late structural failures, sites were requested to submit all available imaging studies to date to allow the core laboratory to assess for structural failures such as type IIIb endoleaks, stent ring fractures, and stent ring enlargement. Of the 100 patients originally enrolled in the trial from 2016 to 2018, the core laboratory assessed the imaging studies performed at ≥1 year for 83 patients. RESULTS: No structural failures of the graft were reported through 1 year of follow-up. At 1 to 4 years, graft structural failures were detected in 11 patients with descending thoracic aortic aneurysms. Of the 11 patients, 5 had a type IIIb endoleak. Four of the five had imaging findings showing stent fractures consistent with the location of the graft seam and one had a type IIIb endoleak attributed to calcium erosion with no stent fracture or ring enlargement. Of the four patients with stent fracture in line with the graft seam, three underwent a relining procedure that successfully excluded the type IIIb endoleak. One of these three patients died 4 days later of suspected thoracic aortic rupture because the distal thoracic endovascular aortic repair extension had been landed in a previously dissected and fragile section of the aorta. The remaining six patients had had stent ring enlargement. One of the six patients had had persistent aneurysm expansion from the time of implantation onward and had died of unknown causes. The remaining five patients have continued to be monitored. CONCLUSIONS: In the present preliminary analysis, the imaging patterns associated with type IIIb endoleaks, stent fractures, and stent ring enlargement appear to be related to the loss of seam integrity or detachment of the stent rings from the surface of the graft material. The imaging patterns we have detailed should be closely monitored using computed tomography angiography surveillance to allow structural failures to be promptly identified and treated.

Five-year results of the INSPIRATION study for the INCRAFT low-profile endovascular aortic stent graft system.

OBJECTIVE: We present the 5-year results of a prospective regulatory study of the INCRAFT device, a low-profile endovascular stent graft system for repair of abdominal aortic aneurysms. METHODS: This was an open-label prospective nonrandomized single-arm study enrolling in centers in the United States and Japan. The primary effectiveness outcome was successful aneurysm treatment and the primary safety outcome was the incidence of major adverse events at 30 days after the procedure. Major long-term outcomes were mortality, reintervention, adverse limb outcomes, and suprarenal stent fracture. RESULTS: One hundred and ninety patients (mean age, 73.8 ± 7.6 years; 90% male; 69% white and 30% Asian) were enrolled from 32 centers throughout the United States and Japan. Minimal access vessel size was less than 7 mm on both sides in 43.9% of the study cohort. Thirty-day major adverse events occurred in 3.2% of patients (6/190). Periprocedural technical success was 94.1% (176/187). Successful aneurysm treatment was 100% at 30 days and 87.9% at 1 year. Two patients required open conversion for thromboembolic complications, 3 developed new type I or III endoleaks, and 7 experienced graft or limb occlusion. Freedom from graft occlusion was 96 ± 2% at 1 year and 94 ± 2% at 5 years. Freedom from stent fracture was 97 ± 1% at 1 year and 87 ± 3% at 5 years. Freedom from aneurysm-related mortality was 99 ± 1% at 1 and 5 years. CONCLUSIONS: This study demonstrates good efficacy and safety and a very low rate of aneurysm related deaths with the INCRAFT device in a population with a high proportion of challenging anatomy.

Remodeling of Abdominal Aortic Angulation and Curvature After Endovascular Aneurysm Repair in Patients With vs Without Late Type Ia Endoleak or Endograft Migration.

PURPOSE: To investigate aortic remodeling of the supra- and infrarenal aorta from preoperative to 1 month and midterm follow-up after endovascular aneurysm repair (EVAR) by analyzing changes in angulation and curvature in patients with vs without late type Ia endoleak or device migration. MATERIALS AND METHODS: From a multicenter database, 35 patients (mean age 76±5 years; 31 men) were identified with late (>1 year) type Ia endoleak or endograft migration (≥10 mm) and defined as the complication group. The control group consisted of 53 patients (mean age 75±7 years; 48 men) with >1-year computed tomography angiography (CTA) follow-up and no evidence of endoleaks. Suprarenal and infrarenal angles were measured on centerline reconstructions of the preoperative, 1-month, and midterm CTA scans. The value and location relative to baseline of maximum suprarenal and infrarenal curvature were determined semiautomatically using dedicated software. Changes were determined at 1 month compared with the preoperative CTA and at midterm compared with 1 month. RESULTS: Preoperative suprarenal angulation was significantly greater in the complication group compared to the controls (34°±18° vs 24°±17°, p=0.008). It decreased significantly at 1 month in the complication group (29°±16°, p=0.011) and at midterm follow-up in the controls (20°±19°, p<0.001). Preoperative infrarenal angulation was not significantly different (57°±15° vs 49°±24°, p=0.114). This measurement increased significantly through midterm follow-up in the complication group (63°±23°, p<0.001) but remained stable in the controls (46°±22°). Preoperative suprarenal curvature was not significantly different (38±22 m-1 vs 29±25 m-1, p=0.115). This variable increased significantly through midterm follow-up in the complication group (44±22 m-1) but remained constant in the controls (28±22 m-1). Preoperative infrarenal curvature was significantly greater in the complication group (77±29 m-1 vs 65±28 m-1, p=0.047) and decreased significantly in both groups during midterm follow-up (50±17 m-1 vs 41±19 m-1 p=0.033). The location of the maximum curvature with regard to baseline shifted significantly distally in the complication group (54±43 to 72±41 mm, p<0.001), while it remained stable in the controls (46±33 to 48±31 mm). CONCLUSION: At midterm follow-up, significant differences in supra- and infrarenal angulation and curvature were observed between patients with vs without type Ia endoleak or migration. The location of the maximum curvature shifted distally in patients with complications. The aortic morphology is more stable during midterm follow-up in the patients without endoleaks.

Mortality Assessment of Paclitaxel-Coated Balloons: Patient-Level Meta-Analysis of the ILLUMENATE Clinical Program at 3 Years.

BACKGROUND: A recent summary-level meta-analysis comprising randomized, controlled trials (RCTs) of femoropopliteal paclitaxel-coated balloon and stent intervention identified excess late mortality in the paclitaxel-treated patients. METHODS: We evaluated the safety of the Stellarex drug-coated balloon (DCB) for femoropopliteal artery disease with an independently performed meta-analysis of patient-level data from all patients in the Stellarex femoropopliteal clinical program. To compare mortality after DCB or uncoated percutaneous transluminal angioplasty (PTA), we aggregated data from 2 RCTs comprising 419 patients treated with DCB and 170 patients treated with PTA. In an additional analysis, data were aggregated from 6 poolable Stellarex DCB studies (2 RCTs, 3 single-arm studies, and 1 registry). All serious adverse events including deaths were adjudicated by a blinded, third-party, independent Clinical Events Committee. Kaplan-Meier estimates in the RCTs were compared with restricted mean survival time. Predictors of death were assessed with hazard ratios (HRs) and Cox proportional hazards modeling. RESULTS: Baseline characteristics were similar in the patients treated with DCB and PTA in the pooled RCT analysis, with the exception that the DCB cohort was younger (67.4±9.7 versus 69.4±9.4 years, P=0.02), smoked more frequently (86.6% versus 78.8%, P=0.02), and were less often treated for recurrent lesions (8.8% versus 14.7%, P=0.04). In the RCTs, patients treated with DCB had all-cause mortality rates that were not different from those of patients treated with PTA (Kaplan-Meier estimates 1.8±0.7% versus 1.3±0.9%, 6.5±1.2% versus 5.9±1.9%, and 9.3±1.5% versus 9.9±2.4% at 1, 2, and 3 years, respectively, P=0.86). All-cause mortality rates were similar in a 1906-patient pooled nonrandomized DCB data set (Kaplan-Meier estimates of 2.1%, 4.9%, and 7.0% at 1, 2, and 3 years, respectively). Clinical Events Committee-adjudicated causes of death were balanced between the DCB and PTA cohorts. Multivariable Cox modeling identified age (HR, 1.06; 95% CI, 1.04-1.08; P<0.001), diabetes mellitus (HR, 1.42; 95% CI, 1.01-2.00; P=0.04), congestive heart failure (HR, 1.88; 95% CI, 1.12-3.16; P=0.02), and renal insufficiency (HR, 2.00; 95% CI, 1.33-3.01; P<0.001) as predictors of mortality. Paclitaxel exposure was unrelated to mortality (HR, 1.04; 95% CI, 0.98-1.10; P=0.23). CONCLUSIONS: The mortality rates for patients treated with the DCB and uncoated PTA were indistinguishable over 3-year follow-up. Additional patient-level, adequately powered meta-analyses with larger RCT data sets will be needed to confirm the generalizability of these findings. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT02110524, NCT01858363, NCT01858428, NCT03421561, NCT01912937, NCT01927068, and NCT02769273.

A systematic review of covered balloon-expandable stents for treating aortoiliac occlusive disease.

OBJECTIVE: To evaluate and compare studies reporting the outcomes of the use of covered balloon-expandable (CBE) stents for the treatment of aortoiliac occlusive disease. METHODS: A systematic literature search was conducted to identify studies that investigated the use of CBE stents for the treatment of aortoiliac occlusive disease and were published between 2000 and 2019. Baseline demographic data, procedural variables, and long-term outcomes were extracted from publications for analysis. RESULTS: A total of 15 published articles about 14 studies were included in the review. Of these, eight studies were prospective clinical trials and six studies were retrospective real-world studies. The articles included data regarding five different CBE stents, namely, the iCast/Advanta V12, Viabahn VBX, BeGraft, LifeStream, and JOSTENT. Lesion severity was higher in real-world studies, with more TransAtlantic Inter-Society Consensus Classification class D lesions and a higher percentage of occlusions. All studies showed high rates of technical success and patency over the course of 12 months. Long-term data were only available for the iCast/Advanta V12 device, which had a primary patency rate of 74.7% at 5 years. CONCLUSIONS: CBE stents are a viable treatment option for patients with complex aortoiliac lesions because of their high rates of technical success and favorable patency across all devices at 12 months. However, long-term data are only available for a single device, the iCast/Advanta V12. The results of using this device were favorable over the course of 5 years.

One-year results from the DETOUR I trial of the PQ Bypass DETOUR System for percutaneous femoropopliteal bypass.

OBJECTIVE: The objective of this study was to evaluate the 1-year safety and effectiveness outcomes associated with the PQ Bypass DETOUR System (PQ Bypass, Milpitas, Calif) for the percutaneous bypass of long-segment femoropopliteal occlusive disease. METHODS: This prospective, single-arm, multicenter trial enrolled patients with long-segment femoropopliteal arterial disease. The DETOUR System percutaneously deploys modular stent grafts to bypass femoropopliteal lesions through a transvenous route. Eligible patients included those with TransAtlantic Inter-Society Consensus C and D lesions >100 mm in length. The primary safety end point was the major adverse event (MAE) rate through 1 month, defined as the composite of death, clinically driven target vessel revascularization (CD-TVR), or major amputation. The primary effectiveness end point was stent graft patency through 6 months, defined as freedom from stenosis ≥50%, occlusion, or CD-TVR. RESULTS: During a 24-month period, 78 patients (82 limbs) were enrolled. The average core laboratory-measured lesion length was 371 ± 55 mm; 79 of 82 lesions (96%) were chronic total occlusions, and 55 of 82 lesions (67%) had severe calcification. The rates of technical and procedural success measured during the index procedure were both 96%, with satisfactory delivery and deployment of the device without MAEs in 79 of 82 limbs. Through 1 month, there were no deaths or amputations; CD-TVRs occurred in 2 of 81 limbs (3%), and freedom from MAEs was 98% (79/81). The 1-year Kaplan-Meier primary, assisted primary, and secondary patency rates were 81% ± 4%, 82% ± 4%, and 90% ± 3%, respectively. The ankle-brachial index increased an average of 0.25 ± 0.27 between baseline and 1 year (P < .001). Through 1 year, the Kaplan-Meier estimates of freedom from stent graft thrombosis, CD-TVR, and MAE were 84% ± 4%, 85% ± 4%, and 84% ± 4%, respectively. At 1 year, the Rutherford class improved in 77 of 80 limbs (96%), and 65 of 80 (81%) were asymptomatic. Deep venous thrombosis developed in 2 of 79 target limbs (3%) through 1 year, both at the femoropopliteal vein level. There were no instances of pulmonary embolism. CONCLUSIONS: The 1-year results from the DETOUR I trial show that the PQ Bypass DETOUR System is a safe and effective percutaneous treatment option for patients with longer, severely calcified, above-knee femoropopliteal lesions.

Paclitaxel exposure: Long-term safety and effectiveness of a drug-coated balloon for claudication in pooled randomized trials.

BACKGROUND: Paclitaxel drug-coated balloons (DCB) prevent recurrent claudication after angioplasty, yet data from randomized trials with incomplete follow-up have raised uncertainty regarding long-term mortality. OBJECTIVES: To evaluate the effect of paclitaxel exposure on the long-term safety and efficacy of angioplasty of femoropopliteal artery lesions in the combined IN.PACT randomized trials. METHODS: The IN.PACT randomized trials (SFA, N = 331 and Japan, N = 100) each compared the DCB with standard percutaneous transluminal angioplasty (PTA) for claudication, and consented patients for 5 and 3 years, respectively. To address long-term safety, sites were requested to obtain vital status follow-up. In the pooled, updated data set, we examined the association between randomized treatment and mortality by cumulative incidence and hazard ratio (HR), and freedom from clinically driven target lesion revascularization (CD-TLR). Multivariable Cox regression with adjustment for baseline characteristics was used to evaluate the dose effect. Causes of death were adjudicated by a blinded clinical events committee that included oncologists with paclitaxel expertise. RESULTS: The rate of long-term vital status ascertainment increased from 81% to 97% for DCB and from 85% to 97% for PTA in the IN.PACT SFA trial. The cumulative incidence of mortality was 14.7% DCB versus 12.0% PTA at 5 years, HR 1.39, log-rank p = .286. Paclitaxel dose (mg) was not an independent predictor of mortality (HR 1.02, p = .381), but was an independent predictor of reduced risk of CD-TLR (HR 0.79; p < .001). Causes of death did not differ by treatment arm. CONCLUSIONS: In pooled randomized trial data with updated vital status ascertainment, paclitaxel was associated with improved efficacy but was not associated with increased mortality.

Percutaneous Thrombectomy in Emergency Department Patients with Pulmonary Embolism: The FLARE ED Sub-study.

BACKGROUND: The FlowTriever Pulmonary Embolectomy Clinical Study (FLARE) was a multicenter, single-arm trial that demonstrated effectiveness of the FlowTriever percutaneous pulmonary embolectomy system in reducing right ventricular/left ventricular (RV/LV) diameter ratio in patients with acute intermediate-risk pulmonary embolism (PE). Patients diagnosed in emergency departments (EDs) with acute PE may have a different presentation from those diagnosed in an in-hospital setting. OBJECTIVES: The goal of this sub-study was to evaluate the safety and effectiveness of mechanical embolectomy in ED patients with acute intermediate-risk PE. METHODS: ED patients with acute PE and RV/LV ratio ≥ 0.9 enrolled in the FLARE study were core laboratory analyzed. The primary efficacy endpoint was the change in RV/LV ratio from baseline to 48 h post procedure. The change in RV/LV ratio of patients with nonelevated cardiac troponin (cTn) and zero simplified PE Severity Index (sPESI) score (normal cTn-sPESI: intermediate-low risk) was also examined. Major adverse events (MAEs) included major bleeding, device-related death or clinical deterioration, and vascular or cardiac injury. RESULTS: Seventy-six ED patients were included. Thirty-nine had a sPESI score of ≥ 1 and 32 had elevated cTn. The median preprocedure RV/LV ratio for all ED patients was 1.50 (0.88-2.52), with a change by -0.37 postprocedure (p < 0.001.) Three patients experienced MAEs. Seventeen patients (22.4%) presented with normal cTn-sPESI and had an RV/LV ratio reduced by 0.27 (p < 0.001) after embolectomy. CONCLUSION: ED patients with intermediate-risk PE had significant improvement in their RV/LV ratio and low complication rates when treated with mechanical embolectomy, irrespective of their baseline cTn-sPESI risk score.

Aortoiliac remodeling and 5-year outcome of an ultralow-profile endograft.

BACKGROUND: Remodeling of the aortoiliac anatomy is a challenge to the long-term performance of stent grafts for endovascular aneurysm repair. Changes in vessel diameter and length can result in loss of seal at attachment sites, limb disunion, or kinking, with the development of high-pressure endoleaks, migration, or limb occlusion. The aim of this study was to assess the durability and conformability of the ultralow-profile INCRAFT AAA endograft (Cordis Corporation, Milpitas, Calif) during 5-year follow-up. METHODS: From 2010 to 2011, there were 60 patients (median age, 74 years; range, 60-94 years) with intact abdominal aortic aneurysms who were enrolled in the INNOVATION trial to evaluate the safety, effectiveness, and durability of the INCRAFT AAA device. Clinical and technical success was assessed with protocol-specified, monitored follow-up clinic visits and core laboratory-assessed computed tomography (CT) at 1 month, 6 months, and 12 months after implantation and annually through 5 years thereafter. Diameter and angulation changes at the proximal aortic neck and diameter changes at the iliac attachment zones were measured in addition to the standard CT assessments. RESULTS: Significant aortoiliac remodeling was observed throughout long-term follow-up after endovascular aneurysm repair. Proximal aortic neck diameter 15 mm below the lowest main renal artery increased from 23.5 ± 2.5 mm at 1 month to 27.3 ± 2.8 mm at 5 years (P = .002). Neck dilation >5 mm was observed in 8 of 38 patients with 5-year CT studies (21%). The aortic neck straightened, with angulation decreasing from 34 ± 14 degrees preoperatively to 31 ± 11 degrees at 1 month (P < .001) and to 20 ± 12 degrees at 5 years (P = .018). Straightening of the neck was most prominent in patients who presented with a high degree of preoperative angulation (r = 0.61; P < .001). Between 1 month and 5 years, iliac attachment zone diameter increased from 13.5 ± 1.9 mm to 15.0 ± 2.4 mm on the right (P = .002) and from 13.9 ± 2.3 mm to 16.8 ± 2.7 mm on the left (P < .001). During 5 years, 9 of 72 (13%) iliac arteries enlarged >5 mm. There was a significant relationship between main body oversizing and aortic neck enlargement (r = 0.42; P = .009). No similar association was observed between iliac limb oversizing and iliac dilation over time (r = 0.10 and P = .549, right side; r = 0.14 and P = .400, left side). There were no aneurysm-related deaths in the series. There were two type IA endoleaks, both of which were present on the 1-month CT scan and associated with challenging aortic neck anatomy. No patient experienced endograft migration or rupture through 5 years. Type IB endoleaks occurred in two patients, both accompanied by iliac artery dilation and loss of seal. Stent fracture occurred in two struts of the bare transrenal stent of one patient, without loss of fixation or seal. One patient experienced graft limb occlusion and was observed without intervention. There were three patients (5%) with aneurysm sac enlargement (>5 mm) through 5 years, each of whom had type II endoleak. CONCLUSIONS: Significant aortoiliac remodeling occurs after endograft implantation, including proximal aortic neck dilation, straightening of the neck, and iliac artery enlargement. The ultralow-profile INCRAFT device adapted well to these changes, with acceptably low 5-year rates of device-related endoleaks, endograft migration, and limb occlusion.

Analysis of the position of EndoAnchor implants in therapeutic use during endovascular aneurysm repair.

OBJECTIVE: The aim of this study was to analyze the penetration depth, angles, distribution, and location of deployment of individual EndoAnchor (Medtronic Vascular, Santa Rosa, Calif) implants. METHODS: Eighty-six primary and revision arm patients (procedural success, 53; persistent type IA endoleak, 33) treated for type IA endoleaks with a total of 580 EndoAnchor implants from a subset of the Aneurysm Treatment Using the Heli-FX Aortic Securement System Global Registry (ANCHOR) were included in this study. Procedural success was defined as the absence of a type IA endoleak on the first postprocedural computed tomography scan after the EndoAnchor implantation procedure. Endograft malapposition along the circumference was assessed at the first postoperative computed tomography scans and expressed as clock-face range and width in degrees and normalized such that the center was translated to 0 degrees. The position and penetration of each EndoAnchor implant were measured as the clock-face orientation. EndoAnchor implant penetration into the aortic wall was categorized as follows: good penetration, ≥2 mm; borderline penetration, <2 mm or ≥2-mm gap between the endograft and aortic wall; or no penetration. The orthogonal and longitudinal angles between the EndoAnchor implant and the interface plane of the aortic wall were determined. Location of deployment was investigated for each EndoAnchor implant and classified as maldeployed when it was above the fabric or in a gap >2 mm between the endograft and aortic wall due to >2-mm thrombus or positioning of the EndoAnchor implant below the aortic neck. RESULTS: A total of 170 (29%) EndoAnchor implants had maldeployment and were therefore beyond recommended use and not useful. After EndoAnchor implantation, the procedural success and persistent type IA endoleak groups had 3 (1%) and 4 (2%) EndoAnchor implants positioned above the fabric as well as 60 (18%) and 103 (42%) placed in a gap >2 mm, respectively. The amount of EndoAnchor implants with good, borderline, and no penetration was significantly different between both groups (success vs type IA endoleak) after exclusion of maldeployed EndoAnchor implants (235 [87.4%], 14 [5.2%], and 20 [7.4%] vs 97 [68.8%], 18 [12.8%], and 26 [18.4%], respectively; P < .001). Good penetration EndoAnchor implants were more closely aligned with a 90-degree orthogonal angle than the borderline penetration and nonpenetrating EndoAnchor implants. The longitudinal angle was more distributed, which was observed through all three penetration groups. CONCLUSIONS: In this subcohort of ANCHOR patients, almost 30% of the EndoAnchor implants had maldeployment, which may be prevented by careful preoperative planning and measured intraoperative deployment. If endoleaks are due to >2-mm gaps, EndoAnchor implants alone may not provide the intended sealing, and additional devices should be considered.

Sustainability of Individual EndoAnchor Implants in Therapeutic Use to Treat Type Ia Endoleak After Endovascular Aneurysm Repair.

PURPOSE: To investigate changes in penetration depths and angles of EndoAnchor implants with initially good penetration after therapeutic use in endovascular aneurysm repair. MATERIALS AND METHODS: Patients were selected from the Aneurysm Treatment Using the Heli-FX Aortic Securement System Global Registry (ANCHOR; ClinicalTrials.gov identifier NCT01534819). Inclusion criteria were (1) EndoAnchor implantation to treat intraoperative or late type Ia endoleak and (2) at least 2 postoperative computed tomography angiography (CTA) scans. Exclusion criteria were the use of adjunct procedures. Based on these criteria, 54 patients (44 men) with 360 EndoAnchor implants were eligible for this analysis. Penetration depth of each EndoAnchor implant into the aortic wall was judged as (1) good (≥2-mm penetration), (2) borderline (<2 mm or when there was a gap between the endograft and the aortic wall), or (3) no penetration. The penetration depth and longitudinal angles of EndoAnchors with good penetration were investigated on the last available postprocedure CTA scan. Endoleaks were also analyzed. RESULTS: EndoAnchor penetration on the first postprocedure CTA scan was good in 187 (51.9%), borderline in 69 (19.2%), and missing in 104 (28.9%). On the last CTA scan, 182 (97.4%) of the 187 initially well-positioned EndoAnchors remained good. Five (2.6%) EndoAnchors in 4 patients changed configuration over time (4 became borderline and 1 became nonpenetrating), all without any clinical sequelae. The median orthogonal angles of the EndoAnchor implants with good penetration on the first and last CTA scans were 92° [interquartile range (IQR) 85, 98] and 90° (IQR 84, 97), respectively (p=0.822); for longitudinal angles, medians of 85° (IQR 71, 96) and 84° (IQR 70, 96) were found (p=0.043). Of the 18 (33%) patients who had a type Ia endoleak on the first postprocedure CTA, 6 resolved over time. Median follow-up was 13 months, during which no new type Ia endoleak was found. CONCLUSION: Despite the small number of EndoAnchors analyzed, this study showed that the sustainability of EndoAnchor implants with initially good penetration is satisfactory at 1-year follow-up. The vast majority of EndoAnchor implants with good penetration initially remained in good position; <3% of implants became borderline or nonpenetrating, without any clinical consequence.

Matched cohort comparison of endovascular abdominal aortic aneurysm repair with and without EndoAnchors.

OBJECTIVE: The objective of this study was to examine whether prophylactic use of EndoAnchors (Medtronic, Santa Rosa, Calif) contributes to improved outcomes after endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms through 2 years. METHODS: The Aneurysm Treatment Using the Heli-FX Aortic Securement System Global Registry (ANCHOR) subjects who received prophylactic EndoAnchors during EVAR were considered for this analysis. Imaging data of retrospective subjects who underwent EVAR at ANCHOR enrolling institutions were obtained to create a control sample. Nineteen baseline anatomic measurements were used to perform propensity score matching, yielding 99 matched pairs. Follow-up imaging of the ANCHOR and control cohorts was then compared to examine outcomes through 2 years, using Kaplan-Meier survival analysis. RESULTS: Freedom from type Ia endoleak was 97.0% ± 2.1% in the ANCHOR cohort and 94.1% ± 2.5% in the control cohort through 2 years (P = .34). The 2-year freedom from neck dilation in the ANCHOR and control cohorts was 90.4% ± 5.6% and 87.3% ± 4.3%, respectively (P = .46); 2-year freedom from sac enlargement was 97.0% ± 2.1% and 94.0% ± 3.0%, respectively (P = .67). No device migration was observed. Aneurysm sac regression was observed in 81.1% ± 9.5% of ANCHOR subjects through 2 years compared with 48.7% ± 5.9% of control subjects (P = .01). Cox regression analysis found an inverse correlation between number of hostile neck criteria met and later sac regression (P = .05). Preoperative neck thrombus circumference and infrarenal diameter were also variables associated with later sac regression, although not to a significant degree (P = .10 and P = .06, respectively). Control subjects with thrombus were significantly less likely to experience later sac regression than those without thrombus (6% and 43%, respectively; P = .001). In ANCHOR subjects, rate of regression was not significantly different in subjects with or without thrombus (33% and 36%, respectively; P = .82). Control subjects with wide aortic necks (>28 mm) were observed to experience sac regression at a lower rate than subjects with smaller diameter necks (10% and 44%, respectively; P = .004). Wide neck and normal neck subjects implanted with EndoAnchors experienced later sac regression at roughly equivalent rates (44% and 33%, respectively; P = .50). CONCLUSIONS: In propensity-matched cohorts of subjects undergoing EVAR, the rate of sac regression in subjects treated with EndoAnchors was significantly higher. EndoAnchors may mitigate the adverse effect of wide infrarenal necks and neck thrombus on sac regression, although further studies are needed to evaluate the long-term effect of EndoAnchors.

Influence of aortic neck characteristics on successful aortic wall penetration of EndoAnchors in therapeutic use during endovascular aneurysm repair.

OBJECTIVE: This study sought to quantify EndoAnchor (Medtronic Vascular, Santa Rosa, Calif) penetration into the aortic wall in patients undergoing endovascular abdominal aortic aneurysm repair and to assess predictors of successful penetration and its relationship to postprocedural type IA endoleak. METHODS: A subset of patients from the Aneurysm Treatment Using the Heli-FX Aortic Securement System Global Registry (ANCHOR) were included if they met the following criteria: the indication for EndoAnchor use was to treat a type IA endoleak, and postprocedure contrast-enhanced computed tomography (CT) scans of sufficient quality were available for core laboratory review. Patients undergoing implantation of cuffs or stents during the EndoAnchor implantation procedure were excluded. Baseline anatomic characteristics were recorded. The cohort was divided into patients with and without persistent type IA endoleaks at the first postoperative CT scan. Penetration of each EndoAnchor measured on this CT scan was defined as good penetration when the EndoAnchor penetrated ≥2 mm into the aortic wall, borderline penetration when EndoAnchor penetration was <2 mm or a gap remained between the endograft and aortic wall, or no penetration when the EndoAnchor did not penetrate into the aortic wall. Differences between the groups were analyzed with the Mann-Whitney U test or Fisher exact test. Multivariate analyses were performed to identify independent predictors of EndoAnchor penetration, and procedural success was defined by absence of type IA endoleak. RESULTS: Eighty-six patients of the primary (n = 61 [71%]) and revision (n = 25 [29%]) arms of the ANCHOR registry were included. There were 53 (62%) without and 33 (38%) with persistent type IA endoleaks on the first postprocedural CT scan. The median number of EndoAnchors with good penetration was significantly greater in the cohort without endoleaks, 4 (interquartile range, 3-5) vs 3 (interquartile range, 1.5-4), respectively (P = .002). A multivariate model for EndoAnchor penetration identified use of a Medtronic Endurant endograft as a factor associated with good penetration (P = .001), whereas poor penetration was associated with a larger aortic neck diameter 10 mm distal to the lowest renal artery (P < .001) and greater proximal neck calcium thickness (P = .004). EndoAnchor penetration was the only variable that attained significance (P < .001) in the multivariate model for successful treatment of a type IA endoleak. CONCLUSIONS: Adequate EndoAnchor penetration into the aortic wall is less likely when the aortic neck diameter is large or when the neck contains significant mural calcium. No penetration of the EndoAnchor was the only factor predictive of postprocedural type IA endoleak. This study stresses the importance of careful selection of patients based on preoperative assessment of the infrarenal neck on CT angiography and emphasizes careful deployment of EndoAnchors into the aortic wall to improve successful treatment of type IA endoleaks.