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.

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.

Effectiveness and Safety of a Paclitaxel-Eluting Stent for Superficial Femoral Artery Lesions up to 190 mm: One-Year Outcomes of the Single-Arm IMPERIAL Long Lesion Substudy of the Eluvia Drug-Eluting Stent.

Purpose: To report the clinical effect of a drug-eluting stent on femoropopliteal occlusive disease in patients with long lesions. Materials and Methods: The global IMPERIAL Long Lesion substudy (ClinicalTrials.gov identifier NCT02574481) is a prospective, single-arm, multicenter trial of the Eluvia Drug-Eluting Vascular Stent for treating femoropopliteal lesions >140 mm and ≤190 mm in length. Fifty patients (mean age 68.2 years; 32 men) with long lesions (mean length 162.8±34.7 mm) were enrolled; 20 patients had diabetes. Fourteen of the lesions were severely calcified and 16 were occluded. Primary patency (duplex ultrasound peak systolic velocity ratio ≤2.4 in the absence of clinically-driven target lesion revascularization or bypass of the target lesion) and major adverse events [30-day all-cause death and 1-year target limb major amputation or target lesion revascularization (TLR)] were assessed at 12 months. Results: At 12 months, no deaths, target limb amputations, or stent thrombosis had occurred. The Kaplan-Meier estimate of primary patency was 91.0% (95% CI 82.5% to 99.6%). The MAE-free rate at 12 months was 93.5% due to 3 clinically-driven TLRs. The corresponding Kaplan-Meier estimate of freedom from TLR was 93.9% (95% CI 87.2% to 100%). Conclusion: The IMPERIAL Long Lesion substudy demonstrated excellent patency and safety through 1 year among patients with long femoropopliteal occlusive disease treated with the Eluvia stent.

Lower Extremity Revascularization Using Optical Coherence Tomography-Guided Directional Atherectomy: Final Results of the EValuatIon of the PantheriS OptIcal COherence Tomography ImagiNg Atherectomy System for Use in the Peripheral Vasculature (VISION) Study.

PURPOSE: To evaluate the safety and efficacy of a novel optical coherence tomography (OCT)-guided atherectomy catheter in treating patients with symptomatic femoropopliteal disease. METHODS: The VISION trial ( ClinicalTrials.gov identifier NCT01937351) was a single-arm, multicenter, global investigational device exemption study enrolling 158 subjects (mean age 67.2±10.5 years; 87 men) across 20 participating sites. In this cohort, 198 lesions were treated with an average length of 53±40 mm using the Pantheris catheter alone or Pantheris + adjunctive therapy. The primary safety endpoint was the composite of major adverse events (MAEs) through 6 months (objective performance goal 43.2%). Technical success (primary efficacy outcome) was defined as the percent of target lesions with a residual diameter stenosis ≤50% after treatment with the Pantheris device alone (objective performance goal 87.0%). Procedural success was defined as reduction in stenosis to ≤30% after Pantheris ± adjunctive therapy. Tissue specimens retrieved from each treated lesion were histologically analyzed to evaluate the accuracy and precision of OCT image guidance. RESULTS: The primary efficacy outcome was achieved in 192 (97.0%) of the 198 lesions treated with the Pantheris catheter. Across all lesions, mean diameter stenosis was reduced from 78.7%±15.1% at baseline to 30.3%±11.8% after Pantheris alone (p<0.001) and to 22.4%±9.9% after Pantheris ± adjunctive therapy (p<0.001). Of the 198 target lesions, 104 (52.5%) were treated with the Pantheris alone, 84 (42.4%) were treated with Pantheris + adjunctive angioplasty, and 10 (5.1%) with Pantheris + angioplasty + stenting. The composite MAE outcome through 6 months occurred in 25 (16.6%) of 151 subjects. There were no clinically significant perforations, 1 (0.5%) catheter-related dissection, 4 (2%) embolic events, and a 6.4% clinically driven target lesion revascularization rate at 6 months. The 40-lesion chronic total occlusion (CTO) subset (mean lesion length 82±38 mm) achieved a similar significant reduction in stenosis to 35.5%±13.6% after Pantheris alone (p<0.001). Histological analysis of atherectomy specimens confirmed <1% adventitia in 82.1% of the samples, highlighting the precision of OCT guidance. Characterization of the OCT-guided lesions revealed evidence of an underestimation of disease burden when using fluoroscopy. CONCLUSION: OCT-guided atherectomy for femoropopliteal disease is safe and effective. Additionally, the precision afforded by OCT guidance leads to greater removal of plaque during atherectomy while sparing the adventitia.

The significance of automatically measured transient ischemic dilation in identifying severe and extensive coronary artery disease in regadenoson, single-isotope technetium-99m myocardial perfusion SPECT.

BACKGROUND: The critical threshold and clinical significance of transient ischemic dilation (TID) for regadenoson, single-isotope (99m)Tc SPECT myocardial perfusion imaging (MPI) are not defined. METHODS: From 100 patients with low likelihood of CAD, we derived the abnormal TID threshold (mean + 2 SD). We validated the threshold in a cohort of 547 patients who received one-day, rest/regadenoson-stress, (99m)Tc-tetrofosmin SPECT-MPI followed by coronary angiography within 6 months. Patients were classified into three CAD severity strata: no significant CAD, mild to moderate CAD, and severe and extensive CAD. RESULTS: The abnormal TID threshold was determined to be 1.31. Though mean TID ratios were different between the three CAD severity groups and the derivation cohort (P < .001), there was no difference in the mean TID ratios between the categories of CAD severity or in the prevalence of severe CAD between TID+ and TID- groups (P = .74). By ROC analysis, TID had a poor discriminatory capacity in identifying severe and extensive CAD [AUC of 0.55 (95% CI 0.47-0.62, P = .25)]. Stepwise multivariate logistic analysis demonstrated that adding TID to clinical and perfusion data did not provide incremental diagnostic value (P = .87). CONCLUSIONS: The clinical utility of TID with regadenoson-stress MPI in this era of declining CAD burden is questionable.

Temporal trends and outcomes of patients with chronic limb-threatening ischemia with and without history of coronary artery disease: insights from the us national inpatient sample database.

BACKGROUND: The burden and prognostic significance of coronary artery disease (CAD) in adults with peripheral artery disease and chronic limb-threatening ischemia (CLTI) is unknown. METHODS: Temporal trends in prevalence of significant CAD (history of myocardial infarction or coronary revascularizations) in hospitalizations for CLTI were determined using the 2000 to 2018 National Inpatient Sample (NIS) database. A multivariable regression analysis of outcomes was performed based on presence or absence of CAD. RESULTS: Among 13 575 099 hospitalizations for CLTI (41% female, 69% white, mean age 69 years), 23% had concomitant CAD, of which 11% underwent lower extremity arterial revascularization (43.6% endovascular and 56.4% surgical). The prevalence of concomitant CAD with CLTI increased from 15.3% in 2000 to 23.1% in 2018. Furthermore, the frequency of endovascular revascularization in adults with CAD and CLTI increased from 15.1% to 48.3%, while there was a decreasing trend of surgical revascularization, from 84.9% to 51.7%. After multivariate adjustments, CLTI with CAD was associated with increased risk of in-hospital mortality (OR, 1.40; 95% CI, 1.32-1.47; P less than .0001) and bleeding requiring transfusion (OR, 1.10; 95% CI, 1.06-1.12; P less than .0001) compared with patients with CLTI without CAD. As compared with surgical revascularization, endovascular revascularization was associated with lower risk of in-hospital mortality in both patients with CLTI with CAD (OR, 0.69; 95% CI, 0.63-0.76; P less than .001) and CLTI without CAD (OR, 0.71; 95% CI, 0.67-0.76; P less than .001). CONCLUSIONS: Prevalence of CAD has increased in adults presenting with CLTI and is associated with poor outcomes, warranting the need for effective interventions and secondary prevention in this high-risk population.

Optical coherence tomography: guided therapy of in-stent restenosis for peripheral arterial disease.

Approximately 27 million people in Europe and North America currently have peripheral arterial disease (PAD). The endovascular treatment of stenosis or blocked peripheral arteries in PAD include percutaneous transluminal angioplasty with or without a drug coated balloon (DCB), atherectomy (rotational, directional, orbital or laser), and stenting. The development of next generation peripheral stents and drug-coated stents have led to the improved treatment of complex superficial femoral artery (SFA) lesions, and consequently increased their usage. Additionally, the technologies developed for PAD intervention have further improved the overall adoption of endovascular procedures leading to increased utilization of stents to address procedural dissections (bailout stenting), as support scaffolding for complex lesions, and to prevent preventing elastic recoil post balloon angioplasty. For example, bail-out stenting after DCB angioplasty has been reported to be as high as 40% in long lesions and as high as 46% in chronic total occlusions lesions. In total, approximately 200,000 stents are placed annually in the femoral and popliteal arteries in PAD patients in the USA, with 30% to 40% of these stents expected to develop in-stent restenosis within 2-3 years of implantation. Accordingly, the treatment of in-stent restenosis (ISR) remains a substantial healthcare burden. Few technologies reported on improved ISR patency rates as compared to PTA treatment alone, including drug-eluting stents and balloons, laser atherectomy or covered stents. However, the reported longer-term patency for ISR remains suboptimal creating a cyclical treatment pattern that burdens patients and providers. In this review, we present the rational and clinical evidence for utilizing OCT-guided therapies for the treatment of ISR for PAD.

Value of absence of a transient myocardial perfusion defect during stress myocardial perfusion study in patients undergoing major vascular surgery.

Pre-operative cardiac assessment is important in the evaluation of patients undergoing major vascular surgery. Our study aims to evaluate the value of absence of a transient myocardial perfusion defect during radionuclide myocardial perfusion study for prediction of cardiac events (myocardial infarction, sudden cardiac death, unstable angina, coronary artery revascularization and congestive heart failure) in patients undergoing major vascular surgery. We studied 63 consecutive patients (ages 35-83 [avg. 64], male 39, female 24) with radiographically proven, abdominal aortic aneurysm or severe aortofemoral occlusive disease who underwent major vascular surgery (abdominal aortic aneurysm repair [38] or aortofemoral bypass [25]). The subjects all had multiple coronary artery risk factors (hypertension 48, diabetes 10, hyperlipidemia 23, tobacco use 39, family history of coronary artery disease 10), but a negative pre-operative stress myocardial perfusion study for myocardial ischemia. Of these 63 patients, 17 patients were able to exercise and achieve their adequate 85% maximal predicted heart rate. Thirty-eight patients received adenosine infusion of 140 microg/kg/min for 6 min. Six patients received dipyridamole infusion of 0.56 mg/kg over 4 min. Two patients received dobutamine infusion at 5, 10, 20, 30, and 40 mg/kg/min. Of the 63 patients, 60 received 3-4 mCi of thallium-201 ((201)Tl) and 3 patients received 8-9 mCi of technetium-99m (99mTc) at rest and 25-30 mCi 99mTc during stress. The subjects all underwent major vascular surgery and were followed up to one year for any cardiac events. Of the 63, who underwent pre-operative cardiac assessment with myocardial perfusion testing, 25 had a fixed myocardial perfusion defect (scar) and none had evidence of transient myocardial perfusion defect (ischemia). One subject had coronary artery bypass grafting 11 months after aortofemoral bypass surgery. One died from a stroke one month after aortofemoral bypass surgery. Of the remaining 61 patients, none had any cardiac events up to one year after major vascular surgery.