Three-year clinical course after fluoropolymer-based drug-eluting stent implantation for femoropopliteal lesions.

BACKGROUND: Although the 1-year clinical outcomes of fluoropolymer-based drug-eluting stents (FP-DES) were favorable for the treatment of real-world femoropopliteal lesions in symptomatic peripheral artery disease (PAD), their performance beyond 1 year remained unknown. The current study determined the 3-year clinical course of FP-DES implantation for real-world femoropopliteal lesions. METHODS: This multicenter, prospective, observational study evaluated 1204 limbs (chronic limb-threatening ischemia, 34.8%; mean lesion length, 18.6 ± 9.9 cm, chronic total occlusion: 53.2%) of 1097 patients with PAD (age, 75 ± 9 years; diabetes mellitus, 60.8%) undergoing FP-DES implantation for femoropopliteal lesions. The primary outcome measure was 3-year restenosis. The secondary outcome measures included 3-year occlusive restenosis, stent thrombosis, target lesion revascularization (TLR), and aneurysmal degeneration. RESULTS: The 3-year cumulative occurrence of restenosis was 27.3%, whereas that of occlusive restenosis, stent thrombosis, and TLR was 16.1%, 7.3%, and 19.6%, respectively. The annual occurrence of restenosis decreased by 12.0%, 9.5%, and 5.8% in the first, second, and third year, respectively (p < 0.001). Similarly, the rates of occlusive restenosis and stent thrombosis decreased (p < 0.001 and p = 0.007, respectively), whereas the rate of TLR remained unchanged for 3 years (p = 0.15). The incidence of aneurysmal degeneration at 3 years (15.7%) did not significantly differ from that at 1 and 2 years (p = 0.69 and 0.20, respectively). CONCLUSIONS: This study highlights the favorable long-term clinical course of FP-DES in real-world practice, emphasizing the importance of monitoring for occlusive restenosis and stent thrombosis while considering the potential onset of aneurysmal degeneration.

Sodium-glucose co-transporter 2 inhibitor use in patients with diabetes mellitus undergoing endovascular therapy for symptomatic peripheral artery disease.

BACKGROUND: This study aimed to reveal the prevalence of sodium-glucose co-transporter 2 (SGLT2) inhibitor treatment and its association with restenosis risk in patients with diabetes mellitus undergoing endovascular therapy for symptomatic peripheral artery disease. METHODS: We used the database of a multicenter prospective study registering patients with symptomatic peripheral artery disease undergoing femoropopliteal drug-coated balloon treatment in Japan. The current analysis included 1058 patients with diabetes mellitus free from end-stage renal disease. The association of clinical characteristics with SGLT2 inhibitor use was investigated using the logistic regression model. The propensity score matching was adopted to compare the primary patency, i.e., freedom from restenosis, after endovascular therapy between patients treated with and without a SGLT2 inhibitor. RESULTS: The proportion of SGLT2 inhibitor treatment at revascularization was 14.8% (95% confidence interval, 12.8-17.1%). Younger age, increased body mass index, and increased hemoglobin A1c levels were independently associated with SGLT2 inhibitor use (all P < 0.05). The proportion of SGLT2 inhibitor reached 38.2% (95% confidence interval, 25.4-52.3%) in patients with the three associated factors. The propensity score-matching analysis demonstrated that primary patency was not different between patients treated with a SGLT2 inhibitor and those without it (72.0% [95% confidence interval, 64.1-80.9%] versus 67.8% [62.7-73.3%] at 2 years; P = 0.45). CONCLUSIONS: SGLT2 inhibitors were not rarely used in patients with diabetes mellitus who underwent femoropopliteal endovascular therapy using a drug coated balloon for symptomatic peripheral artery disease in real-world settings. SGLT2 inhibitor treatment was not associated with an increased risk of restenosis.

Angiographic patterns of restenosis after drug-coated balloon angioplasty for femoropopliteal lesions and 1-year prognosis after repeat endovascular therapy.

AIM: The aim of the current study sought to investigate the angiographic patterns of restenosis after drug-coated balloon (DCB) angioplasty for femoropopliteal (FP) lesions and which repeat endovascular therapy (EVT) for DCB restenosis would provide more freedom from recurrent restenosis. METHODS: This retrospective multicenter study included 119 limbs (chronic limb-threatening ischemia [CLTI]: 55%, lesion length: 136.9 ± 89.6 mm, chronic total occlusion: 25%) of 95 patients (diabetes mellitus: 70%, hemodialysis: 56%) who were diagnosed with DCB restenosis between January 2018 and December 2019. The cases were classified into three groups based on angiographic patterns of restenosis: Class I: focal lesions ≤50 mm, Class II: diffuse lesions >50 mm, and Class III: totally occluded lesions. The DCB restenosis patterns and frequency and predictors of recurrent restenosis after repeated EVT (re-EVT) were investigated. RESULTS: The mean follow-up duration was 29.8 ± 9.5 months. Groups I, II, and III comprised of 30 (25.2%), 55 (46.2%), and 34 (29.0%) cases, respectively. The overall rate of 1-year freedom from recurrent restenosis was 58.2%. One-year rate of freedom from recurrent restenosis after repeat DCB was not statistically different from that after scaffolding (71.1% vs. 74.6%, respectively, p = 0.911); however, it was significantly better than that after noncoated balloon angioplasty (repeat DCB vs. noncoated balloon angioplasty: 71.1% vs. 25.7%, respectively, p < 0.001). Multivariate analysis demonstrated that CLTI (hazard ratio [HR]: 5.15, p < 0.001) and re-EVT with noncoated balloon (HR: 3.16, p < 0.001) were significantly associated with recurrent restenosis; however, Class III pattern of DCB restenosis was not associated with recurrent restenosis (HR: 1.04, p = 0.918). CONCLUSIONS: This study revealed the angiographic patterns of restenosis after DCB therapy for FP lesions and the 1-year rate of recurrent restenosis after repeat revascularization. Repeat DCB therapy demonstrated acceptable 1-year recurrent restenosis rates.

The Effect of Clinical Frailty on Wound Healing in Patients With Chronic Limb-Threatening Ischemia.

PURPOSE: Clinical frailty increases the risk of adverse outcomes in older people. Patients with Chronic limb-threatening ischemia (CLTI) also had several clinical frailties. The aim of this study was to investigate the correlation between clinical frailty scales (CFS) at discharge and wound healing rate in patients with tissue loss. METHODS: A total of 510 limbs in 431 CLTI patients who were undergone endovascular treatment (EVT) from January 2013 to November 2018 were enrolled in this study. Patients were categorized into 4-groups based on the CFS stages: CFS 1 to 4 (well), CFS 5 (mild), CFS 6 (moderate) and CFS ≥7 (severe). And the change in patient's activities during hospitalize was classified into 3 groups based on CFS; improve, stable, worse. Primary endpoint was correlation between CFS at discharge and wound healing rate. Secondary endpoint was relationship between the changes in patient's activities and wound healing rate. RESULTS: A total of 365 limbs were obtained complete wound healing during this study period. Patient distribution into the 4 CFS groups was as follows: 13.3% (well), 21.8% (mild), 25.3% (moderate) and 39.6% (severe). Wound healing rate in severe CFS group was significantly lower than that in other CFS groups (p<0.0001). Wound healing rate in the patients who achieved improvement of activity was significantly higher than that in the other groups (p=0.008). CONCLUSIONS: CFS might be useful for risk stratification in patients with tissue loss. And improvement of activity during hospitalization might lead to increase the wound healing rate. CLINICAL IMPACT: Although the association between clinical frailty and prognosis outcome of Chronic limb-threatening ischemia (CLTI) has been reported, the effect of clinical frailty on wound healing remains unclear. Clinical frailty scale is independently associated with wound healing and might be useful for risk stratification in patients with tissue loss. Improvement of activity during hospitalization might lead to increase the wound healing rate.

Factors Associated With Early and Late Restenosis Following Drug-Coated Balloon Treatment for Patients With Femoropopliteal Lesions.

PURPOSE: Clinical trials have demonstrated the superiority of drug-coated balloon (DCB) to noncoated balloon angioplasty for the treatment of femoropopliteal (FP) lesions. In those trials, the difference of primary patency between DCB and noncoated angioplasty widens especially after 6 months, speculating that the antirestenosis effect of paclitaxel is manifested after 6 months. Factors associated with restenosis after 6 months differ from those associated with restenosis within 6 months. This study aimed to elucidate the prognostic factors associated with early (within 6 months) and late (after 6 months) restenosis following DCB treatment in real-world FP practice. MATERIALS AND METHODS: This multicenter, retrospective study analyzed 486 FP lesions (mean lesion length, 11.9±10.1 cm; chronic total occlusion, 21.0%) in 423 patients (diabetes mellitus, 59.3%; hemodialysis, 37.1%; chronic limb-threatening ischemia, 41.6%) who underwent successful DCB treatment between January 2018 and December 2019. The outcome measure was restenosis which is defined as a peak systolic velocity ratio >2.4 based on duplex ultrasound findings. Early and late restenosis were classified by the cutoff period of 6 months after the procedure. The associations of baseline and procedural characteristics with early and late restenosis were explored using Cox proportional hazards regression analysis. RESULTS: The mean follow-up period was 25.3±12.1 months. The 6, 12, 18, and 24 month cumulative incidences of restenosis were 7.4%±2.4%, 20.9%±3.9%, 29.9%±4.5%, and 38.4%±5.1%, respectively. During the follow-up period, early and late restenosis was evident in a total of 31 lesions and 138 lesions, respectively. Multivariate analysis revealed that chronic total occlusion (hazard ratio [HR], 2.29; 95% confidence interval [CI], 1.07-4.92; p=0.033) and superficial femoral artery ostial lesion (HR, 2.73; 95% CI, 1.28-5.80; p=0.009) were significantly associated with early restenosis. On the other hand, calcification circumference over 270° (HR, 1.67; 95% CI, 1.17-2.37; p=0.004), distal external elastic membrane diameter under 5 mm assessed by intravascular ultrasound (HR, 1.90; 95% CI, 1.29-2.79; p=0.001), and involving popliteal arterial lesion (HR, 1.54; 95% CI, 1.08-2.21; p=0.017) were significantly associated with late restenosis. CONCLUSION: The prognostic factors associated with late restenosis differed from those associated with early restenosis in the real-world FP-DCB practice. CLINICAL IMPACT: The current multicenter, retrospective study revealed that factors associated with early restenosis differed from those with late restenosis in the real-world FP-DCB practice. CTO and SFA ostial lesion were associated with early restenosis, while severe calcification, smaller vessel, and involving popliteal arterial lesions were associated with late restenosis.Early restenosis indicates "balloon failure" and would potentially result from recoil, which primary stent implantation might be required. On the other hand, late restenosis after 6 months would be attributed to "DCB failure", with inadequate drug uptake into the arterial wall, which might be minimized by the use of atherectomy devices.

Endovascular Therapy with Interwoven Nitinol Stent Placement after Predilation for Heavily Calcified Femoropopliteal Artery Disease: Results of the BURDOCK Study.

PURPOSE: To investigate the 1-year and 2-year clinical outcomes of interwoven stent (IWS) implantation for symptomatic femoropopliteal arterial disease with calcification. MATERIAL AND METHODS: This prospective multicenter study evaluated 308 limbs (63% with the peripheral arterial calcium scoring system 3 and 4 severe calcification and 87% with ≥180° calcification on intravascular ultrasound) of 299 patients (diabetes in 66.9%, chronic renal failure in 52.8%, and dialysis in 49.2%) who underwent IWS (Supera; Abbott, Abbott Park, Illinois) implantation after sufficient predilation (residual stenosis < 30%) for calcified femoropopliteal lesions. The primary outcome measure was primary patency (freedom from restenosis) at 1 and 2 years, whereas the secondary outcome measure included freedom from clinically driven target lesion revascularization (CD-TLR). Clinical parameters associated with loss of patency were explored. RESULTS: Kaplan-Meier analysis showed that primary patency was 88.2% (95% confidence interval [CI], 84.5%-92.1%) at 1 year and 80.8% (95% CI, 76.1%-85.8%) at 2 years. The CD-TLR-free rate was 96.5% and 94.8% at 1 and 2 years, respectively. The characteristics associated with loss of patency were restenotic lesion with and without stent implantation (adjusted hazard ratio, 1.96 and 2.40; P = .047 and .041, respectively), chronic total occlusion (adjusted hazard ratio, 1.88; P = .022), and popliteal involvement (adjusted hazard ratio, 2.60; P = .002). CONCLUSIONS: The implantation of IWS after sufficient predilation for calcified femoropopliteal atherosclerotic disease demonstrated clinically acceptable primary patency.

Impact of postprocedural minimum lumen area on clinical outcome after femoropopliteal drug-eluting stent implantation.

INTRODUCTION: Although favorable results of fluoropolymer-based drug-eluting stent (FP-DES) treatment for femoropopliteal lesions have been reported, it is unclear whether minimal lumen area (MLA) after FP-DES implantation affects clinical outcomes. This study aimed to reveal the association between intravascular ultrasound (IVUS)-evaluated MLA and the 1-year risk of restenosis and aneurysmal degeneration after FP-DES implantation for femoropopliteal lesions. METHODS: A subanalysis of the CAPSICUM (Contemporary outcomes After Paclitaxel-eluting peripheral Stent implantation for symptomatic lower limb IsChemia with sUperficial feMoral or proximal popliteal lesion) study analyzed 718 limbs in 686 patients with available IVUS-evaluated MLA data. The association of MLA with the 1-year risk of restenosis and aneurysmal degeneration was analyzed using the generalized propensity score method. RESULTS: The 1-year incidence rate of restenosis was estimated to be 8.8% (95% CI, 6.1% to 12.5%) for the upper quartile of MLA (21.1 mm2) versus 14.3% (95% CI, 10.7% to 18.7%) for the lower quartile of MLA (15.2 mm2), with an odds ratio of 0.58 (95% CI, 0.36 to 0.93; p = 0.024), whereas the 1-year incidence rate of aneurysmal degeneration was 23.8% (95% CI, 19.5% to 28.8%) for the upper quartile versus 16.8% (95% CI, 12.6% to 22.0%) for the lower quartile, with an odds ratio of 1.55 (95% CI, 1.04 to 2.32; p = 0.031). CONCLUSION: A large MLA after FP-DES implantation for femoropopliteal lesions was associated with decreased restenosis risk but increased aneurysmal degeneration risk. These findings suggest that MLA is a valuable predictor of clinical outcomes.

Twelve-month safety and effectiveness of TCD-17187 drug-coated balloon for the treatment of atherosclerotic lesions in the superficial femoral and proximal popliteal artery.

PURPOSE: The aim of this preapproval trial was to evaluate the 12-month safety and effectiveness of the TCD-17187 drug-coated balloon (DCB) for the treatment of atherosclerotic lesions in the superficial femoral artery (SFA) and/or proximal popliteal artery (PA). METHODS: This was a prospective, multicenter, core laboratory adjudicated, single-arm trial. From October 2019 to November 2020, a total of 121 symptomatic peripheral artery disease patients with SFA and/or proximal PA lesions were enrolled. The primary effectiveness endpoint was 12-month primary patency defined as freedom from restenosis as determined by duplex ultrasonography in the absence of clinically driven target lesion revascularization (CD-TLR). The safety endpoint was the major adverse event (MAE) rate defined as freedom from a composite of device- and procedure-related death within 30 days, and index limb major amputation and/or CD-TLR through follow-up. RESULTS: Average age was 74.5 ± 7.3 years and the frequency of diabetes mellitus was 67.5%. Average lesion length and vessel diameter were 106.0 ± 52.6 and 5.2 ± 0.8 mm, respectively. The frequency of chronic total occlusion and bilateral calcification was 17.5% and 50.8% of patients, respectively. The 12-month primary patency rate calculated by Kaplan-Meier analysis was 81.1%, while 12-month freedom from CD-TLR was 95.8%. The MAE rate at 30 days was 1.7% and all events comprised CD-TLR. There were no instances of device- or procedure-related deaths, major amputations, or thrombosis throughout the 12-month evaluation period. CONCLUSION: This preapproval trial confirmed the safety and effectiveness of TCD-17187 DCB in the treatment of atherosclerotic lesions in the SFA and/or proximal PA.

Vessel Diameter Evaluated by Intravascular Ultrasound Versus Angiography.

PURPOSE: Although reference vessel diameter (RVD) is conveniently measured by angiography during femoropopliteal (FP) endovascular therapy (EVT) in clinical practice, angiography will potentially underestimate RVD. On the other hand, intravascular ultrasound (IVUS) can measure RVD precisely. The aim of this study was to reveal the difference between angiography- and IVUS-assessed RVD in patients undergoing FP-EVT for symptomatic peripheral artery disease (PAD). METHODS: We analyzed a prospective and multicenter database including 1967 limbs of 1725 patients with symptomatic PAD undergoing IVUS-supported FP-EVT. The study outcome measure was the difference between IVUS- and angiography-assessed distal RVD (ΔRVD), calculated as angiography-assessed RVD subtracted from IVUS-assessed RVD. The clinically important difference was defined as 1 mm or larger. RESULTS: IVUS-assessed RVD was significantly larger than angiography-assessed RVD (6.0±1.0 mm vs 5.0±1.0 mm; p<0.001). Mean ΔRVD (IVUS- minus angiography-assessed RVD) was 0.98 mm (95% CI, 0.94-1.03 mm). ΔRVD was 1 mm or larger in 48.8% (46.5%-51.0%) of the whole population. Multivariate analysis demonstrated that small angiography-assessed RVD, angiography-assessed bilateral calcification, and history of stent implantation were significantly associated with an increasing risk of ΔRVD ≥1mm, whereas presence of chronic total occlusion (CTO) was significantly associated with a decreasing risk of ΔRVD ≥1 mm. CONCLUSION: The current study revealed the difference between angiography-assessed reference lumen diameter and IVUS-assessed reference EEM diameter of FP lesions. About half of population had ΔRVD ≥1 mm. IVUS-assessed RVD was more likely to be different by angiography in cases with small vessels, CTO, bilateral calcification, and history of stent implantation.

Characteristics, Antithrombotic Patterns, and Prognostic Outcomes in Claudication and Critical Limb-Threatening Ischemia Undergoing Endovascular Therapy.

PURPOSE: The underlying difference between intermittent claudication (IC) and critical limb-threatening ischemia (CLTI) still remains unclear. This prospective multicenter observational study aimed to clarify differences in clinical features and prognostic outcomes between IC and CLTI, and prognostic factors in patients undergoing endovascular therapy (EVT). MATERIALS AND METHODS: A total of 692 patients with 808 limbs were enrolled from 20 institutions in Japan. The primary measurements were the 3-year rates of major adverse cardiovascular event (MACE) and reintervention. RESULTS: Among patients, 79.0% had IC and 21.0% had CLTI. Patients with CLTI were more frequently women and more likely to have impaired functional status, undernutrition, comorbidities, hypercoagulation, hyperinflammation, distal artery disease, short single antiplatelet and long anticoagulation therapies, and late cilostazol than patients with IC. Aortoiliac and femoropopliteal diseases were dominant in patients with IC and infrapopliteal disease was dominant in patients with CLTI. Patients with CLTI underwent less frequently aortoiliac intervention and more frequently infrapopliteal intervention than patients with IC. Longitudinal change of ankle-brachial index (ABI) exhibited different patterns between IC and CLTI (pinteraction=0.002), but ABI improved after EVT both in IC and in CLTI (p<0.001), which was sustained over time. Dorsal and plantar skin perfusion pressure in CLTI showed a similar improvement pattern (pinteraction=0.181). Distribution of Rutherford category improved both in IC and in CLTI (each p<0.001). Three-year MACE rates were 20.4% and 42.3% and 3-year reintervention rates were 22.1% and 46.8% for patients with IC and CLTI, respectively (log-rank p<0.001). Elevated D-dimer (p=0.001), age (p=0.043), impaired functional status (p=0.018), and end-stage renal disease (p=0.019) were independently associated with MACE. After considering competing risks of death and major amputation for reintervention, elevated erythrocyte sedimentation rate (p=0.003) and infrainguinal intervention (p=0.002) were independently associated with reintervention. Patients with CLTI merely showed borderline significance for MACE (adjusted hazard ratio 1.700, 95% confidence interval 0.950-3.042, p=0.074) and reintervention (adjusted hazard ratio 1.976, 95% confidence interval 0.999-3.909, p=0.05). CONCLUSIONS: The CLTI is characterized not only by more systemic comorbidities and distal disease but also by more inflammatory coagulation disorder compared with IC. Also, CLTI has approximately twice MACE and reintervention rates than IC, and the underlying inflammatory coagulation disorder per se is associated with these outcomes. CLINICAL IMPACT: The underlying difference between intermittent claudication (IC) and critical limb-threatening ischemia (CLTI) still remains unclear. This prospective multicenter observational study, JPASSION study found that CLTI was characterized not only by more systemic comorbidities and distal disease but also by more inflammatory coagulation disorder compared to IC. Also, CLTI had approximately twice major adverse cardiovascular event (MACE) and reintervention rates than IC. Intriguingly, the underlying inflammatory coagulation disorder per se was independently associated with MACE and reintervention. Further studies to clarify the role of anticoagulation and anti-inflammatory therapies will contribute to the development of post-interventional therapeutics in the context of peripheral artery disease.

Vascular Pathology and Impact of Stent Eccentricity for Stent Restenosis in Femoropopliteal Endovascular Therapy.

PURPOSE: To explore the clinical features associated with stent eccentricity and reveal the impact of stent eccentricity on the risk of 1-year restenosis after femoropopliteal stent implantation for symptomatic atherosclerotic peripheral artery disease (PAD). MATERIALS AND METHODS: The clinical database of a multicenter prospective study was used. It registered 2,018 limbs of 1,766 patients in whom intravascular ultrasound (IVUS)-supported femoropopliteal endovascular therapy (EVT) for symptomatic atherosclerotic PAD was planned from November 2015 to June 2017. The study included 1,233 limbs of 1,088 patients implanted with a bare nitinol stent, drug-eluting stent (DES), or stent graft and administered ≥2 antithrombotic drugs. The stent eccentricity was evaluated using IVUS, calculated as [(maximum diameter) / (minimum diameter) - 1] at the cross-sectional segment with the lowest lumen area after stent implantation. RESULTS: Chronic total occlusion and bilateral arterial calcification (peripheral artery calcification scoring system Grades 3 and 4) were positively associated with stent eccentricity, whereas renal failure while receiving dialysis, DES use, and stent graft use were negatively associated with stent eccentricity (all P < .05). Stent eccentricity was associated with an increased risk of 1-year restenosis (odds ratio [OR], 1.18; 95% CI, 1.01-1.37; P = .034). However, after adjustment for lesion severity and implanted stent types, the association was no longer significant (OR, 1.07; 95% CI, 0.91-1.24; P = .43). CONCLUSIONS: Stent eccentricity was not significantly associated with the risk of 1-year restenosis after femoropopliteal EVT.

Independent Predictors of Major Adverse Cardiovascular Events at 3 Years after Aortoiliac Stent Implantation.

PURPOSE: To identify the risk factors for major adverse cardiovascular events (MACEs) in real-world practice for symptomatic peripheral artery disease in Japan. MATERIALS AND METHODS: Data on Japanese patients (N = 880) from the Observational Prospective Multicenter Registry Study on Outcomes of Peripheral Arterial Disease Patients Treated by Angioplasty Therapy for Aortoiliac Artery who underwent de novo aortoiliac stent placement. The 3-year risk of incident MACEs was investigated. RESULTS: The median age of the patients was 72.6 years (range, 34-97 years), and 83.1% of the patients were men. The patients had the following conditions: smoking (35.6%), hypertension (94.1%), dyslipidemia (81.7%), diabetes (48.0%), renal failure on dialysis (12.6%), myocardial infarction (12.7%), stroke (15.8%), and chronic limb-threatening ischemia (7.1%). Femoropopliteal lesions were present in 38.8% of the limbs with aortoiliac lesions. The 3-year rate of freedom from MACEs was 89.1%. Baseline characteristics, such as age, renal failure on dialysis, myocardial infarction, stroke, and femoropopliteal lesions, were independently associated with the risk of incident MACEs. When the study population was stratified according to these risk factors, the rate of MACEs was highest in patients with at least 3 risk factors (32.9% at 3 years). CONCLUSIONS: The 3-year rate of freedom from MACEs was reported. Baseline characteristics, such as age, renal failure on dialysis, myocardial infarction, stroke, and femoropopliteal lesions, are independent risk factors for MACEs after aortoiliac stent placement.

The impact of plaque morphology in patients with peripheral artery disease on vessel dissection: an intravascular ultrasound observational study.

Drug-coated balloon (DCB) is now available for endovascular treatment (EVT) of superficial femoral arteries (SFA). Although it has been reported that severe vessel dissection after balloon angioplasty was risk of restenosis, it is difficult to predict the vessel dissection patterns before balloon angioplasty. We investigated the correlation between plaque morphology and vessel dissection pattern after balloon angioplasty using the intravascular ultrasound (IVUS). A total of 73 de novo SFA lesions were enrolled in this study. IVUS examinations were measured at the minimum lumen area in the control angiogram. Plaque morphology, minimum lumen area (MLA) and vessel diameter at the same point were evaluated before and after the initial balloon angioplasty. Vessel dissection patterns after the initial balloon angioplasty were classified into 7 types (A to F). There were no severe dissection patterns which were more than type D dissection in this study. All patients were treated with DCB without any bailout stenting. No dissection was found in 35.6% (26/73). Type A, B and C dissections were seen in 17.8% (13/73), 40% (27/73) and 9.6% (7/73), respectively. Although there were no relations between plaque morphology and vessel dissection patterns (p = 0.547), the MLA with dissection was larger than that without dissection (5.78 mm2 versus 4.63 mm2, p = 0.032). Although the dissection patterns could not be predicted in non-severe (Non or A to C) dissection, our result might suggest that IVUS image has the potential to reduce severe dissection.

10-Year clinical outcomes of hemodialysis patients with peripheral arterial disease due to infrainguinal disease undergoing endovascular therapy.

Although symptomatic peripheral arterial disease (PAD) is common in patients with hemodialysis (HD), few studies have evaluated the long-term clinical outcomes of revascularization in this population. The aim of the current study was to investigate the 10-year clinical outcomes of HD patients with PAD undergoing endovascular therapy (EVT). We retrospectively analyzed 750 limbs from 578 HD patients with symptomatic PAD due to infrainguinal lesions, treated with EVT, between May 2004 and November 2011. The primary outcome was 10-year mortality and the secondary outcome was 10-year freedom from major adverse limb events (MALEs). Predictors for each outcome were evaluated by Cox proportional-hazards model. The 10-year rate of survival and freedom from MALEs was 23.6 ± 3.1% and 76.4 ± 2.9%, respectively. In the multivariate analysis, patients with over 80 years [hazard ratio (HR) 2.10; 95% confidence interval (CI) 1.58-2.80; p < 0.001], non-ambulatory status (HR 1.55; 95% CI 1.19-2.03; p = 0.001), absence of hypertension (HR 1.59; 95% CI 1.19-2.08; p = 0.001), heart failure (HR 1.36; 95% CI 1.02-1.80; p = 0.03), and tissue loss (HR 1.65; 95% CI 1.28-2.12; p < 0.001) were at an increased risk of 10-year mortality. Cerebrovascular diseases (HR 1.60; 95% CI 1.03-2.49; p = 0.038), no cilostazol use (HR 1.69; 95% CI 1.09-2.70; p = 0.021), tissue loss (HR 3.87; 95% CI 2.37-6.34; p < 0.001), and poor below-the-knee (BTK) run-off (HR 1.68; 95% CI 1.04-2.71; p = 0.035) were significantly associated with MALEs. After risk stratification analysis based on risk score assignment according to number of predictors, 10-year survival and freedom from MALE were lower in the higher score groups (10-year survival rates according to number of risk factors: 0, 35.1%; 1, 20.3%; 2-5, 10.8%; respectively, p < 0.001, 10-year freedom from MALE rates in patients with greater number of risk factors: 0-1, 90.2%; 2-3, 65.5%; 4-5, 61.6%; respectively, p < 0.001). The 10-year clinical outcomes after EVT for HD patients with PAD due to infrainguinal disease were clinically suboptimal. Risk stratification based on these predictors before EVT would be useful in estimating future adverse outcome.

One-year results for Japanese patients in RANGER II SFA.

The RANGER II SFA objective was to evaluate the safety and effectiveness of the Ranger Drug-Coated Balloon (DCB) for treating superficial femoral artery and/or proximal popliteal artery lesions; the purpose of this cohort analysis is to assess the results among Japanese study participants. Patients eligible for RANGER II SFA had symptomatic lower limb ischemia (Rutherford classification 2-4) and were randomly assigned (3:1) to treatment with the Ranger DCB or standard percutaneous transluminal angioplasty (PTA). At 12 months, assessments included freedom from major adverse events (i.e., target lesion revascularization, major amputations, or death within 1 month of the index procedure) and core laboratory-assessed primary patency. Japanese patients (n = 102) comprised 27.1% of the overall study sample. Mean lesion lengths were 79.5 ± 44.0 mm and 84.0 ± 56.8 mm among Japanese patients treated with Ranger DCB (n = 77) or PTA (n = 25), respectively. All major adverse events were clinically driven TLRs (6.6% [5/76] for Ranger DCB and 16.0% [4/25] for PTA; p = 0.2194). Kaplan-Meier estimates of primary patency were 89.3% and 72.0%, respectively, at 12 months (log-rank p = 0.2134). Japanese patients treated with Ranger DCB maintained a high patency rate through 12 months and a low re-intervention rate.Trial registration clinicaltrials.gov identifier: NCT03064126.

Clinical outcomes of polymer-free, paclitaxel-coated stents vs stent grafts in peripheral arterial disease patients with femoropopliteal artery lesions.

OBJECTIVE: Zilver PTX polymer-free, paclitaxel-coated stents and Viabahn stent grafts are effective for the treatment of femoropopliteal lesions. The aim of this study was to compare clinical outcomes between the two devices in patients with symptomatic peripheral arterial disease in real-world settings. METHODS: This multicenter, retrospective study concerned a clinical database of 445 patients with symptomatic peripheral arterial disease (Rutherford categories 1-6) who underwent either Zilver PTX or Viabahn implantation for a femoropopliteal lesion of 10 cm or longer with reference vessel diameters of 4.0 to 7.5 mm between 2012 and 2018 at five hospitals in Japan. Outcome measures were primary patency, freedom from stent thrombosis, freedom from any target lesion reintervention, limb salvage, and overall survival. After propensity score matching, these clinical outcomes were compared between patients treated with the Zilver PTX and those treated with the Viabahn. Also assessed were the interaction effects of baseline characteristics on the association of the Zilver PTX and Viabahn with restenosis and stent thrombosis. RESULTS: In total, 271 patients were treated with the Zilver PTX, and 174 patients were treated with the Viabahn. Propensity score matching extracted 133 patient pairs with no major intergroup differences in baseline characteristics. The Zilver PTX group had a lower rate of 3-year primary patency (59.5%; [95% confidence interval (CI), 53.0%-66.2%] vs 69.6% [95% CI, 59.3%-79.4%]; P = .005), but a higher rate of 3-year freedom from stent thrombosis (93.6% [95% CI, 90.0%-96.3%] vs 82.4% [95% CI, 74.5%-89.0%], P = .038). There was no significant difference in overall survival, limb salvage, or freedom from reintervention (all P > .05). An interaction analysis showed that the restenosis risk of the Zilver PTX was significantly higher vs the Viabahn in patients with no or one below-the-knee runoff vessel and in those with intravascular ultrasound use than in patients with two or three below-the-knee runoff vessels and in those without intravascular ultrasound use, respectively (P for interaction = .046 and .010, respectively), whereas the stent thrombosis risk of the Zilver PTX was significantly smaller vs the Viabahn in patients not on dialysis than in those on dialysis (P for interaction = .034). CONCLUSIONS: Compared with Viabahn stent grafts, Zilver PTX stents have a lower rate of primary patency but a higher rate of freedom from stent thrombosis.

New lesion after endovascular therapy of femoropopliteal lesions for intermittent claudication.

BACKGROUND: Although the incidence of target lesion revascularization (TLR) was decreased in patients who underwent endovascular therapy (EVT) for femoropopliteal (FP) lesions, the clinical impact of newly developed lesions could not be disqualified in those patients. METHODS: Between January 2012 and December 2018, 911 patients with intermittent claudication (IC) who have not been previously treated for this condition underwent a successful EVT for de novo FP lesions in a multicenter registry (WATERMELON registry: neW lesion AfTer EndovasculaR therapy for interMittEnt cLaudicatiON). RESULTS: The mean follow-up duration was 3.5 ± 1.9 years. At 5 years, 53% patients underwent limb revascularization, (new lesion: 42% and TLR: 31%). We developed an ordinal risk score to predict the possibility of new lesion revascularization the following risk factors: body mass index (<23 kg/m2 , 1 point), diabetes (2 points), hemodialysis (3 points), and atrial fibrillation (2 points). The patients were divided into three groups: low risk group (0-1 points: N = 283), intermediate risk group (2-3 points: N = 395), and high risk group (≥4 points: N = 233). The cumulative 5-year incidence of new lesion revascularization was 28% in the low risk group, 40% in the intermediate group, and 68% in the high risk group (p < 0.001). CONCLUSION: within 5 years after the first EVT, more than half of the patients underwent limb revascularization. Of these patients, 42% underwent new lesion revascularization. Patients with a body mass index <23 kg/m2 , diabetes, hemodialysis, and atrial fibrillation had increased risk for new lesion revascularization.

Roles of Angioplasty With Drug-Coated Balloon for Chronic Ischemia in Wound Healing.

PURPOSE: Clinical trials have demonstrated sustained benefits of drug-coated balloon (DCB) angioplasty compared with noncoated balloon angioplasty in symptomatic peripheral artery disease (PAD) presenting with femoropopliteal (FP) artery disease. However, there is still controversy whether particulate embolization caused by crystalline paclitaxel, the so-called "downstream effect," is adversely associated with clinical outcomes after use of FP DCB among chronic limb-threatening ischemia (CLTI) patients. The current RADISH (Roles of Angioplasty with Drug-coated balloon for chronic ISchemia in wound Healing) study investigated wound healing following DCB therapy vs non-DCB therapy for real-world CLTI patients presenting with FP lesions. MATERIALS AND METHODS: This multicenter, retrospective study analyzed 927 patients with CLTI (mean age, 76±10 years; male, 57.8%; diabetes mellitus, 64.5%; dialysis, 50.7%) presenting with FP lesions and treated endovascularly via DCB (138 patients) vs non-DCB therapy (789 patients) between April 2014 and March 2019. The primary outcome measure was 1-year wound healing, while the secondary outcome measure was 1-year primary patency. Clinically-driven target lesion revascularization (CD-TLR), limb salvage and overall survival were also analyzed by using propensity score matching analysis. RESULTS: The propensity score matching extracted 111 pairs (as many patients in the DCB group and 629 patients in the non-DCB group). The 1-year cumulative incidence of wound healing (95% CI) was 74.4% (62.6% to 82.5%) in the DCB group and 71.9% (60.4% to 80.1%) in the non-DCB group, with no significant intergroup difference (p=0.93). The DCB group had a higher rate of primary patency (p=0.002) and freedom from CD-TLR (p=0.010) than the non-DCB group, whereas there was no significant intergroup difference in limb salvage (p=0.21) or overall survival (p=0.93). CONCLUSION: The current analysis of data from the RADISH study demonstrated that DCB therapy did not lead to delayed wound healing and reduced restenosis rate in CLTI patients presenting FP lesions. From this results, DCB therapy would be a reasonable treatment option for CLTI patients.

Intravascular Ultrasound Imaging During Aortoiliac Stenting: No Impact on Outcomes at 1 Year.

PURPOSE: To investigate the effect of intravascular ultrasound (IVUS) imaging use on clinical outcomes after aortoiliac stenting in patients with peripheral artery disease (PAD). MATERIALS AND METHODS: Subjects for this retrospective analysis were derived from the OMOTENASHI registry database, which contained 803 symptomatic PAD patients (Rutherford categories 2-4) who were treated with self-expanding stent implantation for aortoiliac atherosclerotic lesions at 61 centers in Japan between January 2014 and April 2016. Of the 803 patients, 545 (67.9%) patients (mean age 73±9 years; 453 men) underwent IVUS-supported stent implantation and were compared with the 258 patients (mean age 73±8 years; 217 men) treated without IVUS. A propensity score analysis of 138 matched pairs was conducted to compare treatment strategies and clinical outcomes between patients having IVUS-supported endovascular therapy and those treated without IVUS. RESULTS: Endovascular strategies and postoperative medications were not significantly different between the IVUS and no-IVUS groups. A procedure time under 1 hour was less frequent in the IVUS group, which had a longer fluoroscopy time. The 12-month restenosis rate was not significantly different between the 2 groups [10.2% (95% CI 6.9 to 14.9%) vs 10.3% (95% CI 5.4 to 18.6%), p=0.99]. There was no interaction between baseline characteristics and the association of IVUS use with restenosis risk. CONCLUSION: Propensity score matching analysis revealed that duration and fluoroscopy time during IVUS-supported procedures were significantly longer than in cases without IVUS use, whereas the 12-month restenosis rate was not significantly different between the groups. IVUS use in aortoiliac lesions may be unnecessary.

Real-World Clinical Outcomes of IN.PACT Admiral Drug-Coated Balloon for Femoropopliteal Artery Disease　- 12-Month Results From Japan Post-Market Surveillance Study.

BACKGROUND: To confirm the safety and efficacy of the IN.PACT Admiral drug-coated balloon (DCB) based on the indication approved by the Pharmaceuticals and Medical Devices Agency Japan in real-world patients with femoropopliteal artery disease.Methods and Results:IN.PACT PMS Japan was a prospective, multicenter, single-arm, post-market surveillance (PMS) study conducted in Japan that enrolled 304 participants (mean age 75.3±7.9 years). The primary endpoint was primary patency at 6 months following the index procedure, defined as freedom from clinically driven target lesion revascularization (CD-TLR) and freedom from restenosis as determined by duplex ultrasound (DUS) peak systolic velocity ratio (PSVR) ≤2.4 (assessed by the independent DUS core laboratory). Secondary endpoints included acute outcomes, primary patency at 12 months post-index procedure, freedom from CD-TLR, and major adverse events at 12 months. The mean lesion length was 97.81±58.97 mm. The primary endpoint, 6-month primary patency, was 91.3% (240/263). Kaplan-Meier estimates of primary patency and freedom from CD-TLR through 12 months were 91.5% and 94.1%, respectively. The CD-TLR rate was 5.8% (14/240) with low rates of thrombosis (0.8%) and target limb amputation (0.4%) at 12 months. CONCLUSIONS: The results of this real-world PMS study were consistent with outcomes from previous IN.PACT DCB studies, confirming the safety and efficacy of the IN.PACT Admiral DCB for broader use in patients seen in everyday practice.