CD163+ Macrophages Induce Endothelial-to-Mesenchymal Transition in Atheroma.

BACKGROUND: Cell phenotype switching is increasingly being recognized in atherosclerosis. However, our understanding of the exact stimuli for such cellular transformations and their significance for human atherosclerosis is still evolving. Intraplaque hemorrhage is thought to be a major contributor to plaque progression in part by stimulating the influx of CD163+ macrophages. Here, we explored the hypothesis that CD163+ macrophages cause plaque progression through the induction of proapoptotic endothelial-to-mesenchymal transition (EndMT) within the fibrous cap. METHODS: Human coronary artery sections from CVPath's autopsy registry were selected for pathological analysis. Athero-prone ApoE-/- and ApoE-/-/CD163-/- mice were used for in vivo studies. Human peripheral blood mononuclear cell-induced macrophages and human aortic endothelial cells were used for in vitro experiments. RESULTS: In 107 lesions with acute coronary plaque rupture, 55% had pathological evidence of intraplaque hemorrhage in nonculprit vessels/lesions. Thinner fibrous cap, greater CD163+ macrophage accumulation, and a larger number of CD31/FSP-1 (fibroblast specific protein-1) double-positive cells and TUNEL (terminal deoxynucleotidyl transferase-dUTP nick end labeling) positive cells in the fibrous cap were observed in nonculprit intraplaque hemorrhage lesions, as well as in culprit rupture sections versus nonculprit fibroatheroma sections. Human aortic endothelial cells cultured with supernatants from hemoglobin/haptoglobin-exposed macrophages showed that increased mesenchymal marker proteins (transgelin and FSP-1) while endothelial markers (VE-cadherin and CD31) were reduced, suggesting EndMT induction. Activation of NF-κB (nuclear factor kappa ß) signaling by proinflammatory cytokines released from CD163+ macrophages directly regulated the expression of Snail, a critical transcription factor during EndMT induction. Western blot analysis for cleaved caspase-3 and microarray analysis of human aortic endothelial cells indicated that apoptosis was stimulated during CD163+ macrophage-induced EndMT. Additionally, CD163 deletion in athero-prone mice suggested that CD163 is required for EndMT and plaque progression. Using single-cell RNA sequencing from human carotid endarterectomy lesions, a population of EndMT was detected, which demonstrated significant upregulation of apoptosis-related genes. CONCLUSIONS: CD163+ macrophages provoke EndMT, which may promote plaque progression through fibrous cap thinning.

Effect of EDTA with porous balloon on calcified lesion: An atherosclerotic cadaver study.

BACKGROUND: Ethylene diamine tetra-acetic acid (EDTA) is a chelating agent used to dissolve calcium deposits but evidence in decalcifying atherosclerotic lesions is limited. AIMS: We assessed the feasibility and efficacy of EDTA delivered via porous balloon to target calcified lesions in cadaveric below-the-knee (BTK) arteries. METHODS: Using porcine carotid arteries, EDTA concentration was measured in the arterial wall and outside the artery at the 0-, 0.5-, 4-, and 24-h circulation after the injection through a porous balloon. In cadaver BTK samples, the proximal and distal anterior tibial artery (ATA) and distal posterior tibial artery (PTA) were studied. EDTA-2Na/H2O or EDTA-3Na/H2O were administrated using a porous balloon, then circulated for 6 h for EDTA-3Na/H2O and 24 h for EDTA-2Na/H2O and EDTA-3Na/H2O. Micro-CT imaging of the artery segments before and after the circulation and cross-sectional analyses were performed to evaluate calcium burden. RESULTS: In the porcine carotid study, EDTA was delivered through a porous balloon present in the arterial wall and was retained there for 24 h. In BTK arteries, cross-sectional analyses of micro-CT revealed a significant decrease in the calcium area in the distal ATA segment under 24-h circulation with EDTA-2Na/H2O and in the distal ATA segment under 24-h circulation with EDTA-3Na/H2O. The proximal ATA segment under 6-h circulation with EDTA-3Na/H2O showed no significant change in any parameters of calcium CONCLUSION: EDTA-3Na/H2O or EDTA-2Na/H2O with longer circulation times resulted in greater calcium reduction in atherosclerotic lesion. EDTA may have a potential therapeutic option for the treatment of atherosclerotic calcified lesions.

Impact of 12-Month Angioscopic Thrombi and Yellow Plaque After Drug-Eluting Stent Implantation.

BACKGROUND: Coronary angioscopy (CAS) has 2 unique abilities: direct visualization of thrombi and plaque color. However, in the recent drug-eluting stent (DES) era, serial CAS findings after DES implantation have not been fully elucidated. We investigated the impact of CAS findings after implantation of a polymer-free biolimus A9-coated stent (PF-BCS) or durable polymer everolimus-eluting stent (DP-EES).Methods and Results: We investigated serial CAS and optical coherence tomography (OCT) findings at 1 and 12 months in 99 patients who underwent PF-BCS or DP-EES implantation. We evaluated factors correlated with angioscopic thrombi and yellow plaque, and the clinical impact of both thrombi and yellow plaque at 12 months (BTY). The BTY group included 17 (22%) patients. The incidence and grade of thrombi and yellow plaque decreased from 1 to 12 months. Although no patients had newly appearing thrombi at 12 months, 2 DP-EES patients had newly appearing yellow plaque at 12 months. Multivariable analysis revealed HbA1c, minimum stent area, and adequate strut coverage were significant factors correlated with 12-month angioscopic thrombi, and DP-EESs were significantly correlated with 12-month yellow plaque. However, BTY was not correlated with clinical events. CONCLUSIONS: The management of diabetes, stent area, and adequate stent coverage are important for intrastent thrombogenicity and polymer-free stents are useful for stabilizing plaque vulnerability.

Ultrasound-Assessed Lesion Morphology and Drug-Coated Balloon Treatment for de novo Dysfunctional Arteriovenous Fistula in Hemodialysis Patients.

AIM: This study aimed to evaluate the effect of ultrasound-assessed lesion morphology on the outcomes of drug-coated balloon (DCB) versus plain old balloon angioplasty (POBA) treatment for de novo dysfunctional arteriovenous fistulas (AVF) lesions. METHODS: This single-center retrospective study enrolled 114 consecutive patients (mean age, 73 ± 10 years; male, 69%) with de novo dysfunctional AVF lesions who underwent percutaneous transluminal angioplasty (PTA) using DCB (n = 48) and POBA (n = 66). The morphology of the stenotic lesions, evaluated using ultrasonography, was classified into intimal hyperplasia and shrinking types. The outcome measure was 12-month primary patency. Factors associated with loss of primary patency were evaluated using Cox proportional hazards models. RESULTS: The baseline characteristics were not significantly different between the 2 treatment groups. The 12-month primary patency rate was significantly higher in the DCB group than in the POBA group (66.8 ± 7.1% versus 35.9 ± 6.3%, P = .006). The 12-month primary patency rate in the lesions with intimal hyperplasia type was not significantly different (DCB: 70.3 ± 9.5% versus POBA: 45.9 ± 8.0%; P = .310), whereas that in the shrinking type was significantly higher in the DCB group than in the POBA group (61.9 ± 10.6% versus 15.2 ± 8.1%; P < .001). The interaction analysis demonstrated that lesion morphology had a significantly different hazard ratio (HR) for restenosis between the POBA and DCB groups (P for interaction = .031). The multivariate analysis revealed that DCB usage (adjusted hazard ratio [aHR], 0.49; 95% confidence interval [CI]: [0.28, 0.87]; P = .015), ultrasound-assessed lesion morphology (shrinking type: aHR, 1.77; 95% CI: [1.07, 2.93]; P = .026), and location of stenosis (aHR, 2.26; 95% CI: 1.15, 4.46; P = .018) were significantly associated with AVF patency after PTA. CONCLUSION: This study revealed that lesion morphology evaluated using ultrasonography had a differential impact on DCB and POBA outcomes. The therapeutic effect of DCB was unexpectedly confirmed in the shrinking type. CLINICAL IMPACT: The effectiveness of DCB in inhibiting smooth muscle cell proliferation in intimal hyperplasia lesions was expected based on the known mechanism of action of paclitaxel. However the therapeutic effect of DCB was unexpectedly confirmed in the shrinking type too. We may not need to hesitate usage of DCB for shrinking type.

Comparison of 1-Month and 12-Month Vessel Responses Between the Polymer-Free Biolimus A9-Coated Stent and the Durable Polymer Everolimus-Eluting Stent.

BACKGROUND: A polymer-free biolimus A9-coated stent (PF-BCS) may achieve better arterial healing than a durable polymer drug-eluting stent owing to its polymer-free feature.Methods and Results: This multicenter, prospective, observational study enrolled 105 patients (132 lesions) who underwent PF-BCS (51 patients, 71 lesions) or durable polymer everolimus-eluting stent (DP-EES, 54 patients, 61 lesions) implantation. Serial coronary angioscopy (CAS) and optical coherence tomography (OCT) examinations were performed at 1 and 12 months, and the serial vessel responses were compared between PF-BCS and DP-EES. The primary outcome measure was the incidence of subclinical intrastent thrombus on CAS. The secondary outcome measures were: adequate strut coverage (≥40 µm) on OCT and maximum yellow color grade on CAS. The incidence of thrombus was high at 1 month (100% vs. 93%, P=0.091), but decreased at 12 months (18% vs. 25%, P=0.56), without a significant difference between PF-BCS and DP-EES. The adequate strut coverage rate was significantly higher (84±14% vs. 69±22%, P<0.001) and yellow color was significantly less intense (P=0.012) at 12 months in PF-BCS than in DP-EES; however, they were not significantly different at 1 month (adequate strut coverage: 47±21% vs. 50±17%, P=0.40; yellow color: P=0.99). CONCLUSIONS: Although the thrombogenicity of PF-BCS was similar to that of DP-EES, the adequate coverage and plaque stabilization rates of PF-BCS were superior to those of DP-EES at 12 months.

Baseline and Updated Information on Nutritional Status in Patients With Chronic Limb Threatening Ischaemia Undergoing Revascularisation.

OBJECTIVE: The aim of this study was to assess the impact of baseline and updated nutritional status on prognosis in patients with chronic limb threatening ischaemia (CLTI) undergoing revascularisation. METHODS: The clinical database of the Surgical reconstruction versus Peripheral INtervention in pAtients with critical limb isCHemia (SPINACH) study, a prospective, multicentre, observational study, was used. The current analysis included 499 patients who underwent endovascular therapy or surgical reconstruction for CLTI. Nutritional status at baseline was evaluated using the Geriatric Nutritional Risk Index (GNRI; baseline GNRI). A GNRI <82 points indicates major nutrition related risk. GNRI was also calculated at 1, 3, 6, 12, 24, and 36 months after revascularisation (updated GNRI). The association between baseline and updated GNRIs and the mortality risk was analysed with the Cox regression model. RESULTS: Mean ± standard deviation (SD) GNRI at baseline was 89.9 ± 9.8 points. The proportion of patients alive with a GNRI ≥82 points was 78% (95% confidence interval [CI] 74-81) at baseline but gradually decreased during follow up, finally reaching 19% (95% CI 0-42) at 36 months. In patients with a GNRI <82 points at baseline, a GNRI of ≥82 points was increased to 37% (95% CI 6-68) 12 months after revascularisation. In the multivariable analysis, baseline and updated GNRIs were associated with a reduced mortality risk independently of each other; the adjusted hazard ratios per 1 SD were 0.80 (95% CI 0.65-0.98; p = .031) and 0.66 (95% CI 0.49-0.91; p = .015), respectively. Similar findings were observed when nutritional status was evaluated using the Controlling Nutritional Stats (CONUT) score, except for the association between its updated value and mortality risk, which marginally lost significance. CONCLUSION: There was still room for improvement in nutritional status after revascularisation for patients with CLTI. Updated GNRI was associated with death independently of baseline GNRI.

Drug-coated stent implantation vs. bypass surgery for in-stent occlusion after femoropopliteal stenting.

The optimal revascularization for in-stent occlusion (ISO) lesions after femoropopliteal (FP) bare-nitinol stenting has not been established. We, therefore, investigated the comparison between drug-coated stent (DCS) implantation and bypass surgery (BSX) for ISO lesions after FP bare-nitinol stenting. This study was a dual-center, observational study from January 2004 to December 2015. A total of 172 ISO lesions were observed, and after excluding 120 ISO lesions, 52 ISO lesions (50 patients; mean age, 71.0 ± 9.2 years; male, 59.6%) after FP bare-nitinol stenting were enrolled. The included patients with clinical symptoms underwent either DCS implantation (n = 28) or BSX (n = 22). The primary endpoint was recurrent in-stent restenosis (ReISR); secondary endpoints were recurrent target lesion revascularization (ReTLR), recurrent occlusion (reocclusion) and major adverse limb events (MALE), and perioperative complications (POCs), respectively. ReISR or reocclusion was defined as ISR or occlusion after TLR. Stent restenosis was defined as a peak systolic velocity ratio (PSVR) > 2.4 on a duplex scan or ≥ 50% stenosis on angiography. Graft restenosis was defined as a PSV > 300 cm/s and velocity ratio 3.5 or uniformly low PSV < 45 cm/s throughout the entire graft based on graft surveillance. The mean follow-up period was 36.6 ± 25.5 months. At 2 years, the rates of freedom from ReISR, ReTLR, and MALE were not significantly different between the DCS implantation and BSX groups (68.9% vs. 73.7%, p = 0.81; 84.7% vs. 73.7%, p = 0.45; 84.7% vs. 78.6%, p = 0.60, respectively). However, the freedom from reocclusion rate was significantly lower in the DCS implantation group (81.6% vs. 100%, p = 0.04). The occurrence of POCs was not significantly different between the DCS implantation and BSX groups (7.1% vs 4.2%, p = 1.0). Although BSX was the gold-standard therapy for ISO lesions after FP bare-nitinol stenting, DCS implantation might be a good option because the rates of freedom from ReISR, ReTLR, and MALE were similar.

Limb-Based Patency After Surgical vs Endovascular Revascularization in Patients with Chronic Limb-Threatening Ischemia.

PURPOSE: To determine whether limb-based patency (LBP) after infrainguinal revascularization for chronic limb-threatening ischemia (CLTI) is similar between bypass surgery and endovascular therapy (EVT). MATERIALS AND METHODS: The database for the Surgical Reconstruction vs Peripheral Intervention in Patients With Critical Limb Ischemia (SPINACH) study was interrogated to identify 130 patients (mean age 73±8 years; 94 men) who underwent bypass surgery and 271 patients (mean age 74±10 years; 178 men) who underwent EVT alone. Skin perfusion pressure (SPP) and the ankle-brachial index (ABI) were measured before the procedure and at 0, 1, and 3 months after revascularization. The outcome measure was hemodynamically evaluated LBP (SPP ≥10 mm Hg or ABI ≥0.1) maintained over the first 3 months after treatment. Any reintervention or major amputation was regarded as loss of LBP. The associations between the revascularization strategy (bypass vs EVT) and between the preoperative characteristics and the study outcome (ie, SPP- or ABI-based LBP), were determined using generalized linear mixed models with a logit link function. Patency rates are presented with the 95% confidence interval (CI). RESULTS: The bypass surgery group had a higher stage of limb severity (WIfI) and anatomic complexity (GLASS) than the EVT group, whereas the EVT group had a higher prevalence of heart failure. Both SPP- and ABI-based LBP rates were higher in the bypass group than in the EVT group. SPP-based LBP rates at 3 months were 73.8% (95% CI 63.4% to 84.2%) in the bypass group and 46.2% (95% CI 38.5% to 53.8%) in the EVT group; the corresponding ABI-based LBP rates were 71.5% (95% CI 61.8% to 81.2%) and 44.0% (95% CI 37.3% to 50.7%). CONCLUSION: LBP is an important concept in the new global vascular guidelines for assessing the anatomic and hemodynamic status of CLTI patients. The present study found that LBP was significantly lower in the EVT group vs the bypass surgery group.

Long-Term Clinical Outcomes after Endovascular Therapy for Anti-Centromere Antibody-Positive Patients with Critical Limb-Threatening Ischemia.

PURPOSE: To examine the long-term clinical outcomes of patients with anti-centromere antibody (ACA)-positive critical limb-threatening ischemia (CLTI) who were treated with endovascular therapy (EVT). MATERIALS AND METHODS: This was a retrospective analysis using a database of 423 consecutive CLTI patients (543 limbs, Rutherford class 4-6) who underwent EVT between January 2011 and March 2013. The patients were divided into 2 groups: an ACA-positive group (10 limbs, 8 patients) and a control group (46 limbs, 43 patients). The control group was defined as female, non-dialysis, and those who were able to obtain a below-knee angiogram. RESULTS: None of the 8 ACA-positive CLTI patients had previously been diagnosed as ACA positive. No significant difference was observed in the below-the-knee lesion distribution and severity between the ACA-positive group and the control group. The median observational period was 51 months. The survival rate was 54% in the ACA-positive group and 76% in the control group at 5 years after EVT (P = .732). The freedom from major amputation rate was 60% in the ACA-positive group and 91% in the control group at 5 years after EVT (P = .029). The technical EVT success rate in the ACA-positive group was 70% (7/10). Of the successful EVT cases, 71% (5/7) of patients achieved complete wound healing or rest pain relief; however, 60% (3/5) had a recurrence of wounds. CONCLUSIONS: In a series of ACA-positive patients with CLTI, successful EVT had acceptable outcomes with respect to wound healing with short-term results. However, the major amputation rate for ACA-positive patients was high in long-term follow-up.

Diagnostic performance of coronary angiography utilizing intraprocedural 320-row computed tomography with minimal contrast medium.

Recently developed coronary angiography with intraprocedural 320-row computed tomography can be performed in a catheterization laboratory (XACT) by injecting contrast medium from a place close to the coronary arteries, thereby requiring a minimal amount of contrast medium. However, its clinical application has not yet been established. This study aimed to evaluate the diagnostic accuracy of XACT angiography with a minimal volume of contrast medium in patients with suspected coronary artery disease (CAD). A total of 167 coronary segments were analyzed in 14 patients (9 males, median age 70 years) with suspected CAD by XACT angiography with 7.5 ml of contrast medium and invasive coronary angiography (ICA) with standard techniques. The segmental-based diagnostic accuracy of XACT angiography in detecting stenosis of ≥ 50% and ≥ 75% and visualized by ICA was good (sensitivity: 74% and 62%, specificity: 99% and 99%, positive predictive value: 93% and 80%, and negative predictive value: 97% and 97%, respectively). These results suggest that XACT angiography with a very low amount of contrast medium may have strong clinical utility for screening coronary arteries in patients with renal dysfunction or undergoing clinical procedures such as pacemaker implantation.

Impact of Lesion Morphology on Durability After Angioplasty of Failed Arteriovenous Fistulas in Hemodialysis Patients.

PURPOSE: To investigate if morphological patterns of arteriovenous fistula (AVF) venous lesions affect primary patency after percutaneous transluminal angioplasty (PTA). METHODS: From July 2014 to June 2015, 262 patients underwent PTA for failed AVFs. A total of 104 patients were excluded owing to (1) calcification or AVF occlusion precluding ultrasound examination, (2) central venous or arterial lesions, and (3) no follow-up, leaving 158 patients (mean age 71±12; 96 men) for analysis. More than half of the patients had one or more previous PTAs for the failed AVF. Prior to PTA the stenotic lesions were assessed using ultrasonography to determine stenotic patterns at the minimum lumen area site and to evaluate the flow volume in the brachial artery. Three stenotic patterns were identified: intimal hyperplasia (IH) stenosis (n=110), shrinking lumen stenosis (n=32), and venous valve-related stenosis (n=16). The main outcome measure was primary patency after PTA estimated using Kaplan-Meier analysis. Predictors for loss of primary patency were determined using a multivariate Cox proportional hazards model; the results are presented as the adjusted hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Median follow-up after PTA was 6.3 months (interquartile range 3.3, 10.5). The 6-month primary patency estimates were 56%±5% in the IH group, 40±9% in the shrinking lumen group, and 100% in the valve stenosis group (IH vs shrinking, p=0.013; IH vs valve, p=0.003). In multivariate analysis, shrinking lumen morphology had a negative impact on primary patency (HR 2.05, 95% CI 1.25 to 3.36, p=0.005), while venous valve-related stenosis had a positive impact (HR 0.19, 95% CI 0.04 to 0.79, p=0.023). Flow volume (10-mL/min increments; HR 0.97, 95% CI 0.96 to 0.99, p=0.004) and history of PTA (HR 1.66, 95% CI 1.06 to 2.60, p=0.029) were also independently associated with primary patency after PTA. CONCLUSION: The patterns of AVF stenosis as determined by ultrasound can affect the outcome of treatment with balloon dilation.

Impact of Stent-to-Vessel Diameter Ratio on Restenosis in the Superficial Femoral Artery After Endovascular Therapy.

BACKGROUND: Although stent-to-vessel (S/V) diameter ratio has been described as a restenotic factor after superficial femoral artery (SFA) stenting, the reference vessel diameter is commonly measured distally at a healthy site. It remains unclear whether S/V ratio assessed at the lesion site would be more predictive than that assessed distally at a healthy site.Methods and Results:A total of 117 patients (mean age, 73±7 years; 74% male) who underwent successful nitinol stent implantation in SFA lesions (mean lesion length, 172±104 mm) on intravascular ultrasound (IVUS) were retrospectively analyzed. S/V ratio at the proximal and distal healthy site, and at the smallest lesion site, was evaluated on IVUS. One-year restenosis predictors were evaluated on multivariate analysis. Mean S/V diameter ratio on IVUS at proximal and distal healthy sites, and at the lesion site, was 0.98±0.11, 1.02±0.11 and 1.15±0.16, respectively. One-year primary patency was 77%. On multivariate analysis, lesion length (OR, 1.06 per 10-mm increment; P=0.046) and S/V ratio measured at the lesion site (OR, 1.34 per 0.1 increment; P=0.032), but not that at the distal healthy site (OR, 1.05 per 0.1 increment; P=0.705), were significantly associated with 1-year restenosis. CONCLUSIONS: S/V ratio assessed on IVUS at the lesion site, but not at the distal healthy site, was independently associated with 1-year restenosis after SFA stenting.

Predicting loss of patency after forearm loop arteriovenous graft.

OBJECTIVE: Although arteriovenous grafts (AVGs) for dialysis access have been applied to patients who were poor candidates for an arteriovenous fistula, durability after AVGs has been clinically suboptimal. This retrospective study investigated whether forearm AVGs based on radial artery inflow would have superior patency to those with brachial artery inflow and evaluated the operative predictors for loss of patency after AVG. METHODS: This multicenter retrospective study included 156 upper limbs in 150 consecutive patients (50% male; age, 70.5 ± 12.8 years) who underwent forearm loop AVG formation from January 2010 to October 2013. The outcome measures were the primary and secondary functional graft patency rates and factors related to primary patency. Primary and secondary patency of AVGs was evaluated by Kaplan-Meier analysis, and predictors for loss of primary patency of AVGs were determined using a Cox proportional hazards model. RESULTS: The median observation period was 10 months (interquartile range, 6-18 months). The 1-year primary patency rate was 32.4%, and the secondary patency rate was 83.4%. Use of the radial artery as the inflow arteriovenous anastomosis (hazard ratio, 0.56; 95% confidence interval, 0.30-0.99) was independently associated as an operative predictor for primary patency after AVG. The primary patency rate was significantly different between radial artery inflow and brachial artery inflow at 1 year (53.8% vs 24.4%; P = .032). CONCLUSIONS: Radial artery selection as inflow artery was independently associated with primary patency after AVG.

Impact of Drug-Eluting Stent Implantation for Femoropopliteal In-Stent Occlusion.

PURPOSE: To compare optimal balloon angioplasty with nitinol stenting and drug-eluting stent (DES) implantation for femoropopliteal in-stent occlusion (ISO). METHODS: A dual center, retrospective study was performed from January 2004 to December 2014 encompassing 110 ISOs after bare nitinol stenting for a femoropopliteal lesion in 100 patients (mean age 72.7±10.1 years; 58 men). These patients underwent optimal balloon angioplasty with implantation of a bare stent (conventional group, n=79) or a DES (n=21). The primary endpoint was recurrent in-stent restenosis (Re-ISR); secondary endpoints were recurrent target lesion revascularization (Re-TLR), reocclusion, and major adverse limb events (MALE). Re-ISR or reocclusion was defined as ISR or occlusion after TLR. Restenosis was defined as a peak systolic velocity ratio >2.4 on a duplex scan or >50% stenosis on angiography. Univariate Cox regression analysis was used to identify any relationships between patient and procedure variables and the occurrence of Re-ISR; the results are presented as the hazard ratio (HR) and the 95% confidence interval (CI). RESULTS: The mean follow-up period was 34.9±27.4 months. At 2 years, Kaplan-Meier estimated freedom from Re-ISR rates were 79.3% in the DES group and 20.2% in the conventional group, respectively (p<0.001). The rates of freedom from Re-TLR, reocclusion, and MALE at 2 years were 85.7%, 85.9%, and 85.7% in the DES group and 27.1%, 42.5%, and 25.3% in the conventional group, respectively (p<0.001, p=0.006, and p<0.001, respectively). Univariate analysis showed only postprocedure stenosis (HR 1.04, 95% CI 1.02 to 1.07, p<0.001) as a predictor of Re-ISR. Postprocedure ABI (HR 0.06, 95% CI 0.01 to 0.30, p<0.001) and DES use (HR 0.20, 95% CI 0.07 to 0.44, p<0.001) were associated with a lower likelihood of developing Re-ISR. CONCLUSION: In this small comparative study, DES stent implantation gives more favorable outcomes than conventional treatment for ISO after femoropopliteal stenting.

Impact of Calcification on Clinical Outcomes After Endovascular Therapy for Superficial Femoral Artery Disease: Assessment Using the Peripheral Artery Calcification Scoring System.

PURPOSE: To investigate whether the severity of lesion calcification assessed by the novel peripheral artery calcification scoring system (PACSS) was associated with clinical outcomes after endovascular therapy (EVT) for superficial femoral artery (SFA) lesions. METHODS: A retrospective analysis was conducted of 394 consecutive patients (mean age 72±8 years; 290 men) with intermittent claudication [223 (57%) with diabetes, 81 (21%) on hemodialysis] who underwent successful EVT for de novo SFA lesions [length 152.1±95.7 mm; 199 (50%) TransAtlantic Inter-Society Consensus II class C/D] between January 2010 and December 2013. The patients were retrospectively categorized using the PACSS classification (grades 0-4: no visible calcification of the target lesion, unilateral wall calcification <5 cm, unilateral calcification ≥5 cm, bilateral wall calcification <5 cm, and bilateral calcification ≥5 cm, respectively). The main outcome was primary patency, while the secondary outcome measures were mortality and major adverse limb events [MALE: any intervention (repeat EVT or surgical revision) or major (above ankle) amputation]. Cox proportional hazards analysis was used to explore whether the PACSS classification was an independent predictor of clinical outcomes. Results are presented as the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: The distribution of PACSS grades was 0 in 54%, grade 1 in 16%, grade 2 in 12%, grade 3 in 9%, and grade 4 in 9%. The 2-year primary patency rates in these grades, respectively, were 70.0%, 66.6%, 72.1%, 55.6%, and 36.3% (p<0.001). After multivariate analysis, PACSS grade 4 (HR 2.74, 95% CI 1.56 to 4.83, p<0.001), diabetes (HR 1.52, 95% CI 1.06 to 2.20, p=0.022), lesion length (HR 1.04, 95% CI 1.01 to 1.07, p=0.006), and vessel diameter (HR 0.80, 85% CI 0.65 to 0.98, p=0.038) were associated with loss of primary patency. PACSS grade 4 was also associated with MALE and mortality (p=0.048 and 0.011, respectively). Bare metal stent use (HR 0.47, 95% CI 0.30 to 0.73, p<0.001) was positively associated with primary patency. CONCLUSION: PACSS grade 4 calcification was independently associated with clinical outcomes after EVT for de novo SFA lesions.

Impact of deteriorated calcium-phosphate homeostasis on amputation-free survival after endovascular revascularization in patients with critical limb ischemia on hemodialysis.

Patients on hemodialysis (HD) have abnormalities of calcium-phosphate (CaP) homeostasis and high CaP product contributes to atherosclerosis pathogenesis and adverse events. Patients on HD with critical limb ischemia (CLI) are at risk for major amputation and death because of advanced systemic atherosclerotic disease. The aim of this study was to evaluate the relationship between CaP product and amputation-free survival (AFS) in CLI after endovascular treatment (EVT). We retrospectively analyzed 221 CLI patients on HD. In Kaplan-Meier analysis, AFS was significantly lower in patients with CaP product ⩾ 55 mg(2)/dL(2) compared to those with CaP product <55 mg(2)/dL(2) (54.3% vs 78.5%, p = 0.002). However, neither serum phosphate nor calcium levels were individually associated with AFS. In multivariate analysis, CaP product ⩾ 55 mg(2)/dL(2) was an independent predictor for AFS in CLI patients on HD (hazard ratio, 3.03; 95% confidence interval, 1.78-5.15; p-value < 0.001). We concluded abnormal CaP homeostasis was associated with lower AFS after EVT in CLI patients on HD, and can serve for their risk stratification.

Predictors of 2-Year Mortality and Risk Stratification After Surgical or Endovascular Revascularization of Infrainguinal Artery Disease in Hemodialysis Patients With Critical Limb Ischemia.

PURPOSE: To examine the 2-year mortality in hemodialysis (HD) patients with critical limb ischemia (CLI) and determine predictors that may aid in the selection of a revascularization strategy [bypass surgery or endovascular therapy (EVT)] according to current guidelines. METHODS: From 2007 to 2009, 246 consecutive CLI patients (mean age 69±10 years; 170 men) on HD underwent revascularization for de novo infrainguinal lesions (178 EVT and 68 bypass grafting). The majority of the patients had diabetes (170, 69%) and tissue loss (194, 79%); nearly half (111, 45%) were nonambulatory. Overall survival after revascularization was estimated by Kaplan-Meier analysis. Predictors for 2-year mortality after revascularization were determined using a Cox proportional hazards model; results are given as the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Overall survival rate was 77% at 1 year and 66% at 2 years. Predictors of 2-year mortality after revascularization were age >75 years (HR 1.82, 95% CI 1.14 to 2.91, p=0.012), albumin <3 g/dL (HR 2.31, 95% CI 1.39 to 3.84, p=0.001), and ejection fraction <50% (HR 1.73, 95% CI 1.06 to 2.83, p=0.027). Patients with more predictors had a higher incidence of death within 2 years after revascularization. CONCLUSION: Advanced age, low albumin level, and low ejection fraction were independently associated with 2-year mortality after revascularization in HD patients with CLI. Risk stratification by these factors would be useful for deciding on a revascularization strategy.

Novel echocardiographic approach to the accurate measurement of pulmonary vascular resistance based on a theoretical formula in patients with left heart failure -- pilot study.

BACKGROUND: Several non-invasive methods for measuring pulmonary vascular resistance (PVR) have been proposed to date, but they remain empirical, lacking sufficient accuracy to be used in clinical practice. The aims of this study were to propose a novel echocardiographic measurement of PVR based on a theoretical formula and investigate the feasibilty and accuracy of this method in patients with heart failure. METHODS AND RESULTS: Echocardiography was performed in 27 patients before right heart catheterization. Peak tricuspid regurgitation pressure gradient (TRPG), pulmonary regurgitation pressure gradient in end-diastole (PRPGed), and cardiac output derived from the time-velocity integral and the diameter in the left ventricular outflow tract (COLVOT) were measured. PVR based on a theoretical formula (PVRtheo) was calculated as (TRPG-PRPGed)/3COLVOTin Wood units (WU). The results were compared with PVR obtained by right heart catheterization (PVRcath) using linear regression and Bland-Altman analysis. Mean PVRcathwas 2.4±1.4 WU. PVRtheocorrelated well with PVRcath(r=0.83, P<0.001). On Bland-Altman analysis the mean difference was 0.1±0.7 WU. The limits of agreements were smaller than for other non-invasive estimations previously reported. CONCLUSIONS: The new echocardiographic approach based on a theoretical formula provides a non-invasive and accurate assessment of PVR in patients with heart failure.

Usefulness of Endovascular Therapy for Penile Gangrene Secondary to Calciphylaxis: A Case Report.

We here report a case of successful endovascular therapy for penile gangrene in a patient with calciphylaxis and a long history of diabetes mellitus and end-stage renal disease on dialysis. The internal iliac artery, with 75% stenosis, was treated with balloon-expandable bare metal stent implantation, whereas the inferior gluteal artery, 75% stenosis, was treated with balloon dilatation. After endovascular therapy, the intractable penile pain immediately resolved, and penile salvage with complete wound healing was achieved 6 months after the procedure.

Predictive scoring model of mortality after surgical or endovascular revascularization in patients with critical limb ischemia.

OBJECTIVE: The latest guideline points to life expectancy of <2 years as the main determinant in revascularization modality selection (bypass surgery [BSX] or endovascular therapy [EVT]) in patients with critical limb ischemia (CLI). This study examined predictors and a predictive scoring model of 2-year mortality after revascularization. METHODS: We performed Cox proportional hazards regression analysis of data in a retrospective database, the Bypass and Endovascular therapy Against Critical limb ischemia from Hyogo (BEACH) registry, of 459 consecutive CLI patients who underwent revascularization (396 EVT and 63 BSX cases between January 2007 and December 2011) to determine predictors of 2-year mortality. The predictive performance of the score was assessed with the area under the time-dependent receiver operating characteristic curve. RESULTS: Of 459 CLI patients (mean age, 72 ± 10 years; 64% male; 49% nonambulatory status, 68% diabetes mellitus, 47% on regular dialysis, and 18% rest pain and 82% tissue loss as treatment indication), 84 died within 2 years after revascularization. In a multivariate model, age >75 years (hazard ratio [HR], 1.77; 95% confidence interval [CI], 1.10-2.85), nonambulatory status (HR, 5.32; 95% CI, 2.96-9.56), regular dialysis (HR, 1.90; 95% CI, 1.10-3.26), and ejection fraction <50% (HR, 2.49; 95% CI, 1.48-4.20) were independent predictors of 2-year mortality. The area under the time-dependent receiver operating characteristic curve for the developed predictive BEACH score was 0.81 (95% CI, 0.76-0.86). CONCLUSIONS: Predictors of 2-year mortality after EVT or BSX in CLI patients included age >75 years, nonambulatory status, regular dialysis, and ejection fraction <50%. The BEACH score derived from these predictors allows risk stratification of CLI patients undergoing revascularization.