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Abstract Renal denervation is a promising new non-pharmacological treatment for resistant hypertension. However, there is a lack of data from Asian patients. The REQUIRE trial investigated the blood pressure-lowering efficacy of renal denervation in treated patients with resistant hypertension from Japan and South Korea. Adults with resistant hypertension (seated office blood pressure ≥150/90 mmHg and 24-hour ambulatory systolic blood pressure ≥140 mmHg) with suitable renal artery anatomy were randomized to ultrasound renal denervation or a sham procedure. The primary endpoint was change from baseline in 24-hour ambulatory systolic blood pressure at 3 months. A total of 143 patients were included (72 renal denervation, 71 sham control). Reduction from baseline in 24-hour ambulatory systolic blood pressure at 3 months was not significantly different between the renal denervation (−6.6 mmHg) and sham control (−6.5 mmHg) groups (difference: −0.1, 95% confidence interval −5.5, 5.3; p = 0.971). Reductions from baseline in home and office systolic blood pressure (differences: –1.8 mmHg [p = 0.488] and −2.0 mmHg [p = 0.511], respectively), and medication load, did not differ significantly between the two groups. The procedure-/device-related major adverse events was not seen. This study did not show a significant difference in ambulatory blood pressure reductions between renal denervation and a sham procedure in treated patients with resistant hypertension. Although blood pressure reduction after renal denervation was similar to other sham-controlled studies, the sham group in this study showed much greater reduction. This unexpected blood pressure reduction in the sham control group highlights study design issues that will be addressed in a new trial. Clinical trial registration NCT02918305 (http://www.clinicaltrials.gov).

Genetic engineering of eggplant using fruit-specific EEF48 promoter-driven bacterial PSY gene, crtB, confers β-carotene accumulation in fruit. Eggplant (Solanum melongena L.) is globally cultivated especially in Asia and is an important source of nutrients in the diets of low-income consumers in developing countries. Since fruits of eggplant have low provitamin A carotenoid content, it is expected to develop eggplant with high carotenoid content for combatting vitamin A deficiency. To achieve this, the present study implemented a metabolic engineering strategy to modify the carotenoid biosynthetic pathway in eggplant. Expression analysis of carotenogenic genes in eggplant tissues showed that the expression of the endogenous phytoene synthase (PSY) was low in fruit and callus. Orange-colored calluses were generated from ectopic expression of crtB gene, which encodes bacterial PSY, in eggplant cells. The orange calluses accumulated > 20 μg g−1 FW of β-carotene, which was approximately 150-fold higher than that of the untransformed calluses. These observations suggest that the PSY expression is the rate-limiting step for β-carotene production in callus and fruit. Since the orange calluses did not regenerate plants, we chose eggplant EEF48 gene, which is presumably expressed in fruit. We amplified its promoter region by TAIL-PCR and showed that the EEF48 promoter is indeed active in eggplant fruit. Subsequently, transgenic eggplant lines having EEF48 promoter-driven crtB were produced. Among the transgenic lines produced, one line set fruit containing 1.50 μg g−1 FW of β-carotene, which was 30-fold higher than that of the untransformed fruits (0.05 μg g−1 FW). The self-pollinated progenies showed a 3:1 segregation ratio for the presence and absence of the transgene, which was linked to the β-carotene accumulation in fruit. These results provide a strategy for improvement of carotenoid content in eggplant fruit.

Purpose:Drug-coated balloons (DCBs) are commonly used for endovascular treatment of femoropopliteal lesions. Here, we employed intravascular ultrasound (IVUS) to investigate the predictors of restenosis after DCB treatment.Methods:This retrospective and single-center study was performed to examine 1-year primary patency after DCB treatment and to identify the risk factors for restenosis by analyzing clinical characteristics, angiographic findings, and IVUS measurements. We included 111 consecutive patients undergoing DCB treatment for de novo femoropopliteal lesions at our hospital from July 2018 to March 2020.Results:The primary patency rate was found to be 80.0% at 1 year. The Cox proportional hazard multivariate analysis revealed that restenosis was independently associated with chronic total occlusion (CTO; p < 0.001), circumferential calcification (p = 0.023), and smaller postprocedural minimum lumen area (MLA; p = 0.036). Furthermore, receiver operating characteristic curve analysis showed that the cutoff value of postprocedural MLA to prevent restenosis was 12.7 mm2, with an area under the curve of 0.774 (p< 0.001). The multivariate analysis indicated that patients with a postprocedural MLA below 12.7 mm2(n = 44) had a significantly smaller distal reference vessel size (p 2(n = 67).Conclusions:Restenosis after DCB treatment was shown to correlate with CTO, circumferential calcification, and postprocedural MLA as evaluated by IVUS. Moreover, smaller vessel sizes might represent a particular challenge to the DCB strategy due to the difficulty of restoring a sufficient postprocedural lumen area by balloon dilatation.

There are limited data regarding the use of antithrombotic therapy in patients with atrial fibrillation (AF) who underwent percutaneous coronary intervention (PCI) with drug-eluting stents (DES). In this prospective interventional study, we evaluated the feasibility of short-term dual-antiplatelet therapy (DAPT) after DES implantation in AF patients treated with oral anticoagulation (OAC). The antithrombotic regimen in the present study was 1-month DAPT, followed by single-antiplatelet therapy with OAC. A total of 285 consecutive patients were enrolled between 2015 and 2017. The mean CHA2DS2-VASc score was 3.91 ± 1.51. The duration of DAPT was 28.5 ± 11.5 days. At 1-year follow-up, serious bleeding complications, defined as Bleeding Academic Research Consortium type ≥ 2, were observed in 27 patients (9.5%). Multivariate analysis showed that previous history of bleeding episodes (P = 0.009) and continuation of aspirin (P = 0.003) were independent predictors for the serious bleeding complications. High ORBIT (P = 0.008) and PRECISE-DAPT (P = 0.002) scores were associated with the bleeding complications, and the cut-off values were 5.00 and 49.0, respectively. No definite stent thrombosis occurred in any of the patients. Short-term DAPT is feasible in AF patients treated with OAC after undergoing PCI with DES. The previous history of bleeding episodes and long-term aspirin use were associated with their 1-year serious bleeding events.

Background The short-term efficacy of paclitaxel-coated balloons (PCBs) has been established in femoropopliteal in-stent restenosis (ISR) lesions. The aim of this study was to compare 5-year clinical outcomes of patients with femoropopliteal ISR lesions undergoing percutaneous transluminal angioplasty (PTA) with and without PCB. Methods After 1:1 propensity score matching, we extracted 50 patients with femoropopliteal ISR lesions undergoing PTA with (n = 25) and without (n = 25) IN.PACT PCB (Medtronic, Minneapolis, MN) from 106 consecutive ISR patients treated in our hospital between 2009 and 2015. We compared the 5-year outcomes between PCB and non-PCB groups. The primary endpoint was the cumulative 5-year incidence of recurrent restenosis. All-cause mortality, target lesion revascularization (TLR) and unplanned major amputation were also assessed. Results The primary patency after PCB treatment at 5 years was significantly higher than the patency after non-PCB treatment (65.7% vs. 18.7%; hazard ratio [HR]: 6.11; 95% confidence intervals [CI]: 2.57–16.82; p p = 0.020). All-cause mortality and unplanned major amputation rates did not significantly differ between the two groups. The Cox proportional hazard multivariate analysis showed that PCB was independently associated with preventing recurrent restenosis (HR: 0.17; 95% CI: 0.06–0.41; p Conclusions At 5 years, patients with femoropopliteal ISR lesions undergoing PCB treatment showed significantly lower recurrent restenosis than those that underwent non-PCB treatment. Evidence-based medicine Level of Evidence: Level 2b, Non-randomized controlled cohort/follow-up study.

Purpose: To investigate the efficacy of scoring balloons for immediate success of percutaneous transluminal angioplasty (PTA) in femoropopliteal lesions. Materials and Methods: Between 2013 and 2019, 398 consecutive patients with de novo femoropopliteal lesions were treated using PTA in our hospital. The procedure success rate was compared among patients undergoing PTA with vs without scoring balloons after 1:1 propensity score matching on hemodialysis, TransAtlantic Inter-Society Consensus II classification, Peripheral Arterial Calcium Scoring System (PACSS) grade, lesion length, and use of intravascular ultrasound. Propensity matching produced 84 patients (mean age 73.4±8.3; 65 men) treated with scoring balloons and 84 patients (mean age 75.6±8.7; 56 men) treated with plain balloons. Kaplan-Meier analysis investigated patency after the procedure in both groups; estimates are given with the 95% confidence interval (CI). Results: Residual stenosis

Increasing the urine flow rate (UFR) reduces the toxic effect of contrast media. Use of the RenalGuard system enables the achievement of a high UFR by maintaining intravascular volume and prevents the development of contrast-induced acute kidney injury (CI-AKI). However, the efficacy and safety of RenalGuard system have not yet been evaluated in Japan. This multicenter prospective study evaluated the efficacy and safety of the RenalGuard therapy in preventing CI-AKI development in 60 Japanese patients with renal dysfunction [estimated glomerular filtration rate (eGFR)

Purpose: To investigate the midterm safety and effectiveness of cilostazol treatment in claudicant patients undergoing endovascular therapy. Methods: The Sufficient Treatment of Peripheral Intervention by Cilostazol (STOP-IC) study ( ClinicalTrials.gov identifier NCT00912756; University Hospital Medical Information Network identifier UMIN000002091) enrolled 200 patients (mean age 73 years; 131 men) treated for femoropopliteal disease from March 2009 to April 2011 at 13 cardiovascular centers in Japan. The participants were randomized 1:1 to receive oral aspirin with or without cilostazol. Of the 100 patients assigned to the 2 treatment groups, 7 patients in the cilostazol group and 2 patients in the no-cilostazol group were withdrawn from the study without undergoing endovascular treatment, leaving 93 patients in the cilostazol group and 98 patients in the no-cilostazol group for follow-up analysis. The primary outcome measure was primary patency; secondary outcome measures were freedom from clinically-driven target lesion revascularization (CD-TLR) and overall survival. Outcomes were analyzed on an intention-to-treat basis using the Kaplan-Meier method; estimates were compared with the log-rank test. Results: The median follow-up was 38.1 months (interquartile range 25.1, 47.7). Among the 93 subjects in the cilostazol group, 7 died and 26 withdrew from administration 1 year after the endovascular procedure. Discontinuation of cilostazol was not a significant factor for restenosis. Primary patency was significantly higher in the cilostazol group than in the no-cilostazol group (69% vs 54%, p=0.026) at 3 years. The cilostazol group also had better 3-year freedom from CD-TLR (78% vs 63%, p=0.014), although overall survival estimates did not differ significantly (p=0.95). Conclusion: These results suggest that the safety and effectiveness of cilostazol treatment were sustained in patients with femoropopliteal disease undergoing endovascular treatment.

AIMS The aim of this study was to compare incidences of radial artery occlusion (RAO) and spasm (RAS) associated with transradial coronary intervention (TRI) using a 6.5 Fr SheathLess hydrophilic-coated guide catheter (SH-GC) vs. a 6.0 Fr Glidesheath Slender (GSS). METHODS AND RESULTS We conducted an open-label, single-centre, randomised study to compare radial complications in 600 consecutive patients undergoing elective TRI using 6.5 Fr SH-GC (n=300) or 6.0 Fr GSS (n=300) between 2015 and 2016. The primary endpoint was a composite of RAO evaluated by sonography and symptomatic RAS. The mean diameter of radial arteries was 2.20 mm in both groups; however, the sheath/radial artery diameter (S/RA) ratio was significantly smaller in the SH-GC group (1.03 vs. 1.17, p

We investigated the efficacy and safety of using paclitaxel-coated balloon (PCB) to treat small vessel disease. In this multicenter, prospective, randomized controlled trial, one-hundred and thirty-five patients with native coronary lesions in small vessels were randomized into a PCB group and plain balloon angioplasty (POBA) group at a ratio of 2:1. There were no differences in target vessel failure (TVF) that was defined as cardiac death or target vessel-related myocardial infarction or target lesion revascularization (TLR), between the two groups (3.4 vs. 10.3%; P = 0.20), and TLR was slightly lower in the PCB group (2.3%) than that in the POBA group (10.3%) during 24 weeks follow-up. The late lumen loss (LLL) was significantly lower in the PCB group (0.01 ± 0.31 vs. 0.32 ± 0.34 mm; P

Transcatheter aortic valve implantation is an established alternative and less invasive procedure to replace heart valves in symptomatic aortic stenosis patients; however, severe, life-threatening complications still exist. Coronary artery occlusion is a primary complication. We report a case of left main coronary artery occlusion after transcatheter aortic valve replacement, which was ameliorated using a double stent implantation technique.

Background Ureteroarterial fistula is a rare life-threatening complication of indwelling ureteral stents. The mechanism has not yet been fully evaluated using intravascular imaging. Case presentation An-84-year-old female was referred to our unit because of large volume pulsatile bleeding from the left ureter during routine stent exchange in the urology department. The hematuria was initially managed by rapidly exchanging for a new stent; however, the patient went into hypovolemic shock due to acute blood loss. The patient underwent implantation of the bilateral ureteral stents due to urinary retention caused by retroperitoneal fibrosis 2 years ago. To prevent ureteral infection, occlusion of the stents and stone formation, the stents were exchanged every 6 months. Computed tomography revealed contact between the left ureter and the common iliac artery. Therefore, ureteroarterial fistula was suspected and endovascular therapy was performed. Although angiography did not show definite blood flow into the ureter, a soft guidewire was advanced from the subintima of the external iliac artery to the left ureter. The diagnosis of ureteroarterial fistula was confirmed. Intravascular ultrasound identified the stent in the ureter and its connection to the subintima of the external iliac artery. The ureter did not contact directly to the inner lumen of the iliac arteries according to the ultrasound findings; therefore, we considered that the risk of stent-graft infection might not be high. After coil embolization of the ipsilateral internal iliac artery, a covered stent was implanted in the external iliac artery to seal the subintimal entry. The patient had no further episodes of any gross hematuria on dual anti-platelet therapy, when the ureteral stent was exchanged three time during 1 year after the endovascular therapy. Conclusions We demonstrated a case of ureteroarterial fistula, in which intravascular ultrasound allowed to visualize the communication between the ureter and the subintimal lumen in the external iliac artery. Electronic supplementary material The online version of this article (10.1186/s42155-019-0060-6) contains supplementary material, which is available to authorized users.

Background: Although there is increasing evidence of the effectiveness of endovascular therapy for complex aortoiliac (AI) occlusive disease, it is not universally applied to TASC D lesions. Methods: A total of 2096 patients, 2601 limbs with AI occlusive disease, were enrolled. The lesions were categorized as TASC D (395) or TASC A-C (2206), and we compared baseline data, procedure, and follow-up result between the 2 groups. Results: The success rate of the procedure was significantly lower in the TASC D group (91.6% vs 99.3%, P < .01), and more procedure complications occurred in the TASC D group (11.1% vs 5.2%, P < .01). The results of a 5-year follow-up revealed no significant difference in primary patency (77.9% vs 77.1%, P = .17) and major adverse cardiovascular and limb events (MACLE; 30.5% vs 33.4%, P = .42) between the 2 groups. A multivariate analysis revealed complications and critical limb ischemia are independent predictors of MACLE in the TASC D group. Conclusion: The success rate of the procedure was lower in the TASC D group. Complications were more frequent in the TASC D group, and they were related to MACLE.

Purpose: To investigate if balloon angioplasty with a prolonged inflation time (>3 minutes) can prevent postdilation dissection in femoropopliteal lesions. Methods: A retrospective single-center analysis examined 294 consecutive patients (mean age 74.1±8.7 years; 215 men) with de novo femoropopliteal lesions treated with balloon angioplasty between 2013 and 2018. The patients were classified into 2 groups to compare angiographic dissection patterns: 175 patients treated with balloon angioplasty for 3 minutes (3-minute group) and 119 treated for >3 minutes (>3-minute group). Results: Mean balloon inflation time was 7.8±2.7 minutes in the >3-minute group. Severe dissections (type C or higher) were observed less frequently after balloon dilation in the >3-minute group (22.7% vs 50.9%, p3-minute group had successful endovascular treatment after initial balloon angioplasty (57.1% vs 38.3%, p=0.001). Additional balloon dilation was attempted more frequently in the 3-minute group (30.9% vs 14.3%, p=0.001); as a result, there were more patients in whom additional balloon dilation repaired severe dissection that occurred after the initial dilation (25.1% vs 10.9%, p=0.001). Multivariate analysis revealed that chronic total occlusion (p3 minutes) may be effective as an initial strategy to prevent severe dissection in femoropopliteal lesions compared to inflation for 3 minutes.

We present a 77-year-old female with heavily calcified chronic total occlusions (CTO) in a superficial femoral artery treated by endovascular therapy using a Wingman crossing catheter, which is an over-the-wire catheter with a metallic blade, controlled manually. The blade could probe and track the calcified cap of CTO, wherein any hydrophilic guidewires or looped wires could not penetrate. Moreover, the Wingman could proceed through the occlusion and introduce a guidewire into distal intramedial lumen as a support catheter. Finally, wire crossing was achieved using a bi-directional approach. The Wingman can be a simple solution for crossing calcified peripheral CTO.

Objectives The aim of this study was to assess the safety and efficacy of sheathless guide catheters in transradial percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). Background Transradial PCI for STEMI offers significant clinical benefits, including a reduced incidence of vascular complications. As the size of the radial artery is small, the radial artery is frequently damaged in this procedure using large-bore catheters. A sheathless guide catheter offers a solution to this problem as it does not require an introducer sheath. However, the efficacy and safety of sheathless guide catheters remain to be fully determined in emergent transradial PCI for STEMI. Methods Data on consecutive STEMI patients undergoing primary PCI at the Sendai Kousei Hospital between September 2010 and May 2013 were analyzed. The primary endpoint was the rate of acute procedural success without access site crossover. Secondary endpoints included door-to-balloon time, fluoroscopy time, volume of contrast, and radial artery stenosis or occlusion rate. Results We conducted transradial PCI for 478 patients with STEMI using a sheathless guide catheter. Acute procedural success was achieved in 466 patients (97.5%). The median door-to-balloon time was 45 min (range, 15–317 min). The median fluoroscopy time was 16.4 min (range, 10–90 min). The median volume of contrast was 134 mL (range, 31–431 mL). Radial stenosis or occlusion developed in 14 (3.8%) of the 370 evaluable patients. Conclusions This study showed that use of a sheathless guide catheter taking a transradial approach was effective and safe in primary PCI for STEMI. © 2015 Wiley Periodicals, Inc.

Objectives This study sought to investigate the 3-year follow-up results of OLIVE registry patients. Background Although favorable 12-month clinical outcomes after endovascular therapy (EVT) in OLIVE registry patients with critical limb ischemia (CLI) from infrainguinal disease have been reported, long-term results after EVT remain unknown. Methods This was a prospective multicenter registry study that consecutively enrolled patients who received infrainguinal EVT for CLI. The primary outcome was 3-year amputation-free survival (AFS), whereas secondary outcome measures were 3-year freedom from major adverse limb events (MALE), wound-free survival, and wound recurrence rate. Prognostic predictors for each outcome were also elucidated by Cox proportional hazard regression analysis or the log-rank test. Results The completion rate of 3-year follow-up was 95%. Three-year AFS, freedom from MALE, and wound-free survival rates were 55.2%, 84.0%, and 49.6%, respectively. Wound recurrence out to 3 years was 43.9%. After multivariable analysis, age (hazard ratio [HR]: 1.43, p = 0.001), body mass index ≤18.5 (HR: 2.17, p = 0.001), dialysis (HR: 2.91, p Conclusions In CLI patients with infrainguinal lesions, 3-year clinical results of EVT were reasonable despite high reintervention and moderate ulcer recurrence rate. (A Prospective, Multi-Center, Three-Year Follow-Up Study on Endovascular Treatment for Infra-Inguinal Vessel in Patients With Critical Limb Ischemia [OLIVE 3-Year Follow-Up Study]; UMIN000014759 )

Although coronary artery calcium (CAC) is an established marker of coronary atherosclerosis, whether it also reflects the physiological significance is unknown. This study aims to evaluate if CAC could indicate physiological ischemia in intermediate stenosis defined by an invasive fractional flow reserve (FFR). CAC score (CACS) derived from either whole coronary arteries or individual arteries was measured by computed tomography among patients with intermediate de novo lesions (percent diameter stenosis from 30% to less than 70%). All stenoses were evaluated by invasive FFR; lesions with an FFR ≤ 0.80 were considered significant. We enrolled 119 patients with 143 lesions. Of these, 42 lesions (29.4%) demonstrated significant ischemia by FFR measurement. FFR values had modest but significant correlations with CACS in individual arteries with intermediate stenosis (r = − 0.290; p < 0.001). A receiver operating characteristic curve analysis showed that CACS of individual arteries with intermediate stenosis had 71.4% sensitivity and 67.3% specificity as a predictor of significant ischemia at a cut off value of 145.9. Multivariable analysis showed that percent diameter stenosis and CACS in individual arteries with intermediate stenosis were independent predictors for significant ischemia. By net reclassification improvement analysis, CACS in individual arteries with intermediate stenosis provided incremental prediction for significant ischemia over minimum lumen diameter, percent diameter stenosis, and lesion length. CACS measured in each artery, but not the total CACS, provides additional information as to whether an angiographically intermediate stenosis within the artery is significant enough to cause myocardial ischemia.

Therapeutic protein solutions for subcutaneous injection must be very highly concentrated, which increases their viscosity through protein-protein interactions. However, maintaining a solution viscosity below 50 cP is important for the preparation and injection of therapeutic protein solutions. In this study, we examined the effect of various amino acids on the solution viscosity of very highly concentrated bovine serum albumin (BSA) and human serum albumin (HSA) at a physiological pH. Among the amino acids tested, l-arginine hydrochloride (ArgHCl) and l-lysine hydrochloride (LysHCl) (50-200 mM) successfully reduced the viscosity of both BSA and HSA solutions; guanidine hydrochloride (GdnHCl), NaCl, and other sodium salts were equally as effective, indicating the electrostatic shielding effect of these additives. Fourier transform infrared spectroscopy showed that BSA is in its native state even in the presence of ArgHCl, LysHCl, and NaCl at high protein concentrations. These results indicate that weakened protein-protein interactions play a key role in reducing solution viscosity. ArgHCl and LysHCl, which are also non-toxic compounds, will be used as additives to reduce the solution viscosity of concentrated therapeutic proteins.

Placing an atrial lead in the inferior interatrial septum (IAS) reportedly reduces the incidence of paroxysmal atrial fibrillation (AF) and slows the progression to chronic AF; however, in certain cases, inferior IAS pacing is technically difficult. When this procedure is unsuccessful, insertion of the lead in the right atrial appendage can be considered, but it is associated with a risk of cardiac perforation. Here, we describe a technique for lead insertion in the inferior IAS via a 9.0 Fr guiding catheter, which may serve as an alternative technique for inferior IAS pacing when the conventional stylet-guided insertion is not successful.

Patient Initials or Identifier Number 110110 ### Relevant Clinical History and Physical Exam The patient is 90 years old gentleman with intermittent claudication. He is active and received a maximal medical therapy including cilostazol. But he still has a severe symptom. The rt-popliteal

A 75-year-old hemodialysis patient with right critical limb ischemia received endovascular therapy for a chronic total occlusion (CTO) in a diffusely calcified superficial femoral artery (SFA). During a retrograde approach, a Brockenbrough needle (BN) was able to penetrate the calcified hard plaque formed in the middle segment of the CTO. Moreover, bougie dilatation with the BN allowed balloon crossing and stent deployment, even after failure to pass a 2.0-mm monorail balloon across the plaque. These results suggest that the BN offers a new therapeutic option in the penetration and modification of severely calcified CTO in SFA.

Stanford type A and open false lumen are accepted predictors for in-hospital mortality in patients with acute aortic dissection (AAD). However, the association of renal dysfunction on admission with in-hospital mortality is not well known. The aim of this study was to investigate the prognostic value of renal dysfunction in patients with AAD. A total of 250 patients with type B AAD admitted to our institution between January 2003 and August 2011 were enrolled in this study. In multivariate logistic regression analysis, the significant predictors of in-hospital mortality were age (odds ratio [OR] 1.575, 95% confidence interval [CI] 1.078-2.864, p = 0.024), maximum aortic diameter measured by an initial computed tomography (CT) (OR 1.740, 95% CI 1.029-2.940, p = 0.039), decreased enhancement of kidney (OR 7.716, 95% CI 2.335-25.501, p = 0.001) and estimated glomerular filtration rate (eGFR)

To investigate the long-term outcomes of nitinol stenting in femoropopliteal lesions and to determine the factors associated with restenosis.Between December 2003 and December 2009, 861 patients (603 men; mean age 72 years) underwent nitinol stenting of the femoropopliteal segment in 1017 limbs. A quarter (26%) of the patients had critical limb ischemia. Mean lesion length was 152±93 mm. Stent patency was assessed by either duplex ultrasound or angiography and analyzed by Kaplan-Meier estimation. The determinants of restenosis were explored with Cox proportional hazard regression analyses; the results are presented as the hazard ratio (HR) and 95% confidence interval (CI). Risk stratification of primary patency was subsequently analyzed using a score based on the significant prognostic factors identified in the multivariate model.Stent fracture occurred in 10% (104 limbs) of the lesions. At 1, 3, and 6 years, the primary patency rates were 77%, 67%, and 63%; secondary patency rates were 91%, 87%, and 87%; freedom from femoropopliteal bypass grafting was 99%, 97%, and 96%, respectively. Multivariate Cox regression analysis identified female gender (HR 1.899; 95% CI 1.318 to 2.737, p0.001), ankle-brachial index0.6 (HR 1.921; 95% CI 1.348 to 2.736, p0.001), TASC II C/D lesion (HR 2.068; 95% CI 1.346 to 3.177, p = 0.0009), stent fracture (HR 1.937; 95% CI 1.203 to 3.118, p = 0.006), and the absence of cilostazol administration (HR 2.102; 95% CI 1.394 to 3.172, p0.001) as strong independent factors associated with restenosis. After assigning a risk score based on the outcomes of the multivariate regression analysis (1 each for female gender, ABI0.6, TASC II C/D, stent fracture, and absence of cilostazol therapy), primary patency was found to be lower in limb groups with a higher cumulative score (12-month primary patency: score 0: 93%, score 1: 80%, score 2: 73%, score 3; 47%, score 4: 0%, respectively; p0.001).Endovascular therapy using nitinol stents for FP lesions yielded acceptable outcomes up to 6 years. Risk stratification for patency can play an important role in estimating future occurrence of restenosis after nitinol stent implantation in FP lesions.

The purpose of the present study was to evaluate the 3-year clinical outcomes after percutaneous coronary intervention with sirolimus-eluting stents in patients with insulin-treated diabetes mellitus (DM-insulin) and those with non-insulin-treated DM (DM-non-insulin) compared to patients without DM. Of 10, 778 consecutive patients treated exclusively with sirolimus-eluting stents in the j-Cypher registry, we identified 996 patients with DM-insulin, 3, 404 with DM-non-insulin, and 6, 378 without DM. Compared to the non-DM group, the adjusted risk of a serious cardiovascular event (composite of all-cause death, myocardial infarction, and stroke) was significantly greater in the DM-insulin group (hazard ratio 1.12, 95% confidence interval [CI] 1.03 to 1.23; p = 0.01), but not in the DM-non-insulin group (hazard ratio 1.02, 95% CI 0.96 to 1.09; p = 0.47). The adjusted risk of target lesion revascularization was significantly greater in both the DM-insulin group (odds ratio 1.52, 95% CI 1.19 to 1.92; p = 0.0006) and the DM-non-insulin group (odds ratio 1.24, 95% CI 1.05 to 1.45; p = 0.009). In conclusion, a diabetes-associated excess risk of target lesion revascularization was found, regardless of insulin use in this large, real-world study of Japanese patients with sirolimus-eluting stent implantation. However, regarding serious cardiovascular events, an excess risk was seen only in the DM-insulin group. The risk of serious cardiovascular events was similar between the DM-non-insulin and non-DM groups.

Background: The use of a stent in the treatment of lesions of the superficial femoral artery (SFA) remains controversial. Although some reports have suggested that use of a nitinol stent in conjunction with aggressive medical management is effective for long SFA lesions, few long-term, large-scale studies have been done. Methods and Results: A retrospective analysis was conducted of data from a multicenter study in which the S.M.A.R.T. ControlTM stent was used for treatment of de novo SFA lesions. A total of 528 lesions in 432 patients were included. Mean patient age was 72.5±9.1 years; mean stent length was 15.7±8.1cm; 259 lesions (49%) were classified as C/D according to the TransAtlantic Inter-Society Consensus (TASC) II classification. Primary and secondary patency at 4 years was 66% and 87%, respectively. No cilostazol administration (41% re-stenosis group vs. 29% no-restenosis group, P

To calculate the cutoff value for radial artery occlusion (RAO) in patients undergoing transradial percutaneous coronary interventions (PCI) using sheathless guiding catheters for acute coronary syndrome (ACS). We prospectively screened 936 consecutive patients undergoing primary PCI for ACS, and

Background— The influences of antiplatelet therapy discontinuation on the risk of stent thrombosis and long-term clinical outcomes after drug-eluting stent implantation have not yet been addressed adequately. Methods and Results— In an observational study in Japan, 2-year outcomes were assessed in 10 778 patients undergoing sirolimus-eluting stent implantation. Data on status of antiplatelet therapy during follow-up were collected prospectively. Incidences of definite stent thrombosis were 0.34% at 30 days, 0.54% at 1 year, and 0.77% at 2 years. Thienopyridine use was maintained in 97%, 62%, and 50% of patients at 30 days, 1 year, and 2 years, respectively. Patients who discontinued both thienopyridine and aspirin had a significantly higher rate of stent thrombosis than those who continued both in the intervals of 31 to 180 days, 181 to 365 days, and 366 to 548 days after stent implantation (1.76% versus 0.1%, P P =0.02; and 2.1% versus 0.14%, P =0.004, respectively). When discontinuation of aspirin was taken into account, patients who discontinued thienopyridine only did not have an excess of stent thrombosis in any of the time intervals studied. Adjusted rates of death or myocardial infarction at 24 months were 4.1% for patients taking thienopyridine and 4.1% for patients not taking thienopyridine ( P =0.99) in the 6-month landmark analysis. Conclusions— Discontinuation of both thienopyridine and aspirin, but not discontinuation of thienopyridine therapy only, was associated with an increased risk of stent thrombosis. Landmark analysis did not suggest an apparent clinical benefit of thienopyridine use beyond 6 months after sirolimus-eluting stent implantation.

A 78-year-old woman with severe aortic stenosis underwent transcatheter aortic valve implantation (TAVI) with a balloon expandable bioprosthesis: a 23-mm Sapien XT valve (Edwards Life Sciences, Inc., CA, USA). A set of the valve and a balloon (NovaFlex, Edwards Transfemoral Balloon Catheter, Edwards Life Sciences, Inc., CA, USA) was successfully delivered to an optimal position using a 16-French expandable introducer hydrophilic sheath. Inflation of the balloon was commenced, and expansion was initially smooth. However, it ruptured immediately before completion of expansion, resulting in a rapid deterioration in hemodynamics. Even though no migration of the stent valve was observed, transesophageal echocardiography and aortography revealed massive paravalvular aortic regurgitation (AR), suggesting that AR was attributable to insufficient expansion. After post -dilatation of the stent valve using a 23- mm balloon (Edwards Transfemoral Balloon Catheter, Edwards Life Sciences, Inc., CA, USA), the patient’s condition began to improve, and further aortography indicated an improvement in paravalvular AR. This case represented that balloon rupture could led to sudden onset massive paravalvular AR. Interventional cardiologists should recognize it as a significant complication in patients undergoing TAVI using a balloon-expandable bioprosthesis, with the possibility of severe cardiogenic shock.

Background Success of coronary stenting is limited by in-stent restenosis. We aimed to determine whether circulating levels of the cytokines, which have anti-inflammatory properties such as adiponectin or interleukin-10, could be associated with the occurrence of coronary in-stent restenosis in patients with end-stage renal disease (ESRD). Methods We enrolled 71 consecutive ESRD patients undergoing haemodialysis (mean age: 64.9+/-8.9 years; 19 women, 52 men; mean haemodialysis duration: 78.2+/-87.5 months), who received stenting for a single coronary lesion. Plasma concentrations of adiponectin and IL-10 were measured within one week before coronary stenting. Results Of the 71 patients who had received stenting, in-stent restenosis occurred in 37 patients (52.1%) within 6 months after stenting. In univariate logistic analysis, the homeostasis model assessment index of insulin resistance, blood haemoglobin, serum concentrations of high density lipoprotein-cholesterol or triglycerides and plasma concentrations of insulin or adiponectin were significantly associated with coronary in-stent restenosis. In a multiple logistic regression analysis among these variables, however, only the plasma adiponectin concentration was associated with the coronary in-stent restenosis: the odds ratio of the increase in 1 microg/ml of plasma adiponectin concentration for having restenosis was 0.651 (P = 0.001, 95% confidence interval: 0.506-0.839). Patients with restenosis had lower plasma adiponectin concentrations than those without [6.2+/-2.2 microg/ml (2.1-10.4 microg/ml; n = 37) vs 27.2+/-10.8 microg/ml (17.9-79.8 microg/ml; n = 34); P = 0.0001]. Conclusions Circulating adiponectin concentrations may be associated with the occurrence of coronary in-stent restenosis in ESRD patients undergoing maintenance haemodialysis.

BACKGROUND Traditional risk factors of cardiovascular disease do not fully explain the accelerated atherosclerosis present in patients with end-stage renal disease (ESRD). The goal of this study was to identify the association of clinical and laboratory factors including seropositivity for Chlamydia pneumoniae determined by a specific enzyme-linked immunosorbent assay (ELISA) with the presence of coronary artery disease identified by coronary angiography in ESRD patients. METHODS We prospectively enrolled 161 consecutive ESRD patients undergoing haemodialysis for >6 months (106 men, 55 women; mean age 63.1+/-10.2 years; mean dialysis duration 91.3+/-90.1 months). All patients underwent coronary angiography within 1 week after blood sampling. The associations of coronary artery disease with clinical parameters including C. pneumoniae IgA and IgG seropositivity were analysed using multiple logistic regression models. RESULTS Coronary stenosis >50% was found in 102 of 161 haemodialysis patients (63.4%). Of the 102 patients, 75.5% were asymptomatic. Seropositivity for C. pneumoniae IgA was found in patients with coronary stenosis (77 out of 102, 75.5%) more frequently (P

虚血性心疾患は血液透析患者の主要な死因の一つである. 冠動脈疾患の検出に心臓核医学検査は有用であるが運動・薬剤負荷を必要とし, 透析患者では, その実施・判定に困難を伴うことが多い. 正常心筋はエネルギー源の70%以上を効率のよい脂肪酸β酸化に依存しているが, 心筋虚血時には脂肪酸のβ酸化が抑制され, 代わってグルコースを利用した解糖系へ移行する. 透析患者の冠動脈病変検出における心筋脂肪酸代謝イメージング製剤である123I-BMIPPの安静時検査の有用性を検討した.慢性腎不全による維持血液透析患者130例 (平均透析期間88.5か月, 男性77例, 女性53例, 平均年齢63.8歳) に対し心筋血流製剤である塩化タリウム (201TI) ならびに123I-BMIPPのSPECT (single photon emission computed tomography) を施行し, その後60日以内に施行された冠動脈造影検査所見と対比した. 左室心筋を17分画し, TIおよびBMIPP SPECT所見を視覚的に判定, スコア化し (0: 正常-4: 欠損), その総計をTIならびにBMIPP summed scoreとした.冠動脈造影の結果, 対象患者の71.5%に75%以上の有意狭窄を認めた. BMIPP summed score 6以上を陽性とした場合, BMIPP-SPECTの冠動脈病変の総合正診率は90.0% (感度: 98.0%, 特異度: 65.6%) であった. 一方, TI-SPECTでは, TI summed score 1以上を陽性とした場合, 感度84.7%, 特異度46.9%, 総合正診率75.0%であった. ROC解析の結果, 冠動脈病変診断能を示すAUC (area under the curve) は, BMIPP SPECT 0.895, TI SPECT 0.727であった.BMIPP-SPECTはTI-SPECTに比して高い精度で冠動脈病変を検出できる. 慢性血液透析患者の冠動脈造影検査の適応判定ならびに冠動脈疾患合併の安全なスクリーニング検査として臨床的に有用である.

We experienced an entrapped rotablator burr that could not be retrieved even by deep seating of the guiding catheter. We successfully retrieved the burr by balloon inflation after the tapered tip of a Conquest wire managed to penetrate the quite hard plaque and pass through the outer lumen of the burr.

In the treatment of NSTEMI or UAP patients, the primary system of transradial coronary intervention (TRI) may be controversial, because they do not usually undergo immediate revascularization after diagnostic coronary angiography (CAG). A Sheathless Eaucath guide catheter (SH-GC) could be inserted

Background: The reentry circuit of the slow-fast AV nodal reentrant tachycardia (AVNRT) has not been precisely delineated. Although conventional right-sided slow pathway ablation at the inferoseptal to midseptal tricuspid annulus (TA) or inside the coronary sinus (CS) is effective in most slow-fast AVNRT cases, rare cases of the left-variant form resistant to the conventional right-sided slow pathway ablation and requiring the left-sided ablation along the mitral annulus (MA) have been reported. Purpose: To evaluate the effects of the left-sided ablation along the MA in patients with the slow-fast AVNRT resistant to the conventional right-sided slow pathway ablation. Methods & Results: In 5 out of 250 cases with the slow-fast AVNRT who underwent the slow pathway ablation, extensive right-sided slow pathway ablation at the mid to inferoseptal TA, CS ostium or inside the CS (>10 applications) failed to eliminate tachycardia inducibility. In those 5 cases, the left-sided ablation along the inferoseptal to inferolateral MA with transseptal approach was performed during the sinus rhythm. In 2 cases, accelerated junctional rhythm was induced during the ablation along the MA and tachycardias were rendered non-inducible (upto one AV nodal echo beat). In other 2 cases, accelerated junctional rhythm was not induced during the ablation along the MA, but tachycardia became non-sustained (2-5 AV nodal echo beats). In the remaining one case, tachycardia still remained inducible even after extensive left-sided ablations. Conclusion: The left-variant forms of the slow-fast AVNRT were observed in 1.6% of all slow-fast AVNRT cases and the slow pathway ablation along the inferoseptal to inferolateral MA was effective for eliminating the tachycardia inducibility. The left-sided deviation of the reentrant circuit might explain the resistance to the right-sided slow pathway ablation and efficacy of the left-sided ablation along the MA in those cases.

Unacceptably high viscosity is observed in high protein concentration formulations due to extremely large therapeutic dose of antibodies and volume restriction of subcutaneous route of administration. Here, we show that a protein aggregation suppressor, arginine hydrochloride (ArgHCl), specifically decreases viscosity of antibody formulations. The viscosities of bovine gamma globulin (BGG) solution at 250 mg/mL and human gamma globulin (HGG) solution at 292 mg/mL at a physiological pH were too high for subcutaneous injections, but decreased to an acceptable level (below 50 cP) in the presence of 1,000 mM ArgHCl. ArgHCl also decreased the viscosity of BGG solution at acidic and alkaline pHs. Interestingly, ArgHCl decreased the viscosity of antibody solutions (BGG, HGG, and human immunoglobulin G) but not globular protein solutions (α-amylase and α-chymotrypsin). These results indicate not only high potency of ArgHCl as an excipient to decrease the solution viscosity of high concentration antibodies formulations but also specific interactions between ArgHCl and antibodies.

To investigate the role of human hepatocyte growth factor (hHGF) in vascular lesions associated with endothelial injury, we measured serum hHGF concentrations in subjects with retinal arteriosclerosis, coronary atherosclerosis, or arteriolitis due to Henoch-Schonlein pur- pura. Individuals with more advanced grades of retinal arterioscle- rosis showed higher serum hHGF concentrations (grade 0, 0.053 6 0.005 ng/mL (n 5 68); grade 1, 0.144 6 0.022 ng/mL (n 5 21; P , 0.01 vs. grade 0); grade 2, 0.338 6 0.036 ng/mL (n 5 20; P , 0.01 vs. grade 0 or 1); grade 3, 0.526 6 0.051 ng/mL (n 5 9; P , 0.01 vs. grade 0, 1, or 2)). Patients with active arteriolitis due to Henoch-Schonlein pur- pura showed higher (P , 0.01) serum hHGF concentrations (0.347 6 0.038 ng/mL; n 5 14) than those in the remission phase (0.097 6 0.017 ng/mL; n 5 19). Mean serum hHGF concentrations were higher in subjects with coronary atherosclerosis than in those without, but a significant overlap in serum hHGF concentrations was found between subjects with and those without coronary atherosclerosis. Serum hHGF may be an indicator of the presence or development of arte- riolar lesions. (J Clin Endocrinol Metab 84: 2475-2480, 1999)

The SYNTAX study showed significant improvement in the efficacy of PCI using 1st generation DES for unprotected left main coronary artery (LMCA) disease. It has been proposed that the 2nd generation DES will provide better PCI outcomes for LMCA compared with SYNTAX trial. In Japan, PCI was

Renal artery stenting is expected to improve or stabilize renal function. However, the efficacy of renal artery stenting in severely reduced renal function is unclear. We evaluated 23 patients with class IV or V renal dysfunction who were treated for renal artery stenosis between 2004 and 2009. Improvement in renal function was found in 7 (30%) patients, all of whom were treated with distal protection device. Deterioration of renal function was found in 4 (17%) cases. In these 4 cases, distal protection device could not be used for anatomical reasons. The use of distal protection device was associated with significantly less renal deterioration after the procedure ( P < .05, odds ratio 0.21 [confidence interval 0.09-0.50]). Renal artery stenting can stabilize or improve renal function in patients with severe renal dysfunction. Distal protection devices may be beneficial in patients who require renal artery stenting due to severely reduced renal function.

Background: A strong association exists between diabetes mellitus and critical limb ischemia. Methods and Results: We performed endovascular therapy on 1060 limbs in 884 patients with below knee lesions only. The patients were divided into diabetes (DG) and nondiabetes groups (NDG). Limb salvage was poorer in the DG (79% vs 89%, P = .0061). No significant difference was observed in mortality, amputation-free survival (AFS), and target vessel revascularization (TVR). Multivariate analysis revealed diabetes status, infection, poor activity of daily living (ADL), younger age, and procedure failure as independent predictors of major amputation in DG. In the NDG, procedure failure was the predictor, and younger age and poor ADL showed tendency of major amputation. Conclusions: Mortality, AFS, and TVR showed no significant difference between the 2 groups, but major amputation was more frequent in DG. Not only revascularization but also infection and diabetes control were very important for limb salvage in DG.

Background— It remains unclear whether cilostazol, which has been shown to improve the clinical outcomes of endovascular therapy for femoropopliteal lesions, also reduces angiographic restenosis. Methods and Results— The Sufficient Treatment of Peripheral Intervention by Cilostazol (STOP-IC) study investigated whether cilostazol reduces the 12-month angiographic restenosis rate after percutaneous transluminal angioplasty with provisional nitinol stenting for femoropopliteal lesions. Two hundred patients with femoropopliteal lesions treated from March 2009 to April 2011 at 13 cardiovascular centers were randomly assigned 1:1 to receive oral aspirin with or without cilostazol. The primary end point was 12-month angiographic restenosis rate. Secondary end points were the restenosis rate on duplex ultrasound, the rate of major adverse cardiac events, and target lesion event-free survival. Researchers evaluated all follow-up data and assessed the end points in a blinded fashion. The mean lesion length and reference vessel diameter at the treated segment were 128±86 mm and 5.4±1.4 mm, respectively. The frequency of stent used was similar between groups (88% versus 90% in the cilostazol and noncilostazol group, respectively, P =0.82). During the 12-month follow-up period, 11 patients died and 152 patients (80%) had evaluable angiographic data at 12 months. The angiographic restenosis rate at 12 months was 20% (15/75) in the cilostazol group versus 49% (38/77) in the noncilostazol group ( P =0.0001) by intention-to-treat analysis. The cilostazol group also had a significantly higher event-free survival at 12 months (83% versus 71%, P =0.02), although cardiovascular event rates were similar in both groups. Conclusions— Cilostazol reduced angiographic restenosis after percutaneous transluminal angioplasty with provisional nitinol stenting for femoropopliteal lesions. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00912756; and URL: https://www.umin.ac.jp . Unique identifier: UMIN000002091.

Background— Recent technical advances have made endovascular treatment (EVT) an alternative first-line treatment for critical limb ischemia. Methods and Results— A prospective multicenter study was conducted to evaluate the clinical outcomes of 314 Japanese critical limb ischemia patients (mean age, 73±10 years) with infrainguinal arterial lesions who underwent EVT. Patients were enrolled from December 2009 to July 2011 and were followed-up for 12 months. The primary end point was amputation-free survival (AFS) at 12 months. Secondary end points were anatomic, clinical, and hemodynamic measures, including 12-month freedom from major adverse limb events. The 12-month AFS rate was 74%, with body mass index P =0.008), heart failure (HR, 1.73; P =0.04), and wound infection (HR, 1.89; P =0.03) associated with a poor prognosis for AFS. The 12-month major adverse limb event-free rate was 88%, with hemodialysis (HR, 1.98; P =0.005), heart failure (HR, 1.69; P =0.02), and Rutherford classification 6 (HR, 2.25; P =0.002) associated with a poor prognosis for major adverse limb events. The median time for wound healing was 97 days, with body mass index P =0.03) and wound infection (HR, 0.60; P =0.04) being significant risk factors for unhealed wounds after EVT. At 12 months, 34% had undergone reintervention (bypass surgery, 2.6%; repeat EVT, 31.7%), and 73% were major adverse event–free. Conclusions— The high reintervention rate notwithstanding, EVT was an effective treatment for Japanese critical limb ischemia patients with infrainguinal disease, with satisfactory AFS and major adverse limb event-free rates. The results of this study will be helpful for the future evaluation of critical limb ischemia therapy. Clinical Trial Registration— URL: http://www.umin.ac.jp/ctr . Unique identifier: UMIN000002830.

Transradial approach (TRA) improves clinical outcomes driven by less hemorrhagic complications in patients with ST-elevation acute myocardial infarction (STEMI), as compared to transfemoral approach (TFA). However, TRA is sometimes avoided in clinical practice due to its procedural complexity, which