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Background: Individuals with severe motor and intellectual disabilities have become an aging population, and high cancer morbidity and mortality are critical issues affecting their survival. Cancer screening is a crucial method of resolving this issue; however, a suitable screening method for them has not been established., Methods: We used ultrasonography alone and performed breast cancer screening for women over 30 years old in our facility from 2016 to 2023. We observed the outcomes and calculated the recall/detection rate in this screening., Results: Three cases among 379 tested positive in this screening, all of which underwent radical surgery. They are alive and well without relapse present. We detected these breast cancer cases with a low recall rate., Conclusion: We were able to successfully detect breast cancer cases using ultrasonography alone. Ultrasonography is an effective and feasible tool for breast cancer screening in individuals with severe motor and intellectual disabilities., (© 2024 The Authors. Journal of Applied Research in Intellectual Disabilities published by John Wiley & Sons Ltd.)

E7130 is a novel drug candidate with an exceedingly complex chemical structure of the halichondrin class, discovered by a total synthesis approach through joint research between the Kishi group at Harvard University and Eisai. Only 18 months after completion of the initial milligram-scale synthesis, ten-gram-scale synthesis of E7130 was achieved, providing the first good manufacturing practice (GMP) batch to supply clinical trials. This paper highlights the challenges in developing ten-gram-scale synthesis from the milligram-scale synthesis.

Neutralizing potency of humoral immune responses induced by prior infection or vaccination is vital for protecting of individuals and population against severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). However, the emergence of viral variants that can evade neutralization by vaccine- or infection-induced immunity is a significant public health threat and requires continuous monitoring. Here, we have developed a novel scalable chemiluminescence-based assay for assessing SARS-CoV-2-induced cytopathic effect to quantify the neutralizing activity of antisera. The assay leverages the correlation between host cell viability and ATP levels in culture to measure the cytopathic effect on target cells induced by clinically isolated, replication-competent, authentic SARS-CoV-2. With this assay, we demonstrate that the recently arisen Omicron subvariants BQ.1.1 and XBB.1 display a significant decrease in sensitivity to neutralization by antibodies elicited from breakthrough infections with Omicron BA.5 and from receipt of three doses of mRNA vaccines. Thus, this scalable neutralizing assay provides a useful platform to assess the potency of acquired humoral immunity against newly emerging SARS-CoV-2 variants. IMPORTANCE The ongoing global pandemic of SARS-CoV-2 has emphasized the importance of neutralizing immunity in protecting individuals and populations against severe respiratory illness. In light of the emergence of viral variants with the potential to evade immunity, continuous monitoring is imperative. A virus plaque reduction neutralization test (PRNT) is a "gold standard" assay for analyzing neutralizing activity for authentic viruses that form plaques, like influenza virus, dengue virus, and SARS-CoV-2. However, this method is labor intensive and is not efficient for performing large-scale neutralization assays on patient specimens. The assay system established in this study allows for the detection of a patient's neutralizing activity by simply adding an ATP detection reagent, providing a simple evaluation system for neutralizing activity of antisera as an alternative to the plaque reduction method. Our extended analysis of the Omicron subvariants highlights their increasing capability to evade neutralization by both vaccine- and infection-induced humoral immunity., Competing Interests: The authors declare no conflict of interest.

Although the Omicron variant of the SARS-CoV-2 virus shows resistance to neutralizing antibody, it retains susceptibility to the cellular immune response. Here we characterize vaccine-induced T cells specific for various SARS-CoV-2 variants and identified HLA-A*24:02-restricted CD8 + T cells that strongly suppress Omicron BA.1 replication in vitro. Mutagenesis analyses revealed that a G446S mutation, located just outside the N-terminus of the cognate epitope, augmented TCR recognition of this variant. In contrast, no enhanced suppression of replication is observed against cells infected with the prototype, Omicron BA.2, and Delta variants that express G446. The enhancing effect of the G446S mutation is lost when target cells are treated with inhibitors of tripeptidyl peptidase II, a protein that mediates antigen processing. These ex vivo analysis and in vitro results demonstrate that the G446S mutation in the Omicron BA.1 variant affects antigen processing/presentation and potentiates antiviral activity by vaccine-induced T cells, leading to enhanced T cell recognition towards emerging variants., (© 2022. The Author(s).)

Endovascular treatment (EVT) is the main treatment for peripheral artery disease (PAD). Despite advances in device development, the restenosis rate remains high in patients with femoropopliteal lesions (FP). This study aimed to evaluate the effectiveness of exercise training in reducing the 1-year in-stent restenosis rate of bare metal nitinol stents for FPs. This prospective, randomized, open-label, multicenter study was conducted from January 2017 to March 2019. We randomized 44 patients who had claudication with de novo stenosis or occlusion of the FP into an intensive exercise group (n = 22) and non-intensive exercise group (n = 22). Non-intensive exercise was defined as walking for less than 30 min per session, fewer than three times a week. We assessed exercise tolerance using an activity meter at 1, 3, 6, and 12 months, and physiotherapists ensured maintenance of exercise quality every month. The primary endpoint was instant restenosis defined as a peak systolic velocity ratio > 2.5 on duplex ultrasound imaging. Kaplan-Meier analysis was used to evaluate the data. There were no significant differences in background characteristics between the groups. Six patients dropped out of the study within 1 year. In terms of the primary endpoint, intensive exercise significantly improved the patency rate of bare nitinol stents at 12 months. The 1-year freedom from in-stent restenosis rates were 81.3% in the intensive exercise group and 47.6% in the non-intensive exercise group (p = 0.043). No cases of stent fracture were observed in the intensive exercise group. Intensive exercise is safe and reduces in-stent restenosis in FP lesions after endovascular therapy for PAD. Clinical trial registration: University Hospital Medical Information Network Clinical Trials Registry (No. UMIN 000025259)., (© 2022. The Author(s).)

Purpose: Drug-eluting stents (DESs) play an important role in endovascular therapy (EVT) for femoropopliteal (FP) lesions. Cilostazol improves patency after bare-metal nitinol stent (BNS) implantation for femoropopliteal lesions. This study aimed to establish whether cilostazol is effective in improving the patency of DESs and determine whether BNS or DESs with or without cilostazol are more effective in improving the 12-month patency after EVT for FP lesions., Materials and Methods: In this prospective, open-label, multicenter study, 85 patients with symptomatic peripheral artery disease due to de novo FP lesions were enrolled and treated with DESs with cilostazol from eight cardiovascular centers between April 2018 and May 2019. They were compared with 255 patients from the DEBATE SFA study, in which patients were randomly assigned to the BNS, BNS with cilostazol, or DES groups. The primary endpoint was the 12-month patency rate using duplex ultrasound (peak systolic velocity ratio < 2.5). This study was approved by the ethics committee of each hospital., Results: The 12-month patency rates for the BNS, BNS with cilostazol, DES, and DES with cilostazol groups were 77.6%, 93.1%, 82.8%, and 94.2%, respectively (p = 0.007). The 12-month patency rate was higher in the DES with cilostazol group than in the DES group (p = 0.044). In small vessels, the DES with cilostazol group had a higher patency rate than the DES group (100.0% vs. 83.4%, p = 0.023)., Conclusions: DES with cilostazol showed better patency than DES alone. Cilostazol improved patency after EVT with DES in FP lesions and small vessels., Clinical Trial Registration: University Hospital Medical Information Network Clinical Trials Registry (no. UMIN 000032473)., Competing Interests: The authors have declared that no competing interests exist.

Purpose: The purpose of the J-SUPREME (J-S) and J-SUPREME II (J-SII) trials was to evaluate the performance of the Jetstream Atherectomy System for the treatment of Japanese patients with symptomatic occlusive atherosclerotic lesions in the superficial femoral and popliteal arteries., Materials and Methods: The J-S and J-SII trials were both prospective, multicenter, single-arm clinical trials. Patients in J-S underwent Jetstream atherectomy followed by percutaneous transluminal angioplasty (PTA), whereas those in J-SII had adjunctive drug-coated balloon (DCB) treatment following atherectomy. Patients were adults with Rutherford category 2, 3, or 4 and had stenotic, restenotic, or occlusive lesion(s) with a degree of stenosis ≥70 in the superficial femoral artery and/or proximal popliteal artery. In J-S, lesions were required to be calcified, and in J-SII lesions were required to be severely calcified., Results: A total of 50 patients were enrolled in J-S (mean age 72.3±8.7 years, lesion length 82.0±41.5 mm, 36% calcification PACSS Grade 3, 22% Grade 4) and 31 patients in J-SII (mean age 72.5±7.7 years, lesion length 122.6±55.6 mm, 19.4% calcification PACSS Grade 3, 77.4% Grade 4). No bailout stenting or bypass conversions were required. No major adverse events (MAEs) were reported for either trial through 1 month. The 6-month primary patency for J-S, with PTA alone following atherectomy, was 40.4% (19/47). The 6-month primary patency for J-SII, with DCB treatment following atherectomy, was 96.7% (29/30). At 6-month post-procedure, 79.2% (38/48) of patients in J-S, and 100% (30/30) of patients in J-SII had improved by at least 1 Rutherford category., Conclusion: J-SUPREME trial results demonstrate procedural safety and efficacy of the Jetstream Atherectomy System and J-SII showed sustained patency through 6 months following combination treatment with Jetstream atherectomy and DCB.

mRNA-based vaccines have been used globally to eradicate the coronavirus-disease 2019 (COVID-19) pandemic. Vaccine efficacy and adverse reactions depend on immune responses, such as proinflammatory cytokine production and lymphocyte activation. We conducted a prospective cohort study to investigate relationships among specific antibody titers, adverse reactions, proinflammatory cytokine production, and immune-regulatory microRNA (miRNA) levels in serum extracellular vesicles (EVs) after COVID-19 vaccination (BNT162b2). Local adverse reactions after the second dose, such as local pain and swelling, were less correlated with those of systemic symptoms, such as fever and muscle pain, whereas serum TNF-α levels were associated with systemic adverse reactions and with specific antibody titers. Interestingly, EV miR-92a-2-5p levels in sera were negatively correlated with degrees of adverse reactions, and EV miR-148a levels were associated with specific antibody titers. Our data suggest a potential of circulating EV miRNAs as biomarkers for vaccine efficacy and adverse reactions., (© 2022. The Author(s).)

TICAM-1 (also called TRIF) is the sole adaptor of TLR3 that recognizes double-stranded RNA. Here, we report that TICAM-1 is involved not only in TLR3 signaling but also in the cytokine receptor IL-17RA signaling. We found that TICAM-1 bound to IL-17R adaptor Act1 to inhibit the interaction between IL-17RA and Act1. Interestingly, TICAM-1 knockout promoted IL-17RA/Act1 interaction and increased IL-17A-mediated activation of NF-κB and MAP kinases, leading to enhanced expression of inflammatory cytokines and chemokines upon IL-17A stimulation. Moreover, Ticam-1 knockout augmented IL-17A-mediated CXCL1 and CXCL2 expression in vivo, resulting in accumulation of myeloid cells. Furthermore, Ticam-1 knockout enhanced delayed type hypersensitivity and exacerbated experimental autoimmune encephalomyelitis. Ticam-1 knockout promoted accumulation of myeloid and lymphoid cells in the spinal cord of EAE-induced mice. Collectively, these data indicate that TICAM-1 inhibits the interaction between IL-17RA and Act1 and functions as a negative regulator in IL-17A-mediated inflammatory responses., (© 2021 Miyashita et al.)

Purpose: To report the 3-year results of Innova™ stent implantation for the treatment of femoropopliteal (FP) lesions in a real-world setting., Methods: This single-arm, retrospective, multicenter clinical study analyzed 481 lesions from 453 consecutive patients with symptomatic peripheral artery diseases (Rutherford category 1-6) who underwent endovascular therapy with implantation of Innova™ self-expanding nitinol stent for FP lesions. The primary outcome measure was the 3-year restenosis rate based on doppler-ultrasound or angiographic criteria. The secondary outcome measures included the rates of 3-year major amputation and major adverse limb events., Results: Restenosis following Innova™ implantation was found in 61% of the cases at 3 years. At the end of 3 years, the rates of major amputations and major adverse limb events were 3 and 31%, respectively. In cases free from restenosis at 1 year, no predictive factors for restenosis at 3 years could be determined., Conclusion: The present study demonstrated mid-term clinical outcomes after Innova™ stent implantation for the treatment of FP lesions in a real-world population. The Innova™ stent demonstrated acceptable clinical outcomes in a real-world setting., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Chronic kidney disease is a prognostic factor for cardiovascular disease. Worsening renal function (WRF), specifically, is an important predictor of mortality in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention (PCI). We evaluate the prognostic impact of mid-term WRF after PCI on future cardiovascular events. We examined the renal function data of 1086 patients in the first year after PCI using the SHINANO 5-year registry. Patients were divided into two groups, mid-term WRF and non-mid-term WRF, and primary outcomes were major adverse cardiovascular events (MACE) and death. Mid-term WRF was defined as an increase in creatinine (≥ 0.3 mg/dL) in the first year after PCI. Mid-term WRF was found in 101 patients (9.3%), and compared to non-mid-term WRF, it significantly increased the incidence of MACE (p < 0.001), and all-cause death (p < 0.001), myocardial infarction (p = 0.001). Furthermore, mid-term WRF patients had higher incidence of future heart failure (p < 0.001) and new-onset atrial fibrillation (p = 0.01). Patients with both mid-term WRF and chronic kidney disease had increased MACE compared to patients with either condition alone (p < 0.001). Similarly, patients with mid-term WRF and acute kidney injury had increased MACE compared to patients with either condition alone (p < 0.001). Multivariate Cox regression analysis revealed mid-term WRF as a strong predictor of MACE (hazard ratio: 2.50, 95% confidence interval 1.57-3.98, p < 0.001). Mid-term WRF after PCI negatively affects MACE, as well as future admission due to heart failure and new-onset atrial fibrillation, chronic kidney disease, and acute kidney injury., (© 2021. The Author(s).)

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., (Copyright © 2020 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

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.

Extracellular vesicles (EVs) contain microRNAs (miRNAs) that regulate the innate immune responses, such as the production of pro-inflammatory cytokines. The excessive production of pro-inflammatory cytokines after vaccination can cause local adverse reactions, such as pain, itching, swelling, and redness. Previous studies have shown that circulating EV miR-451a regulates innate immune responses, and miR-451a levels in serum EVs are negatively correlated with the pro-inflammatory cytokine expression levels in response to the influenza vaccine. Since excessive pro-inflammatory cytokine production is a cause of the local adverse reactions to vaccination, we investigated whether miR-451a levels in serum EVs correlate with local symptoms at the vaccination site, such as pain, itching, swelling, and redness. Interestingly, miR-451a levels in serum EVs were inversely correlated with the number of symptoms after vaccination. We determined the level of several other immune-regulatory miRNAs in serum EVs. Using the immune-regulatory miRNA levels of miR-22, miR-29a, miR-451a, and miR-107, we calculated a normalized miRNA level for each healthy donor and found that the normalized miRNA levels were significantly correlated with the number of local symptoms after vaccination. Our data indicated that immune-regulatory miRNA levels in serum EVs can be used as biomarkers to assess local symptoms after influenza vaccination., Competing Interests: The authors have declared that no competing interests exist.

Despite their outstanding antitumour activity in mice, the limited supply from the natural sources has prevented drug discovery/development based on intact halichondrins. We achieved a total synthesis of C52-halichondrin-B amine (E7130) on a >10 g scale with >99.8% purity under GMP conditions. Interestingly, E7130 not only is a novel microtubule dynamics inhibitor but can also increase intratumoural CD31-positive endothelial cells and reduce α-SMA-positive cancer-associated fibroblasts at pharmacologically relevant compound concentrations. According to these unique effects, E7130 significantly augment the effect of antitumour treatments in mouse models and is currently in a clinical trial. Overall, our work demonstrates that a total synthesis can address the issue of limited material supply in drug discovery/development even for the cases of complex natural products.

Background: New-generation bare-metal nitinol (BNS) and drug-eluting stents have improved long-term outcomes in patients undergoing endovascular therapy for femoropopliteal lesions. Furthermore, cilostazol reduces in-stent restenosis (ISR) after first-generation BNS implantation for femoropopliteal lesions., Methods and Results: We studied 255 patients with femoropopliteal lesions treated at 25 cardiovascular centers. Patients were randomly assigned to the BNS group (Misago stent implantation without cilostazol), BNS with cilostazol group (Misago stent implantation with cilostazol), or drug-eluting stents group (Zilver PTX stent implantation without cilostazol). Primary end point was 1-year restenosis noted using duplex ultrasound (peak systolic velocity ratio, >2.0). Secondary end point was major adverse limb events (limb-related death, target lesion revascularization, major amputation, and major bleeding). During the 1-year follow-up, 12 patients (4.7%) died and 237 (92.9%) had relevant ultrasound findings. The 1-year ISR rate did not differ significantly among the BNS, BNS with cilostazol, and drug-eluting stents groups (28.4% versus 12.2% versus 21.0%; P=0.052). Although the 1-year ISR rate was significantly lower in the BNS with cilostazol group than in the BNS group, it was similar to that in the drug-eluting stents group ( P=0.16). Major adverse limb event was significantly higher in the BNS group (16.9% versus 6.5% versus 6.3%; P=0.034); however, target lesion revascularization and major bleeding were similar (9.7% versus 5.1% versus 3.6%; P=0.25, 4.8% versus 1.2% versus 2.4%; P=0.37, respectively)., Conclusions: Misago stent implantation with cilostazol showed a comparable 1-year ISR rate with Zilver PTX. Cilostazol reduced the 1-year ISR rate after endovascular therapy when used with new-generation BNS., Clinical Trial Registration: URL: http://www.umin.ac.jp/ctr/ . Unique identifier: UMIN 000010071.

Objectives: We sought to assess whether balloon angioplasty (BA) alone for small femoropopliteal disease improved the outcome following endovascular therapy as compared with stent implantation., Background: The optimal strategy of endovascular therapy for small vessel arteries in femoropopliteal disease remains unclear., Methods: We performed a multicenter retrospective analysis of 337 consecutive patients (371 limbs) with femoropopliteal arteries 4.0 mm or less in diameter and 150 mm or less in length., Results: Cumulative 3-year incidence of primary patency was significantly higher in the BA group than in the stent group (53.8% vs. 34.2%, P = 0.002). While assisted-primary patency and freedom from any major adverse limb events were also significantly higher in the BA group than in the stent group (70.9% vs. 44.2%, P < 0.001 and 60.6% vs. 36.4%, P = 0.001, respectively), secondary patency did not significantly differ between the two groups (86.9% vs. 86.9%, P = 0.67). Predictors of restenosis were diabetes mellitus (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.14-2.31; P = 0.01), no administration of cilostazol (HR, 1.50; 95% CI, 1.07-2.13; P = 0.02), stent implantation (HR, 1.68; 95% CI, 1.15-2.41; P = 0.01), and lesion length >75.0 mm(HR, 2.09; 95% CI, 1.50-2.92; P < 0.001)., Conclusions: Lesions in small (<4.0 mm diameter) FP vessels demonstrated better primary patency at 3 years when successfully treated with balloon angioplasty alone as opposed to routine or bailout stenting. This difference was especially pronounced for lesions 75 to 150 mm in length., (© 2017 Wiley Periodicals, Inc.)

Background: Optimal medical therapy after endovascular therapy in patients with critical limb ischemia (CLI) remains unclear. Therefore, we investigated whether cilostazol reduce restenosis after balloon angioplasty for infrapopliteal lesions in CLI patients., Methods: This study was performed as a multicenter, prospective, randomized, open-label, blinded-end point study with independent angiographic core laboratory adjudication. Sixty patients were eligible and 53 patients were enrolled and allocated. The primary end point was 3-month angiographic restenosis. The main secondary end points included major adverse limb event (MALE defined as requirement of any reintervention or major amputation), perioperative complications, major amputation, all-cause death, and hemorrhagic events., Results: A total of 53 patients were randomized and all received their allocated intervention. Two patients in the cilostazol plus aspirin group and 1 in the aspirin group did not undergo any angioplasty for infrapopliteal stenotic lesions, and therefore were excluded from analysis. Finally, 38 vessels in 25 patients in the cilostazol plus aspirin group and as many cases in the aspirin group were included in the analysis. There were no significant differences in baseline characteristics between the 2 groups. The 3-month restenosis rate was 82% in the cilostazol + aspirin group and 81% in the aspirin group, with no significant difference (P = 0.91). The MALE rate was 11% in the cilostazol plus aspirin group and 8% in the aspirin group (P = 0.73). In addition, no significant difference was observed in any secondary points., Conclusions: Cilostazol did not reduce 3-month angiographic restenosis after balloon angioplasty for below-the-knee lesion in CLI patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Concomitant coronary and peripheral artery disease is associated with higher periprocedural and long-term percutaneous coronary intervention (PCI) complication rates. We evaluated in-hospital and 1-year clinical outcomes of patients with low or borderline ankle-brachial indexes (ABIs) undergoing PCIs in the drug-eluting stent era. We divided 1370 SHINANO registry patients into 3 groups-low (ABI ≤ 0.9), borderline (0.9 < ABI ≤ 1.0), and normal (1.0 ≤ ABI < 1.4). During the 1-year follow-up, more PCI-related complications occurred in the low and borderline ABI groups than in the normal ABI group (7.7% vs 8.8% vs 4.0%, respectively). Low ABI patients were more likely to experience adverse clinical events (6.3% vs 3.6% vs 3.0%, respectively; log-rank P = .020 for low vs normal ABI), with a hazard ratio of 2.27 (95% confidence interval, 1.12-4.61; P = .023), compared with patients with normal ABIs. Patients with abnormal ABIs had a significantly higher incidence of PCI-related complications and a less favorable 1-year prognosis. Routine ABI measurement before PCI may help predict PCI-related complication incidence and 1-year prognosis.

Background: We evaluated the 1-year outcomes of percutaneous coronary intervention (PCI) for elderly patients (aged ≥ 80 years) in the second-generation drug-eluting stent (DES) era., Methods and Results: Between August 2012 and July 2013, 1923 consecutive patients (mean age, 71 ± 11 years; ≥80 years, 23%; men, 77%) who underwent 2250 elective/urgent PCI procedures were enrolled in the Shinshu Prospective Multicenter Analysis for Elderly Patients with Coronary Artery Disease Undergoing Percutaneous Coronary Intervention registry. The primary end point was major adverse cardiovascular events (MACEs; cardiovascular death, myocardial infarction, and stroke) at 1 year. The 1-year incidence of MACEs, cardiac death, and stroke was significantly higher in elderly patients than in nonelderly patients (12.4% vs 5.3%, P < .0001; 7.8% vs 2.2%, P < .0001; and 2.8% vs 1.3%, P = .033, respectively). However, no significant difference in elective PCI procedures was detected. In elderly patients, the incidence of cardiac death and target lesion revascularization was significantly lower for DES than for non-DES (2.7% vs 10.5%, P = .0001 and 4.1% vs 8.6%, P = .029, respectively)., Conclusion: Although elderly patients had a significantly poorer prognosis than younger patients, the adverse events rate was comparable in those patients who underwent elective PCI in the second-generation DES era.

We evaluated the impact of endovascular therapy (EVT) on inflammatory cytokine levels and its relationship with in-stent restenosis in patients with peripheral artery disease. The study prospectively enrolled 35 patients with intermittent claudication who underwent EVT of the iliofemoral artery. Levels of interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor α (TNF-α) were measured using enzyme-linked immunosorbent assay before and at 2 hours, 4 hours, and 3 months after EVT. All cytokine levels increased significantly after EVT (IL-6 [pg/mL]: from 1.51 [0.84-1.93] before EVT to 6.97 [4.05-20.41] at 2 hours and 13.29 [4.57-31.88] at 4 hours; MCP-1 [pg/mL]: from 326.65 [265.60-406.55] before EVT to 411.18 [341.21-566.27] at 2 hours and 519.36 [383.58-644.85] at 4 hours; TNF-α [pg/mL]: from 1.08 [0.77-1.29] before EVT to 1.25 [0.94-1.81] at 2 hours and 1.27 [0.95-1.59] at 4 hours, all P < .001). However, cytokine levels did not differ significantly between lesions with and without in-stent restenosis. Overall, our results suggest that EVT significantly increases IL-6, MCP-1, and TNF-α levels in the ischemic leg, but this effect is not associated with a higher rate of in-stent restenosis.

Little is known about the mid-term outcomes of patients with atrial fibrillation (AF) who undergo coronary stenting in the second-generation drug-eluting stent (DES) era. We evaluated the 1-year outcomes of AF patients undergoing percutaneous coronary intervention (PCI) with second-generation DES. This retrospective cohort analysis used integrated data from the SHINANO registry, a prospective observational multicenter cohort study, which enrolled 1923 consecutive patients undergoing PCI for any coronary artery disease. We retrospectively recruited 917 of these patients (mean age, 71.3 ± 10.0 years; male, 77 %) who received PCI with 2nd generation DES. The primary endpoint was net adverse clinical events (NACE: cardiac death, stroke, MI, stent thrombosis, and major bleeding) at 1 year. The secondary endpoints were major adverse cardiovascular events (MACE: cardiac death, stroke, and MI), stroke, MI, and major bleeding at 1 year. One-year follow-up was completed in 871 (94.9 %) patients, of whom 85 had AF. The incidence of NACE (15.4 vs. 7.3 %, P = 0.008), MACE (10.6 vs. 5.4 %, P = 0.047), and major bleeding (6.0 vs. 2.3 %, P = 0.049) were all significantly higher in AF compared to non-AF patients. On multivariate analysis, AF was an independent predictor of NACE (HR 2.32, 95 % CI 1.24-4.34, P = 0.008). In the second-generation DES era, patients with AF undergoing PCI still have a poorer prognosis, with more thrombotic and bleeding events, than those without AF. More attention should be paid to the thrombotic and bleeding risk in AF patients undergoing PCI.

Although coronary artery disease (CAD) is common in patients with heart failure (HF), little is known about the prognostic significance of coronary lesion complexity in patients with prior HF undergoing percutaneous coronary intervention (PCI). The aim of this study was to investigate whether the coronary Synergy between Percutaneous Coronary Intervention with TAXus and Cardiac Surgery (SYNTAX) score could improve risk stratification in HF patients with CAD. Two hundred patients (mean age 73 ± 11 years, left ventricular ejection fraction 49 ± 15 %) with prior HF who underwent PCI were divided into two groups stratified by SYNTAX score (median value 12) and tracked prospectively for 1 year. The study endpoint was the composite of major adverse cardiovascular events (MACE), including all-cause death, myocardial infarction, stroke, and hospitalization for worsening HF. Adverse events were observed in 39 patients (19.5 %). Patients with high SYNTAX scores (n = 100) showed worse prognoses than those with low scores (n = 100) (26.0 vs. 13.0 %, respectively, P = 0.021). In multivariate Cox-regression analysis, SYNTAX score ≥12 was significantly associated with MACE (hazard ratio: 1.99, 95 % confidence interval: 1.02-3.97; P = 0.045). In patients with prior HF and CAD, high SYNTAX scores predicted a high incidence of MACE. These results suggest that the SYNTAX score might be a useful parameter for improving risk stratification in these patients.

The admission shock index (SI) enables prediction of short-term prognosis. This study investigated the prognostic implications of admission SI for predicting long-term prognoses for acute myocardial infarction (AMI). The participants were 680 patients with AMI who received percutaneous coronary intervention. Shock index is the ratio of heart rate and systolic blood pressure. Patients were classified as admission SI <0.66 (normal) and ≥0.66 (elevated; 75th percentile). The end point was 5-year major adverse cardiac events (MACEs). Elevated admission SI was seen in 176 patients. Peak creatine kinase levels were significantly higher and left ventricular ejection fraction was lower in the elevated SI group, which had a worse MACEs. In multivariate Cox regression analysis, SI ≥0.66 was a risk factor for MACE. Elevated admission SI was associated with poorer long-term prognosis.

Background: Prior reports have revealed that complete revascularization (CR) by percutaneous coronary intervention (PCI) decreased ischemic events. However, little is known about the efficacy of CR using PCI in elderly patients with multi-vessel coronary artery disease (CAD). We evaluated the 1-year effectiveness of CR-PCI in elderly patients (≥75years old) with multi-vessel CAD., Methods: The SHINANO Registry, a prospective, observational, multi-center, all-comer cohort study, has enrolled 1923 patients. From this registry, we recruited 322 elderly patients with multi-vessel CAD. The primary endpoint was major adverse cardiovascular events ([MACE]: all-cause mortality, myocardial infarction, and stroke)., Results: Of the 322 elderly patients with multi-vessel CAD, 165 (51.2%) received CR and 157 (48.8%) received incomplete revascularization (ICR). MACE occurred in 44 (13.7%) patients. The incidence of MACE by survival analysis was significantly lower in the CR group than in the ICR group (7.4% vs. 21.1%, p<0.001). On multivariable Cox proportional hazards analysis of age, sex, and acute coronary syndrome (ACS), ACS and CR were independent predictors of MACE (hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.29-4.80; p=0.007, HR, 0.40; 95% CI, 0.20-0.77; p=0.007, respectively). In propensity score matching of age, sex, previous heart failure, previous intracranial bleeding, ACS, and body mass index, the MACE rate was significantly lower in the CR group than in the ICR group (7.2% vs. 18.4%, p=0.015)., Conclusions: Even in elderly patients over 75years old with multi-vessel CAD, CR-PCI appears to suppress mid-term ischemic events., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

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., (© The Author(s) 2016.)

Objective: Nitinol stenting could bring the better outcome in endovascular therapy for femoropopliteal disease. However, it might be expected that recent marked advances in both device technology and operator technique had led to improved efficacy of balloon angioplasty even in this segment. The aims of this study were to evaluate the clinical impact of balloon angioplasty for femoropopliteal disease and make risk stratification clear by propensity score matching analysis., Methods: Based on the multicenter retrospective data, 2758 patients (balloon angioplasty: 729 patients and nitinol stenting: 2029 patients), those who underwent endovascular therapy for femoropopliteal disease, were analyzed., Results: The propensity score matching procedure extracted a total of 572 cases per group, and the primary patency rate of balloon angioplasty and nitinol stenting groups after matching was significantly the same (77.2% vs 82.7% at 1 year; 62.2% vs 64.3% at 3 years; 47.8% vs 54.3% at 5 years). In multivariate Cox hazard regression analysis, significant predictors for primary patency were diabetes mellitus, regular dialysis, cilostazol use, chronic total occlusion, and intra-vascular ultra-sonography use. The strategy of balloon angioplasty was not evaluated as a significant predictor for the primary patency. After risk stratification using five items (diabetes mellitus, regular dialysis, no use of intra-vascular ultra-sonography, chronic total occlusion, and no use of cilostazol: the DDICC score), the estimated primary patency rates of each group (low, DDICC score 0-2; moderate, DDICC score 3; high risk, DDICC score 4-5) were 88.6%, 78.3%, and 63.5% at 1 year; 75.2%, 60.7%, and 39.8% at 3 years; and 66.0%, 47.1%, and 26.3% at 5 years (p < 0.0001). The primary patency rate of balloon angioplasty and nitinol stenting groups was significantly the same in each risk stratification., Conclusion: This study suggests that balloon angioplasty does not have inferiority to nitinol stenting but does have favorable efficacy in femoropopliteal segment by careful risk stratification with the recent advance of technique.

The use of beta-blockers therapy has been recommended to reduce mortality in patients with left ventricular dysfunction after acute myocardial infarction (AMI). Primary percutaneous coronary intervention (PCI), which has become the mainstay of treatment for AMI, is associated with a lower mortality than fibrinolysis. The benefits of beta-blockers after primary PCI in AMI patients without pump failure are unclear. We hypothesized that oral beta-blocker therapy after primary PCI might reduce the mortality in AMI patients without pump failure. The assessment of lipophilic vs. hydrophilic statin therapy in acute myocardial infarction (ALPS-AMI) study was a multi-center study that enrolled 508 AMI patients to compare the efficacy of hydrophilic and lipophilic statins in secondary prevention after myocardial infarction. We prospectively tracked cardiovascular events for 3 years in 444 ALPS-AMI patients (median age 66 years; 18.2 % women) who had Killip class 1 on admission and were discharged alive. The primary endpoint was all-cause mortality. The 3-year follow-up was completed in 413 patients (93.0 %). During this follow-up, 21 patients (4.7 %) died. In Kaplan-Meier analysis, patients on beta-blockers had a significantly lower incidence of all-cause mortality (2.7 vs. 7.3 %, log-rank p = 0.025). After adjusting for the calculated propensity score for using beta-blockers, their use remained an independent predictor of all-cause mortality (hazard ratio 0.309; 95 % confidence interval 0.116-0.824; p = 0.019). In the statin era, the use of beta-blocker therapy after primary PCI is associated with lower mortality in AMI patients with Killip class 1 on admission.

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., (© The Author(s) 2015.)

The Synergy Between PCI With TAXUS and Cardiac Surgery (SYNTAX) score is effective in predicting clinical outcome after percutaneous coronary intervention (PCI). However, its prediction ability is low because it reflects only the coronary characterization. We assessed the predictive value of combining the ankle-brachial index (ABI) and SYNTAX score to predict clinical outcomes after PCI. The ABI-SYNTAX score was calculated for 1,197 patients recruited from the Shinshu Prospective Multi-center Analysis for Elderly Patients with Coronary Artery Disease Undergoing Percutaneous Coronary Intervention (SHINANO) registry, a prospective, observational, multicenter cohort study in Japan. The primary end points were major adverse cardiovascular and cerebrovascular events (MACE; all-cause death, myocardial infarction, and stroke) in the first year after PCI. The ABI-SYNTAX score was calculated by categorizing and summing up the ABI and SYNTAX scores. ABI ≤ 0.49 was defined as 4, 0.5 to 0.69 as 3, 0.7 to 0.89 as 2, 0.9 to 1.09 as 1, and 1.1 to 1.5 as 0; an SYNTAX score ≤ 22 was defined as 0, 23 to 32 as 1, and ≥ 33 as 2. Patients were divided into low (0), moderate (1 to 2), and high (3 to 6) groups. The MACE rate was significantly higher in the high ABI-SYNTAX score group than in the lower 2 groups (low: 4.6% vs moderate: 7.0% vs high: 13.9%, p = 0.002). Multivariate regression analysis found that ABI-SYNTAX score independently predicted MACE (hazards ratio 1.25, 95% confidence interval 1.02 to 1.52, p = 0.029). The respective C-statistic for the ABI-SYNTAX and SYNTAX score for 1-year MACE was 0.60 and 0.55, respectively. In conclusion, combining the ABI and SYNTAX scores improved the prediction of 1-year adverse ischemic events compared with the SYNTAX score alone., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Inflammatory biomarkers have been proposed for use in the risk stratification of patients with acute myocardial infarction (AMI). We examined the value of inflammatory biomarkers over clinical features for predicting cardiovascular (CV) events in stable outpatients with MI. We enrolled 430 post-MI patients and measured their levels of high-sensitivity C reactive protein (hs-CRP), growth differentiation factor-15 (GDF-15), and the interleukin-1 receptor family member called ST2 (ST2), one month after AMI. Patients were prospectively followed for 3 years. In our study cohort (mean age, 66 ± 12 years; left ventricular ejection fraction, 55 ± 13%), CV events were observed in 39 patients (9.1%). Kaplan- Meier analysis revealed that patients with high levels of GDF-15 (≥ 1221.0 ng/L) showed poorer prognoses than those with low levels of GDF-15 (< 1221.0 ng/L) (20.4% versus 3.6%, P < 0.001); hs-CRP and ST2 did not show a similar correlation with prognoses. GDF-15 remained associated with CV events after adjusting for age, chronic kidney disease, and B-type natriuretic peptide (hazard ratio, 1.001; 95% confidence interval, 1.000 - 1.001; P = 0.046). GDF-15 provided an incremental predictive value for CV events over clinical features (incremental value in global χ(2) = 43.81, P < 0.001). In outpatients with prior MI, GDF-15 was an independent indicator of CV events, unlike hs-CRP and ST2. GDF15 provided an incremental prognostic value over clinical features.

Background: Chronic kidney disease (CKD) is an evolving paradigm for the risk assessment of cardiovascular diseases. We hypothesized that an advanced stage of CKD may predict the presence of peripheral arterial disease (PAD)., Methods: Screening for PAD by an ankle-brachial pressure index (ABI) ≤0.9 was conducted in a consecutive series of 583 subjects (mean age 68.1±12.9 years, 411 men). Levels of estimated glomerular filtration rate (eGFR) and factors associated with the presence of PAD were examined., Results: Sixty patients (10.3%) had PAD and 192 patients (32.9%) had eGFR <60mL/min/1.73m(2) among all subjects. In patients with an advanced stage of CKD (stage ≥3, equivalent to eGFR <60mL/min/1.73m(2)), high prevalence of PAD (17.2%) and lower ABI levels (1.04±0.18) were observed. Univariate analyses revealed that PAD was associated with an advanced stage of CKD [odds ratio (OR) 1.850, 95% confidence interval (CI) 1.322-2.588, p<0.001], as well as age, male gender, systolic blood pressure, and hemoglobin A1c. Multivariate logistic regression analyses revealed that PAD was independently predicted by the CKD stages (OR 1.498, 95% CI 1.011-2.220, p=0.044, adjusted for covariates)., Conclusions: An advanced stage of CKD is independently and significantly associated with the presence of PAD. Targeted screening with ABI measurement can be beneficial in patients with CKD., (Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Although skin perfusion pressure (SPP) is widely used clinically to predict probability of wound healing, correlation between clinical outcomes and SPP has not been systematically studied., Methods: This subanalysis of the prospective multicenter OLIVE registry of patients who received infrainguinal endovascular therapy (EVT) for critical limb ischemia (CLI) assessed the association between clinical outcomes and postoperative SPP in 211 consecutive patients. Logistic regression analysis was performed, with amputation-free survival (AFS), modified major adverse limb events (MALEs), and complete wound healing as dependent variables and postprocedural SPP as independent variable., Result: Pre- and postprocedural SPP was 28 ± 11 and 46 ± 18 mm Hg, respectively. In logistic regression analysis, postprocedural SPP correlated with 1-year AFS (P = .018), modified MALEs (P < .001), and wound healing (P = .022)., Conclusion: Postprocedural SPP correlates with clinical outcomes after EVT for patients with CLI., (© The Author(s) 2015.)

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 < 0.001), and Rutherford 6 (HR: 1.64, p = 0.047) were identified as predictors of 3-year major amputation or death. Statin use (HR: 0.28, p = 0.02), Rutherford 6 (HR: 2.40, p = 0.02), straight-line flow to the foot (HR: 0.27, p = 0.001), and heart failure (HR: 1.96, p = 0.04) were identified as 3-year MALE predictors. Finally, CLI due to isolated below-the-knee lesion was a wound recurrence predictor (HR: 4.28, p ≤ 0.001). Three-year survival, freedom from major amputation, and reintervention rates were 63.0%, 87.9%, and 43.2%., 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)., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: Little is known about the relationship between body composition indicators, including body mass index (BMI), fat mass index (FMI) and lean BMI (LBMI), and adverse outcomes after percutaneous coronary intervention (PCI) in Asian populations. The aim of this study was to clarify this relationship., Methods: The SHINANO registry is a prospective, observational, multicenter cohort registry that enrolled 1923 consecutive patients with coronary heart disease (CHD) from August 2012 to July 2013; 66 patients were excluded because of missing data. We evaluated 1857 patients with CHD who underwent PCI (aged 70±11 years; 23% women; BMI 23.8±3.5 kg/m 2 ; LBMI 18.3±1.8 kg/m 2 ; FMI 5.4±2.2 kg/m 2 ). Patients were divided into three groups, based on BMI, LBMI and FMI tertiles, to assess the prognostic value of the three indicators. The primary endpoint was major adverse cardiac events (MACE), including all cause death, non-fatal myocardial infarction and ischaemic stroke at 1 year., Results: Over a 1 year follow-up period (1776 patients, 95.6%), the cumulative MACE incidence was 8.7% (161 cases). Using Kaplan-Meier analysis, the MACE incidence was significantly higher in patients with lower BMI values (13.4-22.2 kg/m 2 ) (p=0.002) and lower LBMI values (11.6-17.6 kg/m 2 ) (p<0.001); this trend was not observed for FMI. Multivariate Cox regression analysis showed that lower LBMI but not lower BMI values were predictive of a higher MACE incidence (HR 1.55; 95% CI 1.05 to 2.30)., Conclusions: Lower LBMI values are associated with adverse outcomes in an Asian population with CHD undergoing PCI. LBMI is a better predictor of MACE than BMI or FMI., Clinical Trial Registration: UMIN-ID; 000010070.

Background: Little is known concerning the effect of ezetimibe for secondary prevention in post-myocardial infarction (MI) patients. In this study, we investigated the secondary prevention effect of ezetimibe for post-MI patients., Methods: This study is a retrospective analysis of Assessing Lipophilic vs. hydrophilic Statin therapy for Acute MI (ALPS-AMI study). The patients were divided into two groups: those administered a statin to control low density lipoprotein-cholesterol (LDL-C), the ezetimibe(-) group, and those administered ezetimibe in addition to a statin to control LDL-C, the ezetimibe(+) group. The endpoints were Major Adverse Cardiac and Cerebrovascular Event (MACCE), including all-cause death, recurrence of MI, stroke, and heart failure requiring hospitalization, and MACCE with revascularization., Results: The ezetimibe(+) and ezetimibe(-) groups contained 113 and 337 patients, respectively. Incidences of MACCE and MACCE with revascularization were lower in the ezetimibe(+) group than in the ezetimibe(-) group (2.6% vs. 11.5%, p = 0.002; 23.0% vs. 36.7%, p = 0.014, respectively). Moreover, logistic regression analysis revealed ezetimibe(+) was a significant negative predictor of MACCE (OR 0.208, 95% CI 0.048 to 0.903, p = 0.047) and MACCE with revascularization (OR 0.463, 95% CI 0.258 to 0.831, p = 0.008). The preventive effect of ezetimibe against MACCE was observed in both moderate- and high-intensity lipid lowering treatment groups (0% vs. 17%; p = 0.077, 3.1% vs. 9.4%; p = 0.033)., Conclusions: In lipid-lowering therapy post-MI, ezetimibe and statin combination therapy improved MACCE with or without revascularization compared with statin monotherapy. These findings suggest that post-MI secondary prevention should be more intensive.

Objective: Patients categorized Rutherford category IV might have different characteristics compared with Rutherford category V and VI. Our study aims were to estimate the clinical differences between Rutherford category IV and Rutherford category V and VI, for those underwent endovascular therapy for isolated infrapopliteal disease, and also to find risk factors for endovascular therapy in Rutherford category IV., Methods: Based on the Japanese multi-center registry data, 1091 patients with 1332 limbs (Rutherford category IV: 226 patients with 315 limbs, Rutherford category V and VI: 865 patients with 1017 limbs) were analyzed retrospectively., Results: Patients' backgrounds and lesions' characteristics had significant differences. Both freedom rate from major adverse limb event with perioperative death and amputation-free survival rate at 1 year were better in Rutherford category IV than Rutherford category V and VI (93.6% vs 78.3%, 87.7% vs 66.7%) and those maintained to 3 years (p < 0.0001). Significant predictors for major adverse limb event/perioperative death were small body mass index (<18.5 kg/m(3)) and initial endovascular therapy success, and those for amputation-free survival were small body mass index (<18.5 kg/m(3)), non-ambulatory status, high systematic inflammatory reaction (C-reactive protein > 3.0 mg/dL), chronic obstructive pulmonary disease, and coronary artery disease in Rutherford category IV., Conclusion: From the present results, Rutherford category IV should be recognized to have quite different backgrounds and better outcome from Rutherford category V and VI.

Background: The optimal period to achieve target percent reduction of low-density lipoprotein cholesterol (LDL-C) level for secondary prevention of acute myocardial infarction (AMI) is not well established., Methods: The Assessment of Lipophilic vs. Hydrophilic Statin Therapy in AMI (ALPS-AMI) study enrolled 508 patients (mean age, 66.0± 11.6 years; 80.6% male) who were hospitalized for AMI and underwent percutaneous coronary intervention (PCI). Of these patients, 81 were excluded because of the absence of LDL-C measurements at 4 weeks after randomization. In the remaining 427 patients, the target LDL-C level reduction of ≥30% was achieved and not reached within 4 weeks after randomization in 204 cases (early reduction group) and 223 cases (late reduction group). The groups were formed prospectively and analyzed with regard to the composite end point (major adverse cardiovascular event [MACE]: all-cause death, myocardial infarction, and stroke) and clinical outcomes., Results: MACE were significantly more frequent in the late reduction group compared to the early reduction group (9.4% vs. 3.4%, P = 0.013). The incidence of cardiac deaths was also significantly higher in the late reduction group (3.1% vs. 0.5%, P = 0.044). On age-adjusted Cox proportional hazards analysis in statin-naïve patients, percent reduction of LDL-C level during the initial 4 weeks (HR, 0.98; 95% CI: 0.97-0.99, P = 0.042) and baseline LDL-C level (HR, 0.98; 95% CI: 0.97-0.99, P = 0.033) predicted adverse events., Conclusions: Rapid reduction of LDL-C level is strongly associated with favorable outcome in patients with AMI.

We sought to determine whether serial measurements of oxidative stress levels could serve as a predictive marker for cardiovascular (CV) events in patients with ST-segment elevation myocardial infarction (STEMI). Biological antioxidant potential (BAP) levels were measured at admission and at 6, 12, and 24 months in 69 patients with STEMI. The CV events abruptly increased 6 to 10 months after successful percutaneous coronary intervention in patients with STEMI, and the 6-month BAP levels were significantly lower in patients with CV events (2456 μmol/L [interquartile range: 2237-2615 μmol/L]) than in those without (2849 μmol/L [2575-2987 μmol/L], P < .001). A decreased 6-month BAP level was an independent and significant predictor of long-term CV events (hazard ratio = 2.45; 95% confidence intervals 1.10-5.78; P = .04). Our findings suggest that serial changes in antioxidant capacity, assessed by BAP levels, may serve as a predictive marker for CV events after STEMI., (© The Author(s) 2014.)

Background: CHADS 2 or CHA 2 DS 2 -VASc score is used for prediction of stroke in patients with atrial fibrillation (AF). Recently, CHADS 2 score is reported to have prognostic value in acute coronary syndrome without AF. However, clinical validation of CHA 2 DS 2 -VASc score for prognostic stratification in coronary heart disease (CHD) without AF remains uncertain. In this study, we evaluate whether CHA 2 DS 2 -VASc score could predict clinical outcome in CHD without known AF., Methods: SHINANO registry was a prospective, observational, multicenter cohort study, enrolling 1923 consecutive patients with CHD from August 2012 to July 2013. Two hundred nine patients were excluded because of known AF. We calculated CHA 2 DS 2 -VASc score in the remaining 1714 patients (mean age 70 ± 11 years, 23% female) without known AF. To assess the clinical validation of CHA 2 DS 2 -VASc score, we divided patients into 3 groups according to the tertiles (score 0-2, 3-4, and ≥ 5). The primary endpoint was MACE including death, nonfatal myocardial infarction, and ischemic stroke at 1 year., Results: One-year follow-up was completed in 1632 patients (95.2%). Cumulative incidence of MACE was 139 cases. In Kaplan-Meier analysis, incidence of MACE was significantly higher in patients with CHA 2 DS 2 -VASc score ≥ 5 compared to 3-4 and 0-2 (14.6% vs. 6.8% vs. 5.3%, p  < 0.001). In multivariate Cox-regression analysis, CHA 2 DS 2 -VASc score was an independent predictor for MACE (hazard ratio 1.26, 95% confidence interval 1.15-1.39 p  < 0.001)., Conclusions: This study demonstrated that CHA 2 DS 2 -VASc score could provide prognostic information in CHD without known AF.

A 15-year-old asymptomatic male patient presented with an electrocardiographic abnormality and left ventricular (LV) dysfunction (left ventricle ejection fraction of 40%) in a physical examination performed 2 years previously. LV dysfunction did not improve despite optimal medical therapy for dilated cardiomyopathy. Twelve-lead electrocardiography revealed a normal PR interval (138 ms) with a small delta-like wave in V2, but not a typical diagnostic wave that could be diagnosed as Wolff-Parkinson-White (WPW) syndrome by an electrocardiogram auto-analysis. Transthoracic echocardiography showed a remarkable asynchronous septal motion. An electrophysiological study was performed to exclude WPW syndrome. An accessory pathway (AP) was revealed on the lateral wall of the right ventricle, and radiofrequency catheter ablation was successfully performed to disconnect the AP. Thereafter, the dyssynchrony disappeared, and LV function improved. The intrinsic atrioventricular nodal conduction was very slow (A-H, 237 ms). The results of electrocardiogram auto-analysis could not be used to confirm the diagnosis of WPW syndrome because of the atypical delta wave. Conduction via the right lateral AP caused electrical dyssynchrony in the LV. This case suggests that atypical delta waves should be evaluated without depending on electrocardiographic auto-analyses in patients with LV dysfunction accompanied by dyssynchrony.

Although limb salvage rate has improved in critical limb ischemia (CLI), an improvement in CLI prognosis has been scarcely reported. Multidisciplinary therapy (MT) including revascularization, wound bed preparation, treatment of comorbidity, and education of patients with CLI may improve prognosis. The aim of this study was to investigate the effectiveness of MT in prognostic improvement. We retrospectively analyzed 72 patients with CLI and assessed whether MT improved prognosis. The incidence of amputation-free survival (freedom from major amputation [MA] and death) was significantly different between the MT and conventional groups at 2 years (0% vs 33%; P = .024). After multivariate analysis, transfusion (hazard ratio [HR] 5.778; 95% confidence interval [CI], 2.372-14.073; P < .001), multivessel coronary disease (HR 3.353; 95% CI, 1.309-8.590; P = .012), and C-reactive protein >5 mg/dL (HR 3.958; 95% CI, 1.359-11.531; P = .012) were independent predictors for MA or death. We concluded that MT was effective in improved mortality and limb salvage rate., (© The Author(s) 2014.)

Background: Statins reduce the incidence of cardiovascular events, but no randomized trial has investigated the best statins for secondary prevention. We compared the efficacy of hydrophilic pravastatin with that of lipophilic atorvastatin in patients with acute myocardial infarction (AMI)., Methods and Results: A prospective, multicenter study enrolled 508 patients (410 men; mean age, 66.0 ± 11.6 years) with AMI who were randomly assigned to atorvastatin (n=255) or pravastatin (n=253). The target control level of low-density lipoprotein cholesterol (LDL-C) was <100 mg/dl, and patients were followed for 2 years. The primary endpoint was the composite of death due to any cause, non-fatal myocardial infarction, non-fatal stroke, unstable angina or congestive heart failure requiring hospital admission, or any type of coronary revascularization. The primary endpoint occurred in 77 patients (30.4%) and in 80 patients (31.4%) in the pravastatin and atorvastatin groups, respectively (hazard ratio, 1.181; 95% confidence interval: 0.862-1.619; P=0.299), whereas greater reductions in serum total cholesterol and LDL-C were achieved in the atorvastatin group (P<0.001 for each). Changes in hemoglobin A1c, brain natriuretic peptide, and creatinine were not significant between the 2 regimens, and safety and treatment adherence were similar., Conclusions: On 2-year comparison of hydrophilic and lipophilic statins there was no significant difference in prevention of secondary cardiovascular outcome.

Aim: To investigate the prognosis and to clarify the predictors of both patient and limb survival among hemodialysis (HD) patients with critical limb ischemia (CLI) due to isolated below-the-knee (BK) disease., Methods: An observational cohort study, analyzing a total of 546 HD patients with 681 limbs who underwent endovascular treatment (EVT) for CLI with isolated BK disease at 11 hospitals in Japan between March 2004 and June 2011, was performed., Results: The mean patient age was 69.0±9.5 years, and 420 (76.9%) of the subjects were men. The number of patients classified with Rutherford stage 4, 5 and 6 disease was 103 (18.9%), 332 (60.8%) and 111 (20.3%), respectively. The mean HbA1c level was 6.48±1.20%, and 195 (35.7%) of the subjects were active smokers. During the follow-up period (mean: 557.5 days), 191 (35.0%) patients died and 82 (12.0%) limbs underwent major amputation. The freedom from all-cause death was 75.5%, 53.4% and 36.9% and freedom from major amputation was 86.7%, 83.9% and 83.9% at one, three and five years after EVT, respectively. Cox proportional hazard regression analyses revealed that a non-ambulatory status, low serum albumin level and ＜2 runoff vessels after EVT were significant predictors for both all-cause death and major amputation., Conclusions: Although patient survival remains poor, the limb salvage rate after EVT is favorable among those on HD with CLI due to isolated BK disease. The present results allow for the risk stratification of HD patients with CLI undergoing EVT for isolated BK disease.

Background: The dysregulation of systemic blood pressure (BP) variation or cardiac neuroadrenergic dysfunction is associated with adverse cardiovascular events. We aimed to clarify the prognostic significance of neuroadrenergic dysfunction for cardiovascular events in patients with acute myocardial infarction (AMI)., Methods and results: We enrolled 63 AMI patients (mean age, 67±12 years) underwent ambulatory BP monitoring (ABPM) and cardiac iodine-(123)metaiodobenzylguanidine (MIBG) imaging within 4 weeks after AMI onset. We analyzed the circadian BP pattern and heart-to-mediastinum (H/M) MIBG uptake ratio. All the patients were followed for 2 years. The study endpoint was a composite of major adverse cardiovascular events, including all-cause death, MI, coronary revascularization except for the MI culprit lesion, and stroke. Patients with a non-dipper pattern (n=29) or an H/M ratio <1.96 (n=28) had a worse prognosis than those with either a dipper pattern (n=34) or an H/M ratio ≥1.96 (n=35; log-rank, P=0.013 and 0.010, respectively). Patients with both a non-dipper pattern and an H/M ratio <1.96 (n=12) had a significantly worse prognosis than did the other patients (P=0.0020)., Conclusions: Dysregulation of BP variation and cardiac MIBG uptake were associated with cardiovascular events following AMI. Examining ABPM with MIBG imaging may potentially improve risk stratification in these patients.