Synthesis and Properties of Aromatic-Terminated Diacetylene Organogelators and Their Application to Photopatterning of Polydiacetylenes.

A series of simply structured diacetylene-diamide-based gelators (DAGs) with aromatic terminals were synthesized, and their gelation and subsequent photopolymerization abilities were analyzed. DAGs with an adequate spacer length (n) and tolyl terminals (DA-Tn) interacted with aromatic solvents, such as benzene and xylenes, at elevated temperatures. During the subsequent cooling process, the DAGs interacted with each other through CH-π interactions at their terminal positions. They also formed one-dimensional hydrogen bonding arrays through secondary amides, leading to stable organogels. These gels polymerized into π-conjugated polydiacetylenes (PDAs) under ultraviolet irradiation. In the p-xylene gels of DA-Tn, the spacer length exerted characteristic odd-even effects on the photopolymerization rates over a certain range (n = 3-6), which can be explained by periodic changes in the uniformity of the molecular packing modes. When the gelling solvent was changed to cyclohexane, the gelation and photopolymerization abilities were greatly improved because the DA-Tn gel networks became highly crystallized and transparent to ultraviolet light (254 nm). The ultimate conversion to PDA from DA-T8/cyclohexane gels was 45.2 wt %. Applying photolithographic techniques to the DAG with excellent photopolymerizability in the film state, we successfully fabricated microscale photopatterns of PDA. We also established a convenient removal process (development process) of DA monomers in unexposed areas. The resulting PDA patterns were quite stable to ambient light stimuli.

Quick response hydrogen LSPR sensor based on a hetero-core fiber structure with palladium nanoparticles.

A novel fiber optic localized surface plasmon resonance (LSPR) hydrogen sensor has been developed based on the hetero-core structured with palladium nanoparticles (PdNPs) onto a cylindrical cladding surface. In a light-intensity-based experiment with an LED operating at 850 nm, it has been observed that a transmitted loss change of 0.23 dB was induced with response and recovery times of 1.5 and 3.2 s for 4% hydrogen which are the fastest response times among optical fiber hydrogen sensors. The proposed sensor resolved the inevitable trade-off issue between sensitivity and response time which existed in the previously reported SPR sensors, with keeping the response time below 2.0 s even in a high sensitivity region of interest.

Ferroelectric Liquid-Crystalline Binary Mixtures Based on Achiral and Chiral Trifluoromethylphenylterthiophenes.

This paper presents a new family of ferroelectric smectic liquid-crystalline binary mixtures composed of achiral and chiral trifluoromethylphenylterthiophenes. The chiral symmetry breaking of the ferroelectric smectic phases can lead to chiral photovoltaic (CPV) effects, as a type of ferroelectric photovoltaic (FePV) effect, which is caused by the internal electric field originating from the spontaneous polarization. These ferroelectric properties were examined using the Sawyer-Tower method, and the CPV effect was confirmed by measuring the steady-state photocurrent response under zero bias. We found that the remnant polarization and photocurrent density in the polarized ferroelectric phases increased nonlinearly with the increase in the content of the chiral component in the mixture. Moreover, the hole mobility evaluated by time-of-flight measurements was kept constant by varying the composition. More than 40 mol % of the chiral component was required to form the polar structure, inducing the CPV effect. Binary mixture systems are advantageous for not only optimizing liquid crystal structures and temperature ranges but also facilitating the design of materials exhibiting CPV effects.

Multi-Color Photoluminescence Based on Mechanically and Thermally Induced Liquid-Crystalline Phase Transitions of a Hydrogen-Bonded Benzodithiophene Derivative.

Controlling assembled structures of π-conjugated liquid-crystalline molecules is of great interest in the development of stimuli-responsive luminescent materials due to their molecular motility in the ordered states. Herein, we describe a mechanoresponsive hydrogen-bonded benzodithiophene liquid-crystalline molecule that exhibits a tricolor photoluminescence switching at ambient temperature. The compound shows a shear-induced phase transition from a rectangular columnar to a metastable optically anisotropic mesophase, which is accompanied by the luminescent color change from yellow to sky-blue. The metastable mesophase exhibits a time-responsive transformation to another metastable mesophase showing a blue-green emission through isothermal aging at room temperature. The luminescent color of aged sample reverts back to the initial yellow color by thermal annealing at 150 °C. These dynamic structural changes accompanied by the emission color changes are governed by distinct π-stacking modes and hydrogen-bonded patterns. The shear-induced luminescent color change from yellow to blue is found to occur above the shear strain of 390 % at which the shear stress is 2.4×105  Pa as determined from dynamic viscoelastic measurements.

Rotaxane-Based Mechanophores Enable Polymers with Mechanically Switchable White Photoluminescence.

Three mechanoresponsive polyurethane elastomers whose blue, green, and orange photoluminescence can be reversibly turned on by mechanical force were prepared and combined to create a blend that exhibits deformation-induced white photoluminescence. The three polyurethanes contain rotaxane-based supramolecular mechanoluminophores based on π-extended pyrene, anthracene, or 4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran (DCM) luminophores, respectively, and 1,4,5,8-naphthalenetetracarboxylic diimide as an electronically matched quencher. Each polymer shows instantly reversible, strain-dependent switching of its photoluminescence intensity when stretched and relaxed, as deformation leads to a spatial separation of the luminophore and quencher. The present study shows that the photoluminescence color can easily be tailored by variation of the luminophore and also by combining several mechanophores in one material and demonstrates that adaptability is a key advantage of supramolecular approaches to create mechanoresponsive polymers.

Ethanol Measurement Using Hetero-Core Structured Optical Fiber Covered with Layer-By-Layer Thin Film.

Ethanol measurements are performed in an ethanol/water solution utilizing an ethanol sensor based on a hetero-core structured optical fiber covered with a layer-by-layer thin film. The layer-by-layer (LbL) thin film was prepared using poly (allylamine hydrochloride) and poly styrene sulfonate. When the sensor was immersed in water, the propagating light intensity decreased with increasing ethanol concentration. This behavior suggested that the LbL film contracted due to the presence of ethanol, and the refractive index of the film increased, resulting in increasing propagating light leaks at the hetero-core of the fiber. The ethanol sensor was applied to a variety of spirits, and the propagating light intensity decreased with increasing ethanol concentration.

Anomalous photovoltaic effect based on molecular chirality: influence of enantiomeric purity on the photocurrent response in π-conjugated ferroelectric liquid crystals.

(S)- and (R)-forms of chiral π-conjugated ferroelectric liquid crystals were synthesized. The dielectric properties in the ferroelectric liquid-crystalline (FLC) phases were evaluated using the Sawyer-Tower method. Spontaneous polarization of (S)-1 reached 68 nC cm-2 at 127 °C. Hole mobilities in the FLC phases estimated using the time-of-flight (TOF) method were on the order of 10-4 cm2 V-1 s-1. Each chiral π-conjugated compound exhibited a photovoltaic effect based on spontaneous polarization without p-n or Schottky junctions. This phenomenon could be attributed to an anomalous photovoltaic (APV) effect that has been observed in ferroelectric ceramics. In addition, liquid-crystalline enantiomeric mixtures of (S)-1 and (R)-1 were prepared and the APV response under UV illumination was studied. The APV response was enhanced with an increase in enantiomeric purity and was minimized in the racemic mixture. From this result, it was concluded that the APV effect in this FLC compound originated from the molecular chirality.

Critical potential of early cardiac surgery for infective endocarditis with cardio-embolic strokes.

BACKGROUND: Early cardiac surgery may have a trade-off between stabilized hemodynamics with controlled infection and a risk of peri-operative death in patients with infective endocarditis (IE) complicated with cardio-embolic strokes. METHODS: We retrospectively studied clinical characteristics and outcomes in 68 consecutive patients with IE (mean age, 58±3years, 62% male) who admitted in our institute during June 2013 and August 2015. RESULTS: Cardio-embolic strokes were noted in 37% of patients (n=25) with IE and overall in-hospital mortality was 4 times higher in IE with cardio-embolic strokes than IE with an absence of strokes (n=43) (20% vs. 4.7%, p=0.045). Bacteremia of Staphylococcus aureus (p=0.021) and a complication of cardio-embolic strokes (p=0.031) were independently associated with in-hospital death in those with IE. However, in-hospital mortality was quite low in 19 with early cardiac surgery compared with 6 with conventional treatment in those with cardio-embolic strokes (11% vs. 50%, p=0.035). Multivariate logistic analysis demonstrated that lack of early cardiac surgery (p=0.014), a complication of cerebral hemorrhage (p=0.002), and a presence of refractory heart failure (p=0.047) were independently associated with in-hospital death in those with IE complicated with cardio-embolic strokes. CONCLUSION: Early cardiac surgery may provide clinical advantages overcoming peri-operative risks in those with IE complicated with cardio-embolic strokes.

Prognostic impact of spontaneous coronary artery dissection in young female patients with acute myocardial infarction: A report from the Angina Pectoris-Myocardial Infarction Multicenter Investigators in Japan.

BACKGROUND: We sought to compare the prognosis of patients with spontaneous coronary artery dissection (SCAD) and atherosclerosis as the cause of acute myocardial infarction (AMI), especially in young females. METHODS AND RESULTS: A total of 20,195 patients with AMI at 20 institutions between 2000 and 2013 were retrospectively studied. Major adverse cardiac event (MACE: cardiac death, AMI or urgent revascularization) was the endpoint. The overall prevalence of SCAD was 0.31% (n=63; female, 94%). SCAD developed following emotional stress in 29% of patients. Revascularization was performed in 56% (35 of 63 patients), and SCAD recurrence developed in the originally involved vessel in 6 of 35 patients with revascularization, compared to none among 28 patients after conservative therapy (p=0.002). We compared the clinical characteristics of young female AMI patients aged ≤50years in the SCAD (n=45) and no-SCAD groups (atherosclerotic AMI, n=55). During a median follow-up of 50months, SCAD recurred in 27% of patients, of which 42% was in the first 30days. Kaplan-Meier analysis showed a significantly higher incidence of MACE in the SCAD group compared to the no-SCAD group (hazard ratio, 6.91; 95% confidence interval, 2.5 to 24.3; p<0.001), although the rate of successful percutaneous coronary intervention for SCAD was as high as 92%. CONCLUSIONS: Young female patients with SCAD represent a high-risk subgroup of patients with AMI and require close follow-up.

Novel physiological insight into a lotus root appearance in stable coronary artery diseases; Report of two cases.

So far physiological significance of multiple intraluminal channels separated by thin wall structures, so called "a lotus root appearance", in an angiographic insignificant lesion in patients with suspected angina pectoris has remained undetermined. Here we present two cases that showed a "reverse visual-functional mismatch" phenomenon of a lotus root appearance using the indexes of myocardial fractional flow reserve and/or coronary flow velocity reserve. Our findings may provide a novel physiological insight into a lotus root appearance as a high possibility of critical functional stenosis in those with stable coronary artery diseases.

Impact of Acute Kidney Injury on Early to Long-Term Outcomes in Patients Who Underwent Surgery for Type A Acute Aortic Dissection.

Acute kidney injury (AKI) is relatively common after cardiothoracic surgery for type A acute aortic dissection (TA-AAD) and increases mortality. We investigated the incidence and risk factors for AKI in patients with TA-AAD and its impact on their outcomes. The records of 375 consecutive patients who underwent surgical treatment for TA-AAD from October 2007 to March 2013 were analyzed retrospectively. We defined AKI using the Kidney Disease Improving Global Outcomes criteria, which are based on serum creatinine concentration or glomerular filtration rate. We used Kaplan-Meier methods and multivariate Cox proportional hazards regression to assess the impact of AKI on both mortality and major adverse cardiovascular and cerebrovascular events. We also examined the association between risk factors and AKI using logistic regression modeling. Postoperative AKI was observed in 165 patients (44.0%). The overall 30-day and mid- to long-term mortality was 1.6% and 8.8%, respectively. Mortality and major adverse cardiovascular and cerebrovascular events correlated significantly with the severity of AKI, and multivariate analysis showed that AKI stage 3 (the most sever stage) was an independent risk factor for mortality (hazard ratio 6.83, 95% confidence interval 2.52 to 18.52) after adjustment for important confounding factors. Extracorporeal circulation time, body mass index, perioperative peak serum C-reactive protein concentration, renal malperfusion, and perioperative sepsis were found to be risk factors for AKI. In conclusion, AKI was common in patients who underwent surgery for type A acute aortic dissection. The severity of AKI strongly influences patient outcomes, so it should be recognized promptly and treated aggressively when possible.

An inspection of therapeutic hypothermia preceding coronary reperfusion in patients with a cardiogenic shock complicating anterior ST-segment elevation myocardial infarction.

BACKGROUND: We retrospectively investigated our hypothesis that pre-percutaneous coronary intervention (PCI) procedural therapeutic hypothermia may have clinical advantages in patients with a profound cardiogenic shock complicating anterior ST-segment elevation myocardial infarction (STEMI). METHODS: Of 483 consecutive patients treated with PCI for a first anterior STEMI including 31 patients with aborted sudden cardiac arrest between 2009 and 2013, a total of 37 consecutive patients with an anterior STEMI complicated with profound cardiogenic shock defined as the presence of hyperlactic acidemia (serum levels of lactate > 4 mmol/L) with mechanical circulatory support were identified. An impaired myocardial tissue-level reperfusion (angiographic myocardial blush grade 0 or 1) and in-hospital mortality were evaluated in accordance with the presence or absence of pre-PCI procedural therapeutic hypothermia. RESULTS: Thirteen patients were treated with pre-PCI procedural therapeutic hypothermia and 24 were not inducted with therapeutic hypothermia. Five patients with and 18 without pre-PCI procedural therapeutic hypothermia impaired myocardial tissue-level reperfusion (38% vs. 75%, p = 0.037). A total of 26 patients with in-hospital death (overall in-hospital mortality 70%) were composed of 6 with and 20 without therapeutic hypothermia (in-hospital mortality 46% vs. 83%, p = 0.028). A multivariate analysis demonstrated a significant association of pre-PCI procedural therapeutic hypothermia (p = 0.021) with in-hospital survival benefit. Adverse events associated with therapeutic hypothermia were not found in 12 patients who completed this treatment. CONCLUSIONS: The present study may imply a crucial possibility of clinical benefits of pre-PCI procedural therapeutic hypothermia in patients with a cardiogenic shock complicating anterior STEMI.

Prognostic impact of chronic nitrate therapy in patients with vasospastic angina: multicentre registry study of the Japanese coronary spasm association.

AIMS: Although nitrates are widely used as a concomitant therapy with calcium channel blockers (CCBs) for vasospastic angina (VSA), their prognostic contribution remains unclear. The present study aimed to examine the prognostic impact of chronic nitrate therapy in patients with VSA. METHODS AND RESULTS: A total of 1429 VSA patients (median 66 years; male/female, 1090/339) were enrolled. The primary endpoint was defined as major adverse cardiac events (MACE). The propensity score matching and multivariable Cox proportional hazard model were used to adjust for selection bias for treatment and potential confounding factors. Among the study patients, 695 (49%) were treated with nitrates, including conventional nitrates [e.g. nitroglycerin (GTN), isosorbide mono- and dinitrate] in 551 and nicorandil in 306. Calcium channel blockers were used in >90% of patients. During the median follow-up period of 32 months, 85 patients (5.9%) reached the primary endpoint. Propensity score-matched analysis demonstrated that the cumulative incidence of MACE was comparable between the patients with and those without nitrates [11 vs. 8% at 5 years; hazard ratio (HR): 1.28; 95% confidence interval (CI): 0.72-2.28, P = 0.40]. Although nicorandil itself had a neutral prognostic effect on VSA (HR: 0.80; 95% CI: 0.28-2.27, P = 0.67), multivariable Cox model revealed the potential harm of concomitant use of conventional nitrates and nicorandil (HR: 2.14; 95% CI: 1.02-4.47; P = 0.044), particularly when GTN and nicorandil were simultaneously administered. CONCLUSIONS: Chronic nitrate therapy did not improve the long-term prognosis of VSA patients when combined with CCBs. Furthermore, the VSA patients with multiple nitrates would have increased risk for cardiac events.

Non-invasive diagnosis of coronary artery disease by 123I-BMIPP/201TlCl dual myocardial SPECT in patients with heart failure.

BACKGROUND/OBJECTIVES: Detecting the presence of coronary artery disease (CAD) is critically important in managing patients with heart failure of uncertain cause. The recently introduced 123I-BMIPP/201TlCl dual myocardial single-photon emission computed tomography (dual SPECT) is potentially a non-invasive diagnostic tool in detecting ischemic heart disease. The aim of our study is to evaluate the efficacy of detecting CAD by dual SPECT in patients with heart failure. METHODS: We studied 501 consecutive patients (366 males, mean age 68±12 years) who were admitted because of heart failure between January 2005 and April 2009. In all patients, the dual SPECT was performed in clinically stabilized states, followed by coronary angiography within 1 week. The polar map of the SPECT image was divided into 17 segments, each scored on a scale of 0-4 based on segmental percent uptake. The mismatch score was defined as the difference between 123I-BMIPP defect score and 201TlCI defect score. The uptake of 201TlCl and 123I-BMIPP was analyzed quantitatively using the Heart Score View software. RESULTS: The 201TlCI defect score and mismatch score were significantly higher in CAD patients than in non-CAD patients. The receiver operating characteristic (ROC) curve revealed that the mismatch score was a significantly more effective marker in detecting the presence of CAD than 201TlCl defect score (area under the curve: 0.84 versus 0.73, p<0.05). Using the mismatch score, the sensitivity and specificity of dual SPECT in detecting CAD were 84% and 83%, respectively. CONCLUSION: Dual SPECT is a useful non-invasive procedure for the detection of CAD in patients with heart failure.

A hydrogen curing effect on surface plasmon resonance fiber optic hydrogen sensors using an annealed Au/Ta2O5/Pd multi-layers film.

In this paper, a response time of the surface plasmon resonance fiber optic hydrogen sensor has successfully improved with keeping sensor sensitivity high by means of hydrogen curing (immersing) process of annealed Au/Ta2O5/ Pd multi-layers film. The hydrogen curing effect on the response time and sensitivity has been experimentally revealed by changing the annealing temperatures of 400, 600, 800°C and through observing the optical loss change in the H2 curing process. When the 25-nm Au/60-nm Ta2O5/10-nm Pd multi-layers film annealed at 600°C is cured with 4% H2/N2 mixture, it is found that a lot of nano-sized cracks were produced on the Pd surface. After H2 curing process, the response time is improved to be 8 s, which is two times faster than previous reported one in the case of the 25-nm Au/60-nm Ta2O5/3-nm Pd multi-layers film with keeping the sensor sensitivity of 0.27 dB for 4% hydrogen adding. Discussions most likely responsible for this effect are given by introducing the α-ß transition Pd structure in the H2 curing process.

Japanese and non-Japanese patient outcomes in the PLATINUM randomized trial comparing the PROMUS Element and XIENCE V everolimus-eluting stents.

BACKGROUND: The PLATINUM randomized trial enrolled 1530 patients treated with either the platinum chromium PROMUS Element everolimus-eluting stent (PtCr-EES; Boston Scientific, Natick, MA, USA) or the predicate cobalt chromium PROMUS/XIENCE V EES (CoCr-EES; manufactured as XIENCE V by Abbott Vascular, Santa Clara, CA, USA also distributed as PROMUS by Boston Scientific), including 124 patients from Japanese sites. This substudy examines 2-year outcomes in the Japanese and non-Japanese cohorts. METHODS: Patients with 1 or 2 de novo native coronary artery lesions (baseline vessel diameter ≥2.50mm to ≤4.25mm and length ≤24mm) were randomized 1:1 to PtCr-EES (N=63 patients in Japan) versus CoCr-EES (N=61 patients in Japan). RESULTS: Several significant differences were noted in baseline demographics, lesion characteristics, and procedural technique between Japanese and non-Japanese patients, including longer fluoroscopy time, less use of contrast, and greater post-dilatation usage and maximum pressure in Japan. Dual antiplatelet usage at 2 years was also higher in Japan. Despite these differences, the 2-year rates of target lesion failure were comparable in patients treated with PtCr-EES and CoCr-EES both in Japan (3.2% vs 5.0% respectively, p=0.68) and outside Japan (4.7% vs 5.9% respectively, p=0.33; p for interaction=0.82). CONCLUSIONS: This PLATINUM study subanalysis suggests that the PtCr-EES and CoCr-EES provide comparable safety and efficacy in both Japanese and non-Japanese patients.

Prognostic stratification of patients with vasospastic angina: a comprehensive clinical risk score developed by the Japanese Coronary Spasm Association.

OBJECTIVES: The present study aimed to develop a comprehensive clinical risk score for vasospastic angina (VSA) patients. BACKGROUND: Previous studies demonstrated various prognostic factors of future adverse events in VSA patients. However, to apply these prognostic factors in clinical practice, the assessment of their accumulation in individual patients is important. METHODS: The patient database of the multicenter registry study by the Japanese Coronary Spasm Association (JCSA) (n = 1,429; median 66 years; median follow-up 32 months) was utilized for score derivation. RESULTS: Multivariable Cox proportional hazard model selected 7 predictors of major adverse cardiac events (MACE). The integer score was assigned to each predictors proportional to their respective adjusted hazard ratio; history of out-of-hospital cardiac arrest (4 points), smoking, angina at rest alone, organic coronary stenosis, multivessel spasm (2 points each), ST-segment elevation during angina, and beta-blocker use (1 point each). According to the total score in individual patients, 3 risk strata were defined; low (score 0 to 2, n = 598), intermediate (score 3 to 5, n = 639) and high (score 6 or more, n = 192). The incidences of MACE in the low-, intermediate-, and high-risk patients were 2.5%, 7.0%, and 13.0%, respectively (p < 0.001). The Cox model for MACE between the 3 risk strata also showed prognostic utility of the scoring system in various clinical subgroups. The average prediction rate of the scoring system in the internal training and validation sets were 86.6% and 86.5%, respectively. CONCLUSIONS: We developed a novel scoring system, the JCSA risk score, which may provide the comprehensive risk assessment and prognostic stratification for VSA patients.

Gender differences in the clinical characteristics and outcomes of patients with vasospastic angina--a report from the Japanese Coronary Spasm Association.

BACKGROUND: Accumulating evidence has demonstrated the gender differences in the clinical characteristics and outcomes of patients with ischemic heart disease. However, it remains to be elucidated whether it is also the case for vasospastic angina (VSA). METHODS AND RESULTS: We enrolled a total of 1,429 VSA patients (male/female, 1090/339; median age 66 years) in our nationwide multicenter registry by the Japanese Coronary Spasm Association. As compared with male patients, female patients were characterized by older age (median 69 vs. 66 years), lower incidence of smoking (20% vs. 72%) and less significant organic stenosis (9% vs. 16%) (all P=0.001). Multivariate analysis demonstrated that the predictors of major adverse cardiac events (MACE) were considerably different by genders; women were more associated with age and electrical abnormalities, whereas men with structural abnormalities. Overall 5-year MACE-free survival was comparable between both genders. However, when the patients were divided into 3 groups by age [young (<50 years), middle-aged (50-64 years) and elderly (≥65 years)], the survival was significantly lower in the young female group (young 82%, middle-aged 92%, elderly 96%, P<0.01), where a significant interaction was noted between age and smoking. In contrast, the survival was comparable among the 3 age groups of male patients. CONCLUSIONS: These results indicate that there are gender differences in the characteristics and outcomes of VSA patients, suggesting the importance of gender-specific management of the disorder.

Clinical implications of provocation tests for coronary artery spasm: safety, arrhythmic complications, and prognostic impact: multicentre registry study of the Japanese Coronary Spasm Association.

AIMS: Provocation tests of coronary artery spasm are useful for the diagnosis of vasospastic angina (VSA). However, these tests are thought to have a potential risk of arrhythmic complications, including ventricular tachycardia (VT), ventricular fibrillation (VF), and brady-arrhythmias. We aimed to elucidate the safety and the clinical implications of the spasm provocation tests in the nationwide multicentre registry study by the Japanese Coronary Spasm Association. METHODS AND RESULTS: A total of 1244 VSA patients (M/F, 938/306; median 66 years) who underwent the spasm provocation tests were enrolled from 47 institutes. The primary endpoint was defined as major adverse cardiac events (MACEs). The provocation tests were performed with either acetylcholine (ACh, 57%) or ergonovine (40%). During the provocation tests, VT/VF and brady-arrhythmias developed at a rate of 3.2 and 2.7%, respectively. Overall incidence of arrhythmic complications was 6.8%, a comparable incidence of those during spontaneous angina attack (7.0%). Multivariable logistic regression analysis demonstrated that diffuse right coronary artery spasm (P < 0.01) and the use of ACh (P < 0.05) had a significant correlation with provocation-related VT/VF. During the median follow-up of 32 months, 69 patients (5.5%) reached the primary endpoint. The multivariable Cox proportional hazard model revealed that mixed (focal plus diffuse) type multivessel spasm had an important association with MACEs (adjusted hazard ratio, 2.84; 95% confidence interval, 1.34-6.03; P < 0.01), whereas provocation-related arrhythmias did not. CONCLUSION: The spasm provocation tests have an acceptable level of safety and the evaluation of spasm type may provide useful information for the risk prediction of VSA patients.

Lipid-lowering and anti-inflammatory effect of ezetimibe in hyperlipidemic patients with coronary artery disease.

We evaluated the effects of adding ezetimibe to statin therapy in hypercholesterolemic patients with coronary artery disease (CAD) who could not achieve the target cholesterol levels recommended in the 2007 Japan Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases on statin monotherapy. Ezetimibe (10 mg) was added to basal statin therapy for 12 weeks in 35 patients with hypercholesterolemia and a history of CAD who had not achieved their target cholesterol level with statin monotherapy. Changes in serum lipids, obesity markers, an oxidative stress marker, inflammatory markers, and laboratory values were investigated. Total cholesterol (from 200.6 ± 30.4 mg/dL in week 0 to 173.4 ± 33.3 mg/dL in week 12, P < 0.001), low-density lipoprotein cholesterol (LDL-C) (121.3 ± 29.4 vs. 94.6 ± 30.4 mg/dL, P < 0.001), and remnant lipoprotein cholesterol (6.4 ± 3.5 vs. 5.3 ± 3.0 mg/dL, P < 0.05) all decreased significantly after addition of ezetimibe. The LDL-C/high-density lipoprotein cholesterol ratio also decreased significantly (2.5 ± 0.8 in week 0 vs. 1.9 ± 0.7 in week 12, P < 0.001). The percentage of patients achieving the target LDL-C level (<100 mg/dL) increased significantly (70.8 % in week 4 and 65.4 % in week 12, P < 0.001). There were no significant changes in the obesity or oxidative stress markers and high-sensitivity C-reactive protein (an inflammatory marker). However, another inflammatory marker (tumor necrosis factor-α) was decreased significantly by ezetimibe (1.36 ± 1.06 in week 0 vs. 0.96 ± 0.24 in week 12, P = 0.042). In conclusion, when ezetimibe was added to basal statin therapy, serum lipids improved significantly and the rate of achieving the target cholesterol level increased. Thus, ezetimibe efficiently decreases LDL-C and might prevent arteriosclerosis in hypercholesterolemic patients with CAD when added to basal statin therapy.