All-trans retinoic acid induces lipophagy by reducing Rubicon in Hepa1c1c7 cells.

All-trans retinoic acid (atRA), a metabolite of vitamin A, reduces hepatic lipid accumulation in liver steatosis model animals. Lipophagy, a new lipolysis pathway, degrades a lipid droplet (LD) via autophagy in adipose tissue and the liver. We recently found that atRA induces lipophagy in adipocytes. However, it remains unclear whether atRA induces lipophagy in hepatocytes. In this study, we investigated the effects of atRA on lipophagy in Hepa1c1c7 cells and the liver of mice fed a high-fat diet (HFD). First, we confirmed that atRA induced autophagy in Hepa1c1c7 cells by Western blotting and the GFP-LC3-mCherry probe. Next, we evaluated the lipolysis in fatty Hepa1c1c7 cells treated with the knockdown of Atg5, an essential gene in autophagy induction. Atg5-knockdown partly suppressed the atRA-induced lipolysis in fatty Hepa1c1c7 cells. We also found that atRA reduced the protein, but not mRNA, expression of Rubicon, a negative regulator of autophagy, in Hepa1c1c7 cells and the liver of HFD-fed mice. Rubicon-knockdown partly inhibited the atRA-induced lipolysis in fatty Hepa1c1c7 cells. In addition, atRA reduced hepatic Rubicon expression in young mice, but the effect of atRA on it diminished in aged mice. Finally, we investigated the mechanism underlying reduced Rubicon protein expression by atRA in hepatocytes. A protein synthesis inhibitor, but not proteasome or lysosomal inhibitors, significantly blocked the reduction of Rubicon protein expression by atRA in Hepa1c1c7 cells. These results suggest that atRA may promote lipophagy in fatty hepatocytes by reducing hepatic Rubicon expression via inhibiting protein synthesis.

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

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

Novel noninvasive estimation of mixed venous oxygen saturation by echocardiography and expired gas analysis.

Mixed venous oxygen (O2) saturation ([Formula: see text]) is an important measure for evaluating the sufficiency of cardiac output (CO) relative to whole body O2 consumption (V̇o2), while clinical use is limited to the required invasive catheterization. According to Fick's equation, V̇o2 (mL/min) = CO (L/min) × Hb (g/dL) × 1.36 (mL/g) × ([Formula: see text] - [Formula: see text])/10 (Hb = hemoglobin concentration, [Formula: see text] = arterial blood O2 saturation). Because V̇o2, CO, Hb, and [Formula: see text] can be measured noninvasively with expired gas analysis, echocardiography, a simple blood test, and percutaneous O2 saturation, respectively, [Formula: see text] can be calculated noninvasively. We hypothesized that noninvasively calculated [Formula: see text] shows a significant correlation and agrees well with invasively measured [Formula: see text]. In 47 patients (29 men; mean age, 70 ± 12 yr) who underwent right heart catheterization, [Formula: see text] was directly measured by sampling pulmonary artery blood. Noninvasively calculated [Formula: see text] was also obtained by the method described above. The calculated [Formula: see text] was significantly correlated with the measured [Formula: see text] (r = 0.79, P < 0.001) and was significantly smaller than the measured [Formula: see text] (70 ± 5.1 vs. 72.1 ± 4.9%, P < 0.001). Bias at [Formula: see text] was -2.2% (95% confidence interval, -3.2 to -1.1%) with limits of agreement from -9.5 to 5.2%, demonstrating acceptable agreement. The optimal cutoff value of calculated [Formula: see text] was 69% for reduced measured [Formula: see text] < 70% with an area under the curve of 0.94. Reduced calculated [Formula: see text] < 69% indicated a sensitivity of 92.9% and a specificity of 90.9% for reduced measured [Formula: see text] < 70%. Noninvasive [Formula: see text] calculated from echocardiography, expired gas analysis, percutaneous arterial blood O2 saturation, and hemoglobin level significantly correlated and agreed well with direct [Formula: see text] measured by catheterization. This novel method allows for practical evaluation of [Formula: see text] to assess the sufficiency of CO according to whole body metabolism.NEW & NOTEWORTHY Clinical use of mixed venous oxygen saturation ([Formula: see text]) is limited to the required invasive procedure. With Fick's equation, expired gas analysis, echocardiography, simple blood tests, and percutaneous oxygen saturation, [Formula: see text] can be calculated noninvasively. We hypothesized that noninvasively calculated [Formula: see text] shows a significant correlation and agrees well with invasively measured [Formula: see text]. The present study examined the relationship between measured [Formula: see text] and calculated [Formula: see text] in patients who underwent right heart catheterization and demonstrated acceptable agreement. This novel method can expand the indication of evaluating [Formula: see text].

Potential mechanism of left ventricular spherical remodeling: association of mitral valve complex-myocardium longitudinal tissue remodeling mismatch.

Since mitral valve (MV) complex (MVC) longitudinally bridges left ventricular (LV) base end and its middle, insufficient MVC longitudinal tissue length (TL) elongation relative to whole LV myocardial longitudinal TL elongation could limit LV-base-longitudinal-TL elongation, leading to predominant LV-base-transverse-TL elongation, constituting LV spherical remodeling. In 30 patients with dilated cardiomyopathy (DCM), 30 with aortic regurgitation (AR), and 30 controls, LV sphericity, LV-apex- or base-transverse- and longitudinal-TL, MVC-longitudinal-TL, and whole-LV-longitudinal-TL were measured by three-dimensional (3D) echocardiography. Ratio of each measure versus mean normal value (i.e., LV-apex-transverse-TL ratio) was considered to express the directional and regional tissue elongation. [LV-base-longitudinal-TL ratio/global-LV-TL ratio] and [MVC-longitudinal-TL ratio/whole-LV-longitudinal-TL ratio] were obtained as the degree of LV-base-longitudinal-TL or MVC-longitudinal-TL elongation relative to the whole LV elongation. LV-apex-transverse-, LV-apex-longitudinal-, and LV-base-transverse-TL ratios were significantly increased (1.27 to 1.42, P < 0.01) in both DCM and AR, while the LV-base-longitudinal-TL ratio was not increased in DCM [1.04 ± 0.19, not significant (ns)] and only modestly increased in AR (1.12 ± 0.21, P < 0.01). Whole-LV-longitudinal-TL ratio was significantly increased in both DCM and AR (1.22 ± 0.18 and 1.20 ± 0.16, P < 0.01), while MVC-longitudinal-TL ratio was not or only modestly increased in both groups (1.07 ± 0.15, ns, and 1.12 ± 0.17, P = 0.02, respectively). Multivariable analysis revealed that LV sphericity was independently related to a reduced [LV-base-longitudinal-TL ratio/global-LV-TL ratio] (standard ß = -0.42, P < 0.01), which was further related to a reduced [MVC-longitudinal-TL ratio/whole-LV-longitudinal-TL ratio] (standard ß = 0.72, P < 0.01). These are consistent with the hypothesis that relatively less MVC-longitudinal-TL elongation in the process of primary LV myocardial tissue elongation may limit LV-base-longitudinal-TL elongation, contributing to LV spherical remodeling.NEW & NOTEWORTHY Left ventricular (LV) spherical remodeling is associated with poor prognosis and less-effective cardiac performance, which commonly develops in dilated cardiomyopathy. However, its mechanism remains unclear. We hypothesized and subsequently clarified that less mitral valve complex (MVC) tissue longitudinal elongation relative to whole LV myocardial tissue longitudinal elongation is related to disproportionately less LV base longitudinal versus transverse myocardial tissue elongation, constituting spherical remodeling. This study suggests modification of MVC tissue elongation could be potential therapeutic targets.

Relations of Augmented Systolic Annular Expansion and Leaflet/Papillary Muscle Dynamics in Late-Systolic Mitral Valve Prolapse Evaluated by Echocardiography with a Speckle Tracking Analysis.

The mechanism of systolic annular expansion in mitral valve prolapse (MVP) is not clarified. Since annular expansion is systolic outward shift of MV leaflet/chorda tissue complex at superior and outer ends, annular expansion could be related to inward (superior) shift of the complex at another inferior and inner end of the papillary muscle (PM) tip and/or systolic lengthening of the tissue complex, especially MV leaflets.MV annulus systolic expansion, PMs' systolic superior shift, and MV leaflets' systolic lengthening were evaluated by echocardiography with a speckle tracking analysis in 25 normal subjects, 25 subjects with holo-systolic MVP and 20 subjects with late-systolic MVP.PMs' superior shift, MV leaflets' lengthening, MV annular area at the onset of systole and subsequent MV annulus expansion were significantly greater in late-systolic MVP than in holo-systolic MVP (4.6 ± 1.6 versus 1.5 ± 0.7 mm/m2, 2.5 ± 1.4 versus 0.6 ± 2.0 mm/m2, 6.8 ± 2.5 versus 5.7 ± 1.0 cm2/m2 and 1.6 ± 0.8 versus 0.1 ± 0.5 cm2/m2, P < 0.001, respectively). Multivariate analysis identified MV leaflets' lengthening and PMs' superior shift as independent factors associated with MV annular expansion.Conclusions: These results suggest that systolic MV annular expansion in MVP is related to abnormal MV leaflets' lengthening and PMs' superior shift.

Insights into the mechanism of paradoxical low-flow, low-pressure gradient severe aortic stenosis: association with reduced O2 consumption by the whole body.

The mechanism of reduced stroke volume index (SVi) in paradoxical low-flow, low-pressure gradient (PLFLPG) aortic stenosis (AS) remains unclarified. Guyton et al. ( 21 ) demonstrated that SVi is determined by whole body O2 consumption (V̇o2) in many subjects, including patients with heart disease. We hypothesized that reduced SVi in PLFLPG AS is associated with reduced V̇o2 by the whole body. This study investigated the relationship between V̇o2, SVi, and AS severity in patients with AS to examine the association between reduced V̇o2 and PLFLPG AS. In 59 patients (24 men and 35 women, mean age: 78 ± 7 yr old) with severe AS, SVi, AS severity, and type were evaluated by echocardiography, and V̇o2 was measured by the fraction of O2 in expired gases. SVi and V̇o2 were significantly decreased in 20 patients with PLFLPG AS compared with 39 patients with non-PLFLPG AS (30 ± 4 vs. 41 ± 7 ml/m2 and 2.4 ± 0.5 vs. 3.0 ± 0.5 ml·min-1·kg-1, respectively, P < 0.01). The SVi-to-V̇o2 ratio was not different between the two groups (13.1 ± 2.6 vs. 13.6 ± 2.1, not significant). SVi was independently correlated with V̇o2 ( r = 0.74, P < 0.01) but not with the aortic valve area index. Categorized PLFLPG AS was also significantly associated with reduced V̇o2 ( P < 0.001). PLFLPG AS is associated with reduced V̇o2 by the whole body, which may offer insights into the mechanism of PLFLPG AS. NEW & NOTEWORTHY Paradoxical low-flow, low-pressure gradient severe aortic stenosis (PLFLPG AS) is an important and problematic subtype, and its central pathophysiology with reduced stroke volume is yet to be clarified. We hypothesized and subsequently clarified that reduced stroke volume in PLFLPG AS is associated with reduced O2 consumption by the whole body. This study suggests important insights into the mechanism of PLFLPG AS and may further promote studies to investigate further mechanisms and novel treatment.

Comparison between minimum lumen cross-sectional area and intraluminal ultrasonic intensity analysis using integrated backscatter intravascular ultrasound for prediction of functionally significant coronary artery stenosis.

Intravascular ultrasound (IVUS)-derived minimum lumen cross-sectional area (MLA) is useful to predict myocardial ischemia using fractional flow reserve (FFR). Recent studies reported an increase in the intraluminal ultrasonic integrated backscatter (IB) value using IVUS across the coronary artery stenosis (CAS) was significantly correlated with FFR. However, these details have not been fully understood. We evaluated the utility of intraluminal IB analysis for predicting myocardial ischemia based on FFR measurements by comparing that with conventional IVUS-derived MLA. A total of 65 patients with 75 intermediate lesions underwent both FFR and IB-IVUS simultaneously were analyzed. We measured IVUS-derived MLA and intraluminal IB value at the coronary ostial site, 5 mm distal site to the CAS, and far distal site, which is the same as the position of the pressure wire sensor. The increase in IB values was calculated as the distal IB value - the ostial IB value (focal ∆IB) and the far distal IB value - the ostial IB value (total ∆IB). MLA did not show a significant correlation with FFR (p = 0.13); however, focal ∆IB and total ∆IB showed significant correlations with FFR (p = 0.008 and p < 0.001, respectively). The receiver operating characteristic curve analysis shows that the best cut-off value of focal ∆IB and total ∆IB was 8 and 14, respectively. Although the diagnostic abilities to predict FFR ≤ 0.75 among IVUS-derived MLA ≤ 3.0 mm2, focal ∆IB ≥ 8, and total ∆IB ≥ 14 were similar, a multivariate analysis showed that total ∆IB was the most useful index (p < 0.001). In conclusion, total ∆IB, which is measured at the same as the position of FFR measurement, might be useful for functional assessment of intermediate CAS.

Impact of High-Sensitivity Cardiac Troponin Elevation in Relation to Diagnostic Invasive Intravascular Imaging for the Assessment of Coronary Artery Disease.

Recent studies reported that cardiac troponin elevation after percutaneous coronary intervention is related to adverse cardiac events. Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) are often used to assess lesion characteristics in the coronary arteries. However, little is known about the trend of cardiac troponin elevation after diagnostic invasive intracoronary examination and the prognostic influence. We assessed the relationship between myocardial injury manifested by the high-sensitivity cardiac troponin T (hs-cTnT) level after invasive intracoronary examination and future adverse cardiac outcomes. We evaluated 115 patients with stable coronary artery disease who underwent IVUS or OCT for detailed coronary assessment during coronary angiography (CAG). Baseline and post-procedural (within 24 hours after examination) hs-cTnT were measured. In consequence, post-procedural hs-cTnT level and percentage increase were higher in patients with IVUS or OCT during CAG than in those without. Periprocedural myocardial injury (PMI, defined as post-procedural hs-cTnT with upper reference limit greater than five-fold) occurred in 10 (8.6%) patients. There were no significant differences in baseline characteristics between patients with and without PMI, except for left-ventricular diastolic dimension. Only two major adverse cardiac events (MACE, defined as cardiovascular death, nonfatal myocardial infarction, and target lesion revascularization) occurred in non-PMI during a mean observation period of 32 ± 18 months. On Kaplan-Meier analysis, MACE-free survival rate was similar between PMI and non-PMI. In conclusion, a few imperceptible PMI derived by hs-cTnT assay occurred after diagnostic invasive intracoronary examination. However, it was not associated with subsequent poor cardiac outcome.

Contribution of Poststent Irregular Protrusion to Subsequent In-Stent Neoatherosclerosis after the Second-Generation Drug-Eluting Stent Implantation.

Previous optical coherence tomography (OCT) study reported that irregular protrusion (IP) post drug-eluting stent (DES) implantation was an independent predictor of clinical outcome; however, the relationship between IP and the presence of subsequent in-stent neoatherosclerosis remains unclear. This study aimed to assess the relationship between IP and in-stent neoatheroscrerosis formation using OCT. We evaluated 83 patients (101 lesions) who underwent second-generation DES implantation and 8-month follow-up (8M-FU) using OCT. Lesions were divided into two groups in presence of IP (IP: n = 43, non-IP: n = 58). At prepercutaneous coronary intervention (pre-PCI), lipid-rich plaque, lesions with positive remodeling, and in-stent thrombus formation were more frequent in IP than in non-IP. On multivariate analysis, the thrombus at pre-PCI and the lesions with positive remodeling were independent predictors of IP. At 8M-FU, heterogeneous neointima, microvessel, lipid-laden neointima, and thin-cap fibro-atheroma like neointima were more frequent in IP than in non-IP (respectively, P < 0.05). On multivariate analysis, IP was associated with heterogeneous neointima. Binary restenosis was more frequent and late lumen loss tended to be larger in IP than in non-IP (19% versus 5%, P = 0.04; 1.25 ± 1.24 mm versus 0.91 ± 0.63 mm, P = 0.09); however, the target lesion revascularization rate was similar in both groups at 8M-FU. In conclusion, our study suggested that poststent IP was associated with subsequent neoatherosclerosis formation at 8M-FU after the second-generation DES implantation.

Potential Effects of Mild Atrial Secondary Mitral Regurgitation in Patients With Isolated Atrial Fibrillation.

BACKGROUND: Patients with only moderate atrial secondary mitral regurgitation (asMR) frequently develop heart failure (HF). Mechanisms of HF with moderate asMR and the impact of mild asMR remain unclarified. Although mild/moderate primary mitral regurgitation is compensated by left ventricular (LV) dilatation, the LV is not dilated in asMR. We hypothesized that patients with mild asMR without LV dilatation may have impaired hemodynamics and higher risks of subsequent symptomatic HF deterioration. METHODS: Stroke volume, cardiac output, and systolic pulmonary artery pressure were measured by echocardiography in 142 patients with isolated atrial fibrillation and 30 healthy controls. The prognosis of patients with isolated atrial fibrillation was followed up. RESULTS: In the 142 patients with isolated atrial fibrillation, asMR was no/trivial in 55, mild in 83, moderate in 4, while none had severe asMR. Compared with controls and patients with no/trivial asMR, LV end-diastolic volume index was not increased and hemodynamic parameters were abnormal in patients with mild asMR (LV end-diastolic volume index, 65±6 versus 58±8 versus 60±8 mL/m²; stroke volume index, 42±4 versus 35±4 versus 29±6 mL/m²; P<0.001 versus other 2 groups; cardiac output index, 2.8±0.4 versus 2.8±0.5 versus 2.3±0.6 L/min per m²; P<0.001; systolic pulmonary artery pressure, 21±3 versus 26±5 versus 37±9 mm Hg; P<0.001). Although the event-free rate of HF symptomatic deterioration or hospitalization in patients with no/trivial asMR during a median 13.9 months follow-up was 86.9% and 100%, the rate in mild asMR was 59.4% and 85.0% (P<0.001 or P=0.032), respectively. CONCLUSIONS: In the presence of isolated AF and no compensatory LV dilatation, impaired hemodynamics and higher risks of symptomatic HF deterioration were associated with mild asMR, requiring further studies of causalities.

Coronary arterial remodeling and out-stent plaque change after drug-eluting stent implantation--comparison between zotarolimus-eluting stents and paclitaxel-eluting stents.

BACKGROUND: Out-stent plaque characteristics and eosinophilic inflammatory response, which correlates with positive remodeling after first-generation drug-eluting stent implantation, may be associated with late restenosis and very late stent thrombosis. The differences of out-stent plaque characteristics were compared between paclitaxel-eluting stents (PES) and zotarolimus-eluting stents (ZES), using integrated backscatter-intravascular ultrasound (IB-IVUS). METHODS AND RESULTS: Of 78 patients enrolled, 25 receiving PES and 25 receiving ZES had adequate IVUS assessment. Volumetric IVUS analysis was performed after stenting and at 8-month follow-up. Out-stent plaque change in the stented segment was compared on IB-IVUS. The relationship between systemic inflammatory response and out-stent plaque change was evaluated. In PES, vessel volume significantly increased (365-389 mm(3), P<0.0001), whereas it did not change in ZES (315-314 mm(3), P=0.81). In culprit lesions at baseline in PES, fibrous plaque tended to increase (3.1-3.6mm(2), P=0.051) and lipid plaque significantly increased (4.3-5.1mm(2), P=0.02), whereas in ZES the fibrous plaque significantly increased (2.9-4.0mm(2), P<0.0001) but lipid plaque significantly decreased (5.1-3.6mm(2), P<0.0001). Systemic eosinophil increase was significantly correlated with positive remodeling and out-stent lipid plaque increase. CONCLUSIONS: Chronic out-stent plaque change in ZES consisted of less positive remodeling and more favorable effects on out-stent plaque characteristics than PES. Systemic eosinophil change might be a marker of out-stent lipid plaque change.

A rare case of myocardial infarction related to diagnostic intravascular ultrasound.

A 71-year-old man underwent intracoronary stent implantation for acute inferior myocardial infarction (MI). Immediately after diagnostic intravascular ultrasound (IVUS) at 8 months' follow-up, an acute occlusion of the sinus node (SN) artery appeared, which developed sinus arrest with junctional escape rhythm. The serum level of high-sensitivity troponin T (TpT) was markedly elevated on the day after the procedure (2.1-32.5 ng/l), which was indicative of MI related to IVUS. Under continuous intravenous infusion of unfractionated heparin, the escape rhythm changed to lower atrial rhythm on the 4th day, and recovered to sinus rhythm on the 14th day. Coronary angiography (CAG) on 15th day showed a recanalization of the SN artery, but optical coherence tomography identified that disrupted plaque and white thrombus still existed in the ostium of the SN artery. The patient was discharged on maintenance anticoagulation therapy. We hypothesized from this case that IVUS-related myocardial injury may exist without clinical problems. Our retrospective investigation showed that the median levels of high-sensitivity TpT in 20 patients who underwent CAG and subsequent diagnostic IVUS significantly increased from 0.6 (interquartile range 0.3-1.1) to 1.6 (0.7-3.6) ng/l (P < 0.05), suggesting that IVUS may induce very low levels of myocardial injury. In conclusion, we experienced a rare case of IVUS-related MI caused by an acute occlusion of the SN artery. This case reaffirms that we should pay more attention to manipulation of IVUS catheters.

Malnutrition leads to the progression of coronary artery calcification in hemodialysis patients.

BACKGROUND: Malnutrition is considered a risk factor for cardiovascular disease in patients with chronic kidney disease. However, no in vivo studies have reported on using optical coherence tomography to evaluate the effect of nutritional status on coronary atherosclerosis in hemodialysis patients. We aimed to conduct a detailed analysis of the effect of nutritional status on the coronary arteries in hemodialysis patients. METHODS: Among 64 hemodialysis patients who underwent percutaneous coronary interventions, 41 that underwent optical coherence tomography imaging were included in this study. And, among them, 24 patients that could also be evaluated using OCT also at the 6-month follow-up were included in this study. The patients were divided into two groups based on nutritional evaluation using the geriatric nutritional risk index. Culprit and non-culprit lesions were evaluated at baseline and after 6 months. RESULTS: In the culprit lesions at baseline, the length of the lipid plaque was significantly smaller in the malnutrition group. In contrast, the thickness and length of the calcified plaque and the angle of the calcified nodule were significantly larger (each p < 0.01). In the non-culprit lesions, the 6-month change in the angle of the calcified plaque was significantly greater in the malnutrition group (p = 0.02). The significant factors that affected the change in the angle of calcification were "malnutrition at geriatric nutritional risk index" [odds ratio, 8.17; 95% confidence interval, 1.79 to 37.33; p < 0.01] and "serum phosphorus level" (odds ratio, 3.73; 95% confidence interval, 1.42 to 9.81; p < 0.01). CONCLUSIONS: Appropriate management of nutritional status is crucial for suppressing the progression of coronary artery disease in hemodialysis patients.

Effect of intravascular ultrasound-guided adjuvant high-pressure non-compliant balloon post-dilation after drug-eluting stent implantation.

Drug-eluting stent (DES) expansion characteristics after aggressive high-pressure post-dilation using a non-compliant (NC) balloon have not been fully investigated. We evaluated 58 patients with native coronary lesions treated with DESs [24 paclitaxel eluting stents (PES) and 34 sirolimus-eluting stents (SES)]. After post-dilation (12-14 atm) using a stent-mounted semi-compliant balloon to reduce stent edge injury, adjuvant high-pressure post-dilation using NC balloon was performed within the stents. Stent size, stent length, and NC balloon size were selected based on preinterventional intravascular ultrasound (IVUS) assessment. Stent underexpansion was defined according to criteria of the Multicenter Ultrasound Stenting in Coronaries (MUSIC) study as a minimal stent cross-sectional area <90% of the average reference lumen area. Resultant endpoint was to obtain optimal stent expansion. Serial changes of stent expansion and stent symmetry were calculated in each group. After stent-mounted semi-compliant balloon post-dilation, both stents could not achieve adequate percent stent expansion (PES 73 ± 18% vs. SES 67 ± 9%, p = 0.38). After high-pressure post-dilation using an NC balloon, percent stent expansion was 97 ± 14% in PES and 91 ± 13% in SES, respectively (p = 0.25). Axial stent symmetry indices also significantly improved in both groups. Although radial stent symmetry indices improved significantly in PES group, those in the SES group had no significant changes. Finally, frequency of stent underexpansion significantly reduced, 87-20% in PES and 92-15% in SES, respectively (p = 0.01) without any significant stent edge injury. DES expansion improved safely after adjuvant high-pressure post-dilation using an NC balloon under IVUS guidance.

Emergence and control of photonic band structure in stacked OLED microcavities.

We demonstrate an electrically-driven metal-dielectric photonic crystal emitter by fabricating a series of organic light emitting diode microcavities in a vertical stack. The states of the individual microcavities are shown to split into bands of hybridized photonic energy states through interaction with adjacent cavities. The propagating photonic modes within the crystal depend sensitively on the unit cell geometry and the optical properties of the component materials. By systematically varying the metallic layer thicknesses, we show control over the density of states and band center. The emergence of a tunable photonic band gap due to an asymmetry-introduced Peierls distortion is demonstrated and correlated to the unit cell configuration. This work develops a class of one dimensional, planar, photonic crystal emitter architectures enabling either narrow linewidth, multi-mode, or broadband emission with a high degree of tunability.

Healed Erosion: The Role of Pre-interventional Optical Coherence Tomography in a Patient Clinically Suspected of Having Unstable Angina with Coronary Spasm.

A 46-year-old man complained of chest pain at rest for the past three months. His symptoms gradually exacerbated and were suspected of being due to unstable angina. A coronary angiogram revealed focal tight stenosis at the proximal left anterior descending coronary artery with gross spastic coronary findings. Optical coherence tomography (OCT) revealed layered low-intensity structures with microvessels and the accumulation of macrophages, which indicated progressive stenosis with multiple-layered organized thrombus caused by coronary erosion. We treated the stenosis using a drug-coated balloon instead of drug-eluting stents. There was no restenosis, and OCT revealed good plaque healing at follow-up. This case suggests that the pre-interventional OCT plaque morphology can have a positive impact on the revascularization strategy.

Comparison of post-stent irregular protrusion and subsequent neointimal characteristics between second- and third-generation drug-eluting stent implantation.

BACKGROUND: Third-generation drug-eluting-stents (3rd DES) may improve coronary arterial healing and reduce neoatherosclerosis formation. We evaluated post-stent findings and subsequent vascular healing of 3rd DES by comparing to second-generation drug-eluting-stents (2nd DES) at intermediate-term follow-up using optical coherence tomography (OCT). METHOD: We evaluated 170 patients with 170 lesions who underwent DES implantation (2nd DES, n = 98; 3rd DES, n = 72) and OCT-guided follow-up examination. After propensity score (PS) matching for baseline clinical characteristics, OCT findings from 56 pairs of patients with 2nd DES and 3rd DES implants were compared. Post-stent irregular protrusion (IP) was defined as the protrusion of material with an irregular surface into the lumen between the stent struts. Neoatheroscleosis was defined as neointima contained heterogeneous pattern, rupture, lipid-laden, thin-cap fibroatheroma, or calcification. The presence of peri-strut low-intensity area (PLIA) and in-stent neointimal tissue characteristics were also analyzed at 6- to 8-month follow-up. RESULTS: There were no significant differences between the incidence of post-stent IP or neoatherosclerosis formation in the 2nd DES and the 3rd DES (45% vs. 38%, p = 0.44; 30% vs. 20%, p = 0.19, respectively). However, the incidences of PLIA and layered neointimal pattern, which indicate immature neointimal healing, were significantly lower in the 3rd DES compared to the 2nd DES (41% vs. 61%, p = 0.04; 2% vs. 11%, p = 0.04, respectively). As comparing intermediate-term follow-up OCT neointimal findings in patients with IP between 2nd DES and 3rd DES, most neointima tended to have a homogeneous pattern (95% versus 76%, p = 0.06) in the 3rd DES than in the 2nd DES. CONCLUSIONS: The incidence of post-stent IP and subsequent neoatherosclerosis formation at intermediate-term follow-up after stent implantation were similar between patients with 2nd DES and 3rd DES, however, vascular healing might be favorable when using 3rd DES.

Bleeding and ischemic events during dual antiplatelet therapy after second-generation drug-eluting stent implantation in hemodialysis patients.

BACKGROUND: Dual-antiplatelet therapy (DAPT) after second-generation drug-eluting stent (2nd-DES) implantation reduces the risk of stent thrombosis and subsequent ischemic events, with an increase in bleeding risk. Although chronic kidney disease patients have both high ischemic and bleeding events, little is known about both risks during DAPT in hemodialysis (HD) patients. METHODS: From July 2009 to March 2017, we retrospectively analyzed bleeding events and major adverse cardiac and cerebrovascular events (MACCE) in 644 consecutive patients who underwent successful percutaneous coronary intervention (PCI) with 2nd-DES implantation in our institution. We divided the patients into 2 groups [102 HD and 518 non-HD patients] after excluding 24 patients. The primary endpoint was bleeding events of Bleeding Academic Research Consortium (BARC) type 2, 3, or 5. The secondary endpoint was MACCE. We also investigated potential bleeding risk factors in those patients. RESULTS: At a median follow-up of 49 months, bleeding events occurred in 76 (12.3%) patients. Critical bleeding events of BARC type 3 or 5 occurred more frequently in HD (HD vs. non-HD: 16.7% vs. 7.1%; p=0.004). Most events tended to occur within 6 months post PCI. Multivariate analysis demonstrated that HD [hazard ratio (HR) 2.50, 95% confidence interval (CI) 1.03-3.16; p=0.04], body mass index (BMI) (HR 0.91, 95%CI 0.87-0.99, p=0.02), and serum albumin (HR 0.35, 95%CI 0.34-0.96, p=0.03) were independent predictors of bleeding events. MACCE also occurred more frequently in HD (HD vs. non-HD: 53.9% vs. 29.3%; p<0.001). Multivariate analysis demonstrated that pre-dialysis systolic blood pressure (HR 1.03, 95%CI 1.00-1.06, p=0.02) and high-sensitive C-reactive protein level (HR 1.76, 95%CI 1.06-2.72, p=0.03) were independent predictors of bleeding events in HD. CONCLUSIONS: HD displayed more adverse bleeding and ischemic events compared with non-HD. Therefore, practitioners should reconsider the current regimen of DAPT in this patient cohort to prevent critical bleeding complications and spates of ischemic events.

Concerted Photoluminescence of Electrochemically Self-Assembled CuSCN/Stilbazolium Dye Hybrid Thin Films.

Hybrid thin films of crystalline CuSCN and 4-(N,N-dimethylamino)-4'-(N'-methyl)stilbazolium (DAS) in three distinctively different nanostructures were obtained by electrochemical self-assembly from a single pot containing all the chemical ingredients. Their optical properties for UV-vis-NIR absorption, photoluminescence (PL), and PL excitation spectra were examined between 77 and 298 K, in comparison with solution and solid powder of DAS tosylate (DAST). Unlike all other dyes we tested before, PL of DAS was not quenched but rather enhanced when hybridized with CuSCN. DAST exhibited a strong exciton-phonon coupling to weaken, broaden, and red shift PL at room temperature, so that it inversely is strongly enhanced, sharpened, and blue-shifted at 77 K. The PL of the same dye in the hybrid thin film, however, shows a slight red shift and only a moderate enhancement at reduced temperatures due to strong exciton stabilization in dielectric environment of CuSCN and concerted PL by energy transfer from CuSCN to DAS luminophore, making it a unique nearly temperature-independent luminescent material.

Impact of additional intracoronary nicorandil administration during fractional flow reserve measurement with intravenous adenosine 5'-triphosphate infusion.

BACKGROUND: Fractional flow reserve (FFR) is a useful index for determining the functional severity of epicardial coronary artery stenosis as an invasive physiological method. Although intravenous adenosine 5'-triphosphate (ATP) is generally used as a hyperemic agent for FFR measurement in Japan, there are some concerns about the variability of FFR measurement (short half-life, effect of caffeine, cyclic change). It is difficult to confirm sufficient maximum hyperemia after ATP infusion. Recent studies reported that nicorandil (NIC) could be an alternative to ATP as a hyperemic agent. METHODS: Patients who underwent FFR assessments of angiographically intermediate lesions were included. All patients were asked to refrain from caffeine-containing products more than 12hours before FFR measurements. All patients first received intravenous (IV) ATP infusion (180µg/kg/min) for 3min to measure FFR (ATP-FFR). After additional intracoronary (IC) NIC administration (2mg/30s) during ATP infusion, FFR was measured again (NIC-FFR). To check cyclic change in FFR, we measured minimum and maximum FFR values during both ATP and NIC hyperemic phase. RESULTS: In this study, 94 patients with 94 lesions were enrolled. Mean FFR value was 0.81±0.10 in ATP-FFR infusion and 0.80±0.09 in NIC-FFR, respectively. ATP-FFR and NIC-FFR had a strong correlation on the whole (r=0.92, p<0.001). In 18 patients (19%), FFR values were significantly lower in NIC-FFR than in ATP-FFR. In one-third of those patients (6%), it was possible to change therapeutic strategy from deferral range (>0.80) to interventional range (≦0.80) after NIC-FFR measurements. Cyclic change in FFR was smaller in NIC-FFR than in ATP-FFR (0.03±0.02 vs. 0.06±0.05, p<0.0001). CONCLUSION: Additional IC NIC might be useful to confirm sufficient maximum hyperemia after IV ATP infusion in daily clinical practice. Furthermore, IC NIC could reduce cyclic change in FFR; thus, physicians might find it easier to determine FFR value during the procedure.