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Hiroshi Yoshitani, Junko Ito, Hideki Kozono Pharmaceutical & Medical Device Vigilance Department, Toray Industries, Inc., Tokyo, JapanCorrespondence: Hiroshi Yoshitani, Pharmaceutical & Medical Device Vigilance Department, Toray Industries, Inc., 1-1, Nihonbashi-Muromachi 2-chome, Chuo-ku, Tokyo, 103-8666, Japan, Tel +81 3 3245-8615, Email hiroshi.yoshitani.c2@mail.torayBackground: Nalfurafine (Remitch®, Toray Industries, Inc.) is a selective κ-receptor agonist approved in Japan for the improvement of pruritus in patients with chronic liver diseases (only when existing treatments bring insufficient efficacy) in May 2015.Methods: A post-marketing Specific Drug Use Survey was conducted in Japan (March 1, 2016 to June 30, 2020) of the safety and efficacy of nalfurafine for the improvement of pruritus in patients with chronic liver disease.Results: Among 1186 cases analyzed for safety, the incidence of adverse drug reactions was 9.4% (112/1186 cases), lower than 61.4% reported in pre-marketing surveillance (297/484 cases). No specific safety issues were found and no cases of concern for drug dependence identified. Efficacy (itch improvement) was demonstrated in 73.16% (815/1114 cases; 12-week analysis set) and in 85.67% (520/607; general assessment of itch improvement at 1-year analysis set). A significant difference was found in 4 items of itch improvement at 12 weeks and 8 items of itch improvement at 1 year. No noteworthy issues were identified. Mean Visual Analog Scale (VAS) values after 12 weeks and 1 year after the first dose were significantly lower than the baseline (p < 0.0001 for both treatment durations). Mean severity scores (Kawashima’s classification scheme) were significantly lower than the pretreatment score at 12 weeks and 1 year after the first dose (both p < 0.0001). No concerns were identified in the efficacy and safety of nalfurafine in patients with specific background, ie, the elderly (aged ≥ 65 years), those with renal impairment, and those on long-term treatment (≥ 365 days) compared with patients without corresponding background.Conclusion: No new safety issues of concern or cases of insufficient efficacy were identified in this Specific Drug Use Survey of the safety and efficacy of nalfurafine for the improvement of pruritus in patients with chronic liver diseases.Keywords: post-marketing surveillance, safety, efficacy, nalfurafine, pruritus, chronic liver disease

Hideki Kozono,* Hiroshi Yoshitani,* Ryoko Nakano* Pharmaceutical and Medical Device Vigilance Department, Toray Industries, Inc., Tokyo, Japan *The authors contributed equally to this work Background: Intractable pruritus in hemodialysis patients can significantly decrease their quality of life and is also associated with poor vital prognosis. Although combined multiple causes of intractable pruritus in these patients have been identified, no existing treatments are proven to be sufficiently effective. We conducted a post-marketing surveillance to follow-up and assess the safety and efficacy of nalfurafine, a selective κ-opioid receptor agonist, for the treatment of intractable pruritus in patients undergoing hemodialysis. Patients and methods: Hemodialysis patients with intractable pruritus from institutions in Japan who received oral nalfurafine hydrochloride between January 2010 and December 2013 were enrolled in the surveillance. Surveillance was completed in July 2015. Safety data during 1 year after nalfurafine treatment onset, and efficacy data of nalfurafine evaluating the first 12-week treatment period and the following period until 1 year after the initial dose of nalfurafine (using global assessment of the itch improvement by the physician, Visual Analog Scale, and the Shiratori’s severity scores) were collected and analyzed. Results: In total, 3,762 patients were analyzed for safety. Adverse drug reactions were experienced by 402/3,762 (10.69%) patients. The most frequent adverse drug reactions were insomnia (127/3,762 [3.38%] patients), constipation (34 [0.90%]), somnolence (32 [0.85%]), dizziness (23 [0.61%]), nausea (13 [0.35%]), and malaise (9 [0.24%]). No patients developed dependence on nalfurafine. Nalfurafine was effective in 82.50% (2,880/3,491) of patients during the first 12 weeks and in 84.95% (2,167/2,551) on treatment during the subsequent period until 1 year after nalfurafine treatment initiation. Statistically significant decreases were reported in the Visual Analog Scale and the Shiratori’s severity scores (p

Limited data exist regarding drug-coated balloon (DCB) treatment in de novo large coronary arteries. We sought to demonstrate procedural characteristics, residual stenosis, and clinical outcomes following DCB angioplasty for de novo lesions in large versus small coronary arteries. The study included 184 consecutive patients with 223 de novo coronary lesions undergoing paclitaxel DCB angioplasty between January 2019 and August 2020, who were divided according to whether the DCB diameter was ≥ 3.0 mm (large group, n = 58) or < 3.0 mm (small group, n = 125). The large group had a higher proportion of acute coronary syndrome more commonly with ostial, bifurcation, and calcified lesions in large vessels and received lesion preparation with more frequent use of scoring or cutting balloons and atherectomy devices compared to the small group. Postprocedural angiographic diameter stenosis was smaller in the large group compared to the small group (31% [22-37] vs. 35% [26-42], p = 0.032), and intravascular ultrasound revealed no significant difference in postprocedural area stenosis between the groups (66.2 ± 7.7% vs. 67.9 ± 7.8%; p = 0.26). The median follow-up duration was 995 days. The incidence of a composite of all-cause death, myocardial infarction, stroke, or target lesion revascularization was similar between the groups (log-rank p = 0.41) and was influenced by the presence of acute coronary syndrome and anemia but not by DCB diameter. The rate of cardiovascular outcomes after DCB treatment was comparable in de novo large and small coronary arteries. Notably, well-planned lesion preparation with intravascular imaging guidance was prevalent in large vessels., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Background: There is a paucity of data regarding the optimal duration of drug-coated balloon (DCB) inflation for coronary lesions. We sought to explore the effect of DCB angioplasty with versus without long inflation time on residual stenosis and clinical outcomes in patients with coronary artery disease., Methods: This study included 314 consecutive patients with 445 lesions undergoing paclitaxel DCB angioplasty using different inflation time, divided according to whether the total inflation time of the DCB was ≥180 s (prolonged group) or <180 s (standard group). The primary clinical endpoint, defined as a composite of all-cause death, myocardial infarction, stroke, or target lesion revascularization, was examined in 92 propensity score matched pairs., Results: In the matched cohort, the median clinical follow-up period was 947 days. Postprocedural angiographic diameter stenosis was smaller in the prolonged group than in the standard group (30.0% [22.0-37.0] vs. 33.5% [25.5-40.5]; p = 0.042). Intravascular ultrasound measurements revealed that longer DCB inflation time resulted in smaller area stenosis (66.6 ± 7.8% vs. 69.4 ± 7.0%; p = 0.044) and a less mean increase in percent atheroma volume (-11.2 ± 7.1% vs. -7.4 ± 5.9%; p = 0.004) after angioplasty. The rate of the primary endpoint was lower in the prolonged group than in the standard group (log-rank p = 0.025). The efficacy of prolonged DCB inflation was prominent in patients with in-stent restenosis and longer lesions., Conclusion: Prolonged DCB inflation was associated with reduced residual stenosis and improved clinical outcomes in patients with coronary artery disease undergoing percutaneous coronary intervention. Prospective randomized trials are warranted to validate the benefits of DCB angioplasty with long inflation time., (© 2023 Wiley Periodicals LLC.)

Radiation can be visualized using a scintillator and a digital camera. If the amount of light emitted by the scintillator increases with dose, the dose estimation can be obtained from the amount of light emitted. In this study, the basic performance of the scintillator and digital camera system was evaluated by measuring computed tomography dose index (CTDI). A circular plastic scintillator plate was sandwiched between polymethyl methacrylate (PMMA) phantoms, and x-rays were irradiated to them while rotating the x-ray tube to confirm changes in light emission. In addition, CTDI was estimated from the amount of light emitted by the scintillator during the helical scan and compared with the value measured from dosimeter. The scintillator emitted light while changing its distribution according to the movement of the x-ray tube. The measured CTDI vol was 33.20 mGy, the CTDI vol estimated from the scintillation light was approximately 46 mGy, which was 40% larger. In particular, when the scintillator was directly irradiated, the dose was overestimated compared with the value measured from the dosimeter. This overestimation can be because of the reproducibility of the position and the difference between the sensitivity of the scintillator to detect light emission and the sensitivity of the dosimeter, and the non-uniformity of position sensitivity due to the wide-angle lens., (© 2022 IOP Publishing Ltd.)

Lithium-sulfur batteries hold promising potential for next-generation high-energy-density energy storage. One of their major technical problems is the sulfur active material loss and significant volume change during the charge-discharge process, resulting in rapid capacity fading. Here, we propose sulfur-inserted polymer-anchored edge exfoliated graphite as a positive electrode to accommodate the conflicting requirement of physically restraining sulfur dissolution while maintaining structural flexibility to cope with the volume expansion. The introduction of sulfur between the flexible polymer-anchored graphene layers is achieved by a simple chemical reaction at ambient temperature. The obtained sulfur-carbon composite demonstrates superior sulfur efficiency and cyclability compared to mesoporous carbon-based counterparts. The strong interfacial attraction between sulfur and highly-conductive graphene sheets at the confined interlayer space enables rapid charge transfer and effectively inhibits the polysulfide dissolution, resulting in improved redox reaction reversibility and sulfur efficiency. More importantly, the structural flexibility of layered structure, derived from polymer-anchor, guarantees the stable cycling by accommodating the significant volume expansion of sulfur active materials. Our work provides a simple, proof-of-concept strategy for improving the overall performance of carbon-based positive electrode for Li-S batteries., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Gamma cameras are used in nuclear medicine examinations involving radioisotopes; however, they do not provide real-time feedback. We propose a real-time imaging method based on a commercially available digital camera and a scintillator array to provide simple and accurate measurements of radioisotope accumulation and contamination. We evaluate the sensitivity and resolution of the proposed device using x-rays as a proxy for gamma-rays. The performance of the device is demonstrated using PENTAX KP and ORCA-spark C11440-36U digital cameras. A caesium iodide scintillator array is irradiated with x-rays, with the state of light emission confirmed using live view images. The pixel value is evaluated as a function of dose rate. Furthermore, we investigate the state of light emission in response to amplifying the light signal using an image intensifier. For the PENTAX KP, luminescence is observable for a dose rate of approximately 10 mSv h -1 , which changes to 2.1 mSv h -1 when an image intensifier is used. Notably, the ORCA-spark detected emission at a low dose rate of 0.06 mSv h -1 . However, using an image intensifier resulted in noisier images. Therefore, although the ORCA-spark can observe luminescence at a suitable predicted dose rate for application in nuclear medicine examinations, a collimator is required to control the spread of gamma rays. However, as this causes the sensitivity to decrease, increasing the amount of light emitted by the scintillator and improving the sensitivity of the camera is vital., (© 2021 IOP Publishing Ltd.)

Background: Basal interventricular septum (IVS) hypertrophy (BSH) with reduced basal IVS contraction and IVS-aorta angle is frequently associated with aortic stenosis (AS). BSH shape suggests compression by the longitudinally elongated ascending aorta, causing basal IVS thickening and contractile dysfunction, further suggesting the possibility of aortic wall shortening to improve the BSH. Surgical aortic valve replacement (SAVR), as opposed to transcatheter AVR (TAVR), includes aortic wall shortening by incision and stitching on the wall and may potentially improve BSH. We hypothesized that BSH configuration and its contraction improves after SAVR in patients with AS., Methods and results: In 32 patients with SAVR and 36 with TAVR for AS, regional wall thickness and systolic contraction (longitudinal strain) of 18 left ventricular (LV) segments, and IVS-aorta angle were measured on echocardiography. After SAVR, basal IVS/average LV wall thickness ratio, basal IVS strain, and IVS-aorta angle significantly improved (1.11±0.24 to 1.06±0.17; -6.2±5.7 to -9.1±5.2%; 115±22 to 123±14°, P<0.001, respectively). Contractile improvement in basal IVS was correlated with pre-SAVR BSH (basal IVS/average LV wall thickness ratio or IVS-aorta angle: r=0.47 and 0.49, P<0.01, respectively). In contrast, BSH indices did not improve after TAVR., Conclusions: In patients with AS, SAVR as opposed to TAVR improves associated BSH and its functional impairment.

Background: Intractable pruritus in hemodialysis patients can significantly decrease their quality of life and is also associated with poor vital prognosis. Although combined multiple causes of intractable pruritus in these patients have been identified, no existing treatments are proven to be sufficiently effective. We conducted a post-marketing surveillance to follow-up and assess the safety and efficacy of nalfurafine, a selective κ-opioid receptor agonist, for the treatment of intractable pruritus in patients undergoing hemodialysis., Patients and Methods: Hemodialysis patients with intractable pruritus from institutions in Japan who received oral nalfurafine hydrochloride between January 2010 and December 2013 were enrolled in the surveillance. Surveillance was completed in July 2015. Safety data during 1 year after nalfurafine treatment onset, and efficacy data of nalfurafine evaluating the first 12-week treatment period and the following period until 1 year after the initial dose of nalfurafine (using global assessment of the itch improvement by the physician, Visual Analog Scale, and the Shiratori's severity scores) were collected and analyzed., Results: In total, 3,762 patients were analyzed for safety. Adverse drug reactions were experienced by 402/3,762 (10.69%) patients. The most frequent adverse drug reactions were insomnia (127/3,762 [3.38%] patients), constipation (34 [0.90%]), somnolence (32 [0.85%]), dizziness (23 [0.61%]), nausea (13 [0.35%]), and malaise (9 [0.24%]). No patients developed dependence on nalfurafine. Nalfurafine was effective in 82.50% (2,880/3,491) of patients during the first 12 weeks and in 84.95% (2,167/2,551) on treatment during the subsequent period until 1 year after nalfurafine treatment initiation. Statistically significant decreases were reported in the Visual Analog Scale and the Shiratori's severity scores ( p <0.001)., Conclusion: Oral nalfurafine hydrochloride (from 2.5 μg/day to a maximum of 5.0 μg/day) continues to be safe and effective for the treatment of intractable pruritus in hemodialysis patients in real-world clinical settings., Competing Interests: Disclosure Hideki Kozono, Hiroshi Yoshitani, and Ryoko Nakano are employees of Toray Industries, Inc., and report no other conflicts of interest in this work.

Many members of the BTB-ZF family have been shown to play important roles in lymphocyte development and function. The role of zinc finger Znf131 (also known as Zbtb35) in T cell lineage was elucidated through the production of mice with floxed allele to disrupt at different stages of development. In this article, we present that Znf131 is critical for T cell development during double-negative to double-positive stage, with which significant cell expansion triggered by the pre-TCR signal is coupled. In mature T cells, Znf131 is required for the activation of effector genes, as well as robust proliferation induced upon TCR signal. One of the cyclin-dependent kinase inhibitors, p21(Cip1) encoded by cdkn1a gene, is one of the targets of Znf131. The regulation of T cell proliferation by Znf131 is in part attributed to its suppression on the expression of p21(Cip1)., (Copyright © 2015 by The American Association of Immunologists, Inc.)

Background: Heart failure (HF) can be caused by left ventricular (LV) pump failure as well as by bradyarrhythmias. Hemodynamic differences between HF by LV pump failure and that by bradyarrhythmia have not been fully investigated. We hypothesized that HF by LV pump failure could be associated with both reduced cardiac output (CO) and increased LV filling pressure due to associated LV diastolic dysfunction, whereas HF by bradyarrhythmia could be associated with reduced CO but only modestly increased LV filling pressure due to the absence of LV diastolic dysfunction., Methods: In 39 patients with HF by LV pump failure (LV ejection fraction <35%), 24 with HF by bradyarrhythmia, and 22 normal controls, LV volume, ejection fraction, stroke volume, left atrial volume, and early diastolic mitral valve flow to tissue annular velocity ratio (E/E') were measured by echocardiography., Results: Compared to patients with HF by LV pump failure, those with HF by bradyarrhythmia had significantly lower heart rates, less LV dilatation, preserved LV ejection fraction, preserved stroke volume, similarly reduced cardiac index (1.8 ± 0.4 vs. 1.6 ± 0.4 L/min/m(2), n.s.), preserved LV diastolic function (E') (4.4 ± 2.1 vs. 7.1 ± 2.9 cm/s, p < 0.001), less dilated end-systolic LA volume, and preserved E/E' (24 ± 10 vs. 13 ± 7, p < 0.001)., Conclusions: HF by LV pump failure is characterized by both significantly reduced CO and increased LV filling pressure, whereas HF by bradyarrhythmia is characterized by a similar reduction in CO but only modestly increased LV filling pressure.

Objective: Mitral annular/leaflet calcification (MALC) is frequently observed in patients with degenerative aortic stenosis (AS). However, the impact of MALC on mitral valve function has not been established. We aimed to investigate whether MALC reduces mitral annular area and restricts leaflet opening, resulting in non-rheumatic mitral stenosis., Methods: Real-time three-dimensional transoesophageal images of the mitral valve were acquired in 101 patients with degenerative AS and 26 control participants. The outer and inner borders of the mitral annular area (MAA) and the maximal leaflet opening angle were measured at early diastole. The mitral valve area (MVA) was calculated as the left ventricular stroke volume divided by the velocity time integral of the transmitral flow velocity., Results: Although the outer MAA was significantly larger in patients with AS compared to control participants (8.2±1.3 vs 7.3±0.9 cm(2), p<0.001), the inner MAA was significantly smaller (4.5±1.1 vs 5.9±0.9 cm(2), p<0.001), resulting in an average decrease of 45% in the effective MAA. The maximal anterior and posterior leaflet opening angle was also significantly smaller in patients with AS (64±10 vs 72±8°, p<0.001, 71±12 vs 87±7°, p<0.001). Thus, MVA was significantly smaller in patients with AS (2.5±1.0 vs 3.8±0.8 cm(2), p<0.001). Twenty-four (24%) patients with AS showed MVA <1.5 cm(2). Multivariate regression analysis including parameters for mitral valve geometry revealed that a decrease in effective MAA and a reduced posterior leaflet opening angle were independent predictors for MVA., Conclusions: Calcific extension to the mitral valve in patients with AS reduced effective MAA and the leaflet opening, resulting in a significant non-rheumatic mitral stenosis in one-fourth of the patients.

Objectives: This study sought to examine left atrial (LA) mechanics and the prognostic impact of patients with echocardiographic findings of E/A ratio ≤0.75, deceleration time (DcT) of mitral E-wave >140 ms, but E/ε' ≥10., Background: Traditional diastolic dysfunction (DD) grading system could not classify every patient into a specific group. We considered the group of patients with E/A ≤0.75, DcT >140 ms, but E/ε' ≥10 (proposed new DD grade) as a new group in the DD grading system., Methods: A total of 1,362 consecutive patients were stratified according to the new DD grading system, and the LA volumes, strain, and strain rates were measured by 2-dimensional speckle-tracking analysis. All patients were followed up to determine cardiac death and major adverse cardiac events., Results: An E/A ≤0.75, DcT >140 ms, but E/ε' ≥10 was observed in 227 patients (17%). LA volumes in patients with the new DD grade were between those of the impaired relaxation group and the pseudonormal group. LA strain of the new DD grade was similar to that of the pseudonormal group, whereas LA booster function was preserved as in the impaired relaxation group. During a mean follow-up of 3.0 ± 1.1 years, 25 patients had cardiac death and 61 had major adverse cardiac events. Event-free survival for major adverse cardiac events of the new DD grade was worse than that of the impaired relaxation group but similar to that of the pseudonormal group., Conclusions: The new DD grade is frequently observed and has a prognosis similar to that of the pseudonormal group but significantly worse than that of the impaired relaxation group. However, LA booster function was maintained at the expense of LA volume enlargement. Thus, the new grade should be a distinct entity for routine DD grading., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The authors hypothesized that aortic root geometry is different between bicuspid and tricuspid aortic stenosis (AS) that can be assessed using real-time three-dimensional (3D) transesophageal echocardiography. The aims of this study were (1) to validate the accuracy of 3D transesophageal echocardiographic measurements of the aortic root against multidetector computed tomography as a reference, (2) to determine the difference of aortic root geometry between patients with tricuspid and bicuspid AS, and (3) to assess its impact on pressure recovery., Methods: In protocol 1, 3D transesophageal echocardiography and contrast-enhanced multidetector computed tomography were performed in 40 patients. Multiplanar reconstruction was used to measure the aortic annulus, the sinus of Valsalva, and the sinotubular junction area, as well as the distance and volume from the aortic annulus to the sinotubular junction. In protocol 2, the same 3D transesophageal echocardiographic measurements were performed in patients with tricuspid AS (n = 57) and bicuspid AS (n = 26) and in patients without AS (n = 32). The energy loss coefficient was also measured in patients with AS., Results: In protocol 1, excellent correlations of aortic root geometric parameters were noted between the two modalities. In protocol 2, compared with patients without AS, those with tricuspid AS had smaller both sinotubular junction areas and longitudinal distances, resulting in a 23% reduction of aortic root volume. In contrast, patients with bicuspid AS had larger transverse areas and longitudinal distances, resulting in a 30% increase in aortic root volume. The energy loss coefficient revealed more frequent reclassification from severe AS to moderate AS in patients with tricuspid AS (17%) compared with those with bicuspid AS (10%)., Conclusions: Three-dimensional transesophageal echocardiography successfully revealed different aortic root morphologies between tricuspid and bicuspid AS, which have different impacts on pressure recovery., (Copyright © 2014 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Background: The aim of this study was to investigate the effect of out-of-plane motion on discrepancies in strain measurements between two-dimensional (2D) and three-dimensional (3D) echocardiography., Methods: Two-dimensional and 3D data sets were acquired in 54 patients. Using 2D and 3D speckle-tracking software, global circumferential strain (CS) and longitudinal strain (LS) as well as CS and LS at three left ventricular (LV) levels was measured. The effect of through-plane motion was assessed by mitral annular displacement., Results: Although a good correlation of global CS was noted between the two methods (r = 0.80, P < .01), mean values of global CS were significantly higher on 3D compared with 2D echocardiography. Correlations of CS and their mean differences were 0.65 and -4.61 at the basal level, 0.76 and -4.17 at the midventricular level, and 0.60 and -2.23 at the apical level, respectively. Correlation of global CS between the two methods was higher in patients who showed mitral annular displacement < 9.4 mm (r = 0.81) compared with those with mitral annular displacement ≥ 9.4 mm (r = 0.61). A good correlation of global LS (r = 0.89, P < .01) was noted, with no significant bias. Correlations of LS and their mean differences were 0.52 and 1.59 at the basal level, 0.89 and -1.17 at the midventricular level, and 0.73 and 1.46 at the apical level, respectively. Correlation of LS between the two methods was higher in patients who showed LV twist < 12.2° (r = 0.94) compared with patients with LV twist ≥ 12.2° (r = 0.68)., Conclusions: Through-plane motion produced discrepancies in CS measurements, especially at the LV basal level. Larger bias of LS at the basal and apical LV levels compared with the midventricular level between the two methods suggests that LV twisting also affects the calculation of 2D LS., (Copyright © 2013 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Objectives: The hypothesis of this study was that minimal left atrial volume index (LAVImin) by 3-dimensional echocardiography (3DE) is the best predictor of future cardiovascular events., Background: Although maximal left atrial volume index (LAVImax) by 2-dimensional echocardiography (2DE) is a robust index for predicting prognosis, the prognostic value of LAVImin and the superiority of measurements by 3DE over 2DE have not been determined in a large group of patients., Methods: In protocol 1, we assessed age and sex dependency of LAVIs using 2DE and 3DE in 124 normal subjects and determined their cutoff values (mean + 2 SD). In protocol 2, 2-dimensional (2D) and 3-dimensional (3D) LAVImax/LAVImin were measured in 556 patients with high prevalence of cardiovascular disease. After excluding patients with atrial fibrillation, mitral valve disease, and age <18 years, 439 subjects were followed to record major adverse cardiovascular events (MACE). Patients were divided into 2 groups by the cutoff criteria of LAVI in each method., Results: In protocol 1, there was no significant age and sex dependency for each 2D and 3D LAVI. In protocol 2, during a mean of 2.5 years of follow-up, MACE developed in 88 patients, including 32 cardiac deaths. Kaplan-Meier survival analyses showed that all 4 LAVI cutoff criteria had significant predictive power of MACE. After variables were adjusted for clinical variables and left ventricular ejection fraction, all 4 methods were still independently and significantly associated with MACE, but 3D-derived LAVImin had the highest risk ratio. 3D LAVImin also had an incremental prognostic value over 3D LAVImax., Conclusions: LAVIs by both 2DE and 3DE are powerful predictors of future cardiac events. 3D LAVImin tended to have a stronger and additive prognostic value than 3D LAVImax., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Previous studies have suggested an increase in myocardial oxygen demand as a cause of postprandial angina. The purpose of this study was to assess coronary flow velocity reserve (CFVR) in the left anterior descending coronary artery (LAD) before and after glucose ingestion in patients with known significant LAD stenosis., Methods: Fourteen patients with significant LAD stenosis and 20 subjects without LAD stenosis were enrolled. Transthoracic Doppler echocardiography was performed to measure the average peak diastolic coronary flow velocity (APDV) in the LAD at rest and during adenosine infusion. CFVR was calculated as APDV during adenosine infusion (APDVATP) divided by APDV at rest (APDVrest). APDVrest, APDVATP, and CFVR were assessed during fasting and 30, 60, and 120 min after a 75-g oral glucose loading., Results: In patients with LAD stenosis, APDVrest at 30 min after glucose loading was the highest at any time point. However, significant differences were not found in the APDVATP among time points in the patients or controls. Consequently, the CFVR in the patients was the lowest at 30 min after glucose loading (fasting, 1.77 ± 0.19; 30 min, 1.48 ± 0.16; 60 min, 1.69 ± 0.17; and 120 min, 1.76 ± 0.19; p < 0.01, ANOVA), as in the controls., Conclusions: These findings suggested that the value of CFVR in the LAD was reduced after glucose loading. Myocardial risk area supplied by a stenosed coronary artery may be exposed to myocardial ischemia more frequently during oral glucose loading than during fasting in patients with significant coronary artery stenosis.

Background: Although left atrial volume (LAV) by two-dimensional (2D) echocardiography provides prognostic information, the misalignment of the 2D cutting plane of the left atrium could make the measurements inaccurate. The aim of this study was to test the hypothesis that LAV measurement from three-dimensional (3D) echocardiographic data sets using the biplane Simpson's technique is a more reliable approach for measuring LAV., Methods: The accuracy of 3D echocardiographic LAV measurements was retrospectively determined in 20 patients using multidetector computed tomography as a reference. LAV indexed to body surface area (LAVI) was measured using 2D and 3D echocardiography in 200 other subjects. LAV determination by 2D echocardiography was performed using the biplane Simpson's method. A 3D determination of LAV was performed using quantitative software and the biplane Simpson's method using the anterior-posterior and medial-lateral 2D views extracted from the 3D data sets., Results: Although LAV using the 3D volumetric method (mean, 98 ± 24 mL) was slightly but significantly lower than LAV on multidetector computed tomography (mean, 103 ± 23 mL), a significant correlation between the two methods (r = 0.97, P < .001) with acceptable limits of agreement was noted. The left atrial short-axis image extracted from the 3D data sets revealed an ellipsoid shape. Although a good correlation for LAVI was noted between the 2D biplane Simpson's method and the 3D volumetric method (r = 0.96, P < .001), the mean value of 2D echocardiographic LAVI was significantly greater compared with 3D echocardiographic LAVI, with a mean bias of 4.7 mL/m(2). An excellent correlation was noted between the 3D biplane Simpson's and 3D volumetric methods (r = 0.99, P < .001), with a lower bias (0.54 mL/m(2)) and limits of agreement of ±5.8 mL/m(2). The time required for LAV analysis was significantly shorter with the 2D (mean, 82 ± 7 sec) and 3D (mean, 94 ± 11 sec) biplane Simpson's methods (P < .01 vs 2D biplane Simpson's method) compared with the 3D volumetric methods (mean, 135 ± 24 sec) (P < .01 vs 2D and 3D biplane Simpson's methods)., Conclusions: The 2D biplane Simpson's method overestimates LAV because of the misalignment of the 2D cutting plane, and the 3D biplane Simpson's method is a practical and more reliable way to accurately determine LAV., (Copyright © 2012 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Background: In patients with mitral valve prolapse, nonprolapsed leaflets are often apically tented. We hypothesized that secondary left ventricular dilatation attributed to primary mitral regurgitation (MR) causes papillary muscle (PM) displacement, resulting in this leaflet tenting/tethering, and that secondary tethering further exacerbates malcoaptation and contributes to MR severity., Methods and Results: Three-dimensional transesophageal echocardiography was performed in 25 patients with posterior mitral leaflet prolapse with an intact anterior mitral leaflet (AML) and 20 controls. From 3D zoom data sets, 11 equidistant antero-posterior cut planes of the mitral valve at midsystole were obtained. In each plane, tenting area of nonprolapsed leaflet and prolapse area of prolapsed leaflet were measured. Prolapse/tenting volume of each region was obtained as the product of interslice distance and the prolapse/tenting area. AML tenting volume and whole leaflet prolapse/tenting volume were then obtained. The PM tethering distance between PM tips and anterior mitral annulus was measured from 3D full-volume data sets. The severity of MR was quantified by vena contracta area extracted from color 3D transesophageal echocardiography data sets. AML tenting volume was significantly larger in patients with posterior mitral leaflet prolapse compared with that in controls (1.2 ± 0.5 versus 0.6 ± 0.2 mL/m(2); P<0.001). Multivariate regression analysis identified independent contribution to AML tenting volume from an increase in PM tethering distance. Multivariate regression analysis identified independent contributions to MR severity (vena contracta area) from both whole leaflet tenting volume (r=0.44; P<0.05) and prolapse volume (r=0.44; P<0.05). AML tenting volume decreased along with left ventricular volume and PM tethering distance postrepair (n=8; P<0.01)., Conclusions: These results suggest that primary mitral valve prolapse with MR causes secondary mitral leaflet tethering with PM displacement by left ventricular dilatation, which further exacerbates valve leakage, constituting a vicious cycle that would suggest a pathophysiologic rationale for early surgical repair.

Background:  Different influences of left ventricular (LV) remodeling on anterior and posterior mitral leaflet (AML and PML) tethering in ischemic mitral regurgitation (MR) has not been fully investigated. We hypothesized that progressive outward displacement of papillary muscles, including posterior vector, may cause greater tethering to PML compared to AML., Methods and Results:  In 79 patients with LV ejection fraction <50% and 20 controls, LV sphericity, AML and PML tethering angles, apical and posterior displacement of coaptation, mitral annular area, and severity of MR (vena contracta width) were measured using 3-D echocardiography. To examine different influences of LV remodeling on AML and PML tethering, interaction between AML/PML and LV sphericity was tested using multiple regression analysis. Both AML and PML tethering significantly increased with increased LV sphericity (r=0.59 and 0.65, P<0.001). Multiple regression yielded a significant interaction term between AML vs. LV sphericity and PML vs. LV sphericity (t=3.69, P<0.001), indicating greater influence from LV remodeling on PML compared to that for the AML. Multivariate analysis demonstrated independent contributions to MR severity from PML tethering primarily along with posterior and apical displacement of coaptation., Conclusions:  LV remodeling augments tethering of both AML and PML, with greater influence on PML.

Aims: The aim of this study was to determine differences in the acute and chronic impact of adaptive servo-ventilation (ASV) on left chamber geometry and function in patients with chronic heart failure (CHF)., Methods and Results: An acute ASV study was performed to measure echocardiographic parameters before and 30 min after the initiation of ASV therapy in 30 CHF patients (mean age: 69 years, 23 male). The chronic effects of ASV therapy were also evaluated in 26 of these 30 patients over a mean follow-up period of 24 weeks. Patients were divided into two groups according to the status of ASV therapy [ASV group (n= 15) and withdrawal group (n= 11)]. In the acute study, heart rate and blood pressure were significantly decreased 30 min after the ASV therapy compared with baseline. Stroke volume and cardiac output were significantly increased in conjunction with a reduction in systemic vascular resistance. Multivariate regression analysis revealed baseline E/e' to be an independent predictor for absolute increase in cardiac output. In the chronic study, a significant reduction of left ventricular (LV)/left atrial (LA) volumes and the severity of mitral regurgitation (MR), and improved LV diastolic function parameters were noted in the ASV group. These beneficial effects were not observed in the withdrawal group., Conclusion: The acute beneficial impact of ASV is mainly associated with the reduction of afterload resulting in an increase in stroke volume and cardiac output. In contrast, chronic ASV therapy produces LV and LA reverse remodelling resulting in an improvement in LV function and the severity of MR in patients with CHF.

Background: Aging and gender may affect left ventricular (LV) mechanics. The aim of this study was to determine the age and gender dependency of LV mechanical indices obtained from real-time three-dimensional echocardiography (RT3DE)., Methods: RT3DE was performed in 280 healthy subjects (age range, 1-88 years; 137 men). From full-volume data sets, LV endocardial and epicardial borders were semiautomatically traced using quantitative software. LV volumes and corresponding long-axis diameter were measured throughout the cardiac cycle. Sphericity index was defined as the ratio of LV volume and spherical volume, calculated as 4/3 × π × (long-axis diameter/2)(3). LV mass was calculated as (LV epicardial volume - LV endocardial volume) × 1.05. The ratio of LV mass to LV volume was also calculated., Results: The mean value of LV ejection fraction did not change with age. However, LV volumes, mass, sphericity index, and LV mass/volume ratio were altered by age: (1) sphericity index was highest in the first decade of age and then declined until the fifth decade, (2) LV mass/volume ratio significantly increased in older age, and (3) LV mass/volume ratio was significantly higher in aged women compared with age-matched men., Conclusions: Age has heterogeneous effects on LV shape and LV mass/volume ratio, potentially due to the growing process of myocardial fibers and the surrounding architecture in the younger population, as well as the aging process, with an increase in vascular stiffness and a loss of myocytes in older populations. Higher LV mass/volume ratios in older women might be a contributor to the preferential development of diastolic heart failure in this population., (Copyright © 2011 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Background: Precise evaluation of the aortic root geometry prior to transcatheter aortic valve implantation is important for procedural success in patients with aortic stenosis (AS). To determine the potential for 3-dimensional transesophageal echocardiography (3DTEE), the aims of the present study were: (1) to assess the accuracy of 3DTEE measurements of the aortic root using multidetector computed tomography (MDCT) as a reference, and (2) to examine whether aortic root geometry differs between patients with and without AS., Methods and Results:   3DTEE and contrast-enhanced MDCT were performed in 35 patients. Multiplanar reconstruction was used to measure the left ventricular outflow tract (LVOT) and aortic annulus diameter/area, aortic valve area (AVA), and distances between the annulus and coronary artery ostium. The same 3DTEE measurements were performed in patients with (n=71) and without AS (n=80). Aortic annular and LVOT areas measured by 3DTEE were slightly but significantly smaller compared with values obtained with MDCT. Both methods revealed that the aortic annulus and LVOT have an oval shape. Aortic annular and LVOT area, AVA and the distances between the aortic annulus and the coronary ostia correlated well between the 2 modalities. Only minor differences in aortic root geometry were observed between patients with AS and those without., Conclusions: The geometry of the aortic annulus can be reliably evaluated using 3DTEE as an alternative to MDCT for the assessment of aortic root.

Background: Aging and westernization of lifestyle has accelerated the prevalence and severity of atherosclerotic cardiovascular diseases in the Japanese population. The aim of this study was to examine the prevalence of complex plaque formation in the descending thoracic aorta (DTA) as assessed by real-time 3-dimensional transesophageal echocardiography (3DTEE) and its relation to clinical factors., Methods and Results: A prospective analysis of atherosclerotic plaque in the DTA of 350 consecutive patients who were clinically indicated for real-time 3DTEE was performed. Systematic assessment of the DTA plaques was performed using a biplane mode from the aorta at the level of the stomach to the aortic arch. When a large plaque (>4mm) was identified, detailed 3-dimensional (D) observations were performed using a 3D zoom mode. Complex plaque was defined as either mobile or an ulcer-like pouch in the DTA. Complex plaques were detected in 51 patients (15%), who were more advanced in age and had a higher prevalence of chronic kidney disease. A multivariate analysis revealed that the presence of complex plaque was an independent predictor of renal impairment., Conclusions: The prevalence of complex plaque was not low in the this Japanese study population. A close association between complex plaque and renal dysfunction raises the possibility that complex plaque in the DTA is a potential cause of renal dysfunction.

Background: Mitral inflow patterns reflect not only left ventricular diastolic function but also left atrial (LA) remodeling. The aim of this study was to determine the effects of left ventricular diastolic dysfunction on LA volumetric and functional parameters assessed using two-dimensional speckle-tracking echocardiography., Methods: Two-dimensional speckle-tracking analysis of the LA wall in the apical four-chamber view was performed in 268 subjects. Subjects were classified according to diastolic dysfunction grade. Indexed maximum and minimum LA volumes and indexed LA volume before atrial contraction were measured from LA volume waveforms. Expansion, passive emptying, and active emptying indices were calculated., Results: LA volumes increased progressively with advanced stages of diastolic dysfunction. The expansion index and passive emptying index showed progressive decreases according to the grade of diastolic dysfunction. The active emptying index increased until mild diastolic dysfunction and thereafter progressively decreased until reaching severe diastolic dysfunction. Significant correlations were noted between the active emptying index and A-wave velocity (r = 0.31, P < .01) and between the E/E' ratio and the expansion index (r = 0.56, P < .01)., Conclusions: LA volumes and functional parameters derived from two-dimensional speckle-tracking echocardiography vary according to the level of diastolic dysfunction. These results suggest that left ventricular diastolic dysfunction also predicts the severity of LA remodeling., (2010 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Aims: The aims of this study were to (i) investigate aortic annulus dynamics using two-dimensional (2D) speckle tracking echocardiography, (ii) determine optimal 2D short-axis view for the calculation of planimetric aortic valve area (AVA), and (iii) compare 2D planimetric AVA extracted from volumetric three-dimensional data sets using real-time 3DTEE (three-dimensional transoesophageal echocardiography) with standard 2DTEE planimetry., Methods and Results: We studied 60 patients with aortic stenosis (AS) and 10 control subjects. AVA was calculated by standard 2DTEE planimetry method, volumetric 3DTEE method, and continuity equation (CE) from transthoracic echocardiography. In addition, aortic annular motion was studied using 2D speckle tracking. Aortic annulus moves cranially during early systole and subsequently moves caudally during the remainder of systole and isovolumic relaxation. Annulus again moved in the cranial direction during diastole in both groups. Although AVA correlated well between 2DTEE and 3DTEE methods (r = 0.95), 2DTEE showed a significantly larger AVA compared with 3DTEE method (1.26 +/- 0.39 vs. 1.10 +/- 0.39 cm(2), P < 0.001). In patients in whom aortic cusps were visible in 2DTEE short-axis images during systole only (n = 45), AVA using 2DTEE was still larger than that measured with 3DTEE. However, the bias in AVA was significantly lower compared with the remaining 15 patients (-0.13 +/- 0.11 vs. -0.26 +/- 0.12 cm(2), P < 0.005). Although both methods showed moderate correlation with AVA by CE (r = 0.78, 0.75), mean differences were significantly smaller by 3DTEE than 2DTEE (-0.01 +/- 0.25 vs. -0.17 +/- 0.27 cm(2), P < 0.001)., Conclusion: Aortic annular motion affects the calculation of AVA using 2DTEE. Three-dimensional transoesophageal echocardiography has a potential for more accurate determination of anatomical AVA.